jurnal kusta anak

VOLUME 73, NUMBER 4 DECEMBER 2005

INTERNATIONALJOURNAL OF LEPROSYAnd Other Mycobacterial Diseases

Official Organ of theINTERNATIONAL LEPROSY ASSOCIATION

(Association Internationale contre la Lèpre)(Asociación Internacional de la Lepra)

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Images from the History of Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Original ArticlesBikash Ranjan Kar, and C. K. Job. Visible Deformity in Childhood Leprosy—A Ten-Year Study. - - - - - - - - - - - - - - - - - -

Jan H. Richardus, Abraham Meima, Corine J. van Marrewijk, Richard P. Croft, and Trevor C. Smith.Close Contacts with Leprosy in Newly Diagnosed Leprosy Patients in a High and Low Endemic Area:Comparison between Bangladesh and Thailand. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

José L. Alfonso, Fernando A. Vich, Juan J. Vilata, and J. Terencio de las Aguas. Factors Contributing tothe Decline of Leprosy in Spain in the Second Half of the Twentieth Century. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

C. Ajith, Sachin Gupta, Bishan D. Radotra, Sunil K. Arora, Bhushan Kumar, Sunil Dogra, and InderjeetKaur. Study of Apoptosis in Skin Lesions of Leprosy in Relation to Treatment and Lepra Reactions. - - - - - - - - -

Clinical NotesG. N. Malaviya. Myiasis in Leprosy. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

CorrespondenceL. Oskam and S. Bührer-Sékula. A Need for Clarification of the Classification Criteria for Leprosy

Patients. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Dr. Gelber and Colleagues Reply. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

News and NotesLeprosy in the Era of AIDS. Report of a Meeting at Robben Island, SA. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

2005 U.S.-Japan Meeting, Seattle - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

EditorialElimination of (the International Journal of) Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Reviewers - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Special Grantors - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Index 2005 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

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INTERNATIONAL JOURNAL OF LEPROSY and Other Mycobacterial Diseases

CONTENTSVolume 73, Number 4, December 2005

INTERNATIONAL JOURNAL OF LEPROSY Volume 73, Number 4Printed in the U.S.A.

(ISSN 0148-916X)

INTERNATIONAL JOURNAL OF LEPROSY

and Other Mycobacterial Diseases

VOLUME 73, NUMBER 4 DECEMBER 2005

Images from the History of LeprosyChild patients and staff (also patients) at Robben Island Leprosy Hospital, South Africa,

circa 1920. This photo is from an album that belonged to Dr. Hans Peter Lie (1862–1945),a distinguished Norwegian leprologist, founding member of the board of the ILA, and anAssociate Editor of the JOURNAL. This is a digital copy of the original black and whiteprint in the collection of the Leprosy Museum in Bergen, Norway, a part of the BergenLeprosy Archives, and of the UNESCO program ‘Memory of the World’. It was madeavailable courtesy of Sigurd Sandmo, Curator.

241

ABSTRACTDeformity seen in children with leprosy has not often been studied, as the disease itself is

less common in children. Deformity, being synonymous with the stigma of leprosy, is a def-inite social problem in children. In this study we have focused on the burden of deformity inchildren with leprosy, and various factors responsible for the deformities are discussed. Wehave observed an incidence of 10.5% of Grade II deformities in children with leprosy, whichis very high compared to the community rate of 1.4%. Various factors which contributed sig-nificantly to the deformities in our study were: increasing age of children, delay in access-ing health care, multiple skin lesions, multibacillary disease, smear positivity, multiple nerveinvolvement, and reaction at the time of presentation to the hospital. Logistic regressionanalysis showed that children with thickened nerve trunks had 6.1 times higher risk of de-veloping deformities compared to those who did not have nerve enlargement. Children withthe above risk factors should be followed up more frequently so as to detect any deformityas early as possible.

RÉSUMÉLes déformations observées chez les enfants souffrant de lèpre ne sont guère étudiées,

peut-être parce que la maladie chez ces derniers est elle-même moins fréquente. Les défor-mations associées à la lèpre, synonymes de stigmatisation, sont accompagnées de problèmessociaux bien définis chez les enfants. Dans cette étude, nous nous sommes attachés à définirla prévalence des déformations chez les enfants atteints de lèpre, et à discuter les divers fac-teurs associés à ces déformations. Nous avons observé une incidence de 10,5 % de défor-mations de grade II chez les enfants souffrant de la lèpre, ce qui est très élevé par rapport autaux de 1, 4 % pour la communauté. Les facteurs ayant contribué de façon significative auxdéformations observées dans notre étude ont été une corrélation positive avec l’âge, le délaià accéder aux soins de santé, des lésions cutanées multiples, une forme multibacillaire, unexamen bactérioscopique positif du suc dermique, des atteintes nerveuses multiples et desréactions immunopathologique au moment de la présentation à l’hôpital. Une analyse de ré-gression logistique a montré que les enfants présentant des troncs nerveux épaissis avaient

1 Address for correspondence: Dr. Bikash Ranjan Kar, Department of Dermatology, Schieffelin Leprosy Re-search and Training Centre, Karigiri, Vellore – 632106, India; e-mail: [email protected]


(ISSN 0148-916X)

INTERNATIONAL JOURNAL OF LEPROSY

and Other Mycobacterial Diseases

DECEMBER 2005

Visible Deformity in Childhood Leprosy—

A 10-Year Study

Bikash Ranjan Kar, M.D., and C. K. Job, M.D.1

243

244 International Journal of Leprosy 2005

Childhood leprosy is an indicator of en-demicity of the disease (13). To the commonman leprosy is well known because of thestigma that is still prevalent in the society.This stigma is almost synonymous withvisible deformity. Major factors that con-tribute to deformity in various studies inadult leprosy patients are delay in diagnosis(10, 20), high bacillary load (16), multiplenerve enlargements (16), occurrence of reac-tion (19), and delay in provision of propercare of the disease. Therefore deformity is apreventable complication in the majority ofpatients. Deformity occurring in children ismore distressing both socially and psycho-logically, as they have to live their wholelife with stigma and in a hostile environ-ment. This study was carried out to docu-ment the number of children with Grade IIdeformity as well as to identify the role ofvarious risk factors contributing to its de-velopment.

MATERIALS AND METHODSAll the new childhood leprosy cases (<15

yrs) registering at Scheiffelin Leprosy Re-search & Training Center, Karigiri, for 10yrs (from July 1994 through June 2003)were analyzed retrospectively. Details werecollected concerning each patient on admis-sion included sex, age, WHO classification(2), skin smear status, duration of disease,involvement of nerves, occurrence of reac-tion, presence and nature of deformities and

the distribution of any deformities. For thepurpose of this study, deformity was gradedaccording to the WHO classification (25)and only patients with Grade II deformitieswere considered for analysis of risk factors.Nerve involvement was recorded accordingto the examining physician’s perception ofthickened nerves. Details of any previoustherapy received, as well as subsequenttreatment received from this institute, werealso noted. All the patients received mul-tidrug therapy as per WHO schedule (26, 14)and the progress of the disease was assessedin each patient. The odd’s ratio was calcu-lated with 95% CI for each parameter whileanalyzing relative risk. Logistic regressionanalysis was done to determine the signifi-cance of individual risk factors.

RESULTSIn all, 6031 new patients were registered

during the 10 yr period, from July 1994through June 2003, including 275 (4.5%)children with leprosy. Of these, 163(59.2%) were male and 112 (41.8%) werefemales. In age distribution, 13 patientswere below 4 yrs, 71 were between 5–9 yrsand 191 were between 10–15 yrs (Table 1).Comparing both the groups, i.e., those withvisible deformities to those without visibledeformities (Table 2), the majority of thedeformities were in the age group of 10–15yrs, followed by those in the age range of5–9 yrs. Deformities affecting children

un risque 6,1 fois plus élevé de développer des déformations que les enfants sans épais-sissements des nerfs. Les enfants avec les facteurs de risque analysés plus haut devraient êtresuivi plus fréquemment afin de détecter les déformations le plus précocement possible.

RESUMENLas deformidades en los niños con lepra son poco estudiadas porque la lepra en sí, es

menos común en los niños que en los adultos. La deformidad, sinónimo de estigma de lalepra, es un verdadero problema social entre los niños. En este estudio enfocado al estigmade la deformidad en los niños con lepra, se discuten varios factores responsables de la de-formidad. Observamos una incidencia del 10.5% de deformidades del Grado II en los niñoscon lepra. Esta incidencia es muy alta comparada con la incidencia del 1.4% en la comu-nidad general. Varios factores contribuyeron significativamente a la alta incidencia de de-formidades en nuestro estudio, entre ellos: incremento en la edad de los niños, retardo en laprocuración de atención médica, lesiones múltiples en la piel, enfermedad multibacilar, pos-itividad bacilar en la linfa cutánea, afectación nerviosa múltiple, y estados reaccionales almomento de su ingreso al hospital. Los análisis de regresión logística mostraron que losniños con troncos nerviosos engrosados tuvieron un riesgo 6.1 veces mayor de desarrollardeformidades que los niños sin engrosamiento de los nervios. Se concluye que los niños conlos factores de riesgo antes mencionados deben vigilarse con mayor frecuencia con el fin dedetectar cualquier deformidad tan pronto como aparezca.

73, 4 Kar and Job: Visible Deformity in Childhood Leprosy 245

10–15 yrs old was statistically significantwhen compared to the other age groups (p<0.05). Considering disease classification,238 children (86.5%) had paucibacillary(PB) disease whereas 37 (13.4%) hadmultibacillary (MB) disease. Of the 238 PBpatients, 20 (8.4%) had deformities,whereas 9 of the 37 MB cases (24.3%) haddeformities (p = 0.007). One hundredtwelve children (40.7%) presented withsingle patch, 126 (45.8%) with 1–4 patchesand the remaining 37 patients (13.4%) hadmultiple (≥5) patches.

Skin smears were negative at the time ofpresentation for 252 of the patients(91.6%), and 23 (8.4%) patients had a posi-tive skin smear. Deformities were seen in24 of 252 (9.5%) smear-negative patients,whereas 5 out of 23 (21.7%) smear-positivepatients had deformities (p = 0.06).

The average age of onset of the diseaseamong children was 9.49 ± 2.9 yrs. Averageduration of disease at the time of diagnosiswas (1.09 ± 0.8) yrs. Two hundred eleven

(76.7%) children presented to the hospitalwithin one year of onset of the disease,whereas 64 (23.2%) patients presented afterone year of onset of the disease. The major-ity of the patients with deformities (58.6%)attended the hospital before one year of on-set of the disease whereas 42.4% attendedafter one year of the onset of the disease. Inthe group without any deformities, 193(78.4%) presented for health care beforeone year of onset of the disease and the rest53 (21.5%) presented after one year of on-set of the disease. This difference was sta-tistically significant (p = 0.03)

The common peripheral nerve trunks in-volved in leprosy are the ulnar, radial, me-dian, lateral popliteal, posterior tibial andthe facial nerves (17). Thickened nervetrunks were present in 110 out of 275 pa-tients (40%) at the time of presentation, outof which 60 (21.8%) had only one majornerve involved, 22 (8%) had thickening oftwo major nerve trunks, and 28 (8.3%) hadmultiple (≥3 nerves) nerve involvement.The ulnar nerve was the commonest nervetrunk involved in 93 patients (33.8%), fol-lowed by the lateral popliteal nerve in 51(18.55%) and the posterior tibial nerve in12 (4.3%). Of the 110 children who pre-sented with thickened nerve trunks, 24(21.8%) had deformities, whereas only 5 of165 patients (3.0%) who presented withoutany nerve thickening had visible deformi-ties (p <0.001).

TABLE 1. Distribution of children withleprosy by age and sex.

Age Group F (%) M (%) Total (%)

0–4 7 (96.2) 6 (3.6) 13 (4.7)5–9 31 (27.7) 40 (24.6) 71 (25.8)10–15 74 (66.1) 117 (71.8) 191 (69.5)Total 112 (40.7) 163 (59.3) 275 (100)

TABLE 2. Risk factors for deformity in children. Odds rations of risk factors, adjustedand unadjusted by logistic regression.

Risk Without Unadjusted Adjusted byGroup With Logistic Regression

Factors Deformity Deformity O.R. 95% C.I. O.R. Significance (P)

Age 10–15 26 165 4.255 1.251–14.473 2.563 0.1570(years) 0–9 3 81

Sex M 16 147 0.829 0.382–1.799 0.757 0.5173F 13 99

Duration >1 yr 11 53 2.225 0.991–4.999 2.048 0.1137<1 yr 18 193

MB/PB MB 9 28 3.504 1.453–8.443 1.914 0.2124PB 20 218

Smear Skin Smear + 5 18 2.639 0.889–7.743 0.814 0.7457Smear – 24 228

Reaction Yes 11 44 2.806 1.238–6.357 1.546 0.3459No 18 202

Nerve Yes 24 86 8.930 3.290–24.239 6.134 0.0009Enlargement No 5 160


A reaction was present in 55 (20%) of thechildren at the time of admission, and 11(20%) of these patients had deformitiescompared to 18 of 220 patients (8.1%)without reaction at the time of presentation(p = 0.02). All but one of the children hadType I reactions.

Grade II deformity (per WHO grading (1, 27)) was present in 29 patients (10.5%), ofwhom 16 (55.1%) were male and 13(44.9%) were female, a male to female ratioof 1.2:1. There was not a single child withdeformity below 4 yrs of age. Three chil-dren with deformities (10.3%) were in the5–9 yr range and the remaining 26 (89.7%)were in the age range of 10–15 yrs. The av-erage age of onset of the disease among thedeformed children was 12.2 ± 2.3 yrs, andthe average duration of disease was 1.5 ±1.2 yrs. In 24 patients (82.7%), deformitiesinvolved the upper limbs whereas the lowerlimbs were involved in only 3 (10.3%). De-formities of the right hand were seen in 16(55.1%) patients and left hand involvementwas present in 10 of the patients (34.4%).

During the 10 yrs studied, the distributionof deformities had shown no significantchange, although a slight downward trendcan be seen in the new millennium (Table3). This could be due to the increasingawareness of the public regarding leprosy.

DISCUSSIONThis study reveals that 4.5% of the new

cases seen in the outpatient department of areferral hospital during the years 1994 to2003 were children and that 10.5% of thesehad visible deformities. Deformities due toleprosy in children were observed more fre-quently in boys than in girls, although thedifference was not statistically significant.It is well known that leprosy is prevalentmore frequently among males than in fe-males, on the order of 2:1. Other studies ofleprosy in childhood have shown equal in-cidence, or a slight preponderance of males(6, 22). In the present study the male to fe-male ratio in the deformity group is 1.2:1which tallies well with the observationsmade by Meima (10), Kushwah (8), Nilkan-tha Rao (15) and Bravo (2).

The overall consensus among leprosyworkers is that the deformity rate increaseswith an increase in age, as noted down invarious studies by Bravo (2) and Noordeen

(12), though this has not been studied specif-ically in children, and there is a greaterchance of exposure to the disease processwith advancing age. In this study the dis-ability rates were observed to increase withincreasing age of the children. There was nodeformity in the 0–4 yr age group and themaximum frequency of deformity was ob-served in the 10–15 yrs age range, whichagrees with the observations made in theprevious studies.

Deformity affecting children with MBdisease was significantly more frequentthan in PB cases. Studies by Schreuder, etal. (20), Saunderson, et al. (19), and Saha, etal. (18) have also found a significantlyhigher incidence of nerve function impair-ment (NFI) in MB as compared to PB lep-rosy patients. High disability rates amongMB patients is explained by widespreadnerve damage after several years of expo-sure in lepromatous cases and due to exten-sive large nerve involvement in borderlinecases compared to localized nerve involve-ment in PB cases. Children with MB lep-rosy are found to be at higher risk of rever-sal reactions as observed by Selvasekar, etal. (22) and require a regular follow-up andprompt interventions for the prevention ofdeformities.

A higher bacterial load increases the riskof reactions and nerve damage leading todeformities. Roche, et al. (16) has alsoshown high incidence of neuropathy in pa-tients with high BI similar to those reportedby Noordeen (12) and Zhang (28), and can beexplained by the widespread and progres-sive nature of smear positive type of lep-rosy. Other types of leprosy are more local-

TABLE 3. Distribution of Grade II de-formities in children by year of diagnosis.

Year Total number of Number of childrenchildren with leprosy with deformities

1995 13 41996 22 31997 23 41998 42 41999 48 42000 34 22001 37 22002 16 1Total 235 24

73, 4 Kar and Job: Visible Deformity in Childhood Leprosy 247

ized and have a shorter evolution. Thereforeearly detection of the disease and treatmentalong with health education are very impor-tant for disability control. However in ourstudy smear positivity was not found to be asignificant risk factor for development ofdeformities, which could be attributed tothe very low number of smear-positivecases in the cohort.

In this study the deformity rate was ob-served to increase with increased durationof the disease. Studies by Meima (10),Schreuder (20), Wittenhorst (25), and Nichols(11) have reported on increased NFI in pa-tients presenting late after developing skinlesions. In our study of children, the aver-age duration of the disease in those with de-formities was over one year, and 40% of thepatients with deformities attended the hos-pital after one year of onset of their disease.Noordeen (12) and Thappa (24) made similarobservations. Early detection and early ac-cess to the health care system would help toprevent such deformities.

Leprosy is a disease that particularly af-fects peripheral nerves. In our study periph-eral nerve trunk involvement was seen in40% of the patients at the time of presenta-tion. Deformities seen among those withnerve trunk involvement were significantlymore frequent compared to those withoutnerve trunk involvement. The risk of devel-oping deformity in those with nerve en-largement in our study was 6.13 timesgreater than those who did not have nerveenlargement. The ulnar nerve, lateralpopliteal nerve and the posterior tibialnerve are the common nerves involved inour patients. Saha (18) and Sharma (23 ) havereported similar observations. Saundersonand colleagues (19) in their study had re-ported a relative risk of 2.8 and 6.5 respec-tively in case of 1–5 and more than 5 thick-ened nerves. Roche, et al. (16) has also re-ported similar findings.

Reactional episodes are reportedly lessfrequent in children (7) but in our series20% of the children presented with reversalreactions at the time of admission. This isless than the value of 30% reported byHammond (5). In another study by Jain andcolleagues (6), 29.7% of the children devel-oped reaction. Patients with reaction at thetime of presentation had more deformitiescompared to those without reactions. Bravo

(2), Thappa (24) and Gupte (4) also noted re-actions as significant risk factors in the de-velopment of deformities in their studies.Saunderson (19) has reported a relative riskof 14.7 to develop nerve function impair-ment in patients with reversal reaction. Re-actions can be managed with prompt use ofcorticosteroids and hence effectively man-aging them would help to decrease the de-formity load, athough steroid use in chil-dren is likely to lead to many complicationsand to growth retardation.

In our series the majority of the deformi-ties involved the upper limbs, lower limbsbeing involved only in 10% of the patients.Sehgal (21) reported deformities of thehands in 85.7% of patients compared to de-formities of the feet in 48.5%. Martinez-Dominiqueez (9) and Thappa (24) havefound the hands and feet to be affected withequal frequency. However the high fre-quency of right hand involvement in our pa-tients has a definite socioeconomic impact,as the dominant hand is disabled.

CONCLUSIONSThere is no previous study reporting the

deformity rate in children with leprosy, andthis study found an incidence of 10.5% ofgrade II deformity. This is high, comparedto the overall deformity rate in the commu-nity (3), but the results of this hospital-basedstudy may not be comparable with the out-patient community. The unadjusted resultsindicate an increase in risk of deformity forthe following factors: increasing age ofchildren, delay in accessing health care,multiple patches, multiple nerve involve-ment, and reaction at the time of presenta-tion to the hospital. Logistic regressionanalysis, however, reveals that nerve en-largement is the most significant risk factorin children for the development of deformi-ties. Children with these risk factors mustbe followed-up more closely so as to pre-vent deformities. Children presenting late,with stigmatizing deformity, indicates inad-equate early case detection activities as wellas reluctance on the part of children andtheir parents to come forward to access thehealth system. Promoting various ways tomotivate parents to bring their children tothe hospital at the earliest sign of leprosy isof utmost importance in the present situa-tion.


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ABSTRACTBackground: As part of a larger study of the role of close contacts in the transmission of

M. leprae, we explored whether the proportion of newly detected cases with a family historyof leprosy differs with different incidence rates of leprosy in a population.

Methods: Retrospective analysis was performed of contacts of all new leprosy patients di-agnosed during a 10-yr period in well-established leprosy control programs in Thailand andBangladesh. By our definition, a contact group consisted of the new case and of past andpresent cases who were relatives and in-laws of the new case. For a new case, the nearest in-dex case was defined on the basis of time of onset of symptoms for the cases in the contactgroup, in combination with the level of closeness of contact between these cases and the newcase. Three contact levels were distinguished. In Bangladesh these levels were defined as‘kitchen contact’; ‘house contact’; and ‘non-house contact’. In Thailand comparable levelswere defined as ‘house contact’; ‘compound contact’; and ‘neighbor contact’.

Results: In Bangladesh 1333, and in Thailand 129 new patients were included. The aver-age new case detection rate over 10 yrs was 50 per 100,000 general population per year inBangladesh, and 1.5 per 100,000 in Thailand. In the high endemic area 25% of newly de-tected cases were known to belong to a contact group and were not the index case of thisgroup, whereas in the low endemic area 62% of newly detected cases had these characteris-tics. The distribution of the nearest index cases over the three contact levels was compara-ble in both areas. Just over half of the nearest index cases were found within the immediatefamily unit (‘kitchen’ in Bangladesh; ‘house’ in Thailand).

Conclusion: The results indicate that in a low endemic area a higher proportion of newlydetected leprosy cases have a family history of leprosy compared to a high endemic area.Different contact levels and their relative risks to contract leprosy need to be establishedmore precisely. In high endemic situations the circle of contacts that should be surveyed mayneed to be wider than currently practiced.

RÉSUMÉContexte: Cet article est publié dans le cadre d’une étude plus large sur le rôle des con-

tacts étroits dans la transmission de la lèpre. Elle s’est attachée à explorer si la proportion denouveaux cas détectés dans une famille ayant un historique de lèpre diffère des taux variésd’incidence de lèpre dans une population.

Méthodes: Une analyse rétrospective fut entreprise sur les personnes au contact de tousles nouveaux cas diagnostiqués de lèpre, pendant une période de 10 ans au sein de pro-grammes bien établis de contrôle de la lèpre en Thaïlande et au Bengladesh. Selon notre déf-inition, un groupe contact consiste du nouveau cas accompagné des cas présents et passésqui étaient membre de la famille par naissance ou alliance. Pour un nouveau cas, le cas in-dex le plus proche fut défini par le temps d’apparition des symptômes des cas dans le groupe

1 Department of Public Health, Erasmus MC, University Medical Center Rotterdam, The Netherlands.2 The Danish-Bangladesh Leprosy Mission, Nilphamari, Bangladesh.3 McKean Rehabilitation Center, Chiang Mai, Thailand.Address for correspondence: Dr. J. H. Richardus, Department of Public Health, Erasmus MC, University Med-

ical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; e-mail: [email protected]

Close Contacts with Leprosy in Newly Diagnosed

Leprosy Patients in a High and Low Endemic Area:

Comparison between Bangladesh and Thailand

Jan H. Richardus1, Abraham Meima1, Corine J. van Marrewijk1, Richard P. Croft2,and Trevor C. Smith3

249


(ISSN 0148-916X)


contact, combiné à l’étroitesse de contact entre ces cas et le nouveau cas. Trois niveaux decontact furent distingués. Au Bengladesh, trois niveaux furent définis : les « contacts à lacuisine », les « contacts à la maison » et « les contacts hors maison ». En Thaïlande, desniveaux comparables furent définis comme « contact de la maison », « contact composite »et « contact de voisinage ».

Résultats: Au Bengladesh furent incorporés dans l’étude 1 333 nouveaux patients et enThaïlande, 129. Le taux de détection moyen a été durant les dix années de 50 pour 100 000personnes de la population générale et par an au Bengladesh, et de 1,5 pour 100 000 en Thaï-lande. Dans la région hautement endémique, 25% des cas nouvellement détectés étaient con-nus comme appartenant à un groupe contact et ne furent pas le cas index pour ce groupe, tan-dis que dans la région faiblement endémique, 62% des cas nouvellement détectés avaient cescaractéristiques. La distribution des cas index les plus proches parmi les 3 niveaux de per-sonnes contacts était comparable dans les deux régions. Un peu plus de la moitié des cas in-dex fut trouvé dans l’unité familiale immédiate (la cuisine au Bengladesh et la maison enThaïlande).

Conclusion: Ces résultats suggèrent que, dans une région faiblement endémique, la pro-portion de cas de lèpre nouvellement diagnostiquée ayant une histoire familiale de lèpre, estsupérieure à celle rencontrée dans une région hautement endémique. Il sera important deplus précisément établir les niveaux de contact et leurs risques relatifs à contracter la lèpre.Dans les situations de haute endémicité, le cercle des contacts qui devrait être le sujet de sur-veillance épidémiologique devra être plus large que ce qui est couramment pratiqué.

RESUMENPanorama: Como parte de un estudio más extenso sobre el papel que juegan los contac-

tos cercanos en la transmisión de M. leprae, en este estudio exploramos si la proporción denuevos casos con historia familiar de lepra, difiere de la tasa de incidencia de lepra en lapoblación general.

Métodos: Se hizo un análisis retrospectivo de contactos de todos los nuevos pacientes delepra diagnosticados durante un periodo de 10 años en los programas de control de la lepraen Tailandia y Bangladesh. En nuestra definición, un grupo contacto consistió de los nuevoscasos y de los casos pasados y presentes que fueron familiares y parientes de los nuevos ca-sos. Para un nuevo caso, el caso índice más cercano se definió sobre la base del tiempo deaparición de los síntomas en los casos del grupo de contactos en combinación con el gradode contacto entre estos casos y el nuevo caso. Se definieron tres niveles comparables de con-tacto. En Bangladesh: “contactos de cocina,” “contactos domésticos,” y “contactos nodomésticos”; en Tailandia: “contactos domésticos,” “contactos compuestos” y “contactosvecinos.”

Resultados: Se incluyeron 1333 nuevos casos en Bangladesh y 129 en Tailandia. La tasapromedio de detección de casos nuevos en 10 años fue de 50 por 100,000 por año enBangladesh, y de 1.5 por 100,000 en Tailandia. En el área de alta endemia, el 25% de losnuevos casos detectados pertenecieron a un grupo de contactos y no fueron el caso índice eneste grupo; en el área de baja endemia, el 62% de los nuevos casos detectados tuvieron es-tas características. La distribución de los casos índice más cercanos en los tres niveles decontacto fueron comparables en ambas áreas. Un poco más de la mitad de los casos índicemás cercanos se encontraron dentro de la unidad familiar inmediata: “cocina” enBangladesh, “domésticos” en Tailandia).

Conclusión: Los resultados indican que, en comparación con un área de alta endemia, enun área de baja endemia la mayor proporción de los nuevos casos detectados tienen una his-toria familiar de lepra. Se concluye que es necesario establecer con más precisión, los difer-entes niveles de los contactos y sus riesgos relativos de contraer la enfermedad. En las situa-ciones de alta endemia también se requiere una vigilancia dentro del círculo de contactos,mayor que la que se realiza actualmente.

The importance of close contact with aleprosy patient in the transmission of M.leprae is well established. (2, 3, 5, 8) The rela-tive risk for contracting leprosy is increasedin people with contacts to leprosy patients

in comparison to those in an endemic popu-lation without known contacts. The relativerisk is higher for contacts of multibacillary(MB) leprosy patients than of paucibacil-lary (PB) patients. (2, 5, 13) Close contacts are

73, 4 Richardus, et al.: Close Contacts in Leprosy 251

usually, but not necessarily, relatives livingin the same house or compound. For thisreason, leprosy control programs often con-duct contact surveys when new leprosycases are detected. By examining familyand household members of a new case,there is a fair chance to find other cases ofleprosy as well. But questions remainsabout the extent to which these contactscontribute to transmission of M. leprae in acommunity, and whether contact tracingand treatment contribute to interruption oftransmission of the mycobacterium in thatcommunity.

Field workers and control program man-agers often suggest that with declining lep-rosy endemicity, the incidence in contactsof leprosy patients appears to decrease lessrapidly than in the surrounding population.Apparently risk factors for the developmentof leprosy are distributed differently in con-tact groups of leprosy patients and the gen-eral population. The suggested change inthe importance of contact however, hasnever been substantiated. Yet in order to de-sign effective leprosy control measures, it isnecessary to know the relative importanceof (close) contacts in the total transmissionof leprosy in different populations and theunderlying mechanisms of this transmis-sion. As part of a larger program studyingthe transmission of M. leprae, the objectiveof this study was to explore whether theproportion of newly detected cases knownto be a close contact of a leprosy patient dif-fers with different incidence rates of lep-rosy in a population. To this end, a high en-demic area in Bangladesh is compared witha low endemic area in Thailand. All newpatients during a certain period of timewere investigated retrospectively with re-spect to the presence of leprosy patients(past and present) among relatives. In doingso, different levels of closeness of contactwere distinguished. The findings of this ex-ploration are intended to contribute to theinterpretation of a prospective epidemiolog-ical study of the transmission of M. lepraeand the role of close contacts therein. (7)

METHODSStudy area and leprosy control program

I. Bangladesh. The study was conducted inthe subdistrict of Jaldhaka, a highly endemic

area in Nilphamari District in northwestBangladesh, with a population of approx-imately 250,000. The Danish-BangladeshLeprosy Mission (DBLM) has been in-volved in leprosy control activities in thisarea since the late 1970’s, and virtually allleprosy patients in the area are registeredwith DBLM. (9, 10) Jaldhaka was selectedbecause of relatively good quality of con-tact surveys, which were conducted fre-quently by experienced staff. DBLM startedcontact surveillance in 1980 and thisreached a good level of completeness by1985. From 1987 onward, all persons shar-ing a kitchen with a newly detected casewere to be examined once a year, for a pe-riod of 5 yrs in PB cases, and 10 yrs in MBcases. In 1994, the lengths of these periodswere reduced to 2 and 5 yrs respectively.Active case finding also included schoolsurveys, mass surveys and village checks.The study period was between 1987 and1996 (10 yrs).

II. Thailand. The study was conducted inthe Province of Chiang Mai in NorthernThailand. The following nine districts wereselected: Chiang Mai city, Saraphi, Sansai,Doi Saket, Sankampaeng, Mae Rim, MaeTaeng, Hang Dong, and San Patong. Thetotal population of the study area is approx-imately 850,000. Before the 1970’s, almostall new leprosy cases in northern Thailandwere detected by the McKean Rehabilita-tion Center in Chiang Mai, an institution ofthe Church of Christ in Thailand. With theintegration of leprosy control in generalhealth services, new cases in the area werealso detected by the Leprosy Control Divi-sion of Northern Thailand or by PublicHealth Services since the 1970’s. (12) Pa-tient data were collected from both theMcKean Rehabilitation Center and the Lep-rosy Control Division of Northern Thai-land. The study districts were chosen be-cause of the proximity to Chiang Mai cityand good coverage of leprosy control ac-tivities in the past. These activities includedhealth education, contact surveys, andschool surveys. Contact surveys of new pa-tients living in remote areas were not al-ways performed in the house or village.These patients were advised to bring closerelatives to the clinic for inspection on signsof leprosy. The study period was between1988 and 1997 (10 yrs).


DefinitionsLeprosy case definition. Leprosy control

programs in both Bangladesh and Thailandadhered to the WHO definition for a leprosycase as ‘a person showing clinical signs ofleprosy, with or without bacteriological con-firmation of the diagnosis, and requiringchemotherapy’. Following official guide-lines, the program definitions for PB and MBchanged several times in both countries dur-ing the study period. For consistency in dataanalysis, cases with Ridley Jopling classifi-cation BB, BL and LL and all cases withpositive skin smears (BI >0) have in thisstudy been defined as multibacillary (MB),and all other cases as paucibacillary (PB).All new leprosy cases who originated fromthe study area and who were detected duringthe study period were included in the study.

Definition of contact group and close-ness of contact. For each new case, thegroup of patients that was considered con-sisted of the new case and of relatives andfamily-in-law. The relation of a patientfrom this contact group to the new case wasin both study areas defined as: husband,wife, father, mother, son, daughter, brother,sister, grandparent, grandchild, uncle, aunt,nephew, niece, and cousin. There was alsoan ‘other’ category, in which other relation-ships could be specified, such as a steppar-ent or stepchild. Three contact levels weredistinguished. In Bangladesh these levelswere defined as ‘kitchen contact’ (the newcase ate from the same kitchen as a givencase from the contact group); ‘house con-tact’ (new case lived in the same house, butate from a different kitchen: a house in thisarea of Bangladesh can have severalkitchens); and ‘non-house contact’ (newcase lived in a different house, possibly inanother village or town). In Thailand com-parable levels were defined as ‘house con-tact’ (the new case lived in the same house);‘compound contact’ (new case lived in aseparate house, but on the same com-pound); and ‘neighbor contact’ (new caselived in the same village or town, but not inthe same compound). The contact level wastaken to be that level of contact between thenew case and a given case from the contactgroup at the time the given case was knownto have leprosy. No time limit was set re-garding the past duration of the contact.

Index definition. The index case of anygroup of cases with contact to one anotherwas defined as the case with the earliest on-set of symptoms, with time of onset calcu-lated as registration date minus reported du-ration of symptoms at registration. In caseof incomplete information, the registrationdate was used to determine the index case.For newly detected cases, the followingprocedure was adopted: First, it was deter-mined whether the newly detected case wasthe index case of his/her contact group ornot. If not, the index cases of the threecloseness-of-contact circles around thenewly detected case were determined, inwidening order. Next, the nearest indexcase for a newly detected case was definedto be the first index case found, other thanthe new case him/herself. The procedureimplies that the index case of the contactgroup and the nearest index case of thenewly detected case were not necessarilythe same case. The term ‘index case’ in thisstudy does also not necessarily imply thatthis case was responsible for actual trans-mission. All individuals in a contact groupmight have been infected by other (possiblyunknown) leprosy patients in the commu-nity.

Data collection and analysisFor each study area, a data collection

form was developed in order to collect in-formation not available in the existing pa-tient databases. The additionally collecteddata included information on the new pa-tients themselves (such as registration num-ber, duration of symptoms, leprosy type andmode of detection) and information on con-tact related variables (such as contact statuswhich indicates whether the new case be-longed to a contact group or not, level ofcloseness of contact to the contact groupmembers, registration numbers of the groupmembers and relationships). The additionalpatient information was extracted from pa-tient cards.

In Bangladesh, contact information onkitchen level was mainly extracted fromcontact surveillance cards. Information athouse and non-house contact level was usu-ally not recorded during contact surveil-lance, and information for identification ofpossible index cases at these levels was re-


trieved from other sources with the help ofthe responsible leprosy control officers.

In Thailand information on contact sur-veys was incomplete. Therefore an addi-tional effort was made to retrieve the neces-sary data from the patients themselves orimmediate relatives through follow-up vis-its. In total 90 out of 129 (70%) eligible pa-tients or their relatives were visited for thepurpose of this study and the contact surveyforms completed.

The primary objective of the study was toidentify leprosy patients (past and present)who had had contact with the newly de-tected leprosy patients. Enumeration of alleligible contact group members was oftenimpossible, especially outside the closestcontact level considered (Bangladesh:kitchen; Thailand: house), because datawere collected retrospectively and spanneda long period of time.

Data analysis was carried out with SPSS7.0 for windows. Proportions were com-pared using the Chi-square test (p = 0.05).

RESULTSIn Jaldakha (Bangladesh), a total of 1333

new patients were detected between 1987and 1996. The contact status was known for1197 patients (90% of the included popula-tion). For these patients the distribution ofleprosy type, age by sex is given in Table 1.Of the 1197 cases, 744 (62%) were male

and 453 (38%) female, giving a male:fe-male ratio of 1.6:1. There were 996 PBcases (83%) and 198 MB cases (17%). In 3cases the leprosy type was unknown. Theaverage new case detection rate over the pe-riod was 50 per 100,000 general populationper year.

In Chiang Mai (Thailand) a total of 129new cases were detected between 1988 and1997. Of these, the contact status wasknown for 100 patients (78% of the in-cluded population). The distribution of lep-rosy type, age by sex for these patients isgiven in Table 1. Of these, 65 (65%) weremale and 35 (35%) female, giving amale:female ratio of 1.9:1. There were 34PB cases (34%) and 66 MB cases (66%).The average new case detection rate overthe period was 1.5 per 100,000 generalpopulation per year.

In Bangladesh, the overall percentage ofnewly detected cases with a known indexcase was 25% only (Table 2). The percent-age was highest in the youngest age groupof 0–14 yrs (48%), and decreased to 28% inthe age group 15–26 yrs, and 19% and 16%in the age groups 30–44 and 3 45 yrs re-spectively. In the remaining cases (75%),no leprosy patients were found within thethree defined contact levels. Also includedin Table 2 is the distribution of the nearestindex cases over the three levels of close-ness of contact for the newly detected pa-

TABLE 1. Distribution of new leprosy cases, for which the contact status was known, inBangladesh and Thailand, by leprosy type, age and sex.

Study cases

Bangladesh Thailand

Sex Male Female Total Male Female Total

n % n % n % n % n % n %

Leprosy typePB 608 82 388 86 996 83 25 38 9 26 34 34MB 134 18 64 14 198 17 40 62 26 74 66 66Unknown 2 0 1 0 3 0 0 0 0

Age(in years)

0–14 107 14 77 17 184 15 6 9 3 9 9 915–29 210 28 122 27 332 28 17 26 6 17 23 2330–44 247 33 161 36 408 34 17 26 5 14 22 22≥45 180 24 93 21 273 23 25 38 21 60 46 46

Total 744 100 453 100 1197 100 65 100 35 100 100 100


tients with known positive family history.The nearest index cases were found atkitchen level in 53% of the cases. The per-centage of kitchen contact was highest inthe youngest age group (68%), and de-creased to 51% in the age group 15–29 yrs,and to 42% and 43% in the age groups30–44 and ≥45 yrs respectively.

In Thailand, the overall percentage ofnewly detected cases with a known indexcase was as high as 62% (Table 2). The per-centage was highest in the age groups 0–14yrs (67%) and 15–29 (78%), and decreasedslightly to 64% and 52% in the age groups30–44 and ≥45 yrs respectively. In the re-maining cases (38%), no leprosy cases werefound within the three defined contact lev-els. In cases with known positive familyhistory, the nearest index cases were foundat house level in 60% of the cases. The per-centage of house contact was highest in theyoungest age group (100%), and decreasedto 56% in the age group 15–29 yrs, to 79%in the age group 30–44 yrs, and to 42% inthe group 45 yrs and older.

The difference in percentage of newly de-tected leprosy cases with contact to a knownindex case between Bangladesh (overall

25%) and Thailand (overall 62%) is statisti-cally significant (Chi-square test: p < 0.05).

DISCUSSIONThe objective of this study was to explore

whether the proportion of newly detectedleprosy cases with a family history of lep-rosy is higher in a population with a lowerincidence rate of leprosy. To this end, a ret-rospective study was undertaken in two ar-eas; northwest Bangladesh with a high newcase detection rate of approximately 50 per100,000 per year, and northern Thailandwith a low new case detection rate of ap-proximately 1.5 per 100,000 per year. Thisstudy shows that in the chosen high en-demic area approximately only 25% ofnewly detected cases have a known indexcase within the family, whereas in the cho-sen low endemic area this proportion is ashigh as 62%. The distribution of nearest in-dex cases over three different contact levelswas comparable in both areas. Just overhalf of the nearest index cases are foundwithin the immediate family unit (kitchenin Bangladesh; house in Thailand). InBangladesh, children aged 0–14 yrs mostoften have known index cases among rela-

TABLE 2. Status of newly detected cases (by age) in Bangladesh and Thailand, ac-cording to closeness of family contact to the nearest index case.

Age (in years)Total

0–14 15–29 30–44 ≥45

Bangladesh n % n % n % n % n %

Contact toknown index 88 48 92 28 76 19 44 16 300 25Kitchen contact 60 68 47 51 32 42 19 43 158 53House contact 16 18 29 32 24 32 8 18 77 26Non-house contact 12 14 16 17 20 26 17 39 65 22

No contact toknown index 96 52 240 72 332 81 229 84 897 75

Total 184 100 332 100 408 100 273 100 1197 100

Thailand n % n % n % n % n %

Contact toknown index 6 67 18 78 14 64 24 52 62 62House contact 6 100 10 56 11 79 10 42 37 60Compound contact 0 0 6 33 3 21 7 29 16 26Neighbor contact 0 0 2 11 0 0 7 29 9 14

No contact toknown index 3 22 5 22 8 36 22 48 38 38

Total 9 100 23 100 22 100 46 100 100 100


tives, with the nearest index primarilywithin the immediate family unit. The pro-portion with a known index case decreasesover the age groups. Although less marked,in Thailand there is also a difference overthe age groups. However, there is an impor-tant difference in age distribution of thenewly diagnosed patients in both countries,with a higher average age in Thailand. Thisis probably a reflection of the level of trans-mission. In Thailand transmission has beenlow in the past two decades, and many newpatients are likely to have been infected inthe past and have had long incubation peri-ods. Increasing average age of newly de-tected patients with the decline of leprosyincidence has been described previously. (1, 4)

Obviously, there are many limitations todirect comparisons between countries.There are geographical, socio-economicand cultural differences, as well as differ-ences with regard to the provision of healthservices in general and leprosy control inparticular. All these differences will haveeffect on transmission patterns and the de-tection of leprosy. An important difference,for instance, between the countries is theproportion of MB patients. In Bangladeshthis is approximately 20%, while in Thai-land over 60% are MB. Such differencesbetween countries have been observed be-fore, and are possibly explained by geneticdifferences. (1) With a higher proportion ofpatients with MB leprosy, one might expecttransmission of M. leprae in the populationto be more intensive, resulting in a higherendemic level of leprosy. However, this isnot consistent with our findings of propor-tion of MB and the leprosy incidence in thetwo populations studied, which perhapsmight be due to a difference between the in-dividuals in these populations with respectto susceptibility to developing leprosy.

There are also important limitations inthe methodology of the study. It is a retro-spective analysis of routine data. The exactnumber of family members with past orpresent leprosy at the beginning of the ob-servation period, or developing leprosy dur-ing this period, could not be establishedprospectively. Also denominator data, thetotal number of eligible family memberswithin the defined contact levels per newlydetected patient, are absent. Denominatorinformation, however, is not strictly neces-

sary when establishing the presence offamily members with past or present lep-rosy for a newly detected patient. There aredifferences in average size of the contactgroups between the countries, with house-holds in Bangladesh tending to be largerand thus theoretically with a higher chanceof leprosy cases in households. This differ-ence in fact strengthens our findings. Lackof denominator information makes interpre-tation of relative risks for developing lep-rosy in and outside leprosy contact groupsless straightforward, but this kind of calcu-lation was outside the scope of the study.Finally, case detection efforts were more in-tensive at the closest contact level(Bangladesh: kitchen; Thailand: house)compared to the other levels, leading to apossible underestimation of numbers ofcases at these other levels. While takingthese limitations into account, we believethat the very large difference in newly de-tected leprosy patients with a known indexcase between both areas represents a validobservation regarding this proportion in dif-ferent endemic situations. Differences inthe leprosy control program and data col-lection between the two areas alone wouldnot lead to such great difference in outcome(25% versus 62%), suggesting a genuinedifference between the areas. However, theexact extent of the difference can only beestablished if adjustment for these factorswould be possible.

The implications of our findings fortransmission of M. leprae in general are im-portant, but not easily interpreted. It islikely that in a high endemic area such asnorthwest Bangladesh, most transmissionin the population occurs outside close con-tacts of known leprosy patients. Up to 75%of new patients in Jaldakha district did nothave any known index case. But the contactdefinition used in this study was strict, con-sisting of (close) relatives only. In a retro-spective study over 25 yrs in a highendemic village of 2283 inhabitants in Su-lawesi, Indonesia, it was shown that newpatients could also be linked to previouscases other than from their own household.Besides household index cases in 28% ofnew cases, there were first neighbor casesin 24%; second neighbor cases in 12%;cases within the social network in 10%; andcases among relatives living elsewhere in


5% of the new cases. Thus 79% of all newcases could be linked to an index case. (14)Leprosy cases are not distributed evenlyamong the population, but are known tocluster. Our observation of a high percent-age of relatives with leprosy in Thailandcompared to Bangladesh supports the hy-pothesis that the relative importance ofclustering becomes stronger with decliningendemicity of leprosy in a population.

The challenge for leprosy control is todetermine which contact levels need to besurveyed in order to significantly interrupttransmission of M. leprae in the population.In order to do so, it appears that in high en-demic situations, apart from early case find-ing, the circle of contacts to be surveyedneeds to be wider than currently practiced.Also, the different contact levels and theirrelative risks to contract leprosy need to bedefined more precisely. Lessons can possi-bly be learned from tuberculosis control,where contact tracing is performed accord-ing to the ‘stone-in-the-pond’ principle.(6, 15)If the prevalence of tuberculosis withinclose proximity of a new case exceeds anexpected level, the survey is extended to anext, wider range of contacts. This ap-proach is continued until the prevalence oftuberculosis cases in the expanding circle ofcontacts reaches the prevalence level of thegeneral population. The finding in Thailandthat the nearest index case is most oftenfound in very close proximity to the patientcould indicate that with declining incidenceof leprosy, the extent of contact surveyscould be reduced.

From a methodological point of view thisstudy represents only a limited attempt togain insight in the epidemiology of contacttransmission. Further research, preferablyprospective and with precise definitions ofcontact levels, is needed to understand therole of contact in leprosy under various en-demic circumstances, underlying patternsof transmission, and implications for lep-rosy control. The effect of interventions tar-geting contacts such as chemoprophylaxis,on the overall transmission of M. leprae ina population also needs clarification.(11)Such a study is currently underway inBangladesh.(7) The application of advancedtechniques of epidemiological modeling isinvaluable to help analyze and interpret ex-isting and new data in this area. The result

of the present study is just one step towardsthis end.

Acknowledgment. We thank Mr. S. Chowdry ofDBLM in Bangladesh, and Mrs. Orowan Buntham andMs. Janet Greenleaf of McKean Rehabilitation Centerin Thailand for their invaluable assistance in the field-work of the study. This study was made possible by agrant from the American Leprosy Missions (ALM)and from Netherlands Leprosy Relief (NLR).

REFERENCES1. FINE, P. E. Leprosy: the epidemiology of a slow

bacterium. Epidemiol. Rev. 4 (1982) 161–188.2. FINE, P. E., STERNE, J. A., PONNIGHAUS, J. M.,

BLISS, L., SAUI, J., CHIHANA, A., MUNTHALI, M.,and WARNDORFF, D. K. Household and dwellingcontact as risk factors for leprosy in northernMalawi. Am. J. Epidemiol. 146 (1997) 91–102.

3. GEORGE, K., JOHN, K. R., MULIYIL, J. P., andJOSEPH, A. The role of intrahousehold contact inthe transmission of leprosy. Lepr. Rev. 61 (1990)60–63.

4. IRGENS, L. M. Leprosy in Norway. An epidemio-logical study based on a national patient registry.Lepr. Rev. 51 (1980) i–xi, 1–130.

5. JESUDASAN, K., BRADLEY, D., SMITH, P. G., andCHRISTIAN, M. Incidence rates of leprosy amonghousehold contacts of “primary cases.” Indian J.Lepr. 56 (1984) 600–614.

6. MOET, F. J., MEIMA, A., OSKAM, L., andRICHARDUS, J. H. Risk factors for the develop-ment of clinical leprosy among contacts, and theirrelevance for targeted interventions. Lepr. Rev. 75(2004) 310–326.

7. MOET, F. J., OSKAM, L., FABER, R., PAHAN, D., andRICHARDUS, J. H. A study on transmission and atrial of chemoprophylaxis in contacts of leprosypatients: design, methodology and recruitmentfindings of COLEP. Lepr. Rev. 75 (2004)376–383.

8. RAO, P. S., KARAT, A. B., KALIAPERUMAL, V. G.,and KARAT, S. Transmission of leprosy withinhouseholds. Int. J. Lepr. Other Mycobact. Dis. 43(1975) 45–54.

9. RICHARDUS, J. H., and CROFT, R. P. Estimating thesize of the leprosy problem: the Bangladesh expe-rience. Lepr. Rev. 66 (1995) 158–164.

10. RICHARDUS, J. H., MEIMA, A., CROFT, R. P., andHABBEMA, J. D. Case detection, gender and dis-ability in leprosy in Bangladesh: a trend analysis.Lepr. Rev. 70 (1999) 160–173.

11. SMITH, C. M., and SMITH, W. C. Chemoprophy-laxis is effective in the prevention of leprosy in en-demic countries: a systematic review and meta-analysis. MILEP2 Study Group. Mucosal Im-munology of Leprosy. J. Infect. 41 (2000)137–142.

12. SMITH, T. C., and RICHARDUS, J. H. Leprosytrends in northern Thailand: 1951–1990. South-


east Asian J. Trop. Med. Public Health 24 (1993)3–10.

13. SUNDAR RAO, P. S., JESUDASAN, K., MANI, K., andCHRISTIAN, M. Impact of MDT on incidence ratesof leprosy among household contacts. Part 1.Baseline data. Int. J. Lepr. Other Mycobact. Dis.57 (1989) 647–651.

14. VAN BEERS, S. M., HATTA, M., and KLATSER, P. R.Patient contact is the major determinant in inci-dent leprosy: implications for future control. Int. J.Lepr. Other Mycobact. Dis. 67 (1999) 119–128.

15. VEEN, J. Microepidemics of tuberculosis: thestone-in-the-pond principle. Tuber. Lung Dis. 73(1992) 73–76.

ABSTRACTBackground: Leprosy is a chronic infectious disease that is considered to be declining,

though it still remains prevalent in many parts of the world. A study was made to explore thehealth and socioeconomic factors that most influenced the trend of the disease in a typicalMediterranean country.

Materials and methods: An ecological study was conducted, investigating possible social,economic and health factors related to the evolution of leprosy incidence. The time periodconsidered was 50 years—the second half of the twentieth century in Spain.

Results: The variables showing the strongest correlation to evolution of the incidence ofthe disease were employment, the number of physicians, and the gross domestic product(GDP), with negative coefficients—while tuberculosis showed a positive coefficient. How-ever, the GDP showed the highest coefficient (0.5). The model that best explained the evo-lution of leprosy over the last 50 years comprised a 6-year lag period between the socioeco-nomic factors and the incidence of leprosy—explaining 57% of the data obtained. The an-nual decrease in leprosy incidence was 1.6%.

Conclusions: Socioeconomic development, assessed in terms of the GDP, was the mostimportant factor in explaining the evolution of leprosy incidence.

RÉSUMÉContexte: La lèpre est une maladie chronique considérée comme étant sur le déclin, bien

qu’elle reste encore prévalente dans plusieurs régions du monde. Le but de cette étude futd’explorer dans un pays méditerranéen typique, les facteurs sanitaires et socio-économiquesqui ont eu le plus d’impact sur l’évolution épidémiologique de la maladie.

Matériel et méthode: Une étude écologique étudiant les facteurs sanitaires, économiqueset sociaux en relation avec l’évolution de l’incidence de la lèpre fut menée en considérant unintervalle de temps de 50 années - la deuxième moitié du 20ème siècle - en Espagne.

Résultats: Les variables qui ont montré les corrélations les plus robustes avec l’évolutionde l’incidence de la maladie furent l’activité, le nombre de médecins, et le Produit IntérieurBrut (PIB), avec des coefficients négatifs - tandis que la tuberculose montrait un coefficientpositif. Cependant le PIB a montré le plus haut coefficient (0,5). Le modèle qui a le mieuxprédit l’évolution de la lèpre au cours de ces 50 dernières années fut celui ayant un décalagede 6 années entre les facteurs socio-économiques et l’incidence de la lèpre - donnant une ex-plication pour 57% des données acquises. Le taux de diminution annuel de l’incidence de lalèpre a été de 1,6%.

Conclusions: Le développement socio-économique, évalué à l’aide du PIB, était le fac-teur le plus important pour expliquer l’évolution de l’incidence de la lèpre.

RESUMENBackground: Aunque la lepra es una enfermedad infecciosa crónica en decaimiento, aún

permanece vigente en muchas partes del mundo. El presente, es un estudio realizado con elfin de explorar los factores de salud y sanitarios que tienen más influencia en la tendencia dela enfermedad en un típico país Mediterráneo.

1 Servicio de Medicina Preventiva, Consorcio Hospital General Universitario de Valencia.2 Centro Salud Pública de Manises, Consellería de Sanidad de la Comunidad Valenciana.3 Servicio de Dermatología, Consorcio Hospital General Universitario de Valencia.4 Advisor to the International Leprosy Association (ILA).Name and address to whom requests for reprints should be addressed: José L. Alfonso MD, Ph.D., Servicio de

Medicina Preventiva, Consorcio Hospital General Universitario de Valencia, Departamento de Medicina Preventivay Salud Pública, Universidad de Valencia, Blasco Ibáñez 15, 46010 - Valencia (Spain); e-mail: [email protected]

Factors Contributing to the Decline of Leprosy in Spain

in the Second Half of the Twentieth Century

José L. Alfonso1, Fernando A. Vich2, Juan J. Vilata3, J. Terencio de las Aguas4

258


(ISSN 0148-916X)

73, 4 Alfonso, et al.: Factors Contributing to the Decline of Leprosy 259

Leprosy is a chronic infectious diseaseproduced by Mycobacterium leprae that re-sults from an imbalance between the bacte-rium and the host immune response. With ahistory that goes back three thousand years,leprosy is one of the oldest diseases known.

For centuries, the care of leprosy patientslacked a scientific basis. Affected individu-als were isolated from society and fromtheir couples, and diseased children wereseparated from their families. Later, scien-tific evidence came to show that in somecases isolation is not particularly effective,and that no more than 5% of exposed indi-viduals actually develop the disease.

In its third regional conference of lep-rosy, the World Health Organization(WHO) proposed elimination of the diseaseas a health problem in all countries by theyear 2005. However, the number of newcases documented by the WHO in 2003 to-taled 513,798, while the prevalence of thedisease that same year was 457,792 cases.In other words, leprosy is still far from be-ing controlled, and work remains to be donebefore the disease can be relegated to thehistory books. The majority of cases of lep-rosy are found in Southeast Asia. The pres-ent annual incidence of the disease world-wide is almost one new patient per minute,and is fundamentally attributable to devel-oping countries like India—with 70% of allsuch cases. Some studies have even re-ported the incidence of the disease to be in-creasing in these parts of the world (25).

One of the principal factors relating tocontrol of the disease, and which was al-ready suspected many years ago, is the so-cial and economical development of society.In this context, it has been shown that eco-nomical development is accompanied by

important improvements in patient qualityof life (QoL), and a decrease in mortality (3).

Although the incidence of leprosy inSpain has decreased greatly, thanks to factorssuch as economical development, and theprevalence of the disease has also decreasedin recent years, a minimum number of fun-damentally imported cases remain (7, 21), as aresult of which it is difficult to speak of ac-tual eradication of the disease.

The present study explores the influenceof socioeconomic factors in the evolution ofleprosy in Spain—a country illustrative ofthe Mediterranean setting of the disease inthe last 50 years.

MATERIALS AND METHODSTwo leprosy information sources have

been used: the Spanish State Leprosy Reg-istry (Registro Estatal de Lepra), a databaseof the National Epidemiology Center (Cen-tro Nacional de Epidemiología) (6), locatedin the Instituto de Salud Carlos III inMadrid, and which came into operation in1991; and the Annual Statistical Bulletin (An-uario Estadístico) of the National Institute ofStatistics (Instituto Nacional de Estadística,INE) (11) for prior data up until the year 1950.

Economic (national income) data and theirprovincial distribution were in turn obtainedfrom the publications of the Service of Stud-ies of the Banco de Bilbao Vizcaya (1)(presently BBVA). Demographic informa-tion was collected from the Natural Varia-tions of the Spanish Population (MovimientoNatural de la Población Española) (12), andfrom the Spanish population census (13),both being publications of the INE. The lat-ter document reflects the data correspond-ing to the population censuses conductedevery decade.

Material y Métodos: Se realizó un estudio ecológico en el cual se investigaron los posi-bles factores sociales, económicos y sanitarios relacionados con la evolución de la inciden-cia de la lepra. El periodo de tiempo considerado fue de 50 años -la segunda mitad del sigloXX en España.

Resultados: Las variables que mostraron alta correlación con la evolución de la inciden-cia de la enfermedad fueron el desempleo, el número de médicos, y el producto domésticobruto (PDB), con coeficientes negativos -la tuberculosis, en cambio, mostró un coeficientepositivo. El PDB mostró el coeficiente más alto (0.5). El modelo que mejor explicó la evolu-ción de la lepra en el periodo de 50 años analizado comprendió un periodo lag de 6 años en-tre los factores socioeconómicos y la incidencia de lepra - explicando el 57% de los datosobtenidos. La disminución anual en la incidencia de lepra fue del 1.6%.

Conclusiones: El desarrollo Socioeconómico, medido en términos del PDB, fue el factormás importante para explicar la evolución de la incidencia de lepra.


The variables derived from these infor-mation sources were classified into fourgroups. Variables to be included were re-quired to remain stable in terms of both theinformation sources and the way in whichthey were obtained during the 50-year pe-riod covered by the study.

The data were obtained at the provinciallevel, followed by grouping according tothe different Spanish Autonomous Commu-nities. The selected socio-demographicvariables were: the proportion of ruralpopulation (i.e., the percentage of the popu-lation not living in the capital versus the to-tal population), the employment rate withrespect to the total population (per thou-sand), the emigration rate, the schoolingrate (defined as the proportion of the popu-lation in the 6–14 years age range in schoolversus the total population), and the unem-ployment rate.

As economical variables, the gross do-mestic product (GDP) per inhabitant wasrecorded, along with the product per educa-tional and health sectors. The magnitudes ofthe economical variables were determinedfor each year at constant price, using theGDP deflactor, and employing the 1986prices as reference (expressed in euros).The variable corresponding to health careresources was the proportion of physiciansper 1000 inhabitants, and the health vari-ables were the infant mortality rate, the in-cidence of leprosy per 100,000 inhabitants,and the incidence of respiratory tuberculo-sis (TBC) per 1000. Base 100 index num-bers were used for both the GDP and the in-cidence of leprosy and TBC. Retrospec-tively, the 5-year elasticity was calculatedbased on the ratio between the 5-year inci-dence variations and the economical varia-tions corresponding to the same period.

The statistical analyses included, a com-plete study of the type of distribution, fol-lowed by simple and multiple regression,residues analysis with the Kolmogorov-Smirnov test for one sample, and correla-tion between typified residues. Likewise,the co-linearity between variables was stud-ied based on eigenvalues, the condition in-dex and proportions of variance. Finally, fit-ting was carried out based on logarithmictransformation of the data and co-linearitystudy via the tolerance, variance inflationfactor (VIF), and also the study of

residues—including histograms of typifiedresidues and dispersion plots.

In practice, exact co-linearity is rarelyobserved in studies of this kind, though so-called “near co-linearity” is seen with somefrequency (i.e., some variable is found to be“nearly” a linear combination of anothervariable/s). We have jointly applied themethod proposed by Kleimbaum (18) andthe criteria of Belsley (2). The latter authorproposes utilization of the condition indicesand proportion of variance decompositionto conduct the analysis of co-linearity—es-tablishing a value of 0.5 as the upper pro-portion threshold, as a result of which theconclusions are finally reached as follows:high condition indices (over 30) indicatethe number of co-linearities, and their mag-nitude reflects their relative importance. If agiven component possesses a condition in-dex of over 30, and two or more variablespresent a high proportion of variance in thelatter, then these variables are considered tobe co-linear. Taking into account the longincubation period of leprosy (generally be-tween 2–10 years) (26), the incidence rateswere studied with the socioeconomic statusof the population 1–10 years previously,i.e., at the time of contagion.

RESULTSRegarding the mean annual incidence

rates for leprosy, established for 5-year pe-riods and 100,000 inhabitants during the pe-riod 1950–2000 (Fig. 1), and the interannualvariations (Table 1), important differencesare seen among the different regions. In ef-fect, while most regions show reductions at arate of 1% annually, some actually end upshowing increases—such as the Balearic Is-lands, Navarra, and the Basque Country. An-dalucía, in the south of the country, formany years exhibited the highest leprosyincidence for that period, though it is also theSpanish Autonomous Community with thegreatest interannual reductions (almost4.5%), followed by Galicia—with reductionsof 3%—and the Canary Islands and Valencia(2%). Overall, Spain showed a decrease of1.6% annually over this period of 50 years.

In Table 2 the longitudinal study by re-gions presents the mean values from 1950to 2000 for the variables considered in thestudy. Differences between regions areclearly seen, with important variability in

TAB

LE

1.M

ean

annu

al in

cide

nce

(per

100

,000

) an

d in

ter-

annu

al v

aria

tion

of l

epro

sy in

Spa

in b

y co

mm

unit

ies

and

nati

onw

ide,

1950

–200

0.

51–5

556

–60

61–6

566

–70

71–7

576

–80

81–8

586

–90

91–9

596

–200

0%

Var

iatio

n*

AN

DA

LU

CÍA

2.41

1.79

1.24

1.03

0.23

0.79

1.38

0.89

0.38

0.2

–4.4

2A

RA

GÓ

N0.

180.

360.

180.

180.

090

00.

080

0.17

–0.0

2A

STU

RIA

S0

0.21

0.2

0.1

0.1

00

00

00

BA

LE

AR

IC I

SLA

ND

S0

00

1.2

00.

160.

150

00.

671.

34C

AN

AR

YIS

LA

ND

S1.

261.

610.

420.

660.

090.

382.

081.

30.

310.

31–1

.9C

AN

TAB

RIA

0.25

00

00

00

00

0–0

.5C

AST

ILL

AL

EO

N0.

10.

210.

250.

330.

040.

080.

120

00

–0.2

CA

STIL

LA

LA

MA

NC

HA

0.54

0.4

0.46

0.54

0.12

0.18

00.

120.

180.

18–0

.72

CA

TAL

ON

IA0.

830.

730.

131.

261.

090.

760.

620.

030.

020.

26–1

.14

VA

LE

NC

IAN

CO

MM

UN

ITY

1.04

0.63

0.24

0.72

0.33

0.33

0.99

0.42

0.23

0.08

–1.9

2E

XT

RE

MA

DU

RA

0.66

1.53

0.94

0.48

0.35

0.73

0.48

0.28

00

–1.3

2G

AL

ICIA

1.23

0.38

0.19

00.

080.

110.

150.

150.

110.

26–1

.94

MA

DR

ID0.

210.

040.

040.

090.

110.

230.

020.

060.

040.

1–0

.22

MU

RC

IA1.

590.

770.

50

0.12

0.89

0.52

0.2

00.

09–3

NA

VA

RR

A0

0.25

00

0.22

0.41

00

00.

190.

38B

ASQ

UE

CO

UN

TR

Y0.

090.

330.

360.

310.

110.

050.

140

00.

10.

02R

IOJA

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

0.38

n.a.

CE

UTA

/ME

LIL

LA

00

00

00

02.

250.

730

0SP

AIN

0.96

0.75

0.44

0.58

0.29

0.4

0.57

0.3

0.13

0.16

–1.6

Not

e: *

= %

inte

r-an

nual

var

iatio

n; n

.a. =

not

ava

ilabl

e.



both the economical values (with a nearlythree-fold difference between minimumand maximum), and particularly the inci-dence of tuberculosis (with an up to 5.5-fold difference) and leprosy—the latter be-ing the parameter showing the largest differ-ences (up to 25-fold). In relation to this lattervariable, the regions with the highest figureswere Andalucía and Extremadura, alongwith Catalonia and the Canary Islands.

On the other hand, in relation to the 5-yearmeans of the variables considered in thestudy by regions (Table 3), all AutonomousCommunities were seen to exhibit a rela-tively regular evolution with gradual de-creases or increases—the sole exception be-ing emigration, which proved to be some-what irregular.

In reference to 100 base index numbersof the Gross Domestic Product (GDP) andincidences for leprosy and tuberculosis in

Spain (Table 4), a 7.23-fold economical in-crease was observed since the year 1950—this figure being similar to the reduction inthe incidence of leprosy in the same periodof time (7.4-fold). In turn, tuberculosis wasseen to have decreased in incidence 3.7-fold in the course of the period 1950–2000.On the other hand, the mean annual varia-tion in GDP was seen to be 14%, while themean variations for leprosy and tuberculo-sis were quite similar (–1.66 and –1.57, re-spectively). The proportional variations tak-ing economical growth as reference base re-vealed that leprosy varied –0.06 units foreach proportional unit economical incre-ment. The situation was similar in the caseof tuberculosis (–0.07).

Considering that economical status exertsan influence at the time of actual contagion,even though clinically manifest leprosyonly appears some years later, we evaluated

FIG. 1. Mean 5-yearly incidence rates for leprosy in Spain in the second half of the Twentieth Century.Note: Incidence rate = cases per 100,000.


TAB

LE

2.A

nnua

l rat

e pe

r 10

0,00

0 in

habi

tant

s fo

r al

l Spa

nish

reg

ions

, 195

0–20

00.

Em

igra

tion

Em

ploy

-Sc

hool

ing

Phys

icia

nsIn

fant

Une

m-

GD

PR

ural

Hea

lthT

BC

Inci

denc

em

ent

mor

talit

ypl

oym

ent

popu

latio

npr

oduc

tof

lepr

osy

AN

DA

LU

CÍA

4.84

30.7

812

.59

2.02

0.49

40.0

131

7470

870.

391

AR

AG

ÓN

4.76

38.8

10.6

92.

870.

3519

.47

4503

5412

40.

240.

12A

STU

RIA

S2.

9438

.61

10.8

22.

210.

3428

.63

4281

8598

0.6

0.06

BA

LE

AR

IC I

SLA

ND

S2.

444

.54

12.1

42.

190.

2531

.31

6217

6019

00.

180.

22C

AN

AR

YIS

LA

ND

S4.

7734

12.6

81.

790.

4537

.97

4360

6412

50.

120.

82C

AN

TAB

RIA

3.65

39.1

12.0

72.

340.

425

.75

4442

6810

90.

480.

02C

AST

ILL

AL

EÓ

N5.

5937

.41

12.8

42.

290.

6421

.28

3512

6910

30.

350.

12C

AST

ILL

AL

AM

AN

CH

A4.

9734

.33

11.9

91.

590.

6222

.39

3037

8567

0.23

0.29

CA

TAL

ON

IA5.

4640

.38

10.7

22.

570.

2127

.859

8663

193

0.21

0.54

VA

LE

NC

IAN

CO

MM

UN

ITY

4.08

38.5

811

.65

2.15

0.28

34.2

347

3870

123

0.18

0.47

EX

TR

EM

AD

UR

A6.

6132

.42

11.7

1.56

0.69

32.8

624

7286

690.

340.

58G

AL

ICIA

7.61

41.7

11.6

91.

720.

4324

.52

3382

8589

0.36

0.26

MA

DR

ID3.

6337

.76

10.8

43.

450.

3129

.17

6601

2824

60.

110.

09M

UR

CIA

3.29

33.6

812

.86

1.89

0.45

24.2

236

8270

870.

250.

43N

AV

AR

RA

5.04

40.0

411

.78

2.7

0.41

24.1

552

0869

179

0.35

0.11

BA

SQU

E C

OU

NT

RY

5.58

37.9

211

.38

2.48

0.27

32.3

157

1963

168

0.25

0.13

RIO

JA4.

8241

.65

11.8

62.

250.

4416

.99

4799

6312

50.

260.

04C

EU

TA/M

EL

ILL

A7.

7822

.03

10.8

61.

630.

4727

.33

2952

099

0.41

0.29

TAB

LE

3.C

orre

spon

ding

ann

ual r

ates

for

each

of t

he fa

ctor

s an

alyz

ed in

Spa

in, 1

950–

2000

.

Yea

rE

mig

ratio

nE

mpl

oym

ent

Scho

olin

gPh

ysic

ians

Infa

ntU

nem

ploy

men

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the data on economic growth correspondingto the preceding years (1, 2, 3, etc.) in rela-tion to the incidence of Hansen’s Disease. Tothis effect we developed both simple andmultiple regression models, using the annualinformation from all Spanish provinces. Inthis respect, Table 5 shows the results ofmultiple regression, fitted by Naperian loga-rithmic transformation. The explanatorycontribution, measured in terms of R2, isseen to increase until a 6-year lag wasreached; at this point 57% of the incidenceof leprosy was explained. Later, with in-creasing delays, the values began to de-crease—though in an irregular manner.

In the multiple regression analysis, basedon the model involving a 6-year lag and us-ing the annual and provincial data, we inturn developed a complete model (Table 6).The results revealed that the factors seen toinfluence the incidence of leprosy were:employment, the number of physicians, andeconomic growth, all with negative coeffi-cients, while tuberculosis was associatedwith a positive coefficient. Nevertheless, theGDP was found to yield the most importantcoefficient, with a value of 0.5, followed byinfant mortality and the physician rate.

In view of the similar behavior of tuber-culosis as regards economic growth, a studywas made of the interactions and resultingco-linearity. In this context, tolerance andthe variance inflation factor showedmedium tolerance for the variables GDP,infant mortality and health education sectorproduct, unemployment, and the number ofphysicians—while high tolerance wasrecorded for the rest.

DISCUSSION

The main problem posed by studies of thiskind is that the data corresponding to the fac-tors analyzed must offer continuity and reli-ability. This prevented us from examining alarge number of variables which logicallyshould have been included in the study.

The regions with the highest rate andmost total cases of leprosy were Andalucíaand Extremadura (both of which showedthe lowest economic levels), followed byCatalonia and the Canary Islands—possiblydue to the important number of immigrantsfound in these autonomous communities.Within Andalucía, the province of Córdobaclearly stands out—with a mean rate for theglobal study period of 0.6 new cases per100,000 inhabitants per year—togetherwith the province of Jaén (7) . In sum, apreferentially though somewhat irregularMediterranean distribution is observed, incoincidence with the findings of other au-thors, in relation to the cases of leprosy (26).

On the other hand, although the study hasbeen carried out with delimitations in theform of provinces and/or regions, the distri-bution of Hansen’s disease is known to beextremely irregular—with marked intra-re-gional variations in Spain and also else-where in the world (35).

Since 1981, the World Health Organiza-tion (WHO) has recommended multi-drugtherapy for the management of leprosy, andhas considered it possible to eliminate thedisease as a public health problem world-wide. The leprosy-eliminating strategy pro-posed by the WHO has been based on thehypothesis that a reduction in the prevalenceof the disease based on the administration ofmulti-drug regimens (dapsone, clofazimineand rifampicin) entails a low reservoir ofcases in the community (fewer than 1/10,000inhabitants)—as a result of which the trans-mission cycle of the disease cannot be per-petuated (25, 32). The concept underlying thisstrategy is the so-called “basic reproductionrate, R0” (the mean number of individuals di-rectly infected by an infectious case). If R0 is>1, an epidemic may result, while if R0 is <1,the disease may disappear. In the case of lep-rosy, it has been estimated that R0 is <1 whenthe prevalence rate is less than 1/10,000—asituation that has been applicable in Spainfor many years. In our study the observed

TABLE 5. Logistic regression model fordifferent forecast terms of leprosy in Spain,1950–2000.

B Coefficient R2 Sig.

Lag 0 0.309 0.145 0.001Lag 1 –0.005 0.284 0.000Lag 2 –0.006 0.286 0.000Lag 3 –0.012 0.291 0.000Lag 4 –0.041 0.303 0.000Lag 5 –0.096 0.312 0.000Lag 6 –0.484 0.568 0.000Lag 7 –0.201 0.282 0.000Lag 8 0.001 0.166 0.000Lag 9 0.108 0.192 0.012Lag 10 0.102 0.157 0.130


annual reduction rate was 1.6%, while somesources in the literature conclude that coun-tries with endemic disease have annual re-duction rates of 4% (23).

However, certain data and contradictionsspeak against the optimism of the WHOand raise doubts as to the evolution of thedisease—questioning the central argumentof the elimination strategy whereby theonly effective contagion source is the lepro-matous patient, and a reduction in preva-lence therefore necessarily implies a reduc-tion in incidence. The principal unsettledquestions refer to the evidence suggesting aslightly decreasing general incidence(though not in all countries); uncertaintyover the true number of individuals with oc-cult infection; a lack of knowledge of themagnitude of the problem posed by subclin-ical carriers of the disease (20); and the pos-sible existence of animal reservoirs (5, 36).Many authors consider that the diseasefound in armadillos and monkeys is differ-ent from that seen in humans (27). Anotherimportant consideration is the present lackof an effective vaccine (10).

In this context, and in an attempt to ac-count for the evolution of leprosy, socio-sanitary and economic considerations havebeen postulated to be of greater relevancethan multitherapy. In favor of this hypothe-sis would be the declining trend of the dis-ease in China and Spain starting before im-plementation of the WHO multi-drugstrategy, and the spontaneous disappearanceof the disease in Norway (24), Japan (15) andHawaii (37), as well as its continued persis-tence in India, Brazil (17) and Cuba despite

application of the WHO program. In thecase of Norway, the gradual decrease inleprosy incidence was accompanied by anincrease in mean patient age at appearanceof the disease, and a gradual prolongationof the incubation period (24).

Leprosy prevalence data were not used inthis study, because they posed concordanceproblems with the incidence data. Such dis-cordance was mainly due to the repetitionof individuals included in the prevalencelists. Moreover, while the incidence ratewas not affected as a result, the prevalencerates were falsely elevated due to persis-tence in the prevalence lists of cases thathad likely died or healed.

Although the regression analysis cannotconsider only the sum of the effects of vari-ables, since the interference factors absorbpart of the explanation or prediction ofchanges in the incidence of leprosy, the in-teractions among variables do not seem tobe sufficiently intense to compromise inter-pretation of the results. The same applies tothe co-linearity among variables assessedby variance inflation factors and tolerance.The confounding variables and resulting at-tributable bias always pose a considerablerisk and are a source of imprecision in eco-logical studies, due to the scant control af-forded by the use of population instead ofindividual measures (29).

Although some authors have reported tu-berculosis to be antagonistic to leprosy, at-tributing the almost total disappearance ofthe latter to the appearance of tuberculosis,it must be considered that this is an infec-tious disorder, and that the environmental

TABLE 6. Conditioned factors analysis of the trend of leprosy in Spain, 1950–2000(logarithmic regression).

B COEFFICIENT t Sig. ULCI LLCI TOLERANCE VIF

Emigrant 0.241 1.52 0.129 –0.04 0.27 0.35 2.88Employment –0.174 –3.05 0.002 –3.59 –0.78 0.56 1.78Schooling 0.024 0.48 0.631 –0.82 1.36 0.73 1.37Physician –0.202 –3.47 0.001 –0.34 –0.09 0.80 1.25Infant mortality 0.238 1.82 0.068 –0.01 0.04 0.99 1.01GDP –0.484 –4.67 0.000 –2.45 –1.01 0.17 5.91Rural population 0.018 0.31 0.754 –0.69 0.96 0.53 1.87Health product 0.015 0.14 0.886 –0.82 0.95 0.16 6.25Tuberculosis 0.150 6.04 0.000 0.26 0.51 0.23 4.40

Note: B = beta, t = t Student, Sig. = significance, ULCI = upper limit confidence interval, LLCI = lower limitconfidence interval,

VIF = variance inflation factor


conditions and factors of hygiene are there-fore the bases for transmission. In thissense, socioeconomic status could be essen-tial for creating a setting unfavorable for thetransmission of both diseases, as observedin our study.

Previous authors have addressed the pos-sible relationship between socioeconomicdevelopment and concrete health aspects,e.g., mortality in the classical study of Krishnan (19) in India, or Mckeown (22) inEngland; or neonatal mortality in the studyof Shah and Abbey (33) in Baltimore (UnitedStates), among many others. However, a re-view of the literature has yielded almost nostudies relating socioeconomic develop-ment to the evolution of leprosy incidence.In contrast, analyses have been made of thesocial and economic variations observed inleprosy patients, and the need to restore suchparameters to their previous levels in orderto help heal the patients, as in a published In-dian study (29). Other parameters investigatedinclude crowding, domestic conditions,family size (31), and even the inverse relationbetween years of schooling and the incidenceof leprosy in a study from Malawi (28).

The present study made use of the grossdomestic product (GDP), as recommendedby some authors for conducting medium-and long-term studies (9). In this context,GDP was seen to be the factor exerting thegreatest influence upon leprosy evolution,according to the multiple regression analy-sis with a 6-year lag period. It should betaken into account that economic develop-ment is the fundamental factor influencingfamily crowding conditions, schooling, andother factors such as nutritional status (33),likewise related to the incidence of leprosy.The family grouping of leprosy observed insome studies may also be a consequence ofshared socioeconomic status (and thereforehygiene conditions) (16). Therefore someauthors recommend considering this as afactor in chronic diseases (35).

The other two factors with negative andstatistically significant coefficients wereemployment and the number of physicians,and the sum of their beta-coefficients waslower than that of GDP—i.e., they wereseen to jointly exert much less influenceupon leprosy incidence trends. The fourthsignificant factor was tuberculosis; in ef-fect, since the latter is also a transmissibledisease, it is also affected by social and eco-

nomic development. Moreover, it should betaken into account that the results of thepresent study showed a similar interannualchange for both transmissible diseases, andthat Bacillus Calmette Guérin (BCG) vacci-nation produces a certain degree of immu-nity against leprosy as well (8, 38).

In relation to the lag period used to ex-plain the incubation period of leprosy, theestimated period is 2.9 to 5.3 years in thecase of tuberculoid leprosy, and 9.3 to 11.6years in the case of the lepromatous form ofthe disease—though in our study a periodof 6 years was seen to afford the best expla-nation for the observed statistical relation-ship. Other authors have reported periods ofup to 30 years in veterans—a situation notexamined in the present study.

It may have been advisable to separatethe cases according to the type of leprosy,to establish the possible differences in theinfluence of socioeconomic factors accord-ing to the type of disease involved. How-ever, the incidence rates would have beenzero or very close to zero in the last years ofthe study period.

The declining tendency of leprosy inSpain was seen to be gradual since the1950s, i.e., it started before the introductionof multi-drug therapy, and was moreclosely associated with the socioeconomicdevelopment of the country. Similar obser-vations also apply to a number of other Eu-ropean countries (14), in addition to Norwayas noted above (24). Our study illustrates themulticausal model of effects, whereby so-cioeconomic considerations can prove moreimportant than the actual transmissibilityconditions of leprosy.

REFERENCES1. BANCO BILBAO VIZCAYA. Renta Nacional de Es-

paña y su Distribución Provincial. Años 1950 a1995. Servicio de publicaciones.

2. BELSLEY, D. Detecting and assessing the prob-lems caused by multi-collinearity: A use of thesingular-value decomposition. No. 66 in NBERWorking Papers, National Bureau of EconomicResearch, Inc., 1974.

3. BHATTACHARYA, S. N., and SEHGAL, V. N. Leprosyelimination campaign and its impending fallout.Int. J. Dermatol. 39(9) (2000) 667–669.

4. BJARNASON, O. The last lepra patient in Iceland.Nord. Medicinhist. Arsb. (1989) 197–203.

5. BRUCE, S., SCHROEDER, T. L., ELLNER, K., RUBIN,H., WILLIAMS, T., and WOLF, J. Armadillo expo-sure and Hansen’s disease: an epidemiologic sur-


vey in southern Texas. J. Am. Acad. Dermatol.43(2 Pt. 1) (2000) 223–228.

6. CENTRO NACIONAL DE EPIDEMIOLOGÍA. Manual delregistro estatal de lepra. Madrid. Instituto de SaludCarlos III. 1991.

7. DELGADO-RODRIGUEZ, M., RODRIGUEZ-CONTR-ERAS PELAYO, R., EXTREMERA-CASTILLO, F.,SERRANO-ORTEGA, S., and GALVEZ-VARGAS, R.Epidemiologic aspects of leprosy in the provinceof Jaen. Rev. Clin. Esp. 185(2) (1989) 99–103.

8. FINE, P. E. M. Variation in protection by BCG:implications of and for heterologous immunity.Lancet 346 (1995) 1339–1345.

9. GETZEN, T. E. Forecasting health expenditures:short, medium, and long term. J. Health Care Fi-nance 26(3) (2000 Spring) 56–72.

10. GUPTE, M. D., VALLISHAYEE, R. S., ANANTHARA-MAN, D. S., NAGARAJU, B., SREEVATSA, BALASUB-RAMANYAM S., DE BRITTO, R. L., ELANGO, N.,UTHAYAKUMARAN, N., MAHALINGAM, V. N., LOUR-DUSAMY, G., RAMALINGAM, A., KANNAN, S., andAROKIASAMY, J. Comparative leprosy vaccine trialin south India. Indian J. Lepr. 70 (1998) 369–388.

11. INSTITUTO NACIONAL DE ESTADÍSTICA. Anuario es-tadístico Ministerio de Economía. Madrid. Años1950 hasta 2001.

12. INSTITUTO NACIONAL DE ESTADÍSTICA. Censo de lapoblación española. Ministerio de Economía.Madrid. Años 1950 hasta 2000.

13. INSTITUTO NACIONAL DE ESTADÍSTICA. Movimientonatural de la población española Ministerio deEconomía. Madrid. Años 1950 hasta 2001.

14. IRGENS, L. M., MELO-CAEIRO, F., and LECHAT, M.F. Leprosy in Portugal 1946–80: epidemiologicpatterns observed during declining incidencerates. Lepr. Rev. 61(1) (1990) 32–49.

15. ITO, I. The epidemiological situation in south eastAsia. Lepr. Rev. 52 (1981) 43–51.

16. JAIN, S., REDDY, R. G., OSMANI, S. N., LOCKWOOD,D. N., and SUNEETHA, S. Childhood leprosy in anurban clinic, Hyderabad, India: clinical presenta-tion and the role of household contacts. Lepr. Rev.73 (2002) 248–253.

17. KLEINBAUM, D. G., KUPPER, LL., and MORGEN-STERN, H. Epidemiologic research: Principles andquantitative methods. New York: Van NostrandReinhold. 1982.

18. KRISHNAN, P. Mortality decline in India. 1951–1961: developmental versus public health programhypothesis. Soc. Sc. Med. 9 (1975) 475–479.

19. LECHAT, M. F. The source of infection: an un-solved issue. Indian J. Lepr. 72 (2000) 169–173.

20. LOCKWOOD, D. N., and SUNEETHA, S. Leprosy:too complex a disease for a simple eliminationparadigm. Bull. World Health Organ. 83 (2005)230–235.

21. LOPEZ-VELEZ, R., SAEZ-VAQUERO, T., BLANCO-AREVALO, J. L., and GOMEZ-MAMPASO, E. Lep-rosy simulating other diseases. Rev. Clin. Esp. 199(1999) 369–372.

22. MCKEOWN, T., and BROWN, R. G. Medical evi-

dence related to English populations change in theeighteenth century. Pop. Stud. 9 (1965) 119–123.

23. MEIMA, A., GUPTE, M. D., VAN OORTMARSSEN, G.J., and HABBEMA, J. D. F. Trends in leprosy casedetection rates. Int. J. Lepr. Other Mycobact. Dis.65 (1997) 305–319.

24. MEIMA, A., IRGENS, L. M., VAN OORTMARSSEN, G.J., RICHARDUS, J. H., and HABBEMA, J. D. Disap-pearance of leprosy from Norway: an explorationof critical factors using an epidemiological model-ling approach. International Journal of Epidemiol-ogy 31 (2002) 991–1000.

25. MEIMA, A., RICHARDUS, J. H., and HABBEMA, J. D.Trends in leprosy case detection worldwide since1985. Lepr. Rev. 75 (2004) 19–33.

26. NOORDEEN, S. K. Descriptive epidemiology ofleprosy. In: Leprosy. Hasting eds. Edimburgh.Churchill Livingstone Publications, 1985.

27. NOORDEEN, S. K. Toward the elimination of lep-rosy, the challenges and opportunities. Int. J. Lepr.Other Mycobact. Dis. 66 (1998) 218–221.

28. PONNIGHAUS, J. M., FINE, P. E., STERNE, J. A.,MALEMA, S. S., BLISS, L., and WILSON, R. J. Ex-tended schooling and good housing conditions areassociated with reduced risk of leprosy in ruralMalawi. Int. J. Lepr. Other Mycobact. Dis. 62(1994 Sep) 345–352.

29. RAO, V. P., RAO, I. R., and PALANDE, D. D. Socio-economic rehabilitation programmes of LEPRAIndia—methodology, results and application ofneeds-based socio-economic evaluation. Lepr,Rev. 71 (2000) 466–471.

30. ROTHMAN, K. J., and GREENLAND, S. Modern Epi-demiology. Philadelphia. 2nd ed. LippincottWilliams & Wilkins, 1998.

31. SAIKAWA, K. The effect of rapid socio-economicdevelopment on the frequency of leprosy in apopulation. Lepr. Rev. 52 (1981) 167–175.

32. SANSARRICQ, H. Epidémiologie de la lèpre. In: Lalèpre. Chapitre 5. Paris. Edit Ellipses Universitésfrancophones, 1995, pp. 54–72.

33. SHAH, F., and ABBEY, H. Effects of some factorson neonatal and postneonatal mortality. MilbankMem. Fund Q 49 (1971) 33–57.

34. SKINSNES, O. K. Effect of malnutrition on leprosy.Int. J. Lepr. Other Mycobact. Dis. 44 (1976) 374–375.

35. TERENCIO DE LAS AGUAS, J. La lepra, pasado, pre-sente y futuro. Valencia. Ed Generalitat Valen-ciana, 1999, pp. 57–75.

36. VALVERDE, C. R., CANFIELD, D., TARARA, R., ES-TEVES, M. I., and GORMUS, B. J. Spontaneous lep-rosy in a wild-caught cynomolgus macaque. Int. J.Lepr. Other Mycobact. Dis. 66 (1998) 140–148.

37. WORTH, R. M. The disappearance of leprosy in asemi-isolated population (Nihau Island, Hawai).Int. J. Lepr. Other Mycobact. Dis. 31 (1963) 34–35.

38. ZODPEY, S. P., BANSOD, B. S., SHRIKHANDE, S. N.,MALDHURE, B. R., and KULKARNI, S. W. Protectiveeffect of Bacillus Calmette Guérin (BCG) againstleprosy: a population-based case-control study inNagpur, India. Lepr. Rev. 70 (1999) 287–294.

ABSTRACTIn leprosy on treatment, one factor contributing to the healing of skin lesions with mini-

mal fibrosis may be apoptosis of inflammatory cells, even though apoptosis is sparse in lep-rosy as compared to tuberculosis. The degree of apoptosis in skin lesions of leprosy wasstudied by histopathologic examination (HPE) and by DNA fragmentation and elec-trophoresis. The effect of various parameters on apoptosis was noted in untreated disease,during treatment at 3 and 6 months, and in lepra reactions in different parts of the spectrumof leprosy. Of the 31 patients, 13 had paucibacillary (PB) and 18 multibacillary (MB) dis-ease. Twenty one patients were in reaction: 16 had type 1 reaction and 5 had type 2 reaction.The controls included patients with non-granulomatous skin diseases; there were no normalcontrols, and no separate controls for cases with reaction. Apoptosis occurred more fre-quently in patients with leprosy as compared to the controls. In both PB & MB lesions,apoptosis was observed to increase progressively with treatment at 3 and 6 months, and wasmore prominent in the MB cases at 6 months of treatment. When lesions in either type 1 ortype 2 reaction were compared to lesions not in reaction, a significant increase in apoptosis(p = 0.014) was found only in lesions with type 2 reaction and those which were at 6 monthsof treatment. The type of treatment regimen, or oral steroids given for reactions, did not sig-nificantly alter the degree of apoptosis. Our observations indicate that increased apoptosis ispresent in leprosy lesions and that in leprosy it progressively increases with anti-leprosytreatment up to 6 months. If the process of apoptosis in skin lesions is followed up for alonger period of time, the degree of apoptosis may be expected to decline. The study ofapoptosis may help to understand the mechanism of clearance of bacilli and resolution ofgranulomas in leprosy patients.

RÉSUMÉAu cours du traitement de la lèpre, un facteur contribuant à la cicatrisation des lésions cu-

tanées en l’absence de fibrose significative pourrait être l’apoptose des cellules inflamma-toires, même si l’apoptose est rapportée comme peu commune dans la lèpre, comparée à latuberculose. Le degré d’apoptose dans les lésions cutanées de la lèpre fut étudié à l’examenhistopathologique (HPE) et par examen de la fragmentation de l’ADN par électrophorèse.L’effet de divers paramètres sur l’apoptose fut noté lors de maladie non traitée, en cours detraitement à des temps de 3 et 6 mois et dans des réactions lépreuses pour différents pointsdu spectre immunopathologique de la lèpre. Parmi les 31 patients, 13 avaient la forme pau-cibacillaire (PB) et 18 la forme multibacillaire (MB). Vingt-et-un patients étaient en réac-tion, 16 ayant une réaction de type 1 et 5 de type 2. Les contrôles étaient représentés par despatients avec des maladies cutanées non granulomateuses, sans contrôle avec peau normale,et sans contrôle séparé pour les cas avec réactions. L’apoptose était plus fréquente chez les

1 C. Ajith, M.D; B. Kumar, M.D., MNAMS; S. Dogra, M.D., DNB, MNAMS; I. Kaur, M.D., MNAMS; De-partment of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Re-search, Chandigarh, India.

2Sachin Gupta M.Sc; Sunil K Arora, PhD, MNAMS; Department of Immunopathology, Postgraduate Instituteof Medical Education and Research, Chandigarh, India.

3B. D. Radotra, M.D., PhD; Department of Histopathology, Postgraduate Institute of Medical Education andResearch, Chandigarh, India.

Reprint requests to: Dr. Inderjeet Kaur, Department of Dermatology, Venereology and Leprology,Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India; e-mail:[email protected]

Study of Apoptosis in Skin Lesions of Leprosy in

Relation to Treatment and Lepra Reactions

C. Ajith1, Sachin Gupta2, Bishan D. Radotra3, Sunil K. Arora2, Bhushan Kumar1, Sunil Dogra1, and Inderjeet Kaur1

269


(ISSN 0148-916X)


In leprosy, the clinical, bacteriologicaland histopathological manifestations areprofoundly affected by the immunologicalstatus of the host, which determines thetype of leprosy. The clinicopathologic bipo-larity may stem from the dual response oflymphocytes, dendritic cells, monocytesand macrophages to M. leprae (1, 4, 14). Usu-ally chronic granulomatous diseases of theskin heal with fibrosis, eg: the scarring leftbehind by lupus vulgaris or scrofuloderma.However, in leprosy, with proper treatmentor spontaneously as in indeterminate lep-rosy, the majority of skin lesions heal with-out much fibrosis. One factor which may

contribute to this is thought to be apoptosis,a mechanism of cell death which has no ac-companying inflammatory component andthus may explain the relative lack of fibro-sis mentioned above.

Apoptosis is an active, self-destructivecellular process and is considered an inte-gral part of the repertoire available to thecell to respond to deleterious stimuli fromwithin and without (5, 7, 14). In tuberculosis,circulating polymorphonuclear neutrophils(PMN) show increased spontaneous apo-ptosis, and Mycobacterium tuberculosis-induced activation accelerates PMN apo-ptosis.(2)

patients atteints de la lèpre que chez les contrôles atteint de lésions cutanées non granulo-mateuses. A la fois dans les lésions PB et MB, il y eut un accroissement progressif de l’apop-tose aux temps de traitement de 3 et 6 mois, qui fut le plus net chez les cas MB à 6 mois detraitement. Lorsque les lésions de type 1 ou de type 2 furent comparées à celles sans réac-tion, une augmentation significative de l’apoptose (p = 0,014) fut observée dans les réactionsde type 2 et celles qui furent à 6 mois de traitement. Le type de traitement, ou bien les corti-costéroïdes oraux administrés pendant les réactions n’ont pas altéré de façon significative ledegré d’apoptose. Nos observations indiquent qu’il existe une apoptose plus importante dansles lésions de lèpre que dans celles de lésions cutanées non-granulomateuses et qu’elle aug-mente progressivement avec le traitement, et ce au moins jusqu’à 6 mois. Si l’apoptose dansles lésions cutanées avait été suivie au-delà de 6 mois, le degré d’apoptose aurait probable-ment décliné. L’étude de l’apoptose devrait pouvoir permettre de mieux comprendre les mé-canismes d’élimination des bacilles de Hansen et la résolution des granulomes chez les pa-tients souffrant de lèpre.

RESUMENEn el tratamiento de la lepra, un factor contribuyente a la curación de las lesiones de la

piel, con mínima fibrosis, puede ser la apoptosis de las células inflamatorias, aunque sepiensa que la apoptosis en la lepra es rara comparada con la apoptosis en tuberculosis. Eneste estudio se examinó el grado de apoptosis en las lesiones de la piel en la lepra porhistopatología (HP) y por fragmentación y electroforesis del DNA. Se registró el efecto devarios parámetros sobre la apoptosis en la enfermedad no tratada, en la enfermedad con 3 y6 meses de tratamiento, y en las reacciones de la lepra en diferentes partes del espectro de lalepra. De los 31 pacientes estudiados, 13 tenían lepra paucibacilar (PB) y 18 lepra multi-bacilar (MB). Veintiún pacientes estaban en reacción, 16 tenían reacción leprosa tipo 1, y 5reacción leprosa tipo 2. Los controles incluyeron pacientes con enfermedad de la piel nogranulomatosa; no hubo controles sanos ni controles separados para los casos en reacción.La apoptosis ocurrió más frecuentemente en los pacientes con lepra que en los pacientescontrol. Tanto en los pacientes PB como en los MB la apoptosis aumentó progresivamentecon el tratamiento a los 3 y 6 meses, y fue más prominente en los casos MB a los 6 meses detratamiento. Cuando se compararon las lesiones de las reacciones tipo 1 o tipo 2 con las le-siones de la lepra no reaccional, se encontró un significante incremento en la apoptosis (p =0.014) sólo en las lesiones de las reacciones tipo 2 y en aquellas de los pacientes con 6 mesesde tratamiento. El tipo del régimen de tratamiento o los esteroides orales administrados paracontrolar las reacciones no alteraron significativamente el grado de apoptosis. Nuestras ob-servaciones indican que la apoptosis está incrementada en las lesiones de la lepra y que au-menta progresivamente con el tratamiento anti-leproso administrado durante 6 meses. Se es-peraría una disminución en el grado de apoptosis en las lesiones seguidas por periodos másprolongados de tiempo. El estudio de la apoptosis puede ayudar a entender el mecanismo deeliminación de bacilos y la resolución de los granulomas en los pacientes con lepra.

73, 4 Ajith, et al.: Study of Apoptosis in Skin Lesions 271

In the resolution of leprosy granulomaswith treatment, one mechanism of cell lossis believed to be apoptosis, especially forhigh turn-over granulomas. The number anddensity of apoptosis in leprosy may be af-fected by factors such as bacillary load anddegree of cell mediated immunity (4, 10, 14).Since type1 and type 2 reactions in leprosymay be associated with changes in immunestatus, and the type 2 reaction is an acute in-flammatory state, the number and density ofapoptosis is likely to vary in these statesalso. We have therefore studied the degreeof apoptoses by two different standard labo-ratory techniques and observed the effect ofvarious parameters on apoptosis in skin le-sions in untreated leprosy, during treatment,and during reactions.

MATERIALS AND METHODSThe study included 34 patients with lep-

rosy attending the leprosy clinic at our cen-ter. Untreated, histopathologically con-firmed leprosy patients were enrolled in thestudy, including patients with or without re-actions, irrespective of sex, type and dura-tion of disease. For controls, 20 patientsfrom the general skin out-patient depart-ment were studied. Those with granuloma-tous skin disorders such as cutaneous tuber-culosis and sarcoidosis were excluded. Nonormal skin samples were taken for controlpurposes. Also, there were no separate con-trols for those with reactions. Appropriatetreatment regimen recommended by WHO,i.e., multi drug therapy (MDT), eithermultibacillary (MB) or paucibacillary (PB)regimen (15) was given to the patients ac-cording to the type of the disease.

To study the apoptosis in the tissue spec-imens, biopsies were taken before startingtreatment and at 3 and 6 months post-treat-ment, from the most active edge of the mostprominent lesion, regardless of reactionalstate. All the initial biopsies were taken be-fore the treatment started, and all subse-quent biopsies were taken from the same le-sion. For control purposes, biopsies weretaken from 20 patients with skin diseasesother than leprosy or other granulomatousdisorders. From the tissue specimens, apo-ptosis was detected by two different meth-ods for comparison i.e., histopathologic ex-amination (HPE) and by DNA fragmenta-tion and electrophoresis. All the biopsies

were bisected, and the portion for HPE wasfixed in formalin, embedded in paraffin, and6µ thick tissue sections were cut andstained by hematoxylin and eosin. By HPE,apoptotic bodies were identified by the fol-lowing features: nuclear condensation,round to ovoid bodies, eosinophilia of thecytoplasm and karyorrhexis/karyolysis (7)(Fig. 1). The number of apoptotic bodiesper 10 high power fields/sample wasrecorded. The readings were taken by anexperienced histopathologist, who was un-aware of the treatment status of the patient.The fields were within the granulomas, andin biopsies where the granulomas were notprominent, the fields chosen were amongthe inflammatory infiltrates.

The other part of the bisected biopsy tis-sue was transported in normal saline foranalysis of DNA fragmentation. DNA wasisolated from all the samples by the methodof Palmiter et al (14). Briefly, the tissue wasteased and suspended in 500µl of lysisbuffer containing 1% SDS and 0.01% pro-tienase K in Tris-EDTA (TE) buffer (ph 8.0)and incubated at 55°C overnight. After phe-

FIG. 1. Apoptotic cell depicting characteristic nu-clear fragmentation (H&E stain ×550).


nol-chloroform extraction, the DNA wasprecipitated with chilled isopropanol, andresuspended in TE buffer. The preparedDNA was run on 1% agarose gel, stainedwith ethidium bromide, and the gel wasDNA viewed under ultraviolet light, toidentify the typical “ladder pattern” of frag-mented DNA specific to apoptosis. The pic-tures were captured using a gel documenta-tion system (Image master, PharmaciaBiotech). Statistical analyses were done us-ing non-parametric Chi-square tests andMcNemar’s Chi-square tests.

RESULTSOf the 34 patients, 2 patients were lost to

follow up and one patient died after 2months of treatment due to dapsone hyper-sensitivity syndrome. Therefore, skinbiopsy results from 31 patients were avail-able for analysis. These were from 26 malesand 5 females, having a mean age of 35.6±1.7 years. The majority of the patients(75%) were in the 16–45 years age groupfollowed by 46–70 years (22%) and 1 (3%)was aged 14 years. Of the total patients 13(42%) had paucibacillary (PB) and 18(58%) had multibacillary (MB) disease.Twenty one patients were in reaction: 16

(76%) had type 1 reaction (9 in the PB and7 in MB the group) and 5 (24%) had type 2reaction.

Skin biopsies were taken from the controlgroup of 20 patients, (12 males, 8 females)who had a mean age of 34.8 ± 1.8 years.The controls selected had various non-gran-ulomatous dermatoses including lichenplanus (5), discoid lupus erythematosus (4),pemphigus (4), warts (4), leiomyoma (2)and pseudopelade (1). The results obtainedwith both methods were compared in thePB and MB groups and controls at the startof the study, in relation to anti leprosy treat-ment, in Type 1 and Type 2 reactions, and inpatients receiving corticosteroids for con-trol of reaction.

By the method of HPE, apoptotic bodieswere detected in all the specimens at all thestages, whereas by DNA fragmentation andelectrophoresis (Fig. 2), apoptosis was de-tected only in 9 (26%), 16 (52%) and 26(87%) of patients at baseline (untreated)and at 3 and 6 months of treatment respec-tively. Detection of apoptosis by themethod of HPE at baseline and at 3 monthsand 6 months after completing treatment ispresented in Table 1. The detection of apo-ptosis by DNA fragmentation and elec-

FIG. 2 1% Agarose gel electrophoresis showing DNA fragmentation pattern; Lanes 1, 2, 3, 6, 7, 9 and 10showing the typical “ladder pattern” of apoptoses.


trophoresis in PB and MB disease at base-line and at 3 months and 6 months aftertreatment is presented in Table 2. A com-parison of apoptosis by the method of HPE between the different groups is shownTable 3.

Twenty two patients received MDT-MBtherapy, 7 patients received MDT-PB ther-apy and 2 patients received rifampicin,ofloxacin, and minocycline (ROM) therapy.Comparing the different treatment groups,apoptosis was found more frequently withtreatment in all the groups. Comparingapoptosis between the groups, no signifi-cant change in the apoptosis was observedat all the 3 stages of treatment. (The valuesfrom the two patients who received ROMtherapy were not compared with othergroups),

Of the 31 patients, 23 (74%) patients re-ceived corticosteroids (19 for reactions and4 for neuritis); the starting dose of pred-nisolone was 40 mg/day, which was then ta-pered over a period of 3–6 months. Oncomparing apoptoses between the steroid-treated and non-treated patients, both thegroups showed an increase in apoptoseswith the duration of treatment, but the effectof steroids on this trend was not statisticallysignificant in any of the groups at any pe-riod (p >0.05).

In summary, apoptosis was found morefrequently in patients with leprosy as com-pared to the controls. In both PB & MBportions of the leprosy spectrum, apoptosisprogressively increased with treatment at 3and 6 months, but it was more noticeable inthe MB cases, especially at 6 months oftreatment. When biopsies of either type 1 ortype 2 reaction were compared to those notin reaction, a significant increase in apo-

ptoses was found in cases with type 2 reac-tions, also at 6 months of treatment. All ofthe MDT regimens showed increased de-grees of apoptosis, but the process was notaffected by either of the regimens. The ad-ministration of corticosteroids did not ap-pear to significantly alter the degree ofapoptosis.

DISCUSSIONApoptosis is one form of cell death which

is non-inflammatory, and it has been postu-lated to play a role in the resolution of lep-rosy granulomas as a mechanism of cell de-struction. It might represent a strategy ofthe immune system to eliminate infectedcells, but few studies have shown apoptosisto be present in leprosy lesions (1, 4, 15). Onerecent study assessing a small number ofsamples only from untreated patients foundtrends suggesting apoptosis in leprosy le-sions might be more frequent in PB disease(15). However, sufficient information onapoptosis in various situations, such as dur-ing reactions, in different portions of theleprosy spectrum of disease (indirectly indi-

TABLE 1. Apoptoses by the method of HPE at baseline and at 3months and 6 monthsafter completing treatment

Apoptoses (mean ± S.D.)/10hpf

Diagnosis Number of casesBaseline 3 months 6 months

after treatment after treatment

PB with type 1 reaction 9 2.04 ± 1.33 3 ± 1.48 5 ± 1.29PB without reaction 4 2 ± 1.42 2.5 ± 1.34 3.5 ± 1.44MB with type 1 reaction 7 2.12 ± 1.83 3.82 ± 1.40 6 ± 1.60MB with type 2 reaction 5 3.8 ± 1.82 4.8 ± 2.59 9.4 ± 3.21MB without reaction 6 2.5 ± 0.89 3.2 ± 1.3 5.17 ± 1.17

TABLE 2. Detection of apoptosis byelectrophoresis to depict DNA fragmenta-tion at various periods in PB and MB dis-ease.

Number and % age of patients

Disease 3 months 6 monthsspectrum Baseline after after

treatment treatment

PB n = 13(p >0.05) 3 (23%) 6 (46%) 8 (61%)

MB n = 18(p <0.05) 6 (33%) 10 (77%) 18 (100%)


cating immune status), and the effects oftreatment, are not available.

Comparing two methods of apoptosis de-tection i.e., HPE and DNA fragmentationand electrophoresis, the HPE method wasfound to be more sensitive and provided amore exact quantitative difference in apo-ptosis at different stages. However, usingthe HPE method as a readout for apoptosesis not ideal because this method is subjectto observer variability and incorrect inter-pretation if read by an observer not experi-enced in apoptoses (4, 15). The method ofDNA fragmentation and electrophoresis isnot subject to observer variation and the re-sults are more reliable and probably ofgreater value than HPE, but in our study,which required a quantification of apo-ptoses, DNA fragmentation and elec-trophoresis was observed to be less sensi-tive. Using DNA fragmentation and elec-trophoresis, we could not detect theapoptotic process in expected numbers, butthe trends in the detection of apoptoses be-tween HPE and DNA fragmentation andelectrophoresis were similar.

In comparing the frequency of apoptosisin lesions across the disease spectrum, it wasfound that in all subsets of disease, there wasprogressive increase in apoptoses from base-line to 6 months of treatment. Our findingsof significantly more apoptoses in patientswith leprosy compared to controls supportsthe similar observation in previous studies (4, 10, 15). Walsh, et al. (15), using a well estab-lished “TUNEL” assay found apoptosis to bemore frequent in untreated lesions of PB dis-ease in comparison with MB disease; how-ever we observed apoptosis to be greater inlesions of MB compared to PB group. Ourobservation supports a previous in vitrostudy in which apoptosis increased with in-

creasing concentration of M. leprae (6), al-though this was an in vitro study and did notinvolve skin lesion analysis. Generally, thissuggests that apoptoses can be found in lep-rosy, but since it was not present in all thesamples and the numbers of apoptoses weresmall, unlike in tuberculosis, the significanceof apoptoses in leprosy remains unclear.

Regarding the effect of treatment, thenumber and density of apoptoses increasedprogressively with treatment in all thegroups of patients. One previous study hasshown that sulfonamides can induce apo-ptosis of circulating leukocytes, by theirmetabolites becoming attached to thesecells and promoting up regulation of apo-ptosis inducing factors (9). Since sulfon-amides are present in both MDT-MB andMDT-PB regimens and the effect of ri-fampicin and clofazimine on apoptosis isnot known, an exact explanation of the roleof MDT regimens in the increased apo-ptoses is not clear. With treatment, inflam-mation subsides and the bacillary load alsodeclines. Both of these effects should causea fall in apoptosis. But we have found in-creasing apoptosis with both treatment reg-imens at 6 months. Since treatment resultsin the resolution of leprosy granulomaswith a modest proportion of the inflamma-tory cells undergoing apoptosis, this couldexplain the finding of increased apoptosisearly in the treatment. Resolving granulo-mas initially show apoptoses of inflamma-tory cells with treatment. In fully resolvedgranulomas the apoptosis may even ceasecompletely and so there may occur a fall inapoptoses. Also, the apoptotic bodies areunderstood to be spontaneously clearedwith time by phagocytosis. Hence, we spec-ulate that studies carried out for a longer pe-riod may show decreasing apoptosis.

TABLE 3. Comparison of apoptoses by HPE between the various groups at differentperiods.

Disease groupsp-value

Baseline 3 months 6 months

PB with type 1 reaction vs. PB without reaction 0.55 (p >0.05) 0.16 (p >0.05) 0.20 (p >0.05)PB with type 1 reaction vs. MB with type 1 reaction 0.56 (p >0.05) 0.68 (p >0.05) 0.19 (p >0.05)MB with type 1 reaction vs. MB without reaction 1.00 (p >0.05) 0.57 (p >0.05) 0.32 (p >0.05)MB with type 2 reaction vs. MB without reaction 0.07 (p >0.05) 0.16 (p >0.05) 0.014 (p <0.05)MB with type 1 reaction vs. MB with type 2 reaction 0.13 (p >0.05) 0.26 (p >0.05) 0.03 (p <0.05)PB without reaction vs. MB without reaction 0.52 (p >0.05) 0.14 (p >0.05) 0.17 (p >0.05)


In lesions of Type 2 reaction, a significantincrease in apoptosis was observed at 6months of treatment when compared tonon-reactional group as well as to the type 1reactional group. Oliveira and colleaguesfound apoptosis to be greatly accelerated incirculating polymorphonuclear neutrophilsin patients experiencing ENL (11). The in-creased expression of pro-apoptotic mem-bers of Bcl-2 protein family and of TNF-αin type 2 reaction is likely to induce moreapoptosis (11). Sampaio and colleagues haveshown that neutrophils stimulated with M.leprae secrete large amounts of IL-8 andTNF-α, and drugs with anti TNF-α proper-ties such as thalidomide given for severeENL reaction may cause a decrease in apo-ptosis (13). Our findings support the sugges-tions that greater bacillary load and type 2reaction can lead to an increase in apoptosis.

Though the number and density of apo-ptosis was more in the prednisolone treatedgroup, the values were not statistically sig-nificant when compared to the non-pred-nisolone treated group. Though cortico-steroids are among the drugs that can in-duce apoptosis especially in thymic andcirculating lymphocytes, no significant as-sociation with corticosteroid treatment andapoptosis was found in this study. A previ-ous study has shown differential effect ofsteroids on apoptosis, with apoptosis beinginhibited in few specific tissues, especiallyglandular tissues (3). Also the pro-apoptoticeffects of corticosteroids may have beenoffset by the effect of anti-leprosy treat-ment, with M. leprae induced inflammationresolving and the corticosteroids further re-ducing the inflammation.

Apoptosis is the end point of an energy de-pendent cascade of molecular events and isregulated by several genes which induce p53,c-Myc, Bcl-2, CED-3 and Fas genes (7, 17, 18).M. leprae induced apoptosis of circulatingmonocytes has been shown to occur in vitro(6). Studies on blood mononuclear cells inleprosy patients have shown greatly in-creased apoptoses of lymphocytes espe-cially the CD8+ and CD19+ cells comparedto CD4+ cells (10). These results demon-strated that M. leprae can lead to apoptosisof macrophages through a mechanism thatcould be at least partially related to the ex-pression of pro-apoptotic members of theBcl-2 protein family and of TNF-α. Apo-

ptosis may also have a role in nerve damagein leprosy, as shown by a recent studywhich investigated the possibility that hu-man Schwann cells are susceptible to celldeath through the activation of Toll like re-ceptor 2 (TLR2), a pattern recognition re-ceptor of the innate immune system (12).Hence, apoptosis promoted by M. lepraemay induce damage in the affected tissues,also may act as a defense mechanism byshedding the infected and effete macro-phages and lymphocytes.

Further study of apoptosis may help tounderstand the method/mechanism of clear-ance of bacilli and resolution of granulomasin leprosy patients. It is expected that thedegree of apoptosis will decrease in patientswith resolving disease; however an increas-ing trend is likely to be seen in the initialperiod of therapy when immune response isbeing reconstituted and bacillary clearanceis occurring. If the process of apoptosis inskin lesions is followed up for a longer pe-riod of time, the degree of apoptoses is ex-pected to come down. From this study it isnot possible to delineate the exact role ofeach of the factors like type of disease, re-actions, treatment regimens and steroids,with each contributing directly or indirectlyto the final result. Hence further studieswith larger number of patients and pro-longed follow up designed to detect apopto-sis for at least up to 1 year duration are war-ranted.

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genesis updated. Int. J. Dermatol. 38 (1999)321–334.

2. ALEMAN, M., SCHIERLOH, P., DE LA BARRERA, S. S.,MUSELLA, R. M., SAAB, M. A., BALDINI, M., AB-BATE, E., and SASIAIN, M. C. Mycobacterium tu-berculosis triggers apoptosis in peripheral neu-trophils involving toll-like receptor 2 and p38 mi-togen protein kinase in tuberculosis patients.Infect. Immun. 72 (2004) 5150–5158.

3. AMSTERDAM, A., TAJIMA, K., and SASSON, R.Cell-specific regulation of apoptosis by glucocor-ticoids: implications to their anti-inflammatory ac-tion. Biochem. Pharmacol. 64 (2002) 843–850.

4. CREE, I. A., GARDINER, C. A., BECK, J. S., andMEHTA, J. Studies of cell death (apoptosis) andcell division in leprosy granulomas. Int. J. Lepr.Other Mycobact. Dis. 54 (1986) 607–613.

5. CREE, I. A., NURBHAI, S., MILNE, G., and BECK, J. S. Cell death in granulomata: the role of apo-ptosis. J. Clin. Pathol. 40 (1987) 1314–1319.


6. HERNANDEZ, M. O., NEVES, I., SALES, J. S., CAR-VALHO, D. S., SARNO, L. N., and SAMPAIO, E. P. In-duction of apoptosis in monocytes by Mycobacte-rium leprae in vitro: a possible role for tumor necro-sis factor-alpha. Immunology 109 (2003) 156–164.

7. HOCKENBERY, D. Defining Apoptosis. Am. J.Pathol. 146 (1995) 16–19.

8. MUSTAFA, T., BJUNE, T. G., JONSSON, R., PANDO, R. H., and NILSEN, R. Increased expression of fasligand in human tuberculosis and leprosy lesions:a potential novel mechanism of immune evasionin mycobacterial infection. Scand. J. Immunol. 54(2001) 630–639.

9. NAISBITT, D. J., HOUGH, S. J., GILL, H. J., PIRMO-HAMED, M., KITTERINGHAM, N. R., and PARK, B. K. Cellular disposition of sulphamethoxazoleand its metabolites: implications for hypersensi-tivity. Br. J. Pharmacol. 126 (1999) 1393–1407.

10. NIANG, M. N., BALDE, A. T., PERRAUT, R., MANE,I., and CARTEL, J. L. Apoptosis in leprosy pa-tients. Int. J. Lepr. Other Mycobact. Dis. 67 (1999)473–474.

11. OLIVEIRA, R. B., MORAES, M. O., OLIVEIRA, E. B.,SARNO, E. N., NERY, J. A., and SAMPAIO, E. P.Neutrophils isolated from leprosy patients releaseTNF-alpha and exhibit accelerated apoptosis invitro. J. Leukoc. Biol. 65 (1999) 364–371.

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Infestation of ulcers and invasion of nasalcavities of leprosy-affected persons by lar-vae of different flies is still seen in some pa-tients today. Leprosy-affected persons,whether active or released from control,having residual problems like atrophicrhinitis or anesthesia of the hands and feetcan acquire maggot infestations especiallyif they are from economically weaker strataof society, have poor hygiene, suffer fromgeneral debility and have poor near vision.

The term myiasis is derived from Greekword “Myia” meaning a fly. Infestation ofliving tissues by larvae of dipterans flies iscalled myiasis, and Goldstein (2) was prob-ably the first to report myiasis in human be-ings. The flies responsible for myiasis aregrouped as obligatory, facultative and acci-dental parasites depending upon the ovi orlarvipositing habits of the flies. Commongenera causing myiasis in humans are Sar-cophaga, Chrysomyia, Lucilla, and Cal-liphora. Occasionally common house flies(belonging to genus Musca) are also re-sponsible for accidental myiasis. Basedupon the affected organ, myiasis can also beclassified as nasal, aural, ocular, anal, vagi-nal etc. Animal myiasis is well known. Hu-man tissue myiasis involving the skin hasbeen reported from Mexico, the MiddleEast, North Africa and the United States ofAmerica, but few documented reports areavailable (3, 7).

The maggots of certain dipterans flies aremerely scavengers and are sometimesfound to be beneficial. These surgical mag-gots are said to help in healing wounds(9,10). However it is difficult to predict cir-

cumstances under which they act as scav-engers or as a serious parasite. It has beenobserved that once the wounds of the ex-tremities are cleared of maggots they gran-ulate faster. This has been attributed to thepresence of allantoin which is excreted bymaggots into the wound (11).

Myiasis is more commonly seen in thetropics and subtropics where flies are pres-ent in abundance. These are the areas of theworld where leprosy also exists. Myiasiscauses distress, pain and increases tissuedamage. Myiasis is a serious problem whenit occurs, although Sreevatsa, et al. (12)found the incidence to be less than 0.5% in3350 consecutive cases of leprosy of alltypes. Either sex can be affected but therehas been a male predominance, probablydue their involvement in outdoor activities.Poor personal hygiene as well as environ-mental conditions increase the risk of myia-sis. Cases are more frequent during Sep-tember to November—the post monsoonseason (mean temperatures around 25° Cel-sius and humidity 80–90%)—a favorableperiod for flies to breed.

Reports in the literature about tissue myi-asis are scanty; only nasal myiasis been ex-tensively studied. The loss of capability toperceive sensory stimuli contributes signif-icantly to such infestations. Atrophic rhini-tis in BL-LL cases predisposes to nasal in-vasion, and 60–70 % of lepromatous caseshave ulcers of nasal mucosa during thecourse of illness (1). The suppurartivewounds of the nasal cavity and the resultingmuco-purulent discharge provide an attrac-tive and rather secure site for flies to breed.It is likely that flies lay their eggs in thevicinity of nostrils; eggs are subsequentlypushed inside while wiping the nose.Larvipositing flies lay their larvae in thevicinity and they subsequently migrate intothe nasal cavity—a darker area.

1 Dr. G. N. Malaviya, Department of Plastic & Re-constructive Surgery, Central Jalma Institute for Lep-rosy, Tajganj, Agra (India) PIN 282 001;e-mail: [email protected]

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CLINICAL NOTES

Myiasis in Leprosy

G. N. Malaviya1


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Wounds and ulcers in extremities, for var-ious reasons, are seen in 15–20% cases ofall types leprosy (13). Infected suppuratingwounds in these anatomical areas provide acongenial atmosphere for the flies to laytheir eggs/larvae, and for larvae to grow anddevelop further. These larvae burrow deepinto the wounds and damage tissues further.

Clinical presentation of myiasis. Infes-tations of the nose and extremities produceseveral symptoms, some of which are com-mon. Patients may have recurrent infesta-tions, especially in nose. Nasal myiasis,usually seen in lepromatous (LL) and bor-derline lepromatous (BL) cases, gives riseto a feeling of uneasiness, nasal stuffinessand obstruction, headache, irritation, gnaw-ing and/or insect crawling sensations in thenose, and sneezing. Associated features areblood-tinged nasal discharge or frank epis-taxsis, swelling of the nose and nearby fa-cial structures, and at times “insects” (mag-gots) dropping out of the nose, either spon-taneously or on blowing the nose. Patientsmay appear to be disinterested and apa-thetic but are in severe agony.

Sometimes tissue destruction is extensiveand can lead to nasal perforation and othernasal deformities such as collapse of nasalarchitecture, partial absorption of nasalbones, and deviation of the nasal septum(4). Nasal perforation may result in a nasalfistula when edema subsides and tissues be-gin healing. Occasionally the larvae burrowdeep into the floor of the nasal cavity anderode the bony palate to produce a palatalperforation which may result in a perma-nent palatal fistula. These fistulae are diffi-cult to treat because of intense fibrosis inthe surrounding areas (8). Nasal myiasis canprove fatal if cavernous sinus thrombosisdevelops or the floor of the cranium is in-vaded. Many of the patients affected withnasal myiasis keep moustaches which, ifnot cleaned properly, can attract flies. Thenasal discharges and food adhering to thehairs in moustaches and drying up, is againa source of attraction to flies.

Patients having ulcers of the extremitiescomplain of a feeling of insects crawling inareas around the wound, foul smelling dis-charge, swelling and “insects” in thewound. Many times patients try to treattheir wounds themselves with available “in-secticides” before presenting for treatment.

The bacterial flora seen in maggot-infestedwounds of the extremities is mixed (6).Among gram-positive aerobes, Staphylo-coccus aureus, Staphylococcus albus andStreoptococcus pyogenes were more fre-quently isolated; gram-negative aerobes in-cluded Proteus spp. and Escherichia coli.Anaerobes which were isolated include Mi-crococcus and Bacteroids whereas Clostridiawere seen infrequently (2% cases). Even af-ter removal of maggots, Staphylococcus au-reus persisted in the wound, though gramnegative bacteria and anaerobes were dra-matically reduced. These observations re-vealed only the spectrum of bacteria but notthe quantum of bacterial load in maggot in-fested wounds.

Sreevatsa, et al. (12) were able to culturethe larvae obtained from the nose andwounds in laboratory and found that twoflies were mainly involved—Sarcophagaruficornis and Chrysomyia bezziana. Hu-sain, et al. (5) in another study found Sar-cophaga haemorrhoidalis, Chrysomiyabezziana, Callitroga americana and Muscadomestica infested the nose and wounds ofthe extremities in leprosy affected persons.The former two were more frequent, and attimes two or more species were infestingthe same wound.

Management of myiasis. The goal ofmanagement is to remove maggots as fastas one can, kill them to prevent maturation,promote wound healing and prevent sec-ondary complications. Myiasis of the noseand that of the extremities require differentapproaches.

Wounds of the extremities are washedwith pure chloroform (Pharmacopoeiagrade). About 5 to 10 ml is enough for an av-erage size wound. Chloroform kills the mag-gots instantaneously (5) and is innocuous tothe tissues. It must be stored in amber col-ored bottles away from sunlight because itdecomposes in presence of sunlight to forma toxic product. It is better than ether (usedin some clinics) which is more volatile andirritating and has a local freezing effect.

Dead maggots can be manually removedor the wound can be lightly curetted, takingspecial care to remove maggots from underwound margins. Since maggots have a ten-dency to migrate quickly towards deep anddarker areas, it is better to organize materi-als before opening the dressings. Wound

73, 4 Clinical Notes 279

debridement in the extremities should belimited to the essential minimum becausethe wound rapidly granulates and healing isfaster if general debility is not severe. Thewound is then dressed with fluffed gauzesoaked in a mixture of turpentine and water(1:10). This keeps the flies away, masks thebad odor and absorbs the discharges. Dress-ing changes are made after 24 hours and thewound is treated similarly removing deadtissues; additional chloroform treatmentmay be needed if some live maggots re-main. The wound is usually free of maggotsby the second or third day and then can betreated like any other infected wound.

For nasal myiasis, the nasal cavity is co-piously irrigated with a mixture of chloro-form and water (1:2) two to three times aday and then is lightly packed with a ribbongauze soaked in a mixture of turpentine andliquid paraffin (1:15). The process is re-peated until the nasal discharge subsides.Dead maggots are coughed out mixed withdischarges. The patient should be advised toinstill nasal drops made of turpentine oiland liquid paraffin (1:20). Deep posteriorburrowing of maggots makes their manualremoval difficult. Patients are prescribedantibiotics and aspirin in suitable doses tocontrol infection and prevent intracranialcomplications (i.e., cavernous sinus throm-bosis). Patients are also given sedativessuch as diazepam to reduce discomfort. Thenasal cavity is usually free of maggots in 48–72 hours after starting treatment, and localcellulitis subsides in 7 to 10 days. Nasalmyiasis usually does not require any surgi-cal intervention except in cases where tis-sue destruction is extensive and nasal struc-tures have been destroyed by maggots.There also the tissue excision should bedone conservatively. Incisions on the noseto attempt manual removal of maggotsshould be avoided. In patients having recur-rent infestations, partial closure of the nos-trils using local mucosal flaps can be per-formed (14).

Myiasis is an avoidable problem. It canbe prevented by proper ulcer care and bypreventing flies from settling on ulcers bykeeping the wounds well covered with

dressings and by painting the top-mostlayer with a turpentine water mixture (1:5),especially during the post monsoon seasonwhen flies tend to breed. To prevent nasalmyiasis patients need to be educated aboutroutine nasal care and hygiene.

REFERENCES1. DAVEY, T. F., and BARTON, R. P. E. Leprous le-

sions of nose. In: Leprosy. Eds. Dharmendra;Kothari Publishing House: Bombay. Vol I. Chap-ter 12, 1978, pp. 168–173.

2. GOLDSTEIN, M. A. The texas screw-worm and itsinvasion of the nasal cavities. Laryngoscope 3(1897) 335–340. (Quoted by Sahay L K. Ind. J.Otolaryngol.11: 146–148, 1959).

3. GORDON, P. M., HEPBURN, N. C., WILLIAMS, A. E.,and BUNNEY, M. H. Cutaneous myiasis due toDermatobia hominis: a report of six cases. Br. J.Dermatol. 132 (1995) 811–814.

4. HUSAIN, S., MALAVIYA, G. N., GIRDHAR, A., SREE-VATSA, and GIRDHAR, B. K. Nasal Myiasis in Lep-rosy. Lepr. Review. 62 (1991) 389–394.

5. HUSAIN, A., HUSAIN, S., MALAVIYA, G. N., and BA-HADUR, R. R. Myiasis in leprosy. Acta Leprolog-ica 8 (1993) 137–141.

6. HUSAIN, A., SREEVATSA, MALAVIYA, G. N., HUSAIN,S., and BAHADUR, R. R. Characterization of mi-crobial flora of leprous ulcers infested with mag-gots. Acta Leprologica 8 (1993) 143–147.

7. KENNY, R. L., and BAKER, F. J. Botfly (Dermato-bia hominis) myiasis. Int . J. Dermatol. 23 (1984)676–677.

8. MALAVIYA, G. N., and HUSAIN, S. Repair of NasalFistulae in Leprosy. Euro. J. Plastic Surgery 14(1991) 232–234.

9. PECHTER, E. A., and SHERMAN, R. A. Maggottherapy: the surgical metamorphosis. Plastic &Reconstructive Surgery. 72 (1983) 567–570.

10. REAMES, M. K., CHRISTENSEN, C., and LUCE, E. A.The use of maggots in wound debridement. Ann.Plast. Surg. 21 (1988) 388–391.

11. ROBINSON, W. Stimulation of healing in non-heal-ing wounds by allantoin (occurring in maggot se-cretions and of wide biological distribution). J.Bone Joint Surgery 17 (1935) 267–271.

12. SREEVATSA, MALAVIYA, G. N., HUSAIN, S., GIRD-HAR, A., BHAT, H. R., and GIRDHAR, B. K. Prelim-inary observations on myiasis in leprosy patients.Lepr. Review 61 (1990) 375–378.

13. SRINIVASAN, H. Neuropathic ulceration. In: Lep-rosy. Eds. Dharmendra. Kothari PublishingHouse: Bombay. Vol I: Chapter 18. 1978, p. 225.

14. YOUNG, A. Closure of nostrils in atrophic rhinitis.J. Laryngol. Otol. 81 (1967) 514–524.

TO THE EDITOR:

We read with interest the article by Gel-ber et al. (1) in the December 2004 issue ofTHE JOURNAL, in which they observed highrelapse rates in MB leprosy patients withhigh initial bacterial indices (BI). Eventhough we agree with the conclusions fromthe article, we were surprised to see the fol-lowing phrase in the discussion:

“. . . classifying patients as MB or PB.This distinction is now determined simplyby counting the number of skin lesions, MBbeing 5 or more (our emphasis) and PB be-ing less.”

This is actually a misinterpretation of theWHO guidelines and our field experiencehas indicated that this mistake is often madein leprosy control programmes:

The actual WHO classification criteria are:more than 5 lesions for MB (2–7) and 5 le-sions or less (2–4,6,7) or “up to five” (5) for PB.As “more than 5” in our experience is regu-larly interpreted as “5 or more” by fieldworkers (and apparently also by the distin-guished research group at the Leonard WoodMemorial Center in Cebu), we suggest thatthe recommendation be re-stated to state: “6or more” for MB leprosy and “5 or less” forPB leprosy in all protocols and reports.

In the case of the article by Gelber et al.(1) we are aware that the above misinterpre-tation of the WHO guidelines for classifica-tion had no influence on the outcome or in-terpretation of the study results. This is be-cause they made use of BI determinations

and Ridley and biopsies classified accord-ing to the Ridley-Jopling system. This lackof any effect on the results may make ourpoint appear trivial, but if standard criteriaare not used in published studies it under-mines attempts to standardize criteria in thefield.

The same phrase mentioned above alsostates that classification is determined by “.. . simply counting the number of skin le-sions (our emphasis)”. Actually, in ouropinion the information provided by WHOis confusing on this point:

In some documents (2,4,7), dating from1995 and 2005, the inclusion of enlarged or damaged nerve trunks in the classifica-tion of leprosy is advised, with more thanone involved nerve leading to classificationas MB.

In other documents (3,6), dating from1997 and 2000, classification is solelybased on counting skin lesions.

We know from experience that in someleprosy control programs skin lesion counting is the only classification criterionused, while in other programs nerve involvement is included as well. Evenwithin one country different control pro-grams may use different classification crite-ria, making it extremely difficult to com-pare data from different programs, such asPB/MB ratios.

The above observations emphasize theneed that WHO gives clear and consistentcriteria and that the those who collect andanalyze the data (government officials, clin-

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CORRESPONDENCE

This department is for the publication of informal communications that are of interestbecause they are informative and stimulating, and for the discussion of controversialmatters. The mandate of the JOURNAL is to disseminate information relating to leprosy inparticular and also other mycobacterial diseases. Dissident comment or interpretation onpublished research is of course valid, but personality attacks on individuals would seemunnecessary. Political comments, valid or not, also are unwelcome. They might result ininterference with the distribution of the JOURNAL and thus interfere with its prime purpose.

A Need for Clarification of the Classification Criteria for

Leprosy Patients

73, 4 Correspondence 281

icians, leprosy control officers and re-searchers) use unambiguous phrasing ofclassification criteria in protocols and re-ports to prevent misinterpretation, espe-cially among people for whom English isnot the first language and/or for healthworkers in the field who may have rela-tively limited education.

It also emphasizes the importance of a de-tailed description of the exact classificationcriteria used in leprosy studies where classi-fication of the leprosy patients is importantfor the interpretation of study results.

REFERENCES1. GELBER, R. H., BALAGON, V. F., and CELLONA

R. V. The relapse rate in MB leprosy patientstreated with 2-years of WHO-MDT is not low. Int.J. Lepr. Other Mycobact. Dis. 72 (2004) 493–500.

2. WORLD HEALTH ORGANIZATION. A guide to elimi-nating leprosy as a public health problem. Geneva:World Health Organization, 1995. WHO/LEP/95.1.

3. WORLD HEALTH ORGANIZATION. Guide to elimi-nate leprosy as a public health problem. WorldHealth Organization, 2000.

4. WORLD HEALTH ORGANIZATION. 2005. URL:http://www.who.int/lep/disease/classification.htm

5. WORLD HEALTH ORGANIZATION. Global strategyfor further reducing the leprosy burden and sus-taining leprosy control activities 2006–2010.Geneva: World Health Organization, 2005.WHO/CDS/CPE/CEE/2005.53.

6. WHO EXPERT COMMITTEE ON LEPROSY. Seventhreport. Geneva: World Health Organization, 1998.Tech. Rep. Ser. 874.

7. WHO REGIONAL OFFICE FOR THE WESTERN PA-CIFIC. 2005. URL: http://www.wpro.who.int/sites/leprosy/leprosy_wpr/leprosy_classification.htm

—Dr. Linda Oskam —Dr. Samira Bührer-Sékula

KIT (Royal Tropical Institute)KIT Biomedical ResearchMeibergdreef 39, 1105 AZ AmsterdamThe Netherlands.

Dr. Gelber and Colleagues Reply

We entirely agree with the errors notedby Dr. Oskam and colleagues concerningour mistake regarding the number of skinlesions required by the WHO for the classi-fication of MB leprosy, as well as theircomments concerning the WHO’s conflict-ing statements concerning nerve trunk en-largement and damage in classifying lep-rosy cases. Furthermore, we agree that clar-ity in classification standards is necessary.In our report, the utility of counting lesionsfor classification, and not skin smears orhistopathology, was criticized for its poten-tial to fail to identify those leprosy caseswith a high BI and who are BL or LL , thesehaving been established as at high risk forrelapse. Though Scollard (1) has recentlyand eloquently described in detail the impor-tance of skin smears and proper histopatho-logic classification in research papers, thereare 2 additional reasons clinicians requiresmears and biopsies for classification:

1. We have found over 1/3 of our patientswho would be classified as PB by countinglesions are in fact BL or LL with an average

BI (6 sites) of 2.3 (unpublished observa-tions). Such patients at many centers wouldbe treated, we believe inappropriately and totheir detriment, with the PB regimen. Fortu-nately, in Cebu, we still use skin smears andbiopsies for leprosy classification, and thesepatients are treated as MB leprosy.

2. In our MB patients an increasing BI isassociated with an increased risk of reactionalstates after the completion of MDT, occurringparticularly frequently in those treated with1-year MDT as opposed to 2-year MDT andafter 1-year MDT in 48% of patients in thefirst 2 years after the competion of therapy(manuscript submitted for publication). Skinsmears could thus prove particularly usefulin assisting to re-define when patients cansafely be released from control.

In conclusion, for those treating leprosypatients, skin smears and biopsies classifiedby the methods of Ridley and Jopling haveare advantageous methods, compared tocounting lesions, in predicting which pa-tients are at risk for relapse and avoidingunder-treatment, and in identifying patients


at high risk for reactional states after thecompletion of MDT.

1. SCOLLARD, D. M., Classification of leprosy: a fullcolor spectrum, or black and white? Int J LeprOther Mycbact Dis. (2004) 72:166–8.

—Robert Gelber—Roland Cellona

—Maria Balagon—Rodolfo Abalos

—Tranquilino Fajardo—Fe Pardillo

The Leonard Wood Memorial Center forLeprosy Research

Cebu City, Philippines

The Experience of Leprosy in the Era ofHIV/AIDS

Robben Island, South Africa

4–6 February 2005

Sponsored by IDEA and the ILA GlobalProject on the History of Leprosy

in Association with Robben Island Museum

From February 4–6, 2005, individuals from16 countries whose lives have been im-pacted by stigma, either as a result of lep-rosy or HIV/AIDS joined in discussion withhistorians specializing in the fields of lep-rosy, HIV/AIDS and human rights. Thepowerful backdrop of Robben Island, an in-ternational symbol of (in the words of theRobben Island Museum) “the indestructibil-ity of the spirit of resistance against colonial-ism, injustice and oppression”, inspired dis-cussions of how history can effect socialchange. At the same time, the legacy ofRobben Island and all those who resisted itsoppression empowered discussions on howstigma denies both identity and human rightswith a view to developing concrete actionsthat can be used towards eliminating thepower of stigma to destroy people’s lives.

PROGRAMFriday, February 4:

Banishment, Isolation, Resistance & Remembrance—Tour and Discussions:

Interacting With the History of Robben Island

The Maximum Security Prison:Welcome—Dr. Jo RobertsonOpening Remarks—Deirdre Prins-Solani

and Richard WhiteingRemarks by Mr. Yohei Sasakawa, Presi-

dent, The Nippon Foundation

Introduction to the History of Robben Is-land — Dr. Harriet Deacon

The GraveyardRemembrance: IDEA Banner of HonorRev. Albrecht Hahne, Dr. P.K. Gopal,

Zilda Borges, Alhaji Shehu Sarkin Fada,William Malo

Banishment: The Welfare of Society versus The Rights of Individual Freedom

Chairs: Dr. Harriet Deacon & Anwei LawSigurd Sandmo Norwegian segregation

policiesJose Ramirez, Jr. Banishment versus im-

prisonmentRyohei & Suiko Shibata Japan’s absolute

segregation policy

Church of the Good ShepherdIsolation: The Experience of IsolationChairs: Dr. Jo Robertson & William MaloWilliam Malo, Former resident, Kalau-

papa, Hawaii, USACrescencio T. Rosello, Culion, Republic

of the PhilippinesKeteng Feng, Guangdong Province, Peo-

ples Republic of ChinaMiyoji & Mieko Morimoto, JapanDr. Michael Chen, Guangdong, Peoples

Republic of ChinaDr. Arturo Cunanan, Culion, Republic of

the PhilippinesClint An~abieza, Cebu, Republic of the

Philippines

Saturday, February 5: Stigma & Identity

The GuesthouseResistance: Retaining Identity in the

Face of OppressionChairs: Simonne HorwitzPanel: Arega Kassa Zelelew, Artur C.M.

De Sousa (Zackie Achmat—Treatment Ac-

NEWS and NOTES This department furnishes information concerning institutions, organizations, and

individuals engaged in work on leprosy and other mycobacterial diseases, and makes noteof scientific meetings and other matters of interest.

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Stigma, Identity and Human Rights


tion Campaign, South Africa, and YasujiHirasawa, Japan, were unable to participateat the last minute)

Stigma & IdentityCulture, Identity & Stigma:

The African ExperienceChairs: Arega Kassa Zelelew and Dr.

John MantonPanel: Dr. Jean-Paul Bado, Linda Beer

Kumwenda, Jan Mahlangu, Bhekani Memela

The Effect of Stigma on Individuals & Families

Chairs: Jose Ramirez, Jr. and Kofi NyarkoPanel: S.K. Jung, Jae Heung Kim, Mag-

dalena Ramirez, Dr. Harriet Deacon, Ms.Inez Stephney, Amar Timilsina, Adi Yosep,Jaimie Tomas Cabeto, Rev. Albrecht Hahne,

Breaking the Silence: Women & StigmaChairs: Zilda Borges and Mimi BadamutiPanel: Natalia Isabel da Graca Marcal,

Zoica Bakirtzief, Tiruwork Mengistu, BirkeNigatu, Saruto Labbo

Illuminating Ourselves: Redefining Traditional Images

Open discussion—The role of imagesand language in the formation of attitudes.

Achievements of people affected by lep-rosy or living with HIV/AIDS, past and pre-sent, as a means of challenging stereotypesand the stigma that is perpetuated by them.

From Ingeborg Grytten (Author, Norway,17th century) to Akashi Kaijin (Poet, Japan,early 1900’s)

Sunday, February 6—Human Rights(Multi-Purpose Learning Center)

Human RightsProfessor Bernardino Fantini

Ensuring the Rights of HumanityChairs: Professor Bernardino Fantini &

Dr. P.K. GopalPanel: Alhaji Shehu Sarkin Fada, Chamada

Abibo

In Conclusion: History as an Agent forSocial Change

Prof. Megan Vaughan, Zilda Borges andAnwei Law

Excerpts from the meeting follow. Dr. JoRobertson has provided summaries of theacademic papers presented, and Anwei Lawhas provided transcripts of the other pre-sentations and discussion. These have beencombined and edited for brevity, attemptingto preserve the sense and spirit of the dis-cussions. Ed.

Friday, February 4:

Banishment, Isolation, Resistance & Remembrance—Tour and Discussions:

Interacting With the History of Robben Island

The Maximum Security PrisonDeirdre Prins-Solani, Manager, Educa-

tion Department, Robben Island Museum:“Robben Island represents the triumph of

the human spirit against adversity. Whatdoes it mean for the spirit to triumph? Oneof the ways in which we have interpreted itis that we triumph through resistance; thatan act of resistance against oppression, anact of resistance against stigma, an act ofresistance against segregation, is a triumphof the spirit.

“When you came into prison, your namewas written down into a book and you weregiven a number. You were told any commu-nication that happened between you and theauthorities would be done through yournumber. You lost your name, you lost youridentity, your sense of belonging. So therewas an attempt to erase an identity. . .

So when we fight against oppression andsegregation and we fight against erasure,the voices of people who have experiencesof a particular condition should be the peo-ple who speak. And that’s why when welearned who the participants in this work-shop were, we were very excited. We saidyes, this is in keeping with the mission ofthis institution.”

Eugene Mokgoasi, Former Political Pris-oner, Robben Island: “Coming to RobbenIsland . . . . you met people who had a com-mon understanding, a common journey, anddestiny like you. Robben Island was alearning institution. The first morning here,it was kind of cold, and a guy said to me,‘You’re home now. You’re not going to livetomorrow, you’re not going to live yester-day, you’re going to live today and todayonly. Now look around. You’ve got broth-

73, 4 News and Notes 285

ers, you’ve got fathers, you’ve got uncles,you’ve got everything you need. Whateveryou need, approach any one of us.’ And Ifelt safe, for the first time.”

Richard Whiteing, Robben Island Mu-seum: “We can see the prison, but when wego back to the hospital period and . . . we findan erasure that Deirdre mentioned. One of theunique aspects of the people living with lep-rosy and the buildings they lived in is thatthere’s been an attempt to obliterate the builtfabric. We have but one building that remainsthat was used by people with leprosy, andthat is a church. The rest of the buildingswere burned because of the fear of infection.But they can’t obliterate the cultural land-scape, so we still have trees that were plantedat that time. We have a fishpond that wasbuilt for the children in the children’s sec-tion. We have the graveyard. . . So oftenthere has been a silencing, but what we willtry and do is to help you imagine . . .”

The Graveyard: Remembrance: TheIDEA Banner of Honor

Banishment: The Welfare of Society ver-sus The Rights of Individual Freedom

Sigurd Sandmo, Curator, The LeprosyMuseum, Bergen. Norwegian segregationpolicies. The Norwegian contributions tothe struggle against leprosy worldwide arefamous, partly because of Hansen’s discov-ery of the leprosy bacillus in 1873, partlybecause the Norwegian leprosy policies ofthe 19th century served as models for othercountries, especially in terms of legislation.The idea that the Norwegian policies wererather humane and rational, like Hansensaw them, seems however still widespread,but I think we lose an important opportunityto understand the dynamics of banishmentif we attribute the building of modern lep-rosaria to a theory of contagion, discon-nected from public stigma. In the goldenage of Norwegian leprosy work, the physi-cians contributed willingly to the socialbanishment of leprosy sufferers outside theinstitutions, to make them easier to collect,and to make it more difficult for them to es-cape the modern leprosaria. In order todemonstrate both the connections and lackof connectedness between the theory ofcontagion and the Norwegian model of seg-regation, four examples of how the medical

The IDEA Banner of Honor is displayed at the cemetery where people who had leprosy were buried onRobben Island. The Banner of Honor recognizes individuals who have had leprosy who have made significantcontributions to their own countries. Photo by Pamela Parlapiano


Norway fraternity tried out different strate-gies in order to direct sufferers towards hos-pitalization from the 1840s to the 1880s, inthe golden age of Norwegian leprology, arediscussed. In 1877 the Norwegian parlia-ment passed an act making provision forthose suffering from leprosy, which practi-cally forced this group into hospital. And in1885, the parliament passed a much stricteract On Segregation. Outside the inner cir-cles of leprologists, many considered thisact as being a terrible mistake and perhapseven against the constitution. The segrega-tionists and the contagionists won the dis-pute and the last obstinate cases of leprosycould finally be collected.

REFERENCESSIGURD SANDMO. “The Politics of a Bacillus” in Kras-

ner, Robert: Meeting the Microbial Challenge.American Society for Microbiology Press. NewYork, 2002.

SIGURD SANDMO. “En hovedstad for spedalske.Bergens berømte leprahistorie.” (Printed radio lec-ture for Norway’s National Broadcasting) P2-akademiet, Vol. Y. Oslo, 2002. s 163–175.

Ryohei Shibata, IDEA Japan: “The mainidea of the absolute segregation policy inJapan was to abolish and eliminate the pa-tients; it was not to cure them. I was diag-nosed with leprosy in 1947. I was shunnedby society and segregated in a sanatoriumon an isolated island. There, I was forced towait for my life to end.

“A poet living in the sanatorium on the is-land where I was sent once said: ‘Like thoseluminescent fish dwelling in the sunlessdepths of the sea, I will find no light until Ilight myself up from within. . . . After 21long years, I finally returned to society.

“In Johannesburg I went to an ApartheidMuseum. There I saw the history of themen who were put in jail for no reasonother than being black. That particular im-age overlapped with my own experience. Inthis sense, apartheid, the Japanese segrega-tion laws and segregation policy, were sim-ilar. One was for racial discrimination andthe other was discrimination against thosepeople who have leprosy.”

Dr. Jo Robertson, Coordinator, ILAGlobal Project on the History of Leprosy,UK: “I don’t think any of us have any ideahow many places there were in the worldwhere leprosy work was done. Not all of

these places dealt with people who were af-fected by leprosy in the same way. Somewere much more absolute in terms of theisolation than others. Some of the places inAfrica were more treatment places thananything else. Going through this list alpha-betically, it may seem as though the list isendless . . . . What surprised me when Ilooked at the register from Culion were theages of the people . . . . you’d be surprisedhow young they were and I think this is trueof many places, 15 yr olds, 11, yr olds, very,very young people.”

Church of the Good Shepherd: The Experience of Isolation

Dr. Harriet Deacon, Consultant, HumanSciences Research Council, Cape Town,South Africa: “This building is very sym-bolic for this meeting; to be speaking in thisbuilding about the history of leprosy and itsrelationship to other forms of stigmatiza-tion. I think it’s really essential, when wetalk about Robben Island as a leprosarium,to understand the difference between theisolation of patients in the pre-1891 period,before the Leprosy Repression Act waspassed, and the situation after1891, wherepeople were forcibly institutionalized oncethey’d been identified as people with lep-rosy. In 1891, you had a huge influx of pa-tients coming, largely involuntarily, to theisland and often they felt that they weretricked into coming to the island. Thischurch dates from 1895, from the period inwhich the leprosy patients were moved outof the village, and further isolated evenfrom the staff on the island.”

Jose Ramirez, Jr., M.S.W., IDEA USA:“People oftentimes think of ‘banishment’ asthe same as ‘imprisonment’. But for manyof us, we think of ‘banishment’ in terms ofleprosy, because there has been banishment. . . . With imprisonment you find that per-sons end up with a particular term to de-scribe them — political prisoners, jailbirds,etc. But when there’s banishment of a per-son with Hansen’s Disease, there’s thebrand of the word ‘leper’ that we all dislike,so it’s never a multitude of words to de-scribe those with leprosy, it’s only oneword.

“When you talk about the laws related toleprosy, what you’re really talking about arethe laws of silence. People were not speak-


ing out about the injustices of banishmentfor those persons affected by leprosy in thelast 3000 years. It has only been very, veryrecently that this has occurred. Persons withleprosy did not have an opportunity to bedefended as do most who are imprisoned.So, what has happened is that banishmentcontinues until death.”

Cresenciano T. Rosello, Culion, IDEAPhilippines: “. . . the very close family tiesof the Filipinos made them regard segrega-tion as an unmerited punishment that lastedfor life. This condition triggered anti-segre-gation feelings and the families hid the af-flicted family members in the forest and incaves . . . . The people who were banishedto Culion for the last 98 years — theirbones are crying for justice, justice thatthey did not have during their lifetime.”

William Malo, IDEA, Hawai’i: “The peo-ple of Hawai’i knew that if you were takenand sent to Moloka’i, you would never beseen again. So, they were not afraid to hideyou and to keep you at home as long as pos-sible. They would continue to have yourlove at home. That’s why when I was asked

why the mothers were doing that, I said‘Love was greater than fear’. The love fortheir children or husband or wife who hadthe disease was greater than any fear and sothey hid their family members in order tokeep them at home.”

Mieko Morimoto, IDEA Japan: “Whenyou got leprosy in Japan you just basicallyhad to throw away every single thing youhad. Because of leprosy, I had to give upmy education, job opportunities, and to seemy family. I regret that I could not havechildren. I have always, always wanted tohave children. I was young then and I justcouldn’t cope with the fact that I couldn’thave children and it was almost like a sick-ness I had in my heart. However, I have tosay that since I got leprosy I have learned alot. I have also stood up throughout thecountry to regain our humanity.”

Keteng Feng, Handa/IDEA China: “Ifyou go to our village you cannot see anychildren because even now we are still notallowed to get married and have children. Iwas sent to this leprosy village in 1963.Many decades have passed. We have suf-

William Malo, who was isolated at Kalaupapa, Hawaii as a young man but has lived in the community for thelast 40 years, presents his experiences in the panel discussion “The Experience of Isolation”. To his left are Dr. JoRobertson and Dr. Harriet Deacon. To his right are Mr. Feng Keteng and Dr. Michael Chen. Photo by Henry Law.


fered many difficulties and in 1968 somepeople around our village came to attack us.Some people also committed suicide be-cause their family wouldn’t accept them. Iwas sent to the village in 1963 and I haveonly gone back home two times. I had towalk because we are not allowed to ride onthe public bus. I had to spend more than 10hours to walk back home. When I got there,my family didn’t allow me to go into thehouse because they were afraid that I wouldbring them trouble.”

Miyoji Morimoto, IDEA Japan: “Franklyspeaking, and to be honest with you, I reallydo not want to look back . . . . But, I wasspecifically asked to talk about banishmentand also about stigma and discrimination.From the age 14, my life was as leprosy pa-tient Myoji Morimoto and I was never ableto live as Myoji Morimoto alone. This issomething that I still hold in my heart.Japanese law had it that you couldn’t go tocollege; you couldn’t even go out of theSanatorium. Against all advice and recom-mendations from the doctors and nurses andeveryone in Sanatorium, I left the Sanato-rium and went to college for four years.Now, there are 13 national sanatoria inJapan and about 3,500 people live in them.The average age is 78 years old. We werediscarded from our hometowns and familiesand also by the government.”

Clint Añabieza, IDEA Philippines:“When I graduated in 1994, I was also di-agnosed as a person with Hansen’s Disease.Through the discrimination in society, thestigma comes. I decided to isolate myselfbecause my family would face difficultiesbecause of my situation. At that time thedoctor did not confine me at the hospitaland said it was okay to take your medicineoutside. But I faced discrimination—some-times the taxi driver would not allow me toride in the car when they saw I had somepatches on my face and hands. That’s onereason that I isolated myself in a smallhouse beside in the sea. Some of my broth-ers and sisters brought me food to eat, butlater I managed to cook on my own.

“At that time, many people told me thatI’m a person with leprosy, hopeless in thisworld. Some people told me that eventhough you are graduated from college, youwill not be employed. I took my medicinealmost two years but the stigma cannot be

erased in 10 years or 20 years—it goesfrom generation to generation.”

Dr. Michael Chen, Handa/IDEA China:“In China we still have more than 600 lep-rosy villages around the whole country andprobably more than 60,000 people are iso-lated in these leprosy villages. Many ofthese places are in very, very remote areas,in mountainous areas that are not accessibleby a vehicle. Some are even on an islandlike Robben Island and you have to go byboat. This is only the physical part of isola-tion and there are many, many difficultiesfrom the psychological part. For example, ifa chair is sat in by a person who has the dis-ease, other people won’t touch it again.This still happens in some of the generalhospitals. If the hospital has treated peoplewho had leprosy, then they have to destroyall the instruments and equipment after that.I’m glad to say that in China we’re gettingmore and more members of the youngergeneration as volunteers. They go to lep-rosy villages and try to break the world ofisolation and develop more contact betweenpeople affected by the disease and the com-munity. I think we can have a better futureand reach our goals of a world without dis-crimination and stigma in the future.”

Dr. Arturo Cunanan, Jr, Culion, IDEAPhilippines: “I was born and grew up inCulion. I am a third generation descendentof Culion . . . . If you review most of thehistory of isolation, it’s never been towardsthe patients themselves, but towards theprotection of the healthy individuals. Isola-tion was not for the purpose of curing thesick. In the past, there was no cure, but onlycare. Unfortunately, our policy makers anddecision makers approached the issue ofleprosy on medical aspects, whether un-knowingly or knowingly, and the social as-pects of leprosy were left to the religiousside or non-governmental organizations . . . .I am very, very happy that during the lastfew congresses we are now hearing andlearning that leprosy control should notsimply be based on a medical approach.”

Saturday, February 5: Stigma & Identity

The Guesthouse: Resistance: RetainingIdentity in the Face of Oppression

Dr. Harriet Deacon: “There were variouskinds of resistance that both political pris-


oners in the post-1960 period and leprosypatients engaged in. For example, somepeople just buckled down and concentratedon education programs and developing acommunity among the patients. They col-lected lobster and crayfish on the beaches,smuggled contraband and alcohol, andsmuggled newspapers in . . . . With the1892 rebellion led by Franz Jacobs, therewas active resistance against institutional-ization on the island. The way in whichFranz Jacobs’ rebellion was silenced is in-teresting. There is almost nothing in thecolonial archive here in Cape Town aboutthe rebellion. The only place I’ve found anyrecord of it was in London at the PublicRecords office. It has been wiped off theface of the colonial archive and there’s onlyone printed reference to it that talks about asmoking gun . . . . The way in which the pa-tients resisted was that they actually de-

manded the things that they felt should gowith a humanitarian segregation of them-selves and they resisted being treated likeslaves or prisoners.”

Simonne Horwitz, Wellcome Unit for theHistory of Medicine, Oxford University,U.K.:

“It’s very fitting that we are here in sitethat’s linked to rebellion and resistance. Inmy own work on Westfort . . . . (a leprosyhospital that’s just outside of Pretoria) fromabout 1890–1948, one of the themes that Iconstantly find is that the authorities tried tosegregate and oppress people by gender, byrace and by their disease. They were con-stantly trying to segregate them, to takeaway their identity. Yet, it was very clearthat people fought against that . . . . Yester-day there was talk about the political pris-oners signing their names and it’s the samewith Mr. Pipe who was at Westfort . . . . a

Participants in the Robben Island Conference (left to right): Simonne Horwitz, Wellcome Unit for the Historyof Medicine, Oxford; Mimi Badamuti, The Sinikithemba HIV+ Choir, South Africa; Ms. Inez Stephney, HumanSciences Research Council, South Africa; and Saruto Labbo, IDEA Nigeria. Photo by Pamela Parlapiano


man who wrote to the newspapers . . . . notas a person affected by leprosy, but as a per-son — telling about how he was feeling,how he was treated in those early years. Be-cause he spoke out about his oppression, hewas forced to leave Westfort because theythought he was creating too much of an up-roar. But he had created a sense of opti-mism amongst people who were fightingfor their identity. There are a number of oc-casions where the women patients, for ex-ample, had a sit down strike and refused towork until they were called by their names,until they were recognized, until they weregiven some of the same things that Harrietwas talking about on Robben Island. Thesewere people who were very actively en-gaged in maintaining their identity andwhether that was writing a newsletter abouttheir lives or whether that was throughstrikes, [they] . . . actively tried to shape anidentity that was not around their disease . . . .Zackie Achmat from the Treatment ActionCampaign [in South Africa] is a personwho’s led a regeneration of civil societyaround issues of HIV and AIDS and he’staken an identity that has been stigmatized,an identity that was hidden aroundHIV/AIDS, and made it very public.”

Arega Kassa Zelelew, IDEA Ethiopia:“When I remember 39 years back, my lifewas turned upside down. After facing re-peated discrimination, I started to drink; Iwas a chain smoker. One day I thought,‘What am I doing?’ So I started to think be-yond disability, beyond stigma, beyond thedisease. My life started to change. I startedto resist.

“I helped found ENAELP, the EthiopianNational Association for Persons Affectedby Leprosy, and also the Ethiopian Federa-tion for Persons with Disabilities. If youfight, if you struggle, we can win, we willwin. Now we have got the international or-ganization IDEA and we have to resist so-cial stigma, discrimination, isolation . . . .Our colleagues, our companions on RobbenIsland from 1846–1931, they were fightingalone here on this island. Now we areunited and this gives us strength.”

Anwei Law: International Coordinator,IDEA: “We all know that resistance takes alot of different forms. There are lawsuitsbut there is also the creative expression ofresistance through music and art and poetry.

Certainly in Japan there is this wealth of po-etry and creative expression that I think rep-resented strong resistance during those veryhard times. Within the oral history projectand within IDEA, we are very much look-ing for the creative resistance and we en-courage you to help us identify examples ofthis creative resistance.”

Dr. Wim Van Brakel, Royal Tropical Insti-tute (KIT) Leprosy Unit, The Netherlands:“I want to mention another side of the legalaspect. One is the repealing of any laws thatmight still be there that actively represspeople affected by leprosy. On the otherside, there may be some countries wherethere isn’t a law like there was in Japan, butstill you find that people with leprosy andpeople perhaps with other disabilities havebeen marginalized very seriously, either bycivil society, or just by the community.And, you would also find that those coun-tries have also signed disability acts as partof an international effort to try and raise thestatus of people with disabilities. So . . . .[we can] see if there is pro-disability legis-lation which would provide, for example,quotas for jobs or education. If that is there,it is important to fight to get that enforced . . . . for example, in India, part of the strug-gle is to actually get people to recognizethat people with leprosy related disabilitycome under that act and should have theright to have the same facilities that peoplewith other disabilities would be accorded.”

Stigma & Identity

The Effect of Stigma on Individuals &Families

Jose Ramirez, Jr.: “I can trace my familyhistory all the way back to a small fishingvillage in Spain. That is very important tome and to my family . . . . When a person isdiagnosed with Hansen’s Disease, often-times that person’s history is taken away . .. . whether it’s through laws or throughpractices of different countries . . . . If youlook at all of this collectively, the stigmathroughout the world becomes a very pow-erful force . . . . I’m hoping that you will goahead and focus, not so much on what wehave lost, but on what we have gained andcontinue to gain.”

Bhekani Memela, Sinikithemba HIV+Choir, South Africa: “I am HIV positive. I


am part of the choir which is called theSinikithemba HIV+ choir. Our mission is toeducate and help people to be in a positionto disclose their status and to check theirstatus, especially in the rural areas. In SouthAfrica we are still facing the serious prob-lem of stigma. . . .[which] is very high inour country. There are many, many, manydangers which you face when you discloseyour status. We have people who have beenkilled because they disclosed their status . . . .staying quiet and not discussing or sharingyour problems that you are facing with yourdisease doesn’t help; instead it perpetuatesthe stigma.

“Ignorance becomes a barrier for peopleto help other people. We are trying rightnow to educate people, to make themaware, to share our stories. We are HIV+.HIV is here. It’s real and it kills. There ishelp. It’s only that people . . . . don’t want tocome forward to go to the counsellors, to goto the clinics, to say I’m having this prob-lem with my life. If I myself and the other14 members of the choir can go public andtell people that we are HIV positive but weare still living a fruitful and a healthy life,then we think . . . . that we will be in a posi-tion to reduce the level of death, to reducethe level of ignorance and to reduce thelevel of stigma.”

Dr. Harriet Deacon and Inez Stephneyand Sandra Prosalendis: Understanding

HIV/AIDS stigma: a theoretical andmethodological analysis.

This theoretical and methodologicalanalysis is the first phase of a project initi-ated by the HSRC’s Social Cohesion andIntegration programme in Cape Town, incollaboration with the HSRC’s Social As-pects of HIV/AIDS programme (SAHA).The larger project will develop ideas andtest methodologies that can shed light on re-search on stigma in other contexts. We willalso make recommendations about inter-ventions to reduce the impact ofHIV/AIDS-related stigma. This can supportand inform the work of government andNGOs in managing the effects of theHIV/AIDS epidemic.

Most of the research on HIV/AIDSstigma has been done in the US, a countrywith large research resources, an early epi-demic and pronounced stigmatisation of

gay men, African-Americans and Haitianimmigrants as carriers of HIV/AIDS. Con-siderable research attention is now beingfocused on HIV/AIDS research in generalin Africa because of the severity of theAfrican epidemic, the politics of theHIV/AIDS issue, and the fact thatHIV/AIDS seems to be highly stigmatisedin the region. However, the relative ‘lack ofscientific research on the manifestations ofHIV/AIDS-related stigma in [Sub-SaharanAfrica still] presents a serious challenge tothe understanding, alleviation and preven-tion of HIV/AIDS related stigma’(Lorentzen & Morris 2004:27).

The problem of HIV/AIDS stigma inAfrica has been raised in related researchon barriers to testing, treatment, care andadherence, on quality of life, and on socialresponses to HIV/AIDS. It is important tounderstand HIV/AIDS stigma in relation tothe broader social, political, economic andcultural context, and to address stigma asone of a number of causes of discrimina-tion, reluctance to test, therapeutic non-compliance, and so on. First, however, it is,however, essential to clarify exactly whatwe mean by stigma, how it arises, and howit works, so that we can suggest ways of re-ducing its negative impact on society. Im-portant recent work on HIV/AIDS stigmain South Africa includes Posel (2004),Kalichman & Simbayi (2003, 2004), Pa-tient & Orr (2003), POLICY project(2003a), Stein (2003), Shisana & Simbayi(2002), Jennings et al. (2002). Research onHIV/AIDS stigma in other African coun-tries includes ICRW 2002, Muyinda et al.1997, Bond et al. 2002, and several BergenUniversity theses: Lie (1996 cited inLorentzen & Morris 2004), Oduroh (2002cited in Lorentzen & Morris 2004), andLorentzen & Morris 2004.

In order to conduct this literature review,we compiled a database of recent academicwork on disease stigma across various dis-ciplines and across different medical condi-tions (although we focused on HIV/AIDS).Our database (which currently stands atover 3,000 entries) is not yet fully compre-hensive, nor yet fully representative of theadmittedly meagre amount of currentAfrican research, but it provides a goodgeneral overview of the available material.

This paper critically reviews academic


literature on disease stigma that can help usto:

1. Develop more sophisticated theoreticalapproaches to understanding stigma insouthern Africa,

2. Develop research methodologies tobetter understand the historical and culturalspecificity of stigma, and its impact on thetreatment and care of PLHAs in southernAfrica, and

3. Inform the development of better anti-stigma interventions in southern Africa.

REFERENCES1. DEACON, H. J., VAN HEYNINGEN, E., DIGBY, A., and

PHILLIPS, H. (EDS.). The Cape Doctor (Rodopi,forthcoming)

2. DEACON, H. J. “Patterns of exclusion on RobbenIsland, 1654–1992” in C Strange and A Bashford(eds.) Isolation: Places and practices of exclusion(Routledge, 2003)

3. DEACON, H. J. “Racism and Medical Science inthe Cape Colony”, Osiris 15 (2000), 190–206reprinted in J P Jackson (ed.) Science, Race andEthnicity: readings from Isis and Osiris (Univer-sity of Chicago Press, 2002)

4. DEACON, H. J. “Midwives and Medical Men inthe Cape Colony before 1860”, Journal of AfricanHistory, 1998

5. DEACON, H. J. “Cape Town and Country Doctorsin the Cape Colony During the First Half of theNineteenth Century”, Social History of Medicine,10(1) (1997), 25–52

6. DEACON, H. J. (ED.). The Island: a History ofRobben Island, 1488–1992 (David Philip andMayibuye Books, 1996)

7. DEACON, H. J. “Racial Segregation and MedicalDiscourse in Nineteenth-Century Cape Town”,Journal of Southern African Studies, 22(2) (1996),287–308

8. DEACON, H. J. “Leprosy and Racism at RobbenIsland” in E van Heyningen (ed.) Studies in theHistory of Cape Town, vol.7 (Cape Town, 1994),pp.45–83

9. JENNINGS, R., MULAUDZI, J., DAVID EVERATT, HEY-WOOD, M., and RICHTER, M. 2002. ‘Discrimina-tion and HIV/AIDS’, paper for the Department ofHealth written by Strategy & Tactics and the AIDSLaw Project.

10. KALICHMAN, S. C., and SIMBAYI, L. 2004. ‘Tradi-tional beliefs about the cause of AIDS and AIDS-related stigma in South Africa’, AIDS Care, vol.16, no. 5, pp. 572–580.

11. KALICHMAN, S. C., and SIMBAYI, L. C. 2003. HIVtesting attitudes, AIDS stigma, and voluntary HIVcounselling and testing in a black township inCape Town, South Africa. Sex Transm.Infect. 79(6):442–447.

12. POSEL, D. 1983. ‘Rethinking the race-class debate

in South African historiography’, Social Dynamics9(1).

13. STEIN, J. 2003. ‘HIV/AIDS stigma: the latest dirtysecret’, CSSR working paper no.46, University ofCape Town.

14. SHISANA, ET AL. 2003. ‘The Impact of HIV/AIDSon the Health Sector: National survey of healthpersonnel, ambulatory and hospitalised patientsand health facilities’, Pretoria: National Depart-ment of Health

15. SHISANA, O., and SIMBAYI, L. 2002. Nelson Man-dela/HSRC Study of HIV/AIDS: South African Na-tional HIV Prevalence, Behavioral Risks andMass Media, Household Survey 2002. Human Sci-ences Research Council.

Anwei Law, IDEA: “One of the thingsI’ve noticed, and we brought it up in Brazil,too, was that when people do social scienceresearch papers, they use quotations frompeople who have had leprosy, but usuallydon’t use their names. Usually this is said tobe out of ethical considerations. However, Ithink that when dealing with issues ofstigma, one has to rethink this. I just saw apaper on stigma and HIV/AIDS that identi-fied someone simply as ‘a woman fromThailand’ – it’s possible that the women re-quested this, but equally likely that the re-searcher suggested this. In any case, itserves to increase anonymity, which perpet-uates stigma. I think that the people doingsocial science research need to really thinkabout this. We have seen that identity is acritical part of eliminating the stigma andwhen you do not attribute a quote to a per-son, you are taking away their identity,which might also be regarded as unethical.It’s a challenge. It’s important to guard pri-vacy as requested by a person, but impor-tant not to encourage anonymity, whichonly adds to the stigma.”

Jose Ramirez, Jr., IDEA USA: “A scien-tific . . . method [hasn’t been] developed yetthat will measure stigma because there areso many differences in language, in culture,in geography, in laws, so it’s really veryhard. In my opinion, stigma is actually anact of rejection or labelling or unexplainedfear of a person or even of oneself because . . . . we learn about stigma even beforewe’re diagnosed.”

Amar Timilsina, IDEA Nepal: “When Iwas nine years old and was going to school,I used to have needle pricking competitionsamong my friends, because of my loss of


sensation . . . . When I eventually started thetreatment, my suffering started becauseother people came to know that I was suf-fering from the disease. When I went backhome and started going back to schoolagain, they refused to have me in the class.So I was thrown out of the school as well asfrom the community. I was compelled toforsake my family and the love of the vil-lage where I was born and brought up . . . .I made up mind to commit suicide severaltimes, but by the grace of love and goodsupport from the hospital and staff I got ad-ditional energy to tolerate the pain and waitfor the bright future . . . . Slowly I startedgetting the dignity back into my life. I gotmarried, I have two children and am nowthe General Secretary of IDEA Nepal.”

Jaimie Tomas Cabeto, ARPAL/IDEA An-gola: “In 1978 I started hearing and learn-ing about people affected by leprosy. Wewere children and as we saw those peoplein the leprosarium we thought that wassomething very odd, very strange . . . . Ittook a long time for the doctors to find outwhat I had. I went to several clinics, sawseveral doctors but they couldn’t tell what Ihad . . . . When the health professional toldme the diagnosis, I was crushed. I startedtaking the treatment but I was afraid oftelling my family I had the disease. As timewent by and as I got involved in the Associ-ation of People Affected by Leprosy,ARPAL, in Angola, I started feelingcourage to speak about the disease and totell my family about the diagnosis.”

Rev. Albrecht Hahne, South Africa: “Ifyou look at the term stigma, it is a mark. IfI look at my hands, they are marked hands.If I look at my face, it’s a marked face. Inother words, I can say whatever I’d like, butI will always have to live with this mark. Ican tell other people that that mark is noth-ing, but every morning I get up I see thatmark. Every day that I get dressed, I am re-minded of that mark. The stigma is part ofmy life, of my existence. If I try to shyaway from that, I actually need to try to shyaway from a part of my existence . . . .That’ll to my mind be a decimation of myown life. I would return my life to nothing-ness . . . . I myself have come to this pointthat I accept the stigma of my life. . . Mylife is a life marked by leprosy . . . .

“If society is not prepared to accept us as

what we are, society is not worthy of us . . . .I firmly believe that this, my life as it is, is aunique life given to me by my Creator, Icall him God. He said this life is going to beso valuable that I will put everything intothis life that is necessary for this life to de-velop to what it is . . . . All of you know I’ma pastor of a Christian Church. I’ve ledthree churches, one church of over a thou-sand people and I must tell you, there wasnot one house into which I couldn’t go. Atthe moment I’m leading a church of over500 people; there’s not one house that I can-not enter. I believe the main thing . . . . is tosay I accept what I am and with what I am,I will move out into society. If you have torun away, run away.

“Are we going to return into a cocoon ofsilence, cover everything up, don’t talkabout it, or are we going to share it with thesociety where we’re going to live. We shareit. Let us bear this mark, this stigma, withcourage. Let’s face the world with courage.And we can help others to come to termswith the facts of their lives.”

Breaking the Silence: Women & StigmaZoica Bakirtzief, American Leprosy Mis-

sions, IDEA Brazil: “Let’s say a woman isdependent on her husband for income, de-pendent on her husband for housing and forproviding for her children and her futureand old age. If that husband rejects her andshe’s also unskilled and doesn’t have otherresources, that’s a survival threat. It’s not asimple threat. So would you ask her to dis-close her diagnosis? I’m just posing a ques-tion. Maybe the issue, perhaps, is not tohave women so vulnerable to such situa-tions, such as a disease. Economic powerand independence, the possibility to not de-pend upon others for one’s own survival,it’s a basic need for women and for men. Sowe have to consider the economic aspect ofrehabilitation as an important issue in hu-man rights because it has to do with sur-vival, and if you are faced with the threat ofsurvival, it’s very hard to cope with any-thing else. It’s a burden too hard to bear.”

Zilda Borges, Brazil, IDEA Latin Amer-ica: “We know that women have been dis-criminated against in many parts of theworld . . . . in relation to employment, in-come, and participation. We also know thatmany women have fought for their rights all


over the world to overcome discrimination.I have met women with their heads boweddown, women who are part of the women’smovement, or other social movements, butwho do not speak about their experiencewith Hansen’s Disease. I have also metwomen with their heads held up high, whospeak with people in the community aboutthe disease. But the number of women whohave their heads held up high is muchsmaller those who bow their heads.

“In the work I do amongst women, I givepriority to the women who are living in si-lence. The methodology that I found to ad-dress their silence was to promote meet-ings. One woman, two women, three, four,five, that’s all. The groups are different, onefrom the other, and we’ve had groups thatmerged into other groups. The goal is to getthe women involved and engaged andmerged into other social movement groups.”

Mimi Badamuti, Sinikithemba HIV+Choir, South Africa: “The question is, is thestigma ever going to end? That’s the ques-tion I ask myself every day. Every time youare talking about HIV and AIDS, people,they think you are talking about a wild ani-mal that can pounce on them, attack themand kill them instantly. But it’s not. I’ve gota great experience about stigma, because inour country, here in South Africa, we are la-belled. It’s none of anybody’s business thatyou are HIV positive or HIV negative, butpeople think it’s their own business . . . . themain problem is with us women. Once youdisclose your status to your partner it is thelast time you hear from him. He goes, hedisappears. Sometimes, most of us women,we find out when we are pregnant that weare HIV positive, and the man is leavingyou because you just told him that you areHIV positive . . . . Once the man is gone,sometimes you are not working, you are un-employed. You have no one else to buy for-mula for the child. You are not supposed tobreast feed the child, what will happen afterthat? The child will be malnourished andshe or he will have nothing to take into herstomach or his stomach. “For me, I was for-tunate enough that my family was so sup-portive to me and even now they are so sup-portive to me even though I am HIV posi-tive. And I was fortunate enough that thegirl that I give birth to is HIV negative. Sheis now 7 years old and she is healthy, she

looks nice, she is big, she is beautiful likeher mother. So for us women, we muststand up, we must break the chains, wemust break the silence, and speak out . . . .For me, I live positively with my status, Ireduce stress, I talk to my virus. I tell myvirus that if it kills me, we are both goingdown together . . . . So women, men withHIV/AIDS and leprosy, let us stand up andfight together, and fight these diseases . . . .and fight stigma, discrimination.”

Culture, Identity & Stigma: The African Experience

Dr. Jean-Paul Bado: French ColonialAfrica

In the nineteenth century, many explorersin their reports pointed out that they discov-ered many affected by leprosy in WesternAfrica who carried out different social activi-ties, and even married (sometimes with manywives). For many ethnic groups, those withleprosy lived in societies without ostracism,except in some region of Dahomey (currentlyBenin and the northern Ivory Coast) wherethose with the signs of the disease were ban-ished by their societies and more directly bytheir family. With the development of the colo-nial economy, the colonial administration de-cided that those with the disease became moreand more an obstacle to its development plans.In French Sudan (and other colonies, just afterthe International Conference of Leprosy inStrasbourg), certain administrations expelledmany affected by leprosy from colonialtowns for different reasons. They were ar-rested for begging, which was forbidden bythe colonial administration. Dr Marchoux,who had been studying the disease since1897, managed to convince those in chargeof health in the French colonies to build amodern leprosarium for people with leprosyin French Africa. In 1931, the French West-ern Africa health policy makers created “ser-vice de lutte contre lepré”. Three years later,they built the Institut Central de la Lepréwhich was unveiled in 1935. Those affectedby leprosy had a centre where specialists inbiomedicine tried to understand all the mech-anisms of their disease and treat it. The fightagainst leprosy was also a fight for everyone.”

REFERENCESJEAN-PAUL BADO, Médecine coloniale et grandes

endémics en Afrique, Paris: Karthala, 1996.


This image, taken from a missionary jour-nal published in 1907, portrays the acceptedview of the engagement of missionarieswith leprosy: the necessity for a dual heal-ing, and the association of leprosy with sin.

Whilst this image and much otherarchival evidence can lead to the conclusionthat missionaries did target people with lep-rosy, placing them within what has been de-scribed as a ‘total institution’, and thereafterattempted to reconstruct them, a closer ex-amination reveals a more nuanced trajec-tory in Zambia. In this brief presentation, Ishow through the examination of specificstations involved in such work such as thatcarried out at Chitokoloki, by the ChristianMissions in Many Lands; Mbereshi, whereleprosy work was forced upon the LondonMissionary Society; and Fiwila – the ‘vil-lage of mercy’ run by the Universities’ Mis-sion to Central Africa that missionaries inZambia did not target Africans sufferingfrom leprosy. Additionally, whilst they diduse the opportunity provided by settlementsfor evangelism, they generally found thatthe work was, evangelically speaking, un-economic – and did not enlarge their settle-ments until 100% funding was provided bygovernment – and this at a time when treat-ment could be given on an outpatient basis,and opportunities for social reconstructionno longer available. Indeed, whilst somemissionaries applied damaging labels tothose under their care, others saw beyondthe disease to the person. Yet otherschanged their stance over time. Local atti-tudes to leprosy confirm Iliffe’s statementthat African reactions are diverse. The Lu-vale people in the area around Chitokoloki,for example, did not appear to have nega-tive attitudes towards leprosy, whilst themarginality experienced within the Lala

community around Fiwila was such that, onbeing called to sort out a marital disputeChief Shaiwila remarked, ‘These people arealready dead. How can a dead man orwoman be divorced or marry?’

REFERENCES1. From paper by Major-General Sir Leonard Rogers,

read to the Commonwealth section of British Em-pire Leprosy Relief Association (BELRA), 25th June1954: ‘Progress towards the eradication of leprosyfrom the British Commonwealth.’ National Archivesof Zimbabwe F122 455/1, Leprosy Surveys,1941–1956

2. ILIFFE J. ‘Leprosy’ in The African Poor. CambridgeUniversity Press, 1987, p215.

3 NAZ SEC2/622 Mkushi District Tour Report1933–39. Tour Report 3/1938 Sub Chief Mondokaand Chief Shaiwila. Lala-Luano Reserve. DC JohnGaunt. Appendix 3 Health.

Illuminating Ourselves: Redefining Traditional Images

Open discussion – The role of imagesand language in the formation of attitudes.

Achievements of people affected by lep-rosy or living with HIV/AIDS, past and present, as a means of challenging stereo-types and the stigma that is perpetuated bythem.

From Ingeborg Grytten (Author, Norway,17th century), to Akashi Kaijin (Poet,Japan, early 20th century) — to the Music ofBacurau (Brazil) and the Poetry of AntonioBorges, Jr. (Brazil) — to the SinikithembaHIV+ Choir.

Images of Dignity – Pamela ParlapianoSunday, February 6 – Human Rights

Alhaji Shehi s/Fada, IDEA Nigeria:“This is the new era for people affected byleprosy that is marked by freedom, fromhardship to freedom: What I will say is thatin every country we [must] unite ourselves,help each other, cooperate. In Nigeria be-fore, we were not cooperating . . . . but asIDEA came, we began to cooperateamongst ourselves. So let us cooperate,unite, and then face the government . . . . tofight for our own rights.”

Artur C.M. de Sousa, MORHAN, Brazil:“Bacarau was one of our founding mem-bers. His vision was that of a humanitariannature. So when he founded MORHAN, 25years ago . . . . He used to say that we weresupposed to bring other social issues to be

Linda Beer Kumwenda. “To save ourEmpire’s Children ”. Mission Leprosy Set-tlements in Northern Rhodesia.


discussed within the movement . . . . WhenI met him in Rio De Janeiro, it was a cold,rainy evening. And he pointed at a childwho was covered under newspaper sheetson the street. And he also pointed to a carthat had had a rain protection cover. And hesaid—We were supposed to fight againstany form of social injustice. Because thesame situation, same conditions that causeleprosy discrimination, were the same con-ditions that made our society protect a carmore than a child.

We have 40,000 new leprosy cases peryear [in Brazil]. And we have to think thatHansen’s disease is part of a group of dis-eases that are neglected. They have the fol-lowing characteristics – low political en-gagement, little information, little power bythe groups of affected persons . . . . thepoorest or the lowest social strata are themost affected by these diseases, and theyare more de-habilitating or incapacitatingthan deadly.”

Professor Bernardino Fantini, Director, In-stitute of History of Medicine & Health, Uni-versity of Geneva. Health and Human Rights.

“This paper discusses the history of rela-tionships between health, disease, and hu-man rights, and divergent ideas about whathuman rights are, and how history can inte-grate personal experiences and the memoryof individuals, groups, and institutions. Itstarted with a definition of history as a wayto build up our personal and social identity,to preserve our memory, which is the basisof our personal and collective identity, torecognize our being part of a social groupand of the whole humanity, to acknowledgethat we all share ideas, ways of thinking,psychological attitudes, theoretical con-structs, artistic perceptions, and moral andreligious beliefs. It acknowledged that forthe whole of human history, infectious dis-eases killed, disabled, and disfigured. Theyhad and have the capacity to destroy, desta-bilise, and profoundly modify populations,but they also produced and still producepsychological and moral consequencessuch as fear or terror, abandonment, exclu-sion, discrimination, and stigma, but alsosolidarity, compassion, and mutual help.

Leprosy is a paradigm of a global dis-ease, a paradigmatic experience for lookingto the relation between global health andhuman rights. The memories of what thedisease has been and of the human experi-

ences of diseased persons are of fundamen-tal importance in the understanding of thesocial attitudes towards other diseases, likeHIV/AIDS. Many historical examples, in-cluding the history of leprosy, show thatglobal health (health for all in the world)will be the result of social action and theempowering of individuals to pursue theirown safety and self determination.

Human rights are not abstract nor onlythe result of legislation or public state-ments. They refer to the respect for the indi-vidual as a person, for his or her dignity,and the right to pursue his or her life. The“right to health” means the right of eachmember of humanity to realise his or herown potential in life, and this means alsothe obligation of the national and interna-tional authorities to ensure this realisationof potential, even in conditions created bydisease or disability.

In centuries past, health was consideredas a product of other, more fundamentalrights. It was believed that economic growth,scientific progress, education, informationwould be enough to ensure health for every-body (for example the hygienic movementof the nineteenth and twentieth centuries).Once considered as disappearing threats,infectious diseases have come into promi-nence in global health with the emergenceof new viral and bacterial agents; the spreadof resistance to common antibiotics; the dev-astating impacts of new epidemics from “oldenemies” such as cholera, plague, dengue,foot-and-mouth disease, BSE; and resurgentinfections of “silent” or “neglected” dis-eases such as malaria and tuberculosis.Those active in health care can no longersimply act alone without regard for the manyother issues and others involved. Health in-equities are widening and in global health,millions continue to die from diseases ofpoverty, despite the accumulation of impres-sive knowledge and modern technologies.

Historians want to know the social andcultural determinants of this tragic paradox.Human rights are not only the “world of theindividual person”, but are the result of so-cial conquest, collective initiatives, as thepotential for life of each individual be-comes connected to interpersonal relation-ships and social contexts. A human right isindividual, but the defence and implemen-tation of those rights are necessarily collec-tive. Strategies for health and human secu-


rity depend upon individual and collectiveaction. Health equity is the fundamentalvalue underpinning global health; it is bothintrinsically valuable, as well as instrumentalin achieving human freedom. The globalisa-tion of health responses must be based on thevalue of equity, on the diffusion and applica-tion of knowledge, and on moral indignationover injustices associated with health.”

Ensuring the Rights of Humanity: Discussion

Chairs: Professor Bernardino Fantini &Dr. P.K. Gopal

Panel: Alhaji Shehu Sarkin Fada,Chamada Abibo

In Conclusion: History as an Agent forSocial Change

Chairs: Prof. Megan Vaughan, ZildaBorges and Anwei Law

Professor Megan Vaughan, Smuts Profes-sor of Commonwealth History, CambridgeUniversity, U.K.: “. . . though I’ve spent someyears reading in the history of medicine andthe history of leprosy, it really is genuinelytrue, I couldn’t have learned anything thatI’ve learned in the last 2 days if I hadn’t beenhere, listening to peoples’ stories, so it’s re-ally a privilege for me . . . . when you hearabout the history, the stories that we’ve beenlistening to, you wonder if we learn anythingfrom history at all . . . . It’s really rather de-pressing in some ways but there are alsosome more positive aspects of this.

I want to start by just saying somethingabout the history of slavery, partly becausewe’re here on Robben Island, but also be-cause I think there are some parallels . . . .one might draw. We all know that in the his-tory of slavery is a history of struggle. It isa history of struggle against the depriva-tions and stigmatization . . . . What slaveswere deprived of were their names, their

families, their languages . . . . [and] perhapsmost importantly of all, their histories. Sopart of the struggle against slavery andwithin slavery was to recover a history, butintegral to the struggle against slavery wasalways in the telling of stories. It was al-ways telling your story, telling the story ofyour people, telling the story of your resis-tance. And again these stories took differentforms but they were very important in thestruggle, in the oppositionist movement, inthe struggle in slavery.

People who had been slaves whose an-cestors had been slaves felt they carried astigma of slavery. Slavery is not a diseasebut it’s a social condition that can give youa stigma. And they also found that therewere other more complex forms of socialand economic discrimination that they werefaced with. They were faced with racism . . . . they were faced with economic depri-vation, they were faced with the fact thatthey couldn’t get proper jobs, they werefaced with a lack of education, all thosethings we know about.

If there are any lessons to be drawn fromthis then I think for me what I’ve learnedfrom listening to you all is how you foundstrength in unity within this organization,IDEA. And I think this is a very interestingcase of a very successful, political and ad-vocacy organization from which other orga-nizations dealing with other issues maywell want to learn.

I’ve also been incredibly impressed bythe ability of people from such diverseplaces facing quite diverse kinds of strug-gles to come together and give each othersupport and move forward.”

Acknowledgment. This conference was madepossible by support from The Nippon Foundation, TheLeprosy Mission International, The German LeprosyRelief Association, the Sasakawa Memorial HealthFoundation, and Fontilles.

US-Japan Meeting, 2005

ABSTRACTMycobacterium leprae initially infectsmonocytes and produces various cytokines,but the role of these cytokines on the pre-cursors of dendritic cells (DCs) is unclear.M. leprae-infected DCs were differentiatedfrom monocytes treated with low levels ofIL-1β (100 pg/ml), and the functions of

Il-1 at the Early Stage of Monocyte Differentiation to Dendritic Cells Impairs Functional Activities of

Dendritic CellsMasahiko Makino, Yumi Maeda, and

Tetsu MukaiDepartment of Microbiology, Leprosy ResearchCenter, National Institute of Infectious Diseases, Japan


these DCs were evaluated. IL-1β treatedDCs were inefficient in activating autolo-gous T cells. Although these DCs presentedM. leprae antigens, the percentage of DCsexpressing high levels of CD86 and CD83Ag was reduced. When LPS, peptidoglycanor M. bovis BCG was used as stimulator,IL-12 production from these DCs was sig-nificantly reduced, although monocytestreated with other cytokines (TNF-α, IL-6or IL-10) did not have such effect. We canconclude the IL-1β, at the early stage of DCdifferentiation, impairs DC function. There-fore, clear understanding of the immune re-sponses will be vital to the design of vac-cines against mycobacterial infection.

Dendritic Cell Maturation is Suppressedby Mycobacterium Leprae

Rose Ann Murray and Gilla KaplanPublic Health Research Institute, Newark, N.J.

ABSTRACTTo better understand the host innate im-mune response to mycobacterial infections,we are exploring the effect of M. leprae, M.bovis bacillus Calmette-Guerin (BCG) andM. tuberculosis (TB) on antigen presentingcell (APC) maturation. Dendritic cells (DC)are especially good APC, being able toprime naïve T lymphocytes against particu-lar antigens at proximal lymph nodes. How-ever, to function optimally, blood DC mustbe matured by exposure to stimulatory cy-tokines and/or the antigens that inducethese molecules. We have infected mono-cyte-derived immature DC with M. leprae,BCG or TB and examined the extent of DCmaturation, as evaluated by phenotypic sur-face changes and immune response geneexpression. Our results suggest that BCGand TB both stimulate phenotypic andgenotypic DC maturation but BCG is muchmore efficient. In contrast, M. leprae ap-pears to inhibit DC genotypic maturationwithout affecting DC maturation markerexpression.

Polymorphism of the 5′′ Flanking Region of the Il-12 Receptor ββ2 Gene

Partially Determines the Clinical Typesof Leprosy through Impaired

Transcriptional ActivityHideki Ohyama1, Koretsugu Ogata2, Tazu

Takeuchi3, Yasushi Uemura4, Masataka

Oyama5, Masako Namisato6, NahokoKogoe1, Naoko Yamada1, Nobuyuki

Terada1, Sho Matushita4

1Hyogo College of Medicine, 2Shimadzu Corporation,3Okayama University Graduate School of Medicineand Dentistry, 4Saitama Medical School, 5NagasakiUniversity Graduate School of Biomedical Sciences,6National Sanatorium Kuryu–Rakusenen

ABSTRACTPolymorphisms on the 5′ flanking region ofIL12RB2 were analyzed to determined pos-sible immunogenetical factors affecting theestablishment of clinical types of leprosy.Several SNPs, including –1035A>G,–1023A>G, –650delG and –465A>GSNPs, were detected on the 5′ flanking re-gion of IL12RB2. Frequency of haplotype 1(–1035A, –1023A, –650G, –464A), whichexhibited the highest frequency in the gen-eral Japanese population, was significantlylower in lepromatous patients as comparedwith findings in tuberculoid patients andhealthy controls. Reporter gene assays us-ing Jurkat T cells revealed that all haplo-types carrying one or more SNPs exhibitedlower transcriptional activity as comparedwith haplotype 1. These results suggest thatSNPs in the 5′ flanking region of IL12RB2affect the level of expression and may beimplicated in individual differences in cell-mediated immune responsiveness to my-cobacterial antigens, leading to lepromatousor tuberculoid leprosy.

Inhibition of TNF or LTa Impairs Mycobacterium Leprae Growth in Mouse

Foot Pads and Is Accompanied by Dysregulated Granuloma Formation

Deanna A. Hagge1, Bernadette M.Saunders2, Gig Ebenezer3, Vilma Tulaga1,

Nashone A. Ray1, Warwick J. Britton2,James L. Krahenbuhl1 and

Linda B. Adams1

1National Hansen’s Disease Programs Laboratory,Louisiana State University, Baton Rouge, LA, 2Cente-nary Institute and Department of Medicine, Univer-sity of Sydney, Sydney, New South Wales, Australia,and 3Johns Hopkins University, Baltimore, MD

ABSTRACTTNF and lymphotoxin-alpha (LTα) are keycytokines in cell mediated immunityagainst intracellular pathogens. To studytheir role in experimental leprosy, My-

cobacterium leprae foot pad (FP) infectionwas evaluated in TNF knockout (TNF–/–)and LTα-deficient chimeric (LTα–/–) mice.In both TNF–/– and LTα–/– mice, M. lepraegrowth was augmented compared to controlmice. Histopathologically, TNF–/– mice de-veloped more extensive and diffuse lym-phocytic infiltration compared to controlmice. In contrast, few lymphocytes werepresent in LTα–/– mice. Upon M. leprae in-oculation, there was a delayed early re-sponse in FP induration in both strains;however, induration in TNF–/– mice rapidlyincreased to levels higher than controlswhile LTα–/– mice could not sustain indura-tion. Flow cytometric analyses of isolatedFP cells demonstrated elevated percentagesof CD3+ T cells in TNF–/– mice many ofwhich expressed CD69. Expression of vari-ous Th1 cytokines and chemokines in es-tablished granulomas were similar or ele-vated in TNF–/– compared to control mice,but LTα–/– mice demonstrated 5–25 foldlower levels of expression. These studiesindicate the critical but independent rolesfor TNF and LTα in orchestrating andmaintaining an appropriate T cell accumu-lation within the microenvironment of theM. leprae-induced granuloma.

Nerve Damage in a Mouse Model of Mycobacterium ulcerans Infections—Detection of M. ulcerans-specific DNA

from micro-dissected nerve tissueMasamichi Goto1, Kazue Nakanaga2,

Junichiro En1, Thida Aung1, TomofumiHamada1, Shinichi Kitajima1, Norihisa

Ishii2, Suguru Yonezawa1, Hajime Saito3

1Kagoshima University, 2National Institute of Infec-tious Diseases Leprosy Research Center, 3HiroshimaEnvironment and Health Association

ABSTRACTBuruli ulcer is a chronic painless ulcerativeskin disease in tropical and subtropical zonecaused by Mycobacterium ulcerans. Recenthistological and ultrastructural studies haveclarified direct intraneural invasion of acid-fast bacilli and vacuolar change of Schwanncells in M. ulcerans-inoculated mice. In or-der to further investigate the mechanism ofpainlessness, nerve tissues were selectivelycut out from the histological specimens by aUV-laser micro-dissection system, and PCRtechnique was applied. Intraneural bacilli

were proven to possess M. ulcerans-spe-cific DNA sequences, but not M. leprae-specific DNA sequences.

Advances in Molecular Epidemiology of Leprosy

Miyako Kimura1, Nathan A. Groathouse1,Kiran Madanahally1, Becky Rivoire1,Xiaoman Weng2, Huan-Ying Li2, JuanCamilo Beltran Alzate3, Nora Cardona-Castro3, Robert H. Gelber4, Sang-Nae

Cho5, William C. Black1, Patrick J.Brennan1 and Varalakshmi D. Vissa1

1Department of Microbiology, Immunology andPathology, Colorado State University (CSU), FortCollins, U.S.A.; 2Beijing Tropical Medicine Re-search Institute (BTMRI), Beijing, People’s Repub-lic of China; 3Instituto Colombiana de MedicinaTropical (ICMT), Sabaneta, Colombia; 4LeonardWood Memorial (LWM), Center for Biomedical Re-search, Cebu City, Philippines; 5Yonsei University,Seoul, Republic of Korea

ABSTRACTIn order to monitor and break the cycle of

transmission of leprosy, a better under-standing of the source and chains of M. lep-rae infection by means of molecular epi-demiology is necessary. Since M. lepraecannot be grown in vitro and the DNA re-covered from clinical samples such as skinbiopsy is valuable, we first established mul-tiple locus variable number of tandem re-peats analysis (MLVA) as a method ofstrain typing in four clinical M. lepraestrains grown in armadillo host. This ap-proach involved the screening of 25 shorttandem repeat (STR) loci, resulting in thediscovery of polymorphisms at 13 loci.Subsequently, MLVA was applied to addi-tional archived armadillo-derived clinicalisolates from leprosy patients from eightcountries for a total of 21 reference strains,and to recent clinical isolates from Colom-bia, the Philippines and China. These datawere analyzed according to parsimony prin-ciples to discern genetic diversity and phylo-genetic relationships. MLVA has been shownto be a practical and effective method for M.leprae strain typing and classification.

What is Needed to Improve Diagnosticsfor TB and eprosy?

Mark PerkinsFoundation for Innovative Diagnostics


ABSTRACTCase detection is a major problem for thecontrol of both leprosy and tuberculosis,and the need to detect drug resistance con-tinues to rise. In countries where these dis-eases are coming under control, the needfor accurate tests for latent infection is alsopressing. Significant advances have beenmade in unraveling the genome and pro-teome of both M. leprae and M. tuberculo-sis, and a number of promising new diag-nostic targets have been identified. Thesetargets are now being explored for their rel-evance to the development of clinical toolsfor the detection of latent infection, activedisease, and pathogen drug resistance. Thepath from reagent discovery to useable di-agnostic is a long one, however, blocked bya number of financial and logistic as well astechnical obstacles. This talk will put thesearch for novel TB and leprosy diagnosticsinto context, highlight the priority needs,and discuss knowledge gaps that stand inthe way of development of tests that areideally suited for the intended settings ofuse.

Genotyping of Mycobacterium leprae byvariable number tandem repeats and itsapplication for molecular epidemiology

Masanori Matsukoa1, Zhang Liangfen1 andTeky Budiawan2

1)Leprosy Research Center, National Institute ofInfectious Diseases, Tokyo, Japan 2)Leprosy-TBProgram, Health Service, North Sulawesi, Indonesia

ABSTRACTThe transmission mode of leprosy was ex-amined by application of polymorphism ofshort tandem repeat (STR) in Mycobac-terium leprae genome. To substantiatepolymorphic loci from STR as promisingcandidates applied for the molecular typingtools in leprosy epidemiology, 44 STR lociincluding 33 microsatellites and 11 min-isatellites were investigated among the 27laboratory maintained strains. Not all STRswere expectedly polymorphic. Thirty-twoout of the 44 loci were polymorphic. Ninepolymorphic loci were suitable for identify-ing genotypes according to the discrimina-tory capacity, stability and reproducibility.All the strains were classified into indepen-dent genotypes by the selected 9 polymor-phic loci. Three multicase households were

submitted to molecular typing. Two M. lep-rae isolates obtained from one family con-tact cases could be divided into differentgenotypes by these polymorphic loci. Thetransmission of leprosy by some infectioussources other than the multi-bacillary case inthe same dwelling was strongly suggested.

Identification of Specific Proteins andPeptides in Mycobacteruim LepraeSuitable for the Selective Diagnosis

of LeprosyJohn S. Spencer1, Hazel M. Dockrell2, Hee Jin Kim1, Maria A. M. Marques1,Diana L. Williams3, Marcia V. S. B.

Martins4, Marcio L. F. Martins4, Monica C.B. S. Lima4, Maria C. V. Pessolani4,

Euzenir N. Sarno5, Elisabeth P. Sampaio5,Thomas H. M. Ottenhoff6, Sang-Nae Cho7,

Neil G. Stoker8, Stewart T. Cole9, andPatrick J. Brennan1

1Department of Microbiology, Immunology andPathology, Colorado State University, Fort Collins,CO, USA, 2Department of Infectious and TropicalDiseases, London School of Hygiene & TropicalMedicine, London, UK, 3Laboratory ResearchBranch, Division of the National Hansen’s DiseasePrograms, Louisiana State University, Baton Rouge,LA, USA, 4Laboratory of Cellular Microbiologyand 5Leprosy Laboratory, Department of Mycobac-terial Diseases, Oswaldo Cruz Institute, FIOCRUZ,Rio de Janeiro, Brazil, 6Department of Immunohe-matology & Blood Transfusion, Leiden Universitymedical Center, Leiden, The Netherlands, 7Depart-ment of Microbiology, Yonsei University College ofMedicine, Seoul, Republic of Korea, 8Departmentof Pathology and Infectious Diseases, Royal Veteri-nary College, London, UK, 9Unité de GénétiqueMoléculaire Bacterienne, Institut Pasteur, Paris,France.

ABSTRACTAbstract. Comparative genomic analysis ofthe M. leprae genome has identified 1604open reading frames, as well as 1,130 inac-tivated genes (pseudogenes), and up to 165genes with no homologues in M. tuberculo-sis. Diagnosis of leprosy is a major obstacleto disease control, and has been compro-mised in the past by the lack of specificreagents. We have used comparativegenome analysis to identify genes that arespecific to M. leprae, and tested both re-combinant proteins and synthetic peptidesfrom a subset of these for immunological


reactivity. Four of the unique recombinantproteins (ML0008, ML0126, and ML2567)and a panel of 58 peptides were tested forIFN-γ responses in PBMC from leprosy pa-tients and contacts, TB patients and en-demic and non-endemic controls. The re-sponses to the four recombinant proteinsgave higher levels of IFN-γ production, butless specificity, than the peptides. Of the 58peptides tested, 35 have showed IFN-γ re-sponses only in the paucibacillary leprosyand household contact groups, with no re-sponses in the TB or endemic controlgroups. Four of the six 9mer peptides testedalso showed promising specificity, indicat-ing that CD8 T cells epitopes may also havediagnostic potential. Those peptides thatprovide specific responses in leprosy pa-tients from an endemic setting could poten-tially be developed into a rapid diagnostictest for the early detection of leprosy andepidemiological surveys of the incidence ofleprosy, of which little is known.

Isothermal Amplification and MolecularTyping of the Obligate Intracellular

Pathogen Mycobacterium leprae fromTissues of Unknown Origins

Nathan A. Groathouse1, Susan E. Brown2,Dennis L. Knudson2, Patrick J. Brennan1

and Richard A. Slayden1*Department of Microbiology, Immunology andPathology1 and Bioagricultural Science and PestManagement2, Colorado State University, FortCollins, CO 80523

ABSTRACTMolecular based diagnostic and epidemiol-ogy studies require sufficient amounts ofhigh quality DNA. Routine molecular-basedepidemiologic methods have not been ap-plied to the obligate intracellular organismMycobacterium leprae because it is difficultto obtain genomic DNA template from clin-ical materials. Accordingly, we have devel-oped a method based on isothermic multipledisplacement amplification, which will fi-nally allow access to quality DNA template.In this report, we evaluated the usefulnessof this method in error-sensitive, multiplefeature molecular analyses. Using test sam-ples isolated from host tissue, we also eval-uated amplification fidelity, genome cover-age and regional amplification bias. The fi-delity of amplified genomic material was

unaltered and while regional differences inglobal amplification efficiency were seen us-ing comparative microarray analysis, a sig-nificant degree of concordance of amplifiedgenomic DNA was observed. This methodwas also applied directly to archived tissuesfor the purpose of molecular typing via shorttandem repeats. This study demonstratedthat whole genome amplification can becoupled with error-sensitive molecular-based typing methods on low copy numbersequences from clinical biopsies of obligateintracellular pathogens, such as M. leprae.

*Corresponding Author: Richard Slayden,Department of Microbiology, Immunologyand Pathology, Colorado State University,Fort Collins, CO 80523-1682, USA. Phone:(970) 491-1925, Fax: (970) 491-1815, E-mail: [email protected]

The Alternative Sigma Factor sigE and Stress Responses in Mycobacterium Leprae

1Diana L. Williams, 1Tana Pittman, 2Mike Deshotel, 3Sandra Oby-Robinson,

4Issar Smith1Molecular Biology Research Dept., LaboratoryResearch Branch, Division of the National Hansen’sDisease Programs @ SVM-LSU, Baton Rouge, LA,USA, 2Dept. of Microbiology, Immunology andParasitology, LSU Health Sciences Ctr., School ofMedicine, New Orleans, LA, USA, 3Dept. ofVeterinary Clinical Sciences, SVM-LSU, BatonRouge, LA, USA, 4TB Center, Public HealthResearch Institute, Newark, NJ, USA

ABSTRACTMycobacterium leprae lacks a functional

heat shock response mechanism which ap-pears to relegate it to peripheral regions ofthe body including peripheral nerves. Thealternative sigma factor SigH orchestratesthe heat shock response by inducing sigEand sigB gene transcription and their re-spective heat shock regulons in M. tubercu-losis (Mtb). However, M. leprae’s sigE andsigB genes are transcriptional unresponsiveduring heat shock conditions. A likelymechanism for this heat shock defect is thelack of a functional sigH. However, no re-combinant protocols exist for M. leprae todirectly test this hypothesis. Therefore, westudied the functional capability of SigE ofM. leprae, using surrogate genetics in asigE knock-out mutant of Mtb (ST28) con-


taining a functional sigH. The SigE of M.leprae restored the ability of ST28 to re-spond to heat shock and detergent stressand restored its ability to grow in humanmacrophages providing direct evidence thatthe SigE of M. leprae is functionally capa-ble of regulating specific stress responsesand indirect evidence that the lack of a pro-tective heat shock response and potentiallyother environmental stress responses in M.leprae is at least partly due to the lack of afunctional sigH.

Lepra Reactions After Multidrug Therapy for Multibacillary

(MB) LeprosyMa. Victoria Balagon, Roland Cellona,

Rodolfo Abalos, Robert GelberLeonard Wood Memorial Center for LeprosyResearch, Cebu, Republic of the Philippines

ABSTRACTThere are two distinct, commonly occur-

ring, immunologically-mediated reactionalstates in leprosy which complicate itscourse, account for considerable morbidity,including neuropathy, and are the majorreason for patients on chemotherapy to seek

medical attention—lepra type 1 reactions,reversal reaction (RR), and lepra type 2 re-actions, ENL, mediated respectively by Th1and Th2 responses. In this study we evalu-ated in MB patients the incidence, severity,and duration of lepra reactions one and twoyears after the completion of 1-year WHOMDT (139 patients) and 2-year WHO-MDT (295 patients) and compared those re-sults. We have found for the first time thatin MB patients lepra reactions commonlypersist even after the completion of MDT,occurring 48% of the time in the first 2years after the currently recommended 1-year regimen and are of considerable sever-ity and duration. Also, the incidence, sever-ity and duration of lepra reactions and thefrequency of neuritis were consistentlygreater after the completion of 1-year MDTthan 2-year MDT, and lepra reactions andthese complications more frequent in thosewith a high bacterial burden. Since a majorgoal of WHO MDT is to reduce the dura-tion needed to care for leprosy patients to aperiod sufficient to complete MDT, ourfindings suggest this is not feasible withoutcourting the significant morbidity fromlepra reactions observed in this study.


We regret to inform our readers that this73rd volume of THE INTERNATIONAL JOUR-NAL OF LEPROSY is the last and final volumeof the JOURNAL. We have been gratified toobserve that that the JOURNAL has had adedicated readership and has had the confi-dence of veteran as well as new authorssubmitting their work to the JOURNAL rightup to the end of its long and distinguishedcareer. A number of manuscripts awaitingreview, or in revision, have unfortunatelybeen returned to their authors.

Closure of the JOURNAL was, ultimately, abusiness decision. The publication of a highquality, professional, peer-reviewed journalis a costly undertaking. To the best of ourknowledge, this JOURNAL, unique to its ori-gins and purpose, has never been fullyfunded by memberships in the InternationalLeprosy Association, of which it is the offi-cial organ. Rather, the JOURNAL has alwaysdepended upon the generosity of leprosy-ori-ented charitable organizations which have, inrecent years, considered the cost of thisJOURNAL to be excessive. In spite of diligentefforts on the part of the officers of the ILAto trim costs and to find additional revenue, asatisfactory solution was not forthcoming.

Many factors underlie the decision toclose the JOURNAL, and we are probably notaware of all of them. It would be a mistake,however, not to see this development asrepresentative of the broader internationaldecline of resources allocated to efforts todeal with leprosy. While commendableprogress has been made to control leprosyin many countries, approximately 500,000new patients are still being diagnosed annu-ally worldwide, most of them in the severalregions of the world that remain highly en-demic. Even in these highly endemic re-gions, however, pressures are being appliedto reduce the resources available to diag-nose and treat leprosy. Some details ofthese policies have been presented by Drs.Rao and Pratap earlier in this volume ([vol.

73:225]). The details vary, but diminishedresources lead to cuts of all kinds. The re-sult is that a clinic is closed in one district,clinics are merged elsewhere, and in otherdistricts patients are referred to a generalhealth center that lacks specialized exper-tise in leprosy. In this way, a small light isextinguished here and there, but the loss isalmost imperceptible (except to the patientsin that locale). The closure of this JOURNAL,however, represents the extinction of alarger, more conspicuous light that has beenof value to leprosy workers worldwide formany decades. This is a clear sign of thecurrent trend in all aspects of leprosy work.

Some individuals are confident that cur-rent elimination policies are scientificallysound and are being implemented appropri-ately; for these individuals, the closure ofthe JOURNAL should be cause for neithersurprise nor dismay, but will be seen as alogical, natural development. Others arehighly skeptical of the scientific basis forcurrent elimination policies, and think thatimplementation of these policies is beingunnecessarily and prematurely rushed tomeet arbitrary bureaucratic goals, to thedetriment of patient care. For many of theseindividuals the closure of the JOURNAL willprobably come as a surprise and a disap-pointment.

The work will go on, of course, as re-sources permit. Other leprosy-oriented jour-nals will continue, and we wish them well.Much remains to be learned about this dis-ease and much remains to be done to con-trol it. We will not be surprised, however,if—a few decades hence—those who lookback to review leprosy elimination effortsat the beginning of this millennium shouldreach the conclusion that we have been fol-lowing the mistaken paths already well trodin the recent history of programs to ‘elimi-nate’ other diseases such as tuberculosisand malaria.

David Scollard

EDITORIALElimination of (the International Journal of) Leprosy.

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David BakerMirjam BakkerLucia BarkerPatrick BrennanJack CohenIan CreeGraca CunhaEbenezer DanielGigi EbenezerKatrien FransenRobert H. GelberThomas GillisJames HarnischRobert HastingsRobert JacobsonC.K. JobPaul Klatser

Jim KrahenbuhlWayne MeyersSam MoschellaS.K. NoordeenGift NormanWinnie OoiThomas ReaPaul SaundersonDavid ScollardVanaja ShettyMariane StefaniRichard TrumanWim van BrakelMarcos VirmondDouglas WalshCornelius WalterLeo Yoder


(ISSN 0148-916X)

REVIEWERS

2005The Editor, on behalf on the INTERNATIONAL JOURNAL OF LEPROSY and the membership ofthe International Leprosy Association, expresses his deepest appreciation to the followingreviewers who have provided invaluable expertise, criticism, and advice in preparing Vol-ume 73.

304

*Aide aux Lepreux Emmaus-Suisse, Spi-talgasse, CH-3011 Berne, Switzerland.

*American Leprosy Missions, One ALMWay, Greenville, South Carolina 29601,U.S.A.

*Amici dei Lebbrosi, Foundazione ItalianaRaoul Follereau, Via Borselli 4, 40135Bologna, Italy.

Damien-Dutton Society, 616 Bedford Ave-nue, Bellmore, New York 11710, U.S.A.

*Damien Foundation (DF/APD), 16 RueStevin, B-1040 Bruxelles, Belgium.

*Deutsches Aussatzigen-Hilfswerk e. V.,Postfach 9062, D-97090 Würzberg 11,Germany.

*Le Secours aux Lépreux (Canada), 1275Rue Hodge Bureau 12, Montreal H4N3H4, Canada

*Netherlands Leprosy Relief, Wibaut-straat 137K, 1097 DN Ansterdam, TheNetherlands.

*Pacific Leprosy Foundation, 115 Sher-borne Street, Bag 4730, Christchurch,New Zealand.

*Sasakawa Memorial Health Founda-tion, Senpaku Shinko Bldg., 1-15-16Toranomon, Minato-ku, Tokyo 105,Japan.

ACKNOWLEDGMENT

The Board of Directors of the INTERNATIONAL JOURNAL OF LEPROSY gratefully ac-knowledges the financial assistance from special grantors and sustaining memberswhich, with the special donations of certain members, has made possible the con-tinuation of publication of the JOURNAL directly by the International Leprosy Asso-ciation. Without this assistance the official organ of the ILS, so essential to leprosyworkers everywhere, could not be published.

SPECIAL GRANTORS

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Contents

VOLUME 73 2005

INTERNATIONALJOURNAL OF LEPROSYand Other Mycobacterial Diseases

Official Organ of theINTERNATIONAL LEPROSY ASSOCIATION

(Association Internationale contre la Lèpre)(Asociación Internacional de la Lepra)

INTERNATIONAL JOURNAL OF LEPROSYand Other Mycobacterial Diseases

CONTENTSVolume 73, Number 1, March 2005


Original ArticlesNovales-Santa Coloma, J., Navarrete-Franco, G., Iribe, P., and López-Cepeda, L. D. Ulcerative Cuta-

neous Mycobacteriosis Due to Mycobacterium ulcerans: Report of Two Mexican Cases - - - - - - - - - - - - - - - - - - - - - - - - - - -

Cross, H. A Delphi Consensus on Criteria for Contraindications, Assessment Indicators and Expected Out-comes Related to Tibialis Posterior Transfer Surgery - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Case ReportDaniel, E., and G. Ebenezer. Anesthesia of Face Uncovered by Histopathology - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

EditorialScollard, D. M. Leprosy Research Declines, but Most of the Basic Questions Remain Unanswered - - - - - - - - - - - -

CommentariesCross, H. Consensus Methods: A Bridge Between Clinical Reasoning and Clinical Research? - - - - - - - - - - - - - - - - - - - - -

Franzblau, S. A Potentially New Treatment for Tuberculosis; Will a Diarylquinoline Work for Leprosy? - - - - - - - - - -

CorrespondenceOpromolla, D.V.A. Some Considerations on the Origin of Type 1 Reactions in Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Malaviya, G. N. Neuropathic Pain in Leprosy Patients - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Book ReviewsAnderson, G. A. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Mathews, R. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

News and Notes - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Calendar - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Current LiteratureGeneral and Historical - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Chemotherapy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Clinical Sciences - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Immunopathology - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Tuberculosis - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Microbiology - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Tuberculosis - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Experimental Infections and Vaccines - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Epidemiology and Prevention - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Rehabilitation - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Other Mycobacterial Diseases - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Molecular and Genetic Studies - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Special Grantors and Sustaining Members - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

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CONTENTSVolume 73, Number 2, June 2005


Original ArticlesHussain, Tahziba, Sinha, Shikha, Kulshreshtha, K. K., Katoch, Kiran, Yadav, V. S., Sengupta, U., and Ka-

toch, V. M. Seroprevalence of HIV Infection among Leprosy Patients in Agra, India: Trends and Perspective -

Gupta, U. D., Katoch, K., Singh, H. B., Natrajan, M., and Katoch, V. M. Persister Studies in Leprosy Pa-tients after Multi-Drug Treatment - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Narang, Tarun, Kaur, Inderjeet, Kumar, Bhushan, Radotra, Bishan Dass, and Dogra, Sunil. ComparativeEvaluation of Immunotherapeutic Efficacy of BCG and Mw Vaccines in Patients of Borderline Lepromatousand Lepromatous Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Kumar, Anil, Girdhar, Anita, and Girdhar, B. K. Prevalence of Leprosy in Agra District (U.P.) India from 2001to 2003 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Case ReportPandhi, Deepika, Mehta, Shilpa, Agrawal, Subhav, and Singal, Archana. Erythema Nodosum Leprosum

Necroticans in a Child—An Unusual Manifestation - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

CorrespondenceBurdick, Anne E., and Ramirez, Claudia C. The Role of Mycophenolate Mofetil in the Treatment of Leprosy

Reactions - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Asilian, A., Faghihi, G., Momeni, A., Radan, M. R., Meghdadi, M., and Shariati, F. Leprosy Profile in Isfa-han (A Province of Iran) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

CommentariesNelson, Kenrad E. Leprosy and HIV Infection (Rarely the Twain Shall Meet?) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Steinhoff, Ulrich, and Visekruna, Alexander. Leprosy Susceptibility—A Matter of Protein Degradation? TheRole of Proteasomes in Infection and Disease - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Obituary Diltor Vladmir Araujo Opromolla (1934–2004) by Marcos Virmond - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

African Leprosy Congress - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

News and NotesDamien-Dutton Award - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Calendar - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -


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CONTENTSVolume 73, Number 3, September 2005


Original ArticlesThomas H. Rea and Robert S. Jerskey. Clinical and Histologic Variations Among Thirty Patients with Lu-

cio’s Phenomenon and Pure and Primitive Diffuse Lepromatosis (Latapi’s Lepromatosis) - - - - - - - - - - - - - - - - - - - - - - - - -

Nand Lal Sharma, Vikram K. Mahajan, Vikas C. Sharma, Sandip Sarin, and Ramesh Chander Sharma.Erythema Nodosum Leprosum and HIV Infection: A Therapeutic Experience - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Ramanuj Lahiri, Baljit Randhawa, and James L. Krahenbuhl. Effects of Purification and Fluorescent Stain-ing on Viability of Mycobacterium leprae - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Case ReportsTarun Narang, Sunil Dogra, and Inderjeet Kaur. Borderline Tuberculoid Leprosy with Type 1 Reaction in an

HIV Patient—A Phenomenon of Immune Reconstitution - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Tarun Narang, Sunil Dogra, and Inderjeet Kaur. Co-localization of Pityriasis Versicolor and BT Hansen’sDisease - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

CommentaryOttenhoff, Tom H.M., and Klein, Michèl R. Leprosy Bacillus Triggers the Wrong Cells - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

EditorialsRao, P. Narasimha. Leprosy Program in India at the Crossroads - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Ji, Baohong. Comments on WHO/AFRO’s “Post-Elimination” Strategy Paper: A New Bottle with Old Wine ofthe “Final Push” - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

CorrespondencePremkumar, Ramaswamy, Rajan, Pichaimuthu, and Daniel, Ebenezer. Quantitative Measurement of

Sensory Impairment in Referral Centers - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Rada, Elsa María, Zambrano, Edgar A., Aranzazu, Nacarid, and Convit, Jacinto. Serologic Recognitionof Low Molecular Weight Mycobacterial Protein Fractions in Lepromatous Patients with Type II Reactions(ENL) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Santos, Mônica Nunes Souza, Ferreira, Luis Carlos de Lima, and Talhari, Sinésio. PaucibacillaryTreatment for Large Tuberculoid Lesions of Leprosy? - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Kumarasinghe, S. Prasad W., and Kumarasinghe, M. P. Reply to the Editor - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Ganapati, R., and Pai, V. V. Has the Term “Elimination” Outlived It’s Utility? - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

News and Notes - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

U.S.-Japan Meeting, 2004 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -


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CONTENTSVolume 73, Number 4, December 2005


Original ArticlesBikash Ranjan Kar, and C. K. Job. Visible Deformity in Childhood Leprosy—A Ten-Year Study. - - - - - - - - - - - - - - - - - -

Jan H. Richardus, Abraham Meima, Corine J. van Marrewijk, Richard P. Croft, and Trevor C. Smith.Close Contacts with Leprosy in Newly Diagnosed Leprosy Patients in a High and Low Endemic Area:Comparison between Bangladesh and Thailand. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

José L. Alfonso, Fernando A. Vich, Juan J. Vilata, and J. Terencio de las Aguas. Factors Contributing tothe Decline of Leprosy in Spain in the Second Half of the Twentieth Century. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

C. Ajith, Sachin Gupta, Bishan D. Radotra, Sunil K. Arora, Bhushan Kumar, Sunil Dogra, and InderjeetKaur. Study of Apoptosis in Skin Lesions of Leprosy in Relation to Treatment and Lepra Reactions. - - - - - - - - -

Clinical NotesG. N. Malaviya. Myiasis in Leprosy. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

CorrespondenceL. Oskam and S. Bührer-Sékula. A Need for Clarification of the Classification Criteria for Leprosy

Patients. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Dr. Gelber and Colleagues Reply. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

News and NotesLeprosy in the Era of AIDS. Report of a Meeting at Robben Island, SA. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

2005 U.S.-Japan Meeting, Seattle - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

EditorialElimination of (the International Journal of) Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Reviewers - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -


Index 2005 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

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Abalos, R. M., (A) 58Actor, J. K., (A) 71Adachi, J. A., (A) 82Adekambi, T., (A) 77, 78Agrawal, S. K., (A) 46Agrawal, Subhav, (O) 122Aguiar, J., (A) 79Aguilar-Leon, D., (A) 161Ahlem, C., (A) 161Ajith, C., (O) 269Alcaide, F., (A) 78, 83Alderson, M. R., (A) 70Alfonso, Jose L., (O) 258Allix, C., (A) 66Almeida, E. C., (A) 75, 83Alt, J., (A) 62Andersen, P., (A) 74Anderson, George A., (B) 36Andries, K., (A) 44Antia, N. H., (A) 60Appelberg, R., (A) 53Aranzazu, Nacarid, (C) 222Araujo Filho, J. A., (A) 50Arduino, M. J., (A) 80Armitige, L. Y., (A) 71Arora, Sunil K., (O) 269Asilian, A., (C) 127Astarie-Dequeker, C., (A) 57Bagwan, I. N., (A) 58Bahrmand, A. R., (A) 83Bajaj, P., (A) 49Barletta, R. G., (A) 79Barreto, M. L., (A) 76Barrow, R. R., (A) 44Barry, C. E., III, (A) 69Basak, C., (A) 55Basaraba, R. J., (A) 70Bastos, A. P., (A) 59Basu, J., (A) 55Bautista-Lorite, J., (A) 52

Bay, M. L., (A) 63Beery, D., (A) 65Behar, S. M., (A) 62, 62Belisle, J. T., (A) 84Bennedsen, J., (A) 83Berchel, M., (A) 80Bermudez, L. E., (A) 44, 79Besedovsky, H., (A) 63Beveridge, T. J., (A) 65Bhattacharyya, A., (A) 55Blau, S., (A) 42, 42Boldsen J. L., (A) 42Bonato, V. L., (A) 74Bonatti, H., (A) 168Bonilla, F. A., (A) 79Bonnet, D., (A) 52Boom, W. H., (A) 63Bosch, S., (A) 51Boshoff, H. I., (A) 69Bottasso, O. A., (A) 63Bouchot, A., (A) 74Bozza, V., (A) 63Bradbury, A. R., (A) 84Bradbury, E. M., (A) 84Brandt, L., (A) 70Brennan, P. J., (A) 64, 69Breton, G., (A) 52Brooks, D. E., (A) 65Brown, J., (A) 55Buckley, H. R., (A) 43Buhrer-Sekula, S., (C) 280Burdick, Anne E., (C) 129Butlin, C. R., (A) 50Buxton, M., (A) 76Calatayud, L., (A) 78Calza, L., (A) 166Cambau, E., (A) 44Canaday, D. H., (A) 63Carvalho, A. A., (A) 49Cecilia, G. V., (A) 60

313


Index to Volume 73–2005

AUTHOR INDEXAn original article is indicated by (O), editorial (E), correspondence (C), news and notes (N), abstract (A), book

review (B), obituary (Ob), supplement (S).

Chacon, O., (A) 79Chacon-Salinas, R., (A) 65Chae, G. T., (A) 68, 85Chambers, M., (A) 75Chang, J. C., (A) 65Chapman, P. L., (A) 70Cheers, C., (A) 73Chen, H. H., (A) 79Chen, J., (A) 84Chen, X., (A) 84Chen, Z. W., (A) 56Chico-Ortiz, M., (A) 73Chimelli, L., (A) 48Chinchon, D., (A) 52Chinchon, I., (A) 52Chiu, H. C., (A) 79Chua, J., (A) 52, 57Church, J. A., (A) 81Clay, H., (A) 65Co, D. O., (A) 52Coade, S., (A) 72Coelho-Castelo, A. A., (A) 74Colford, J. M., Jr., (A) 54Coloma, Josefa, (O) 5Colombo, M. I., (A) 155Colston, M. J., (A) 71, 72, 75Convit, Jacinto, (C) 222Cooksey, R. C., (A) 80Cooper, A. M., (A) 56Copenhaver, R. H., (A) 71Cordeiro, R. S., (A) 59Couri, C. E., (A) 47Crampin, A. C., (A) 84Crick, D. C., (A) 69Croft, Richard P., (O) 249Cross, Hugh, (C) 28, (O) 13Curcio, M., (A) 83Da Costa Neri, J. A., (A) 48Daffe, M., (A) 46, 57Dahl, J. L., (A) 69Dai, Y. S., (A) 79Dalemans, W., (A) 70Daniel, Ebenezer, (C) 219, (O) 22Das, P. K., (A) 58Dawes, S., (A) 54, 84De Souza, A. O., (A) 74Debacker, M., (A) 79Debbabi, H., (A) 62Dekker, T., (A) 58Del Rey, A., (A) 63Deng, J. Y., (A) 61Deretic, V., (A) 52, 57, 155Deshmukh, S. D., (A) 58Dobos, K. M., (A) 84Dogra, Sunil, (A) 105, (O) 203, 206, 269Dos Santos, C. S., (A) 47Doxsee, D., (A) 65Dramaix, M., (A) 79Drancourt, M., (A) 77, 78Du, G., (A) 56

Duerksen, F., (A) 47Dunst, K. R., (A) 168Duppre, N. C., (A) 75, 83Duval, X., (A) 52de Chaffoy, D., (A) 44de Paula, F. J., (A) 47de St Groth, B. F., (A) 73de las Aguas, J. Terencio, (O) 258deSauvage, F., (A) 56Ebenezer, Gigi, (O) 22Eluru, H. B., (A) 53Enciso-Moreno, J. A., (A) 65Espitia, C., (A) 72Estellat, C., (A) 52Estrada-Garcia, I., (A) 65Estrada-Parra, S. A., (A) 65Etienne, G., (A) 46, 57Faber, R., (A) 149Faber, W. R., (A) 58Faccioli, L. H., (A) 74Faghihi, G., (C) 127Fajardo, T. T., (A) 58Faria, S. C., (A) 48Farroni, M. A., (A) 63Farshchian, M., (A) 47Fauville-Dufaux, M., (A) 66, 83Fazio, J. A., (A) 52Feldman, K., (A) 83Feldmeier, H., (A) 76Ferdinand, S., (A) 80Ferguson, D. D., (A) 80Fernandes, P. V., (A) 48Ferraz, J. C., (A) 72Ferreira, Luis Carlos de Lima, (C) 225Ferri, M., (A) 166Fine, P. E., (A) 84Fitness, J., (A) 84Fletcher, H. A., (A) 82Florido, M., (A) 53Florquin, S., (A) 63Floyd, S., (A) 84Forst, C. V., (A) 84Foss, N. T., (A) 47Franzblau, Scott, (C) 32Fremond C. M., (A) 61Fremond, C., (A) 74Frincke, J., (A) 161Fu, Z. J., (A) 61Ganapati, R., (C) 229Gandhi, G., (A) 59Garcia, V. E., (A) 60Garcia-Tapia, A., (A) 69Geha, R. S., (A) 79Gellis, S. E., (A) 79Germano, S., (A) 73Gershman, K., (A) 80Gevaudan, M. J., (A) 78Ghadiali, A. H., (A) 80Ghilardi, N., (A) 56Ghosh, S., (A) 72


Gilbert, S. C., (A) 82Gilbertson, B., (A) 73Giles, M., (A) 52Gilleron, M., (A) 57Gilmartin, L., (A) 56Girdhar, Anita, (A) 115Girdhar, B. K., (A) 67, 115Goh, K. S., (A) 80Gohlmann, Neefs, J. M., (A) 44Gomes Antunes, S. L., (A) 48Gomez-Aranda, F., (A) 52Gomez-Mampaso, E., (A) 70Goodworth, K. J., (A) 71Gopinath, D. V., (A) 48Greub, G., (A) 78Guillemont, J., (A) 44Gupta, Sachin, (O) 269Gupta, U. D., (A) 100Gupte, M. D., (A) 76Gutierrez, M. G., (A) 155Hailes, H. C., (A) 71Han, J. Y., (A) 81Han, X. Y., (A) 82Hanney, S., (A) 76Harding, C. V., (A) 63Hart, P. D., (A) 71Hatch, G., (A) 74Havelkova, M., (A) 83Hendster, P., (A) 168Henriques, M. G., (A) 59Hernandez-Pando, R., (A) 161Herrewegh, A., (A) 84Herve, A. C., (A) 71Herve, G., (A) 71Hewinson, G., (A) 75Hill, A. M., (A) 71Hill, A. V., (A) 84Hill, A. V. S., (A) 82Hoeve, M. A., (A) 57, 85Hoffner, S., (A) 44Hogan, L. H., (A) 52Holland, S. M., (A) 81Hollis, G., (A) 53Hsiao, C. H., (A) 79Huang, D., (A) 56Huitric, E., (A) 44Hunter, R. L., (A) 71Hussain, Tahziba, (O) 93Huygem, K., (A) 82Iribe, Pedro, (O) 5Ishii, N., (A) 43Iyer, A. M., (A) 58Izzo, A. A., (A) 70, 73Izzo, L. S., (A) 73Jacobs, M., (A) 61Jacobs, M. R., (A) 45Jadhav, M. V., (A) 58Jagannath, C., (A) 71Jain, S., (A) 68, 85Jaishankar, T. J., (A) 48

Jardim, M. R., (A) 48Jarlier, V., (A) 44Jenner, P., (A) 71Jensen, B., (A) 80Jerskey, Robert S., (O) 169Ji, Baohong, (E) 216Jianping, S., (A) 76Jing, G., (A) 53Joaquin, G. E., (A) 60Job, C. K., (O) 243Jogi, R., (A) 81Jones, J. M., (A) 55Jones, T., (A) 76Joshua, J., (A) 49Kadam, P., (A) 58Kai, M., (A) 67Kamath, A. B., (A) 62, 62Kang, T. J., (A) 68, 85Kapur, M., (A) 45Kar, Bikash Ranjan, (O) 243Kasimos, J., (A) 73Katila, M. L., (A) 83Katoch, K., (A) 100Katoch, Kiran, (O) 93Katoch, V. M., (A) 67, 81, 100, (O) 93Kaur, D., (A) 69Kaur, Inderjeet, (A) 105, (O) 203, 206, 269Kawakami, K., (A) 66Keating, S. M., (A) 82Kerr-Pontes, L. R. S., (A) 76Kessler, A. T., (A) 81Khader, S. A., (A) 56Khan, A., (A) 49Khandekar, M. M., (A) 58Kheirandish, A., (A) 47Khuller, G. K., (A) 45, 45, 75Kim, S. I., (A) 52Kim, S. K., (A) 68, 85Kinjo, T., (A) 66Kinkle, B., (A) 53Kishore, B. N., (A) 50Klatser, P., (A) 55Klein, Michel R., (C) 208Kobayashi, K., (A) 54Koksalan, K., (A) 83Koranne, R. V., (A) 49Kourtis, A. P., (A) 81Krahenbuhl, James L., (O) 194Kulshreshtha, K. K., (O) 93Kumar, Anil, (A) 115Kumar, Bhushan, (A) 105, (O) 269Kumarasinghe, M. P., (C) 227Kumarasinghe, S., (C) 227Kundu, M., (A) 55Kyei, G., (A) 52La Scola, B., (A) 78Lahiri, Ramanuj, (O) 194Lasco, T. M., (A) 70Lasuncion, M. A., (A) 70Laverde, C., (A) 51

73, 4 Author Index—Volume 73 315

Lee, E., (A) 44Lee, S. A., (A) 82Lee, S. B., (A) 68Leemans, J. C., (A) 63Legrand, E., (A) 80Leport, C., (A) 52Letvin, N. L., (A) 56Liang, M. G., (A) 79Liangbin, Y., (A) 76Lima, K. M., (A) 74Liu, Q., (A) 61Lobet, Y., (A) 70Lockwood, D. N., (A) 68, 85Longuet, P., (A) 52Lopez-Cepeda, Larissa, (O) 5Lopez-Marin, L. M., (A) 73Lounis, N., (A) 44Lowrie, D. B., (A) 72, 75Lu, H. B., (A) 61la Mora Pedro, G. D., (A) 60lee, S. B., (A) 85Macdonald, M., (A) 51Machowski, E. E., (A) 54, 84Maeda, S., (A) 67Magan, N., (A) 55Mahajan, Vikram K., (O) 189Mahalingam, M., (A) 68Mahmmod, N., (A) 84Mahuad, C., (A) 63Mailaender, C., (A) 46Maillet, I., (A) 74Majka, S., (A) 73Malaviya, G. N., (C) 34Malaviya, G. N., (O) 277Maldonado-Garcia, G., (A) 73Malema, S., (A) 84Mandal, D., (A) 55Manfredi, R., (A) 166Manickam, P., (A) 76Maniero, V. C., (A) 75, 83Manning, E. J., (A) 80Maridonneau-Parini, I., (A) 57Martelli, C. M., (A) 50Martin, R., (A) 78Martin-Casabona, N., (A) 83Martinez, A. N., (A) 75, 83Martinez, G. J., (A) 60Martins, R. S., (A) 49Mast, D., (A) 53Master, S., (A) 52Master, S. S., (A) 155Mateo, L., (A) 83Mathew, D., (A) 50Mathews, Ronnie, (B) 37Matilla, J., (A) 70Mawuenyega, K. G., (A) 84Mazzarelli, G., (A) 80McShane, H., (A) 82Meghdadi, M., (C) 127Mehta, Shilpa, (O) 122

Meima, Abraham, (O) 249Meiwen, Y., (A) 76Meyers, W. M., (A) 79Miyagi, K., (A) 66Mizrahi, V., (A) 54, 84Moel, F. J., (A) 149Momeni, A., (C) 127Montenegro, A. C. D., (A) 76Montero, M. T., (A) 70Moraes, M. O., (A) 75, 83Morelli, S., (A) 166Mori, S., (A) 43Moura, A. C., (A) 59Munoz-Cruz, S., (A) 65Mvondo, D., (A) 52Nakajima, H., (A) 43Nakamura, K., (A) 66Nanetti, A., (A) 166Narang, Tarun, (A) 105, (O) 203, 206Naser, S. A., (A) 80Natrajan, M., (A) 100Navarrete-Franco, Gisela, (O) 5Nelson, Kenrad E., (C) 133Ngai, P., (A) 57Nicolle, D., (A) 74Nicolle, D. M., (A) 61Niederweis, M., (A) 46Nienhuis, W. A., (A) 50Nolla, J. M., (A) 83Norris, S. J., (A) 71Norris-Jones, R., (A) 65Oberoi, S., (A) 46Oerther, D. B., (A) 53Okkels, L. M., (A) 74Olsen, A. W., (A) 74Opromolla, D. V. A., (C) 33Orange, J. S., (A) 79Ordonez, N., (A) 51Orme, I. M., (A) 70Orozco, H., (A) 161Oskam, L., (A) 149, (C) 280Ottenhoff, T. H., (A) 85Ottenhoff, T. H., (A) 57Ottenhoff, Tom H. M., (C) 208Overduin, P., (A) 84Pahan, D., (A) 149Pai, M., (A) 54Pai, R. K., (A) 63Pai, V. V., (C) 229Pandey, A., (A) 67Pandey, R., (A) 45, 75Pandhi, D., (A) 46Pandhi, Deepika, (O) 122Papautsky, I., (A) 53Parkash, O., (A) 67Pasquinelli, V., (A) 60Pathak, S., (A) 55Pathak, S. K., (A) 55Pathan, A. A., (A) 82Pavlou, A. K., (A) 55


Pearl, J. E., (A) 56Pennini, M. E., (A) 63Pereira, G. A., (A) 50Pereira, M. F., (A) 83Pfausler, B., (A) 51Pfyffer, G. E. & Portaels, F., (A) 83Pichon, X., (A) 74Pinto, R., (A) 51Poaletti, X., (A) 52Polaczyk, A., (A) 53Portaels, R., (A) 79Prasad, W., (C) 227Premkumar, Ramaswamy, (C) 219Qiu, L., (A) 56Quesniaux, V. F., (A) 61Quesniaux, V. J., (A) 74Quiroga, M. F., (A) 60Raad, I. I., (A) 82Rada, Elsa Maria, (C) 222Radan, M. R., (C) 127Radotra, Bishan Dass, (A) 105Ragno, S., (A) 75Rai, S., (A) 67Raja, A., (A) 64Rajan, Pichaimuthu, (C) 219Ramakrishnan, L., (A) 65Ramalingam, B., (A) 64Ramirez, Claudia C., (C) 129Randhawa, Baljit, (O) 194Rao, P. Narasimha, (E) 211Raoult, D., (A) 78Rastogi, N., (A) 80Ravi, B., (A) 49Rea, Thomas H., (O) 169Reading, C., (A) 161Redotra, Bishan D., (O) 269Reed, S. G., (A) 70Reid, C. A., (A) 43Reid, S. E., (A) 43Reynaud-Gaubert, M., (A) 78Richardus, J. H., (A) 149Richardus, Jan H., (O) 249Riley, L. W., (A) 54Rivera-Marrero, C. A., (A) 64Riveros, A., (A) 51Rodrigues, F., (A) 83Rodrigues, J. M., (A) 74Rodriguez, G., (A) 51Rodriguez, J. C., (A) 69Roholl, P., (A) 84Roman, J., (A) 64Rook, G. A., (A) 161Rosenzweig, S. D., (A) 81Ross, L. A., (A) 81Royo, G., (A) 69Rufi, G., (A) 83Ruiz, M., (A) 69Ryffel, B., (A) 61, 74Saito, A., (A) 66Sales, A. M., (A) 48, 75, 83

Sanchez-Garcia, F. J., (A) 73Sander, C. R., (A) 82Sandor, M., (A) 52Santin, M., (A) 78Santos, A. R., (A) 75, 83Santos, Monica Nunes Souza, (C) 225Santos, S. A., (A) 74Santosuosso, M., (A) 57Sarin, Sandip, (O) 189Sarkar, S., (A) 49Sarmiento, M., (A) 51Sarno, E. N., (A) 48, 75, 83Save, M. P., (A) 60Saxena, R. K., (A) 72Schmutzhard, E., (A) 51Schneider, L. C., (A) 79Schouls, L., (A) 84Schramm, B., (A) 161Schwarz, R. J., (A) 51Scollard, D. M., (E) 25Scollard, David M., (E) 303Scott, J. T., (A) 79Sehgal, P., (A) 56Sengupta, U., (O) 93Sepp, N., (A) 51Sepulveda, E., (A) 71Serafin-Lopez, J., (A) 65Sergio, N. F., (A) 60Serrano, A., (A) 161Serrano-Pozo, A., (A) 52Shafer, W. M., (A) 64Shariati, F., (C) 127Sharma, A., (A) 45Sharma, Nand Lal, (O) 189Sharma, Ramesh Chander, (O) 189Sharma, S., (A) 45, 45Sharma, Vikas C., (O) 189Shen, L., (A) 56Shen, Y., (A) 56Shenoy, A. R., (A) 68Sherman, D. R., (A) 65Shetty, K. T., (A) 60Shetty, N. J., (A) 50Shetty, V. P., (A) 60Shwethadri, G. K., (A) 50Sichali, L., (A) 84Silva, C. L., (A) 74Singal, A., (A) 46Singal, Archana, (O) 122Singh, B., (A) 59Singh, H. B., (A) 67, 100Singh, S. B., (A) 155Singh, S. B., (A) 52, 57Sinha, Shikha, (O) 93Siqueira, M. G., (A) 49Skeiky, Y. A., (A) 70Smith, Trevor C., (O) 249Sola, C., (A) 80Solache, A., (A) 56Sonia, L., (A) 60

73, 4 Author Index—Volume 73 317

Souza, L. C., (A) 50Sp. Grp Non Tuber. Mycobacteria, (A) 83Sreenath, N. P., (A) 68Sreevatsan, S., (A) 80Srinivasan, A., (A) 80Stavropoulos, E., (A) 71, 72, 75Steele, P., (A) 73Stefani, G. P., (A) 50Stefani, M. M., (A) 50Steinhoff, Ulrich, (C) 131Stelzmueller, I., (A) 168Stephan, J., (A) 46Steunous, C., (A) 79Stewart, J., (A) 64Stokes, R. W., (A) 65Strother, M., (A) 80Sukumar, , (A) 50Suneetha, L. M., (A) 68, 85Suneetha, S., (A) 68, 85Supply, P., (A) 66Talhari, Sinesio, (C) 225Tascon, R. E., (A) 71, 72, 75Tayles, N., (A) 43Taylor, C., (A) 62, 62Taylor, G. A., (A) 155Taylor, G. M., (A) 68, 85Thappa, D. M., (A) 48Thepen, T., (A) 63Thomsen, V. O., (A) 83Thorson, L. M., (A) 65Timmerman, P., (A) 44Tobian, A. A., (A) 63Tortoli, E., (A) 80Tortoli, E. & Vincent, V., (A) 83Trauger, R. ., (A) 161Truffot-Pernot, C., (A) 44Turner, A. P., (A) 55Turner, O. C., (A) 70Turner, S., (A) 73Tyring, S. K., (A) 81Uezu, K., (A) 66Uma Devi, K. R., (A) 64Urgell, J. R. & Rusch-Gerdes, S, (A) 83Valderrama, J., (A) 51Valentini, R., (A) 166Vergne, I., (A) 52, 57Verhasselt, P., (A) 44Verma, I., (A) 75Vermund, S. H., (A) 43Vich, Fernando A., (O) 258Vilata, Juan J., (O) 258Vilde, J. L., (A) 52Villahermosa, L. G., (A) 58

Villenuve, C., (A) 57Virmond, Marcos, (Ob) 137Visekruna, Alexande, (C) 131Visweswariah, S. S., (A) 68Volkman, H. E., (A) 65Vordermeier, M., (A) 75van Brakel, W. H., (A) 50van Gestel, J., (A) 44van Marrewijk, Corine J., (O) 249van Rooijen, N., (A) 63van Soolingen, D., (A) 84van de Vosse, E., (A) 57, 85van de Winkel, J. G., (A) 63van der Poll, T., (A) 63van der Werf, T. S., (A) 50van der Zanden, A., (A) 84Wang, J., (A) 57Wanger, A., (A) 71Warndorff, D. K., (A) 84Watt, B., (A) 83Weijer, S., (A) 63Weng, Y., (A) 62Wenzhong, L., (A) 76Werneck, G. L., (A) 76Wiesmayr, S., (A) 168Williams, A., (A) 74Williams, P., (A) 44Winkler, H., (A) 44Woodworth, J., (A) 62Xie, W. H., (A) 61Xing, Z., (A) 57Xiong, X., (A) 62Xue, T., (A) 75Yadav, V. S., (O) 93Yagodin, V., (A) 42, 42Yakrus, M. A., (A) 80Yamashiro, S., (A) 66Yamazaki, Y., (A) 44Yang, M., (A) 72, 75Yeremeev, V., (A) 61You, E. Y., (A) 68, 85Young, D. B., (A) 68, 85Young, S. K., (A) 68, 85Zambrano, Edgar A., (C) 222Zangerle, R., (A) 168Zganiacz, A, (A) 57Zhang, X. E., (A) 61Zhang, Y., (A) 46Zhang, Z. P., (A) 61Zhou, Y. F., (A) 61Zhu, M., (A) 44Zinsou, C., (A) 79



SUBJECT INDEXThis Subject Index is compiled from key words in the title of each entry. An original article is indicated by (O),

editorial (E), correspondence (C), news and notes (N), obituary (Ob), abstract (A), book review (B), supplement (S),image from the history of leprosy (I).

319

Acquired immunodeficiency syndrome (AIDS),Clinical latency and reactivation of AIDS-related mycobacterial infections. Shen, Y., et al. . . . (A) 56Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii

infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) 166Leprosy in the Era of AIDS. Report of a meeting at Robben Island, SA. . . . . . . . . . . . . . . . . . (N) 283

Adenosine triphosphate (ATP),A Diaryquinoline Drug Active on the ATP Synthase of mycobacterium tuberculosis. Andries,

K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 44

Africa,ALERT Training Courses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 40Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy

Reid, S.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 43Images from the History of Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..(I) 89

Antibody(ies),Improved diagnosis of pulmonary tuberculosis by detection of free and immune complex-

bound anti-30 kDa antibodies. Raja, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 64

Antigen(s),A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy

using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tubercu-losis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 72

A mutant of mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential. Copenhaver, R.H., et al. . . . . . . . . . . (A) 71

Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) 63

Electrochemical antigen-retrieval of formaldehyde fixed and paraffin-embedded archived leprosy skin biopsies. Sergio, N.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 60

Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT-6 in the aerosol guinea pig model. Olsen, A.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 74

RNA encoding the MPT83 antigen induces protective immune responses against myco-bacterium tuberculosis infection. Xue, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 75

Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. McShane, H., et al. . . . . . . . . . (A) 82

The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. (A) 62

Apoptosis,Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions.

Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 269

Asia,International Course on rehabilitation and prevention of disability (RPOD) and course in

community based rehabilitation (CBR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 39Leprosy and tuberculosis in Iron Age Southeast Asia?. Tayles, N. and Buckley, H.R. . . . . . . . (A) 43Osteoarchaeological evidence for leprosy from western Central Asia. Blau, S. and Yagodin, V. . (A) 42Osteoarchaeological evidence for leprosy from western Central Asia. Blau, S. and Yagodin, V. . (A) 42

Assay(s) (see also ELISA),Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai,

M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 54Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium

tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) 61

Bacilli,The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacterium

tuberculosis is associated with increased intracellular survival of bacilli. Rivera Marrero, C.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 64

Bacteriology,Utility of fast mycobacerial interspersed repetitive unit variable number tandem repeat

genotyping in clinical mycobacteriological analysis. Allix, C., et al. . . . . . . . . . . . . . . . . . . (A) 66

Bangladesh,Close contacts with leprosy in newly diagnosed leprosy patients in a high and low endemic

area: Comparison between Bangladesh and Thailand. Richardus, Jan H., et al. . . . . . . . . . (O) 249

BCG (bacille Calmette-Guerin),A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy

using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 72

Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Gutierrez, M.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 155

Comparative evaluation of immunotherapeutic efficacy of BCG and Mw vaccines in patients of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) 105

Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 59

Long term control of mycobacterium bovis BCG infection in the absence of Toll-like recep-tors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-deficient mice. Nicolle, D., et al. (A) 74


The protective effect of the mycobacterium bovis BCG vaccine is increased by coad-ministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . (A) 70

Biopsy,Electrochemical antigen-retrieval of formaldehyde fixed and paraffin-embedded archived

leprosy skin biopsies. Sergio, N.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 60

Blood,Catheter-related bloodstream infection caused by mycobacterium brumae. Lee, S.A., et al. . . . (A) 82Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear

cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) 63Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal

secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) 75Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal

secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) 83

Borderline leprosy,Borderline tuberculoid leprosy with Type 1 reactiion in an HIV patient—A phenomenon of

immune reconstitution. Narang, Tarun, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 203Co-localization of pityriasis versicolor and BT Hansen’s Disease. Narang, Tarun, et al. . . . . . (O) 206Comparative evaluation of immunotherapeutic efficacy of BCG and Mw vaccines in patients

of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) 105

Brazil,Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a

Brazilian referral centre. Jardim, M.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 48Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal




Human immunodeficiency virus type 1 (HIV-1) and mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic profiles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 50

Inequality and leprosy in Northeast Brazil: an ecological study. Kerr-Pontes, L.R.S., et al. . . . (A) 76

Case detection,Trends in case detection influenced by leprosy elimination campaigns in certain areas of

China. Jianping, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 76

Cell(s),16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates

chemotherapy-induced bacterial clearance in a model of progressive pulmonary tuberculosis. Hernandez-Pando, R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 161

A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy. Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 58

Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) 57

Cell biology of mycobacterium tuberculosis phagosome. Vergne, I., et al. . . . . . . . . . . . . . . . . (A) 57Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear

cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) 63Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after mycobacterium

tuberculosis infection. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 62Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment

in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 59Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) 69Human genetics of intracellular infectious diseases: molecular and cellular immunity against

mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 57Human genetics of intracellular infectious diseases: molecular and cellular immunity against

mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85Leprosy bacillus triggers the wrong cells. Ottenhoff, Tom H.M. and Klein, Michel R. . . . . . . (C) 208Mycobacterium tuberculosis functional network analysis by global subcellular protein

profiling. Mawuenyega, K.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacterium


The glycan-rich outer layer of the cell wall of mycobacterium tuberculosis acts as an antiphagocytic capsule limiting the association of the bacterium with macrophages. Stokes, R.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 65

The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 62

Cells, mononuclear,Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear

cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) 63

Cells, T,A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy.

Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 58Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary

tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) 57Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after mycobacterium

tuberculosis infection. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 62The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial

antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 62

Cell-mediated immunity (CMI) (see also Immunology),Human genetics of intracellular infectious diseases: molecular and cellular immunity against


mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85

73, 4 Subject Index—Volume 73 321

Chemotherapy (see also Multidrug therapy),16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates


Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub therapeutic dose against experimental tuberculosis. Sharma, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 45

Fluoroquinolones as chemotherapeutics against mycobacterial infections. Jacobs, M.R . . . . . (A) 45Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with

chemotherapy is a more rapid and efficient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 74

Microsphere technology for chemotherapy of mycobacterial infections. Barrow, R.R . . . . . . . (A) 44

China, People’s Republic of,Trends in case detection influenced by leprosy elimination campaigns in certain areas of

China. Jianping, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 76

Classification,A need for clarification of the classification criteria for leprosy patients Oskam, L. and

Buhrer-Sekula, S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 280Dr. Gelber and Colleagues Reply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 281

Clinic(s),A clinical study of the involvement of cranial nerves in leprosy. Gopinath, D.V., et al. . . . . . . (A) 48An evaluation of clinical and histopathological status in paucibacillary leprosy patients after

completion of fixed duration therapy. Mathew, D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 50Clinical and histologic variations among thiry patients with Lucio’s phenomenon and pure and

primitive diffuse lepromatosis (Latapi’s Lepromatosis). Rea, Thomas H. and Jerskey, Robert S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 169

Clinical latency and reactivation of AIDS-related mycobacterial infections. Shen, Y., et al . . . (A) 56Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a

Brazilian referral centre. Jardim, M.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 48Clinico-histopathological correlation of skin and nerve in leprosy. Khan, A., et al. . . . . . . . . . (A) 49Clinico-pathological study of 12 cases of patients with leprosy admitted to Sina Hospital,

Hamadan, Iran, from 1991 2000. Farshchian, M. and Kheirandish, A. . . . . . . . . . . . . . . . . (A) 47Consensus methods: A bridge between clinical reasoning and clinical research. Cross, Hugh . (C) 28Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii

infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) 166Human immunodeficiency virus type 1 (HIV-1) and mycobacterium leprae co-infection:

HIV-1 subtypes and clinical, immunologic, and histopathologic profiles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 50

Hypercalcemia secondary to leprosy Couri, C.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 47Leprous neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 47Multibacillary leprosy in Tyrol Pfausler, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 51Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium

tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) 61Myiasis in leprosy Malaviya, G.N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 277Utility of fast mycobacerial interspersed repetitive unit variable number tandem repeat


Clinical,A clinical study of the involvement of cranial nerves in leprosy. Gopinath, D.V., et al. . . . . . . (A) 48An evaluation of clinical and histopathological status in paucibacillary leprosy patients after

completion of fixed duration therapy. Mathew, D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 50Clinical and histologic variations among thiry patients with Lucio’s phenomenon and pure and


Clinical latency and reactivation of AIDS-related mycobacterial infections. Shen, Y., et al . . . (A) 56Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a

Brazilian referral centre. Jardim, M.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 48Consensus methods: A bridge between clinical reasoning and clinical research. Cross, Hugh . (C) 28Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii

infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) 166



Hypercalcemia secondary to leprosy Couri, C.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 47Leprous neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 47Multibacillary leprosy in Tyrol Pfausler, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 51Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium

tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) 61Myiasis in leprosy Malaviya, G.N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 277Utility of fast mycobacerial interspersed repetitive unit variable number tandem repeat


Control of leprosy,Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages

and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . (A) 71IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice.

Pearl, J.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 56Long term control of mycobacterium bovis BCG infection in the absence of Toll-like recep-

tors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-deficient mice. Nicolle, D., et al. (A) 74

Cutaneous,A case of isolated tuberculoid leprosy of antebrachial medial cutaneous nerve. Martins, R.S.,

et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 49Successive development of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and

Sweet’s syndrome in a patient with cervical lymphadenitis caused by mycobacterium fortuitum. Chen, H.H., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79

Ulcerative cutaneous mycobacteriosis due to report of two mexican cases. Coloma, Josefa, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 5

Cytokine,Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with

streptozotocin-induced diabetes mellitus infected with mycobacterium tuberculosis. Yamashiro, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 66

Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions. Faber, W.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 58

The effect of iron on the expression of cytokines in macrophages infected with mycobacterium tuberculosis. Serafin-Lopez, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 65

Deformity, disability,International Course on rehabilitation and prevention of disability (RPOD) and course in

community based rehabilitation (CBR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 39Measuring impairment caused by leprosy: inter-tester reliability of the WHO disability

grading system. Nienhuis, W.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 50Visible deformity in childhood leprosy—A ten-year study. Kar, Bikash Ranjan and Job, C.K. (O) 243

Dermal,Characteristics of mycobacterial infection in patients with immunodeficiency and nuclear

factor-kappaB essential modulator mutation, with or without ectodermal dysplasis. Dai, Y.S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79

Diabetes,Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with


DNA,A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy


DNA damage studies in untreated and treated leprosy patients. Gandhi, G. and Singh, B. . . . (A) 59Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal




Detection of mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a preliminary report. Parkash, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 67

Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efficient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 74

Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) 61

Drugs (see also Multidrug therapy and specific drugs),A Diaryquinoline Drug Active on the ATP Synthase of mycobacterium tuberculosis. Andries,

K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 44Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated

antitubercular drugs at sub therapeutic dose against experimental tuberculosis. Sharma, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 45

Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin, moxifloxacin, and four conventional antimycobacterial drugs against mycobacteriumkansasii. Alcaide, F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 78

Liposome technology for drug delivery against mycobacterial infections. Khuller, G.K., et al. (A) 45Multi drug resistant mycobacterium leprae from patients with leprosy. Maeda, S . . . . . . . . . . (A) 67Multidrug resistance of a porin deletion mutant of mycobacterium smegmatis. Stephan, J.,

et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy

patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 68Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy

patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85Persister studies in leprosy patients after multi-drug treatment. Gupta, U.D., et al. . . . . . . . . . (A) 100The magic bullets and tuberculosis drug targets. Zhang, Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46

Electron microscopy (see also Ultrastructure),Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) 69

Elimination,Trends in case detection influenced by leprosy elimination campaigns in certain areas of

China. Jianping, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 76Comments on WHO/AFRO’s “Post-Elimination” strategy paper: A new bottle with old wine

of the “Final Push”. Ji, Baohong . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (E) 216Elimination of the International Journal of Leprosy Scollard, David M . . . . . . . . . . . . . . . . . . . (E) 303

Epidemiology,Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii

infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) 166Factors contributing to the decline of leprosy in Spain in the second half of the twentieth

century. Alfonso, Jose L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 258

Erythema nodosum leprosum (ENL),Erythema nodosum leprosum and HIV infection: A therapeutic experience. Sharma, Nand

Lal, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 189Erythema nodosum leprosum necroticans in a child—an unusual manifestation. Pandhi,

Deepika, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 122Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous

patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) 222

Face,Anesthesia of face uncovered by histopathology. Daniel, Ebenezer and Ebenezer, Gigi . . . . . (O) 22Surface exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the

receptor-dependent phagocytosis of mycobacterial by human macrophages. Villenuve, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 57

Family,Characterization of phylogenetically distant members of the adenylyl cyclase family from

mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 68

Variable presentation of disseminated nontuberculous mycobacterial infections in a family with an interferon gamma receptor mutation. Han, J.Y., et al . . . . . . . . . . . . . . . . . . . . . . . . (A) 81


Genetics,A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy



Characterization of phylogenetically distant members of the adenylyl cyclase family from mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 68

Comparative evaluation of immunotherapeutic efficacy of BCG and Mw vaccines in patients of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) 105

Dissection of phylogenetic relationships among 19 rapidly growing mycobacterium species by 16S rRNA, hsp65, sodA, recA and rpoB gene sequencing. Adekambi, T. and Drancourt, M. . . . (A) 77


Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 57

Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85



TB tools to tell the tale—molecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 54

TB tools to tell the tale-molecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Taxonomic and phylogenetic status of non-tuberculous mycobacteria in a Carribbean setting. Ferdinand, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 80

The protective effect of the mycobacterium bovis BCG vaccine is increased by coad-ministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . (A) 70

Genital,Involvement of genitofemoral nerve with genital lesions in lepromatous leprosy. Agrawal,

S.K., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46

Granuloma(s),A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of

mycobacterium tuberculosis pulmonary infection. Izzo, A.A., et al. . . . . . . . . . . . . . . . . . . (A) 73A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy.

Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 58Granuloma necrosis during Mycobacterium avium infection does not require tumor necrosis

factor. Florido, M. and Appelberg, R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 53Mycobacterial granulomas: keys to a long lasting host-pathogen relationship. Co, D.O., et al. (A) 52Tuberculous granuloma formation is enhanced by a mycobacerium virulence determinant.

Volkman, H.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 65

Hand(s),Mycobacterium chelonae tenosynovitis of the hand. Mateo, L., et al. . . . . . . . . . . . . . . . . . . . (A) 83

Histopathology,An evaluation of clinical and histopathological status in paucibacillary leprosy patients after

completion of fixed duration therapy. Mathew, D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 50Anesthesia of face uncovered by histopathology. Daniel, Ebenezer and Ebenezer, Gigi . . . . . (O) 22Clinico-histopathological correlation of skin and nerve in leprosy. Khan, A., et al. . . . . . . . . . (A) 49Human immunodeficiency virus type 1 (HIV-1) and mycobacterium leprae co-infection:


History of leprosy,Images from the History of Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (I) 1Images from the History of Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (I) 89Images from the History of Leprosy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (I) 241


Images from the History of Leprosy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (I) 167Leprosy and mortality in the Medieval Danish village of Tirup Boldsen J.L . . . . . . . . . . . . . . . (A) 42Leprosy research declines, but most of the basic questions remain unanswered Scollard, D.M (E) 25

Human immunodeficiency virus (HIV),Borderline tuberculoid leprosy with Type 1 reactiion in an HIV patient—A phenomenon of

immune reconstitution. Narang, Tarun, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 203Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected

patients with tuberculosis after initiation of antiretroviral therapy. Breton, G., et al. . . . . . (A) 52Endosomal membrane traffic: convergence point targeted by mycobacterim tuberculosis and

HIV. Deretic, V., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 52Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii

infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) 166Erythema nodosum leprosum and HIV infection: A therapeutic experience. Sharma, Nand

Lal, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 189Human immunodeficiency virus type 1 (HIV-1) and mycobacterium leprae co-infection:


Leprosy and HIV infection (Rarely the Twain shall meet?). Nelson, Kenrad E . . . . . . . . . . . . . (C) 133Seroprevalence of HIV infection among leprosy patients in Agra, India: Trends and

perspective. Hussain, Tahziba, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 93

Immune complexes,Improved diagnosis of pulmonary tuberculosis by detection of free and immune complex-

bound anti-30 kDa antibodies. Raja, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 64

Immune responses,Fatal mycobacterium tuberculosis infection despite adaptive immune response in the absence

of MyD88. Fremond C.M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 61RNA encoding the MPT83 antigen induces protective immune responses against myco-

bacterium tuberculosis infection. Xue, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 75

Immunology,Human immunodeficiency virus type 1 (HIV-1) and mycobacterium leprae co-infection:


Immunotherapy,Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with


India,Leprosy program in India at the Crossroads. Rao, P. Narasimha . . . . . . . . . . . . . . . . . . . . . . . . (E) 211Management of 34 chronic heel sinuses in leprosy, using a modificatiion of a local rotation

flap in Kolkata, India. Joshua, J. and Sarkar, S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 49Prevalence of leprosy in Agra District (U.P.) India from 2001 to 2003. Kumar, Anil, et al. . . . (A) 115Seroprevalence of HIV infection among leprosy patients in Agra, India: Trends and


Interferon,Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai,

M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 54Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton

lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 63

The SLAM-associated protein (SAP) regulates IFN-gamma expression in leprosy. Quiroga, M.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 60

Variable presentation of disseminated nontuberculous mycobacterial infections in a family with an interferon gamma receptor mutation. Han, J.Y., et al . . . . . . . . . . . . . . . . . . . . . . . . (A) 81

Interleukin(s),IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice.

Pearl, J.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 56


INTERNATIONAL JOURNAL OF LEPROSY (IJL),Elimination of the International Journal of Leprosy Scollard, David M . . . . . . . . . . . . . . . . . . . (E) 303Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) 304Special Grantors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) 177Special Grantors and Sustaining Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) 87Special Grantors and Sustaining Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) 238Special Grantors and Sustaining Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) 305

Intestine(s),Johne’s disease, inflammatory bowel disease, and mycobacterium paratuberculosi. Chacon, O.,

et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79

Iran,Clinico-pathological study of 12 cases of patients with leprosy admitted to Sina Hospital,

Hamadan, Iran, from 1991 2000. Farshchian, M. and Kheirandish, A. . . . . . . . . . . . . . . . . (A) 47Leprosy profile in Isfahan (A province of Iran). Asilian, A., et al. . . . . . . . . . . . . . . . . . . . . . . (C) 127

Japan,2005 U.S.-Japan Meeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 297Summary of questionnaires on leprosy in Yokohama City area and university hospitals

Ishii, N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 43U.S.-Japan cooperative medical science program. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 139U.S.-Japan meeting, 2004. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 230

Kidney(s),Mycobacterium chelonae skin infection in kidney-pancreas recipient. Stelzmueller, I., et al. (A) 168

Korea,Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy


patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85

Lepromatous leprosy,Comparative evaluation of immunotherapeutic efficacy of BCG and Mw vaccines in patients

of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) 105Involvement of genitofemoral nerve with genital lesions in lepromatous leprosy. Agrawal,

S.K., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46

Lesion(s),A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy.

Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 58Involvement of genitofemoral nerve with genital lesions in lepromatous leprosy. Agrawal,

S.K., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46Reply to the Editor Kumarasinghe, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 227Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions.

Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 269

Lipid(s),Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment

in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 59High-polarity Mycobacterium avium-derived lipids interact with murine macrophage lipid

rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 73Surface exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the re-

ceptor-dependent phagocytosis of mycobacterial by human macrophages. Villenuve, C., et al. (A) 57

Lipoprotein,Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton

lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 63

Liposome,Liposome technology for drug delivery against mycobacterial infections. Khuller, G.K., et al. . . . . (A) 45

Liver,Liposome technology for drug delivery against mycobacterial infections. Khuller, G.K., et al. . . . . (A) 45


Lucio phenomenon,Clinical and histologic variations among thiry patients with Lucio’s phenomenon and pure and


Lymphocyte(s),Bystander activation of CD8+ T lymphocytes during experimental mycobacterial infection.

Gilbertson, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 73

Macrophage(s),Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages

and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . (A) 71Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival

in infected macrophages. Gutierrez, M.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 155Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on

mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) 72High-polarity Mycobacterium avium-derived lipids interact with murine macrophage lipid

rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 73Macrophages play a dual role during pulmonary tuberculosis in mice. Leemans, J.C., et al. . . (A) 63Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton


Surface exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the receptor-dependent phagocytosis of mycobacterial by human macrophages. Villenuve, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 57



Toll-like receptor 2 and mitogen and stress-activated kinase 1 are effectors of Mycobacterium avium induced cyclooxygenase 2 expression in macrophages. Pathak, S.K., et al. . . . . . . . (A) 55

Malawi,Large scale candidate gene study of tuberculosis susceptibility in the Karonga district of

northern Malawi. Fitness, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Metabolism,Hypercalcemia secondary to leprosy Couri, C.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 47Tuberculosis-metabolism and respiration in the absence of growth. Boshoff, H.I. and Barry,

C.E., III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 69

Mexico,Ulcerative cutaneous mycobacteriosis due to report of two mexican cases. Coloma, Josefa,

et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 5

Mice, murine,A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy


A mutant of mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential. Copenhaver, R.H., et al. . . . . . . . . . (A) 71

Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . . (A) 71

Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) 72


High-polarity Mycobacterium avium-derived lipids interact with murine macrophage lipid rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 73

IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. Pearl, J.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 56



Long term control of mycobacterium bovis BCG infection in the absence of Toll-like recep-tors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-deficient mice. Nicolle, D., et al. . (A) 74

Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with mycobacterium tuberculosis. Yamashiro, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 66

Macrophages play a dual role during pulmonary tuberculosis in mice. Leemans, J.C., et al. . . . . (A) 63The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial


Microscopy,Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) 69

Molecular biology (see also DNA, Genetics),Human genetics of intracellular infectious diseases: molecular and cellular immunity against


mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85Molecular pathogenesis of mycobacterial diseases. Kobayashi, K . . . . . . . . . . . . . . . . . . . . . . (A) 54Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous

patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) 222TB tools to tell the tale—molecular genetic methods for mycobacterial research. Machowski,

E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 54TB tools to tell the tale-molecular genetic methods for mycobacterial research. Machowski,

E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Monocyte(s),The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacterium


Morbidity,Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity. Debacker,

M., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79

Morphology,Alterations in neurofilament protein(s) in human leprous nerves: morphology, immuno-

histochemistry and Western immunoblot correlative study. Save, M.P., et al. . . . . . . . . . . . (A) 60

Mycobacteria (see also individual species),A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy



Amoebal coculture of mycobacterium massiliense sp. nov. from the sputum of a patient with hemoptoic pneumonia Adekambi, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 78

Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . . . (A) 71

Bystander activation of CD8+ T lymphocytes during experimental mycobacterial infection. Gilbertson, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 73

Characteristics of mycobacterial infection in patients with immunodeficiency and nuclear factor-kappaB essential modulator mutation, with or without ectodermal dysplasis. Dai, Y.S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79

Characterization of phylogenetically distant members of the adenylyl cyclase family from mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 68

Clinical latency and reactivation of AIDS-related mycobacterial infections. Shen, Y., et al . . . (A) 56Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin,


moxifloxacin, and four conventional antimycobacterial drugs against mycobacteriumkansasii. Alcaide, F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 78


Developing rapid detection of mycobacteria using microwaves. Jing, G., et al. . . . . . . . . . . . . (A) 53Effects of macrolides and ketolides on mycobacterial infections. Bermudez, L.E. and

Yamazaki, Y. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 44Fluoroquinolones as chemotherapeutics against mycobacterial infections. Jacobs, M.R . . . . . (A) 45Human genetics of intracellular infectious diseases: molecular and cellular immunity against


mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice.

Pearl, J.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 56Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with


Infections due to non tuberculous mycobacteria (NTM). Katoch, V.M . . . . . . . . . . . . . . . . . . . (A) 81Liposome technology for drug delivery against mycobacterial infections. Khuller, G.K., et al. (A) 45Lipsomes as adjuvant for anti-mycobacterial vaccine development. Verma, I., et al. . . . . . . . . (A) 75Microsphere technology for chemotherapy of mycobacterial infections. Barrow, R.R . . . . . . . (A) 44Molecular pathogenesis of mycobacterial diseases. Kobayashi, K . . . . . . . . . . . . . . . . . . . . . . (A) 54Mycobacterial granulomas: keys to a long lasting host-pathogen relationship. Co, D.O., et al. (A) 52Non tuberculous mycobacteria: patterns of isolation. A multi country retrospective survey.

Martin-Casabona, N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 83Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and

naturally acquired antimycobacterial immunity in humans. McShane, H., et al. . . . . . . . . . (A) 82Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous

patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) 222Surface exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the

receptor-dependent phagocytosis of mycobacterial by human macrophages. Villenuve, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 57



Taxonomic and phylogenetic status of non-tuberculous mycobacteria in a Carribbean setting. Ferdinand, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 80


Therapy of nontuberculous mycobacterial infections. Jogi, R. and Tyring, S.K. . . . . . . . . . . . (A) 81Variable presentation of disseminated nontuberculous mycobacterial infections in a family

with an interferon gamma receptor mutation. Han, J.Y., et al . . . . . . . . . . . . . . . . . . . . . . . . (A) 81

Mycobacterium abscessus,Mycobacterium abscessus as a cause of pacemaker infection. Kessler, A.T. and Kourtis, A.P. (A) 81

Mycobacterium avium,Granuloma necrosis during mycobacterium avium infection does not require tumor necrosis

factor. Florido, M. and Appelberg, R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 53High-polarity mycobacterium avium-derived lipids interact with murine macrophage lipid

rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 73Mycobacerium avium subsp. paratuberculosis strains isolated from Crohn’s disease patients

and animal species exhibit similar polymorphic locus patterns. Ghadiali, A.H., et al. . . . . (A) 80Toll-like receptor 2 and mitogen and stress-activated kinase 1 are effectors of mycobacterium

avium induced cyclooxygenase 2 expression in macrophages. Pathak, S.K., et al. . . . . . . . (A) 55Use of multilocus variable number tandem-repeat analysis for typing mycobacterium avium

subsp. paratuberculosis. Overduin, P., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84


Mycobacterium avium complex,Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on

mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) 72

Mycobacterium bovis (see also BCG),A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy



The protective effect of the mycobacterium bovis BCG vaccine is increased by coad-ministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 70

Mycobacterium cheloni (chelonae),Mycobacterium chelonae skin infection in kidney-pancreas recipient. Stelzmueller, I., et al. . . . (A) 168Mycobacterium chelonae tenosynovitis of the hand. Mateo, L., et al. . . . . . . . . . . . . . . . . . . . . . . (A) 83

Mycobacterium fortuitum,Successive development of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and

Sweet’s syndrome in a patient with cervical lymphadenitis caused by mycobacterium for-tuitum. Chen, H.H., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79

Mycobacterium goodii,Mycobacterium goodii infections associated with surgical implants at Colorado hospital.

Ferguson, D.D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 80

Mycobacterium kansasii,Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin,


Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) 166

Mycobacterium leprae,Characterization of phylogenetically distant members of the adenylyl cyclase family from


Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) 75

Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) 83

Detection of mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a preliminary report. Parkash, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 67

Diaminodiphenylsulfone resistance of mycobacterium leprae due to mutations in the dihydropteroate synthase gene. Kai, M . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 67


Effects of purification and fluorescent staining on viability of mycobacterium leprae. Lahiri, Ramanuj, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 194


Microsatellite mapping of mycobacterium leprae populations in infected humans. Young, S.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 68

Microsatellite mapping of mycobacterium leprae populations in infected humans. Young, S.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85

Multi drug resistant mycobacterium leprae from patients with leprosy. Maeda, S . . . . . . . . . . (A) 67Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy


patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 85


Mycobacterium paratuberculosis,Mycobacerium avium subsp. paratuberculosis strains isolated from Crohn’s disease patients

and animal species exhibit similar polymorphic locus patterns. Ghadiali, A.H., et al. . . . . (A) 80Use of multilocus variable number tandem-repeat analysis for typing mycobacterium avium

subsp. paratuberculosis. Overduin, P., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Mycobacterium smegmatis,Multidrug resistance of a porin deletion mutant of mycobacterium smegmatis. Stephan, J.,

et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46

Mycobacterium tuberculosis,16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates


A Diaryquinoline Drug Active on the ATP Synthase of mycobacterium tuberculosis. Andries, K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 44

A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 72

A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of mycobacterium tuberculosis pulmonary infection. Izzo, A.A., et al. . . . . . . . . . . . . . . . . . . (A) 73


A potentially new treatment for tuberculosis; Will a diarylquinoline work for leprosy?. Franzblau, Scott . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 32

Action of fluoroquinolones and Linezolid on logarithmic- and stationary-phase culture of mycobacterium tuberculosis. Garcia-Tapia, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 69


Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . (A) 71

Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy. Reid, S.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 43


Cell biology of mycobacterium tuberculosis phagosome. Vergne, I., et al. . . . . . . . . . . . . . . . . (A) 57Characterization of phylogenetically distant members of the adenylyl cyclase family from


Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated anti tubercular drugs at sub therapeutic dose against experimental tuberculosis. Sharma, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 45


Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after mycobacterium tuberculosis infection. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 62

Decaprenyl diphosphate synthesis in mycobacterim tuberculosis. Kaur, D., et al. . . . . . . . . . . (A) 69Detection of mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in

combination with a neural network system. Pavlou, A.K., et al. . . . . . . . . . . . . . . . . . . . . . (A) 55Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected

patients with tuberculosis after initiation of antiretroviral therapy. Breton, G., et al. . . . . . (A) 52Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on

mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) 72Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) 69Endosomal membrane traffic: convergence point targeted by mycobacterim tuberculosis and

HIV. Deretic, V., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 52Fatal mycobacterium tuberculosis infection despite adaptive immune response in the absence

of MyD88. Fremond C.M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 61Geranylgeraniol regulates negatively caspase-1 autoprocessing: implication in the TH1

response against mycobacterium tuberculosis. Montero, M.T., et al. . . . . . . . . . . . . . . . . . . (A) 70Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with



Improved diagnosis of pulmonary tuberculosis by detection of free and immune complex-bound anti-30 kDa antibodies. Raja, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 64

Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 54

Large scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi. Fitness, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Leprosy and tuberculosis in Iron Age Southeast Asia?. Tayles, N. and Buckley, H.R. . . . . . . . (A) 43Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with


Macrophages play a dual role during pulmonary tuberculosis in mice. Leemans, J.C., et al. . . . (A) 63Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium

tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) 61Mycobacerium avium subsp. paratuberculosis strains isolated from Crohn’s disease patients

and animal species exhibit similar polymorphic locus patterns. Ghadiali, A.H., et al. . . . . (A) 80Mycobacterium tuberculosis functional network analysis by global subcellular protein

profiling. Mawuenyega, K.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton

lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 63

Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT-6 in the aerosol guinea pig model. Olsen, A.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 74

RNA encoding the MPT83 antigen induces protective immune responses against mycobacterium tuberculosis infection. Xue, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 75

The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacteriumtuberculosis is associated with increased intracellular survival of bacilli. Rivera Marrero, C.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 64



The magic bullets and tuberculosis drug targets. Zhang, Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial


The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministra- tion with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 70

Tuberculosis-metabolism and respiration in the absence of growth. Boshoff, H.I. and Barry, C.E., III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 69

Use of multilocus variable number tandem-repeat analysis for typing mycobacterium aviumsubsp. paratuberculosis. Overduin, P., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Mycobacterium ulcerans,Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.

Debacker, M., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79

Nerve(s) (see also Neuritis, Neuropathy),A case of isolated tuberculoid leprosy of antebrachial medial cutaneous nerve. Martins, R.S.,

et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 49A clinical study of the involvement of cranial nerves in leprosy. Gopinath, D.V., et al. . . . . . . (A) 48Alterations in neurofilament protein(s) in human leprous nerves: morphology, immunohisto-

chemistry and Western immunoblot correlative study. Save, M.P., et al. . . . . . . . . . . . . . . . (A) 60Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a

Brazilian referral centre. Jardim, M.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 48Clinico-histopathological correlation of skin and nerve in leprosy. Khan, A., et al. . . . . . . . . . (A) 49Detection of mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in

combination with a neural network system. Pavlou, A.K., et al. . . . . . . . . . . . . . . . . . . . . . (A) 55


Involvement of genitofemoral nerve with genital lesions in lepromatous leprosy. Agrawal, S.K., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46

Neuropathy (see also Nerve(s), Neuritis),Factors contributing to the decline of leprosy in Spain in the second half of the twentieth

century. Alfonso, Jose L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 258Leprosy and neuropathy seen from the perspective of a surgeon. Duerksen, F . . . . . . . . . . . . . (A) 47Leprous neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 47Multibacillary leprosy in Tyrol Pfausler, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 51Neuropathic Pain in Leprosy Patients. Malaviya, G. N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 34Quantitative measurement of sensory impairment in referral centers Premkumar, Rama-

swamy, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 219Sensory polyneuropathy as initial manifestation of endemic leprosy in Spain. Serrano-Pozo,

A., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 52

Nose,A rational approach to nasal reconstruction in leprosy. Schwarz, R.J. and Macdonald, M. . . . (A) 51Close contacts with leprosy in newly diagnosed leprosy patients in a high and low endemic

area: Comparison between Bangladesh and Thailand. Richardus, Jan H., et al. . . . . . . . . . (O) 249Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal


secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) 83Detection of mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in

combination with a neural network system. Pavlou, A.K., et al. . . . . . . . . . . . . . . . . . . . . . (A) 55Myiasis in leprosy Malaviya, G.N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 277Workshop on Hansen’s Disease: The challenge to integrate diagnose and treatment activities

into basic care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 40

Obituaries,Diltor Vladmir Araujo Opromolla (1934-2004) Virmond, Marcos . . . . . . . . . . . . . . . . . . . . . (Ob) 137

Ofloxacin,Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin,


Persisters,Persister studies in leprosy patients after multi-drug treatment. Gupta, U.D., et al. . . . . . . . . . (A) 100

Polymerase chain reaction (PCR),Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal



Prevalence,Prevalence of leprosy in Agra District (U.P.) India from 2001 to 2003. Kumar, Anil, et al. . . . (A) 115Seroprevalence of HIV infection among leprosy patients in Agra, India: Trends and


Prophylaxis,A study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients:

design, methodology and recruitment findings of COLEP. Moel, F.J., et al. . . . . . . . . . . . . (A) 149

Protein(s),A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of

mycobacterium tuberculosis pulmonary infection. Izzo, A.A., et al. . . . . . . . . . . . . . . . . . . (A) 73Alterations in neurofilament protein(s) in human leprous nerves: morphology,

immunohistochemistry and Western immunoblot correlative study. Save, M.P., et al. . . . . (A) 60Detection of mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a

preliminary report. Parkash, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 67Leprosy Susceptibility—A matter of protein degradation? The role of proteasomes in infec-

tion and disease. Steinhoff, Ulrich and Visekruna, Alexande . . . . . . . . . . . . . . . . . . . . . . . . (C) 131


Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling. Mawuenyega, K.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macro-phages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 63

Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) 222

The SLAM-associated protein (SAP) regulates IFN-gamma expression in leprosy. Quiroga, M.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 60


Purification,Effects of purification and fluorescent staining on viability of mycobacterium leprae. Lahiri,

Ramanuj, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 194

Reaction, leprosy,Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal


secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) 83Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients

with reversal reactions. Faber, W.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 58Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous

patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) 222Some considerations on the origin of Type 1 reactions in leprosy. Opromolla, D.V.A . . . . . . . (C) 33Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions.

Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 269The role of mycophenolate mofetil in the treatment of leprosy reactions. Burdick, Anne E.

and Ramirez, Claudia C. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 129

Rehabilitation,International Course on rehabilitation and prevention of disability (RPOD) and course in

community based rehabilitation (CBR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 39Reconstructive surgery & rehabilitation in leprosy and other neuropathies. Anderson, George A (B) 36Reconstructive surgery & rehabilitation in leprosy and other neuropathies. Mathews, Ronnie . (B) 37

Relapse(s),Relapses after multibacillary leprosy treatment. Rodriguez, G., et al. . . . . . . . . . . . . . . . . . . . (A) 51

Review,Estimating the economic value to societies of the impact of health research: a critical review.

Buxton, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 76Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai,

M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 54Leprosy research declines, but most of the basic questions remain unanswered.Scollard, D.M (E) 25Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) 304

Rifampin,Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium

tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) 61

Serum,Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients

with reversal reactions. Faber, W.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 58

Skin,A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy.

Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 58Clinico-histopathological correlation of skin and nerve in leprosy. Khan, A., et al. . . . . . . . . . (A) 49Electrochemical antigen-retrieval of formaldehyde fixed and paraffin-embedded archived

leprosy skin biopsies. Sergio, N.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 60


Mycobacterium chelonae skin infection in kidney-pancreas recipient. Stelzmueller, I., et al. . (A) 168Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions.

Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 269

Social,Summary of questionnaires on leprosy in Yokohama City area and university hospitals

Ishii, N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 43

Social aspects,Summary of questionnaires on leprosy in Yokohama City area and university hospitals

Ishii, N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 43

South America,Workshop on Hansen’s Disease: The challenge to integrate diagnose and treatment activities

into basic care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 40

Southeast Asia,Leprosy and tuberculosis in Iron Age Southeast Asia?. Tayles, N. and Buckley, H.R. . . . . . . . (A) 43

Spain,Factors contributing to the decline of leprosy in Spain in the second half of the twentieth

century. Alfonso, Jose L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 258Sensory polyneuropathy as initial manifestation of endemic leprosy in Spain. Serrano-Pozo,

A., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 52

Stain(s),Effects of purification and fluorescent staining on viability of mycobacterium leprae. Lahiri,

Ramanuj, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 194

Sulfone(s),Diaminodiphenylsulfone resistance of mycobacterium leprae due to mutations in the

dihydropteroate synthase gene. Kai, M . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 67

Surgery,A Delphi Consensus on criteria for contraindications, assessment indicators and expected

outcomes related to tibialis posterior transfer surgery. Cross, Hugh . . . . . . . . . . . . . . . . . . . (O) 13Reconstructive surgery & rehabilitation in leprosy and other neuropathies. Anderson, George A (B) 36Reconstructive surgery & rehabilitation in leprosy and other neuropathies. Mathews, Ronnie . (B) 37

Synovitis,Mycobacterium chelonae tenosynovitis of the hand. Mateo, L., et al. . . . . . . . . . . . . . . . . . . . (A) 83

Thailand,Close contacts with leprosy in newly diagnosed leprosy patients in a high and low endemic

area: Comparison between Bangladesh and Thailand. Richardus, Jan H., et al. . . . . . . . . . (O) 249

Therapy (see also Chemotherapy and Multidrug therapy),16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates


An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of fixed duration therapy. Mathew, D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 50


Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Breton, G., et al. . . . . . (A) 52


Microsphere technology for chemotherapy of mycobacterial infections. Barrow, R.R . . . . . . . (A) 44Therapy of nontuberculous mycobacterial infections. Jogi, R. and Tyring, S.K. . . . . . . . . . . . (A) 81

Toll-like receptors,Long term control of mycobacterium bovis BCG infection in the absence of Toll-like recep-

tors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-deficient mice. Nicolle, D., et al. . . . (A) 74


Training,ALERT Training Courses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 40

Transmission,A study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients:


Treatment,A potentially new treatment for tuberculosis; Will a diarylquinoline work for leprosy?.

Franzblau, Scott . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 32Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with


Paucibacillary treatment for large tuberculoid lesiions of leprosy. Santos, Monica Nunes Souza, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 225

Persister studies in leprosy patients after multi-drug treatment. Gupta, U.D., et al. . . . . . . . . . (A) 100Relapses after multibacillary leprosy treatment. Rodriguez, G., et al. . . . . . . . . . . . . . . . . . . . (A) 51Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions.

Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 269The role of mycophenolate mofetil in the treatment of leprosy reactions. Burdick, Anne E.

and Ramirez, Claudia C. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 129Workshop on Hansen’s Disease: The challenge to integrate diagnose and treatment activities

into basic care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) 40

Trial(s),A study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients:


Tuberculoid leprosy,A case of isolated tuberculoid leprosy of antebrachial medial cutaneous nerve. Martins, R.S.,

et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 49Borderline tuberculoid leprosy with Type 1 reactiion in an HIV patient—A phenomenon of

immune reconstitution. Narang, Tarun, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 203

Tuberculosis,16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates


A Diaryquinoline Drug Active on the ATP Synthase of mycobacterium tuberculosis. Andries, K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 44

A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 72

A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of mycobacterium tuberculosis pulmonary infection. Izzo, A.A., et al. . . . . . . . . . . . . . . . . . . (A) 73


A potentially new treatment for tuberculosis; Will a diarylquinoline work for leprosy?. Franzblau, Scott . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 32

Action of fluoroquinolones and Linezolid on logarithmic- and stationary-phase culture of mycobacterium tuberculosis. Garcia-Tapia, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 69


Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . . . (A) 71



Cell biology of mycobacterium tuberculosis phagosome. Vergne, I., et al. . . . . . . . . . . . . . . . . (A) 57Characterization of phylogenetically distant members of the adenylyl cyclase family from



Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub therapeutic dose against experimental tuberculosis. Sharma, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 45


Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after mycobacterium tuberculosis infection. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 62

Decaprenyl diphosphate synthesis in mycobacterim tuberculosis. Kaur, D., et al. . . . . . . . . . . (A) 69Detection of mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in

combination with a neural network system. Pavlou, A.K., et al. . . . . . . . . . . . . . . . . . . . . . (A) 55Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected

patients with tuberculosis after initiation of antiretroviral therapy. Breton, G., et al. . . . . . (A) 52Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on

mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) 72Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) 69Endosomal membrane traffic: convergence point targeted by mycobacterim tuberculosis and

HIV. Deretic, V., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 52Fatal mycobacterium tuberculosis infection despite adaptive immune response in the absence

of MyD88. Fremond C.M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 61Geranylgeraniol regulates negatively caspase-1 autoprocessing: implication in the TH1

response against mycobacterium tuberculosis. Montero, M.T., et al. . . . . . . . . . . . . . . . . . . (A) 70Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with


Improved diagnosis of pulmonary tuberculosis by detection of free and immune complex-bound anti-30 kDa antibodies. Raja, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 64

Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 54

Large scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi. Fitness, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Leprosy and tuberculosis in Iron Age Southeast Asia?. Tayles, N. and Buckley, H.R. . . . . . . . (A) 43Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with


Macrophages play a dual role during pulmonary tuberculosis in mice. Leemans, J.C., et al. . . . . (A) 63Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium

tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) 61Mycobacerium avium subsp. paratuberculosis strains isolated from Crohn’s disease patients

and animal species exhibit similar polymorphic locus patterns. Ghadiali, A.H., et al. . . . . (A) 80Mycobacterium tuberculosis functional network analysis by global subcellular protein

profiling. Mawuenyega, K.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton


Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT-6 in the aerosol guinea pig model. Olsen, A.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 74

RNA encoding the MPT83 antigen induces protective immune responses against mycobacterium tuberculosis infection. Xue, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 75



The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacteriumtuberculosis is associated with increased intracellular survival of bacilli. Rivera Marrero, C.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 64



The magic bullets and tuberculosis drug targets. Zhang, Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 46




Tuberculosis-metabolism and respiration in the absence of growth. Boshoff, H.I. and Barry, C.E., III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 69

Use of multilocus variable number tandem-repeat analysis for typing mycobacterium aviumsubsp. paratuberculosis. Overduin, P., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 84

Ulcer(s),Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.

Debacker, M., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79Myiasis in leprosy Malaviya, G.N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 277Ulcerative cutaneous mycobacteriosis due to report of two mexican cases. Coloma, Josefa,

et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) 5

Urine,Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages

and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . . . (A) 71Detection of mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a

preliminary report. Parkash, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 67High-polarity mycobacterium avium-derived lipids interact with murine macrophage lipid

rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 73

Vaccine(s), Vaccination,A mutant of mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is

attenuated in mice but retains vaccinogenic potential. Copenhaver, R.H., et al. . . . . . . . . . (A) 71Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary

tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) 57Comparative evaluation of immunotherapeutic efficacy of BCG and Mw vaccines in patients

of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) 105Lipsomes as adjuvant for anti-mycobacterial vaccine development. Verma, I., et al. . . . . . . . . (A) 75Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT-

6 in the aerosol guinea pig model. Olsen, A.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 74Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and

naturally acquired antimycobacterial immunity in humans. McShane, H., et al. . . . . . . . . . (A) 82The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministra-

tion with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 70

Vasculitis,Successive development of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and

Sweet’s syndrome in a patient with cervical lymphadenitis caused by mycobacterium fortuitum. Chen, H.H., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 79

World Health Organization (WHO),A need for clarification of the classification criteria for leprosy patients Oskam, L. and

Buhrer-Sekula, S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 280Comments on WHO/AFRO’s “Post-Elimination” strategy paper: A new bottle with old wine

of the “Final Push”. Ji, Baohong . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (E) 216Dr. Gelber and Colleagues Reply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) 281Has the Term “Elimination” outlived its utility? Ganapati, R. and Pai, V.V. . . . . . . . . . . . . . . . (C) 229Measuring impairment caused by leprosy: inter-tester reliability of the WHO disability

grading system. Nienhuis, W.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) 50


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