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INTERNATIONAL JOURNAL OF LEPROSY^ Volume 68, Number 3
Printed in the U.S.A.(ISSN 0148-916X)
INTERNATIONALJOURNAL OF LEPROSY
and Other Mycobacterial Diseases
VOLUME 68, NUMBER 3^ SEPTEMBER 2000
Single Lesion Paucibacillary Leprosy: Baseline Profile ofthe Brazilian Multicenter Cohort Study'
Celina M. T. Martelli, Mariane M. A. Stefani, Maria Katia Gomes,Paula F. B. Rebello, Silmara Peninni, Kasue Narahashi, Ana Lucia O. Maroclo,
Mauricio B. Costa, Simonne A. Silva, Sylvana C. Sacchetim,Jose Augusto C. Nery, Ana Maria Salles, Thomas P. Gillis,
James L. Krahenbuhl, and Ana Lucia S. S. Andrade 2
In the context of leprosy elimination,there has been an increased effort to detectand treat leprosy as early as possible withshort drug regimens. Single skin lesion pau-
' Received for publication on 4 April 2000. Acceptedfor publication in revised forro on I August 2000.
'C. M. T. Martelli, M.D., Ph.D.; M. M. A. Stefani,Ph.D.; A. L. O. Maroclo, M.D.; M. B. Costa, M.D.,Ms.C.; S. A. Silva, M.D., Ms.C.; S. C. Sacchetim,M.D.; A. L. S. S. Andrade, M.D., Ph.D., Federal Uni-versity of Goias, Goiania, Goias, Brazil. M. K. Gomes,M.D., Ms.C., Federal University of Rio de Janeiro,Hospital Clementino Fraga Filho, Rio de Janeiro, Riode Janeiro, Brazil. P. F. B. Rebello, M.D.; S. Peninni,M.D., Alfredo da Matta Foundation - WHO LeprosyReference Center, Amazon, Brazil. K. Narahashi,M.D., Secretariat of Health, Porto Velho, Rondonia,Brazil. J. A. C. Nery, M.D., Ph.D.; A. M. Salles, M.D.,Ms.C., Reference Leprosy Laboratory, Oswaldo CruzFoundation, Rio de Janeiro, Rio de Janeiro, Brazil. T.P. Gillis, Ph.D.; J. L. Krahenbuhl, Ph.D., LaboratoryResearch Branch, GWL Hansen's Disease Center atLouisiana State University, P.O. Box 25072, BatonRouge, LA 70894, U.S.A.
Reprint requests to Dr. Celina M. T. Martelli, Uni-versidade Federal de Goias, Instituto de PatologiaTropical e Saude Publica, Rua Delenda Rezende deMello, S/N, Setor Universitario, Goiania/GO, Brazil74605-050 or FAX 55-62-202-3066;email: [email protected]
cibacillary leprosy (SSL-PB) may be con-sidered an early chronic stage of the dis-ease, with reported high prevalence in India(s e.26) In Brazil, only recently has the offi-cial notification system distinguished lep-rosy patients with monolesion within thepaucibacillary (PB) group (Ministerio daSaude Brasil. Alterações nas instruções nor-mativas do Plano Nacional de Eliminaçãoda Hanseníase. Ofício Circular No. 67,CNDS/CENEPI, 1998). Therefore, epi-demiological information regarding patientcharacteristics is limited to one outpatientclinic in the Southeast Brazilian region ( 2).Since 1998, the World Health Organization(WHO) has recommended a single-doseROM therapeutic regimen consisting of ri-fampin (600 mg), ofloxacin (400 mg) andminocycline (100 mg) based on a multicen-ter, double-blind field trial conductedamong SSL-PB patients in India. In thisstudy, similar cure rates were observed forthe ROM regimen when compared to thestandard 6-month WHO multidrug therapy(WHO/MDT) (23).
So far the scientific evidence from theavailable publications on single-dose ROM
247
248^International Joumal of Leprosy^ 2000
efficacy has raised many polemic issuesconcerning both the clinical outcome inlong-term follow up and the immune profileamong SSL-PB patients (10. "). Althoughthere is a lack of in-depth investigationsabout the immune status of this category ofpatients, a minimal therapy schedule hasbeen recommended under the assumptionthat this group has low bacterial load, pre-served cell-mediated immunity and highspontaneous cure rates. However, it hasbeen argued that single lesion leprosy pa-tients may not comprise a homogeneousgroup regarding immunological and clinicaiparameters, and these differences may dis-tinctly influence the clinicai prognosiswithin this category ( R16).
Recently, the Pan-American Health Or-ganization and the Brazilian Ministry ofHealth sponsored a multicentric study toimplement the ROM therapy for single le-sion PB leprosy patients in selected arcas ofBrazil. This represented a unique opportu-nity to assess the comparability of an SSL-PB cohort recruited in Reference Centerslocated in different endemic settings.
In this paper we describe the baselineclinicai features of patients enrolled in theBrazilian monolesion leprosy cohort study.The predictive value of the clinicai screen-ing to diagnose single lesion leprosy andthe immunological background of this par-ticular group of patients treated with theone-dose ROM therapy are also presented.
MATERIALS AND METHODSThis study was preceded by the National
Dermatologic Campaign launched by theBrazilian Ministry of Health in October1997 which invoived radio, newspaper andtelevision publicity. Announcements wereplaced in public health centers and in physi-cians' offices in order to optimize popula-tion-based screening for the detection ofearly leprosy. Before the nationwide imple-mentation of single-dose ROM therapy inthe routine attendance of the Leprosy Con-trol Program, we started a standardized sur-veillance in outpatient clinics for recruitingmonolesion PB leprosy patients in three en-demic Brazilian regions.
Selection of centersThe requirements for the selection of the
sites were to have: a local leprosy control
program with expertise in implementingWHO/MDT regimens; an adequatelytrained staff for clinicai exams, reading skinsmears and case management; the capabil-ity to recruit around 50 monolesion leprosypatients within 12 months; a reasonablyequipped base hospital in the arca for pa-tient admission in case of severe side ef-fects or reactions that might occur.
SSL-PB patients were recruited fromhealth centers from four Brazilian states lo-cated in the following regions (Fig. 1): a)North = "Fundação Alfredo da Matta," aWHO Leprosy Reference Center located inthe city of Manaus (1,280,000 inhabitants),Amazon state, and in two health centers inthe municipalities of Porto Velho andAriquemes (300,000 and 70,000 inhabi-tants, respectively), Rondônia state. b)Southeast = "Fundação Oswaldo Cruz," aNational Leprosy Reference Center andoutpatient clinic of the University HospitalClementino Fraga Filho in the city of Riode Janeiro (5,730,000 inhabitants), Rio deJaneiro state. c) Center-West = Regionalreference leprosy outpatient clinic locatedin the city of Goiânia (1,000,000 inhabi-tants), Goiás state.
Ascertainment of casesSSL-PB cases were defined taking into
account clinicai assessment, bacilloscopyand histopathoiogy. Patients were clinicallyscreened by well-trained doctors in the par-ticipating health care centers. Potential eli-gible cases were newly detected, untreatedmonolesion leprosy with a skin lesion char-acterized by hypopigmentation or erythemaor both, with or without infiltration, definitesensory loss without thickened nerve in-volvement. All monolesion cases suspectedof leprosy had a skin smear and a skinbiopsy for bacilloscopy and conventionalhistopathologic exams. Patients were cate-gorized as paucibacillary (PB) if they had anegative bacterial index (BI) on slit-skinsmear and if the biopsy was classified as in-determinate (I), tuberculoid (TT) or border-line tuberculoid (BT) according to Ridieyand Jopling criteria (17).
Criteria for exclusion from the studywere: patients with histopathological read-ings consistent with multibacillary (MB)types of leprosy or with evidence of otherskin diseases; children younger than 7 years
68, 3^Martelli, et al.: Single Lesion PB-Cohort Baseline^249
FI6. I. Brazilian Single-lesion leprosy cohort study cites.
of age; individuais with sensory loss with-out a visible skin lesion; pregnant womenor those breast feeding at the time of drugintake; known HIV seropositive test;chronic diseases (liver dysfunction, dia-betes), or an allergy that might interferewith any of the proposed drugs. The multi-center study design is presented in Figure 2.
Baseline data collectionClinicai features. At the time of enroll-
ment a questionnaire was used to obtain in-formation on age, sex, height, weight, timeof lesion perception and intra-domiciliarycontacts of leprosy cases. A clinicai exami-nation was performed including the numberand size of lesion measured by the larger di-ameter and characteristics of the skin lesion;nerve enlargement; and the presence of aBCG scar. To assess neurological sensoryloss on the lesion (anesthesia), thermal, painsensation and standard monofilament de-
vices were used for ali patients. Motor func-tion was also tested to grade disability.
The Mitsuda test was performed by intra-dermally injecting 0.1 ml of lepromin (samebatch, produced in Brazil, 1997) on the volarsurface of the forearm. The largest transversediameter of palpable induration was mea-sured 4 weeks )ater. A positive Mitsuda testwas defined as having an induration of >_5mm as assessed by the clinicai staff.
Laboratory tests. A slit-skin smear, skinbiopsy and blood samples were taken be-fore ROM therapy. Smears were collectedfrom earlobes, elbows, and the skin lesion,and the BI was determined in each of theparticipating centers. Skin biopsies werecollected, fixed in 10% buffered formalin,and processed for paraffin sections (5 gm).The sections were stained with hematoxylinand eosin (H&E) and Fite-Faraco for acid-fast bacilli (AFB). The histopathological di-agnosis of leprosy was based on Ridley and
Outpatientrecruitment
25 exclusions12 not leprosy7 MB leprosy6 biopsies not available
Clinicai screeningSingle lesion leprosy patients
299 smear negative patients
284 Histopathological exams
15 exclusions8 refusals3 neural involvement2 pregnancy/breastfeeding1 diabetes1 liver dysfunction
ROM intervention259 SLPB patients enrolled
Mitsuda test Blood collectionIgM anti-PGL 1
250^International Journal of Leprosy^2000
FIG. 2. Multicenter study profile.
Jopling criteria ("). All exams were cen-trally read by one experienced pathologistat the Federal University of Goiás in Cen-tral Brazil. (Details of histopathologicalfindings are out of the scope of this paper.)
Blood samples were collected and serumsamples were sent to the Immunology Lab-oratory of the Federal University of Goiás(UFG), stored at —20°C and tested at once.IgM antibodies specific to Mycobacteriumleprae phenolic glycolipid-I (PGL-I) wereassayed by ELISA, using PGL-I syntheticdisaccharide provided by Dr. M. J. Colston(IMMLEP, London). The laboratory staffwere kept blind from the previous clinical,bacteriological and histopathological as-sessments. The cut-off point for positivitywas 0.2 optical density (OD) as describedpreviously (24) . Biochemical tests (he-mogram, AST, ALT, blood sugar and apregnancy test) were performed for ROMexclusion criteria purposes.
All eligible patients were treated with thesingle-dose ROM regímen (25). Children re-ceived a half dose according the BrazilianMinistry of Health recommendation. Sideeffects were actively investigated after drugadministration or recorded by passive re-porting during the first month of follow up.
Data analysisThe data were entered and analyzed cen-
trally at the Coordinator Center in Goiânia,Central Brazil, where a master file with acopy of ali protocols was archived. Thebaseline characteristics of each participat-ing center were polled by the state of re-cruitment. The body mass index (BMI) wascalculated as weight in kilograms dividedby the square of the height in meters forparticipants older than 13 years of age (22).The differences in the distribution of thevariables were tested by the ANOVA or thechi-squared test to compare continuous or
68, 3^Martelli, et al.: Single Lesion PB-Cohort Baseline^251
TABLE 1. Baseline characteristics of single-lesion paucibacillary leprosy patients enrolled ateach of the study sites.
North Southeast Center-West
Variables Amazonas^Rondônia(N = 75)^(N = 45)
Rio de Janeiro(N = 80)
Goiás(N = 59)
Total(N = 259)
Age (yrs.)Mean (S.D.) 27.8 (14.1)^29.4 (13.2) 38.6 (18.0) 32.0 (15.2) 32.4 (16.0)Median (range) 23.0 (7-66)^29.0 (10-64) 39.5 (7-84) 32.0 (7-62) 31.0 (7-84)
Females (%) 40 (53.3)^23 (51.1) 59^(73.8) 38^(64.4) 160 (61.8)Schooling
Illiterate (%) 2 (2.7)^7 (15.6) 5^(6.3) 12^(20.3) 26 (10.0)<8 years (%) 73 (97.3)^38 (84.4) 75^(93.7) 47^(79.7) 233 (90.0)
Household contact (%) 14 (18.7)^16 (35.6) 24^(27.9) 32^(54.2) 86 (33.2)Lesion perception (yrs.)
<1 45 (60.0)^34 (75.6) 48^(60.8) 46^(78.0) 173 (67.1)1-5 25 (33.3)^9 (20.0) 23^(29.1) 12^(20.3) 69 (26.7)>5 5 (6.7)^2 (4.4) 8^(10.1) 1^(1.7) 16 (6.2)
BCG vaccinationa (%) 47 (62.7)^19 (42.2) 24^(30.0) 26^(44.1) 116 (44.8)BMP mean (S.D.) 22.9 (4.8)^22.3 (4.1) 24.4^(5.0) 23.2^(4.5) 21.2 (8.0)
One missing.'For adult population.
categorical variables, respectively. TheSPSS/PC program was used for descriptiveand exploratory data analysis.
Written informed consent was obtainedfrom ali participants, according to the ap-proved protocol in each of the institutions,by the National Human Research EthicalCommittee (CONEP) and by the LeprosyControl Program at the national levei.
RESULTSFigure 2 summarizes the screening pro-
cedures for selecting the participants fromthe Brazilian recruitment centers betweenDecember 1997 and December 1998.Among patients clinically screened to de-tect SSL-PB, 299 patients had negative skinsmears. Fifteen patients were excluded onclinical/laboratory criteria, and the remain-ing 284 had skin biopsies taken. Addition-ally, 25 cases (8.8%) were excluded be-cause either the histopathological resultswere not consistent with PB leprosy or be-cause a skin biopsy was not available. Lep-rosy was classified as TT (33.6%), BT(33.6%) and 1(29.7%) according to Ridleyand Jopling clinico-pathological criteria(17), and 3.1% of the patients were consid-ered to have leprosy by clinical criteriaonly. Taking histopathology as the goldstandard, 12 biopsies were diagnosed asother skin diseases and 7 were consideredMB cases, yielding a total of 19 false-posi-
tive SSL-PB. Therefore, the positive pre-dictive value of the clinical screening was93.2% (259/278).
As shown in Table 1, 259 (86.6%) SSL-PB patients fultilled the eligibility criteriafor ROM intervention. Patients recruitedia the North region accounted for the ma-jority of participants (46.3%), followed bythe Southeast (30.9%) and Central-West(22.8%) regions. There was a preponder-ance of adults, mean age 32.4 (S.D. = 16.0),and patients from the city of Rio de Janeirowere older than patients assembled in theother regions (F3258) = 7.0; p <0.001). Therewas a 1: I male/female ratio ia the North re-gion, but in the other regions females repre-sented 66.5% of the adult population and38.6% of patients younger than 15 years ofage. The presence of a BCG scar variedfrom 30.0% to 62.7% among patients fromdifferent sites. Overall, 33.2% of the partic-ipants had knowledge of a previous leprosycase in the household; 67.1% of the partici-pants reported that the lesion had been per-ceived within a time span of less than 1year. BMI values were within the normalrange for patients older than 13 years, andthere was no statistically significant differ-ence among regions.
Analysis of the dermatological featuresshowed marked similarity among the sites.Children (<15 years) had smaller lesion sizethan adults, 3.7 cm (95%CI 3.0-4.5) versus
252^ International Journal of Leprosy^ 2000
TABLE 2. Clinical features of single-lesionpaucibacillary leprosy patients by age group.a
Variables515 years >15 years
No. % No. %
Females 17 38.6 143 66.5Lesion size (cm)
<3 19 43.2 57 26.63- <5 14 31.8 79 36.7>>5 11 25.0 79 36.7
Lesion descriptionMacular 23 52.3 118 54.9Plaque 20 45.4 96 44.7Nodular 1 2.3
Body areaFace 7 15.9 20 9.3Trunk 8 18.1 18 8.3Limbs 29 66.0 177 82.4
BCG scar 33 76.7 83 42.3
Percentages based on nonmissing data.
5.1 cm (95%CI 4.6-5.6), yielding a statisti-cally significant difference. Independent ofthe age group, most skin lesions were de-scribed as a macular hypochromic or ery-
thematous lesion (47.9%) and only onechild presented with a nodule on the face.Most of the skin lesions were detected onthe limbs of children and adults (Table 2). ABCG scar was detected in 76.7% of thechildren and in 42.3% of adults (x2 = 19.5;p <0.001). All patients were considered tohave at least moderate sensory loss on thelesion by monofilament evaluation, and nograde of disability was detected.
Figures 3 and 4 show box-plot distribu-tions of the Mitsuda readings and the anti-PGL-I serology, respectively. Similar pat-terns were obtained among patients fromdifferent geographical regions: 75.0% ofthe patients were Mitsuda positive (5mm); in 67 patients (24.9%) the indurationwas smaller than the arbitrary "positive-neg-ative" cut-off Mitsuda response at 5 mm.The prevailing values of anti-PGL-I serol-ogy were negative, below the cut-off point(OD of 0.2), among participante from all re-gions. Only 17.3% of the patients were con-
20 -̂
O
15• O O
O
10•
N = 73Amazonas
G 42
Rondônia80^55
Rio de Janeiro^GoiásFIG. 3. Box-plot distribution of Mitsuda skin readings among single-lesion paucibacillary leprosy patients
enrolled at each of the study sites. Boxes = 25th and 75th percentiles with a median bar between. O and * = out-liers and extreme values of the distribution. Dashed fine = cut-off value.
•59
Goiás
•40
Rondônia74
Rio de JaneiroN= 67
Amazonas
68, 3^Martelli, et al.: Single Lesion PB-Cohort Baseline
1,4 ^
1,2 .
1,0
0,8
0,6
0,4
0,2
0,0 •
253
FIG. 4. Box-plot distribution of anti-PGL-I antibodies (OD) among single-lesion paucibacillary leprosy pa-tients enrolled at each of the study sites. Boxes = 25th and 75th percentiles with a median bar between. O and *= outliers and extreme values of the distribution. Dashed line = cut-off value.
sidered positive for anti-PGL-I antibodiescompatible with the low bacillary load of PBpatients; 61.0% (142/233) of SSL-PB pa-tients had a simultaneously positive Mitsudareading and negative anti-PGL-I serology.
The ROM regimen was well toleratedamong adults and children. Slight adverseside effects, mainly gastrointestinal symp-toms such as nausea, stomach ache, and di-arrhea, were reported for approximately15% of the patients shortly after drug in-take. No patient required specific medicalattendance for these symptoms.
DISCUSSIONOnly recently has single skin lesion been
distinguished as a subtype of leprosy in theBrazilian National Control Program follow-ing the classitication proposed by WHOtaking into account the number of lesions(" and Ministerio da saude Brasil. Alter-ações nas instruções normativas do Plano
Nacional de Eliminação da Hanseníase.Ofício Circular No. 67, CNDS/CENEPI,1998). The baseline characteristics of theSSL-PB patients enrolled in this BrazilianROM multicentric study provide a uniqueand comprehensive picture of the clinicaiand immunological profile of monolesionleprosy patients in different epidemiologi-cal settings. Patients recruited from the dif-ferent sites had similar features, however,with a common pattern of variability con-cerning dermatological aspects, size and lo-cation of the lesion. Regardless of the en-demicity of the recruitment site, patientswere mainly adults, a different situationfrom other studies in which the majority ofsingle-lesion leprosy cases were reportedamong children (").
In our multicentric study, the majority ofpatients with monolesion were indeed pau-cibacillary with no grade of disability, sug-gesting early leprosy detection. However,
254^ International Journal of Leprosy^ 2000
among 299 clinically suspected SSL-PBleprosy patients screened, seven MB (2.4%)monolesion cases were detected, in concor-dance with some case reports of multibacil-lary monolesion (9' 28). A wide variation ofdermatological features was observedwithin SSL-PB patients, but lesions smallerthan 5 cm predominated among childrenand adults and the limbs were the prevailingaffected body areas. It has been suggestedby other authors that the monolesion canmainly be distributed on body regions ex-posed to trauma, suggesting the cutaneoussurface as a possible portal of entry (8).
However, it is outside the scope of thisstudy to make any assumption about thepossible transmission routes in leprosy.
Several methodological issues have beenraised about previously published single-le-sion studies. The main concern refers tocase ascertainment and the lack of speci-ficity of an early leprosy diagnosis basedsolely on clinicai evaluation (11.16). Takinginto account the lack of an independentgold standard for the diagnosis of the pau-cibacillary type of leprosy, clinicai exami-nation and conventional histopathology stillremain the standard for diagnosis in theearly chronic stage of the disease for re-search purposes (181 21). In our study, clini-cal, smear-bacilloscopy data and histo-pathology results were combined in an at-tempt to improve the specificity of themonolesion leprosy diagnosis.
It is well known that in many settingsaround the world, including Brazil, clini-cians will not have histopathology supportfor leprosy diagnosis. Considering the case-management expertise of our recruitmentsites, there was a high positive predictivevalue of the clinicai evaluation (around90%). Only 19 (12 not leprosy and 7 MBcases) out of 278 patients were excludedwhen histopathology was taken as the goldstandard for early leprosy diagnosis. Thisrepresents less than 3% of multibacillaryforms among monolesion patients diag-nosed using clinicai and bacilloscopic ente-ria in the three endemic Brazilian regionsstudied. Our observations indicated that inBrazil case ascertainment of SSL-PB can beaccurately defined under a routine controlprogram based upon clinicai examinationand bacilloscopy of skin smears. However,we should keep in mind the difficulties of
assessing false-negative or -positive resultswhen only clinically suspected leprosy issubmitted to skin biopsy, leading to a possi-ble verification bias (19). Refined molecularbiology tools, such as the detection of M.leprae DNA by polymerase chain reaction,may contribute to improve the specificity ofearly leprosy diagnosis (4.7. 20), but this stillremains to be validated under the field con-ditions of a control program.
Single lesion paucibacillary leprosy hasbeen considered the earliest clinicai mani-festation of the disease that may undergoself-healing or progress to any form of thedisease spectrum, eventually evolving tonerve damage (12). It has been widely ac-cepted that the local cellular immunity dic-tates the outcome of leprosy, with the Th lCD4+ lymphocyte as the pivotal cell forprotection or pathogenesis (13. 27). This is awell-established model for the chronicstage of the disease; however, the useful-ness of these markers for prognosis in theearly chronic stage of leprosy remains to bedemonstrated. Up to now, the Mitsuda testhas been one of the most used field tools toassess cellular immunity in leprosy pa-tients, particularly useful in the early stageof disease. In general, our SSL-PB patientshad a strong positive response to leprominwith a strikingly similar profile among therecruitment sites, suggesting intact cell-me-diated immunity and, therefore, favorableclinicai prognosis. Since it is widely ac-cepted that PGL-I positivity refiects bacil-lary load (18. 24) the predominance ofseronegative patients is compatible withlow bacillary load. Taking the Mitsuda andanti-PGL-I results together, it seems rea-sonable to envision a favorable outcome formost of the single-lesion participants of thiscohort. Only an extended clinicai follow upin progress, incorporating additional molec-ular markers, may provide insights aboutthe importance of the immune profile in thedisease prognosis among these early lesionpatients.
SUMMARYIn Brazil, there is little information about
the clinicai and epidemiological character-istics of paucibacillary, single skin lesionleprosy patients (SSL-PB). Only recentlyhas the official notification system distin-guished leprosy patients with a single lesion
68, 3^Martelli, et al.: Single Lesion PB-Cohort Baseline^255
as a clinicai entity, for whom the single-dose ROM (rifampin, ofloxacin and mino-cycline) regimen has been recommended.
In this paper, we describe the baselineclinicai features and the immunologicalbackground of a multicenter cohort of SSL-PB leprosy cases enrolled between Decem-ber 1997-1998. Patients were recruited athealth centers located in the following re-gions: Southeast = Rio de Janeiro; North =Amazon and Rondônia states and Center-West = Goiás state. Eligible cases werenewly detected, untreated single-lesion lep-rosy patients without thickened nerve in-volvement, and were assessed by clinicai,bacilloscopic and histopathological exams.The Mitsuda skin test and anti-PGL-I serol-ogy (ELISA) were also performed. Of the299 SSL-PB leprosy patients, 259 (86.6%)fulfilled the criteria for single-dose ROMintervention. Our results showed that pa-tients recruited from different sites had sim-ilar features, considering the clinicai andimmunological profiles. There was a pre-dominance of adults (mean age 32.4; S.D. =16.0), and a BCG scar was detected in76.7% of the children (515 years old). Only7 cases were diagnosed as the multibacil-lary type, representing less than 3% of thepatients being misclassified. Our data indi-cate that in Brazil SSL-PB case ascertain-ment based on clinicai and bacilloscopiccriteria can be accurately defined under aroutine control program; 75.0% of SSL-PBcases were Mitsuda positive (5 mm) andseropositivity for anti-PGL-I was detectedin 17.3% of the patients. These data arecompatible with effective cell-mediated im-munity and low bacillary load, suggestingfavorable clinicai outcomes for most SSL-PB participants of this cohort.
RESUMENEn Brasil hay poca información sobre las carac-
terísticas clínicas y epidemiológicas de los pacientespaucibacilares con una sola lesión dérmica (SSL-PB).Sólo recientemente el sistema de notificación oficial hareconocido a los pacientes con lepra con lesiones úni-cas, como una entidad clínica definida para la cual seha recomendado el tratamiento con una sola dosis derifampina-ofloxacina-minociclina (ROM).
En este trabajo se describen las característicasclínicas e inmunológicas de un grupo de pacientesSSL-PB registrados entre Diciembre de 1997 y Di-ciembre de 1998. Los pacientes fueron reclutados enlos centros de salud de los estados de Rio de Janeiro
(Sureste), Amazonia y Rondonia (Norte) y Goias(Centro-oeste). Los casos elegibles fueron casosnuevos, no tratados, con lesiones únicas y sin en-grosamiento de nervios valorados por exámen clínico,baciloscópico e histopatológico. En estos pacientestambién se realizaron la reacción de Mitsuda y labúsqueda de anticuerpos por ELISA contra cl GLP-I.De los 200 pacientes SSL-PB, 259 (86.6%) cumpli-eron con los criterios necesarios para su tratamientocon ROM. Los resultados mostraron que los pacientesreclutados de diferentes sitios tuvieron característicasclínicas e inmunológicas similares. Hubo un predo-minio de adultos (32.4 -± 16.0 aiios) y se detectó unacicatriz de BCG en el 76.7% de los nifios (<15 afios deedad) Sólo 7 casos se diagnosticaron como multi-bacilares y representaron menos del 3% de los pa-cientes mal clasificados. Nuestros datos indican que enBrasil la identificación de casos SSL-PB basada en cri-terios clínicos y baciloscópicos puede lograrse acer-tadamente bajo un programa rutinario de control. Se-tenta y cinco porciento de los casos SSL-PB fueronMitsuda-positivos (>5 mm), y el 17% de los pacientestuvieron anticuerpos contra el PGL-I. Estos datos,compatibles con una efectiva inmunidad celular y hajacarga bacteriana, sugieren una evolución favorable enla mayoría de los pacientes SSL-PB de esta cohorte.
RÉSUMÉPeu d'informations existent au Brésil en ce qui
concerne les caractéristiques cliniques et épidémio-logiques des patients qui présentent une lésion cutanéeunique paucibacillaire (LCU-PB). II n'y a que trèsrécemment que le système officiel de dépistage a dis-tingué les patients hanséniens présentant un seule lé-sion comme une entité clinique distincte, pour lesquelsune administration unique de rifampicine, ofloxacineet minocylcine (ROM) a été recommandée.
Nous décrivons ici les caractéristiques cliniques etimmunologiques d'une cohorte de LCU-PB sélection-née entre décembre 1997 et décembre 1998. Les pa-tients furent recrutés dans des centres de soins local-isés dans les régions suivantes: sud-est = Rio deJaneiro; nord = états de Rondônia et de l'Amazone;centre ouest = état de Gaia. Les cas sélectionnésétaient des patients hanséniens nouvellement détectés,non-traités, présentant une lésion unique sans évidencede lésion d'épaississement des nerfs. Ces cas furentévalués par des examens cliniques, bacilloscopiques ethistopathologiques, ainsi que des réactions de Mitsudaet des test sérologiques (ELISA) anti-PGL-I. Parmi299 patients hanséniens LCU-PB, 259 (86,6%) présen-taient les critères pour un traitement unique ROM. Nosrésultats montrent que les patients enrôlés à partir desites différents présentaient des caracteres similaires, sil'on considère les profils cliniques et immunologiques.Les patients étaient en majorité adultes (moyenne de32,4 ans; D.S. = 16,0) et une cicatrice de BCG fut dé-tectée chez 76,7% des enfants (515 ans). II n'y eut que7 cas qui furent diagnostiqués comme étant du typemultibacillaire, ce qui ne represente que 3% des pa-
256^ International Journal of Leprosy^ 2000
^tients qui furent re classifiés à posteriori. Nos données^9.suggèrent que, au Brésil, l'évaluation des cas LCU-PBbasée sur des critères cliniques et bactérioscopiquespeut être définie de façon précise dans le cadre d'un
^
programme de contrôle de routine; 75,0% des cas^10.SLC-PB étaient positifs à la réaction de Mitsuda (>_5mm), et 17,3% des patients étaient séropositifs au test
^
anti-PGL-L Ces données sont compatibles avec une ef-^11.ficace immunité à médiation cellulaire et une chargebasse en bacilles, suggérant une issue clinique favor-
^
able pour la majorité des patients LCU-PB de cette co-^12.horte.
Acknowledgment. We thank Dr. Euzenir Nunes 13.Sarno, Dr. Maria Leide W. de Oliveira and Dr. DavidScollard for helpful suggestions and Dr. M. J. Colstonfor the PGL-I antigen. We also thank Dr. Ilma M.Silva, Dr. Juan Pinem Maceira, Dr. Antonio Pedro M.
^
Schettini, and Dr. Emilia Sayurii Ueda for their help^14.and encouragement in setting up this project. Karen
^
Marcelo de Deus received a fellowship (PIBIC/^15.CNPq). This study could not be done without the co-
^
operation of the participante. This study was partially^16.sponsored by PAHO, the Brazilian Ministry of Health,and FUNAPE-Federal University of Goiás in 1998.
^
This investigation received financial support from the^17.UNDP/World Bank/WHO Special Program for Re-search and Training in Tropical Diseases (TDR).
18.
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