YAWS(FRAMBOESIA)

ETIOLOGYTreponematoses are diseases caused by treponemes. These are bacteria with a spiral structure (trepo = turn; nema = thread)They belong to the Spirochaetaceae. There is no animal reservoir. The various treponemes cannot be cultured in vitro (Treponema pallidum can be cultured with some difficulty in tissue culture and in rabbit testicles).

Yaws and its relativesare caused by spirochete bacteriaTreponema pallidum

ETIOLOGYMorphologically they cannot be distinguished one from another and all give positive results on so called syphilis serology. They are all sensitive to penicillin. There are four different, chronic, exclusively human diseases :Venereal syphilis or LuesNon-venereal syphilis or BejelFramboesia or Yaws or PianPinta

Framboesia or Yaws or Pian The name "Framboesia" is derived from the raspberry-like ulcers resulting from developed yaws. It is particularly common in the rural regions of the moist tropics.Yaws is caused by Treponema pertenue or Treponema pallidum pertenue.

The endemic treponematoses are mainly transmitted by human-to-human contact

Yaws is typically found in tropical areas of Africa, South America, and Asia

TRANSMISSIONInoculation with secretions from patients was demonstrated by Paulet in 1848 and by Charlouis in 1881, even before the discovery of T. pertenue by Castellani in two Ceylonese patients with the disease (called parangi there). Transmitted from person to person via direct skin and mucous membrane contact (small scrapes).

Found in poor isolated rural communities in warm, humid, tropical areas of Africa, Central and South America, and some islands in Southeast Asia. There is practically no congenital transmission. Framboesia has currently become rare, and has been elimiated in some areas (e.g. in Esmeraldas, Ecuador), but may be re-emerging in some areas. This is explained by the deterioration in clinical medical care in certain areas (it is easy to diagnose and the treatment is cheap and simple) and the lack of large-scale treatment campaigns.

T. pertenue can infect baboons, chimpanzees and some other monkeys, but the importance of this fact is not clearIt is unlikely that an animal reservoir plays an important epidemiological role

CLINICAL PRESENTATION

The skin and skeleton are affected. Deep organs are always spared, although there is some doubt about this. The disease is characterised by wart-like skin lesions with the appearance of strawberries (hence the name; yaw = strawberry). The skin lesions return periodically.

The first sign of yaws is a primary lesion known as a mother yaw

CLINCAL PRESENTATIONThe primary lesion is extragenital. It may consist of one warty lesion but sometimes there is an initial parent lesion with various satellite lesions. In most cases the lymph nodes are swollen. If the hypertrophic, papillomatous epidermis is removed, an exudate with a crust forms. There is no deep ulceration. These early lesions heal without leaving scars unlike in the case of the late lesions. After healing some residual skin discoloration may remain.

CLINICAL PRESENTATIONA few weeks to months after the primary lesion, more scattered secondary macular or papillomatous lesions occur. The early skin lesions which contain a great many treponemes, tend to be multiple and moist. They occur in flare-ups which last weeks or months in each case. Without treatment this can last 3 to 5 years. When there is a flare-up, there can be general malaise together with joint pain and fever.

CLINICAL PRESENTATIONThe skin lesions may persist for 3-6 months. On the palms of the hand and the soles of the feet the skin can thicken, become hyperkeratotic and itchy and painful fissures appear. These result in the characteristic gait, the so-called crab gait"A severe infection with Tunga penetrans (sand fleas) can sometimes produce a similar picture, but on closer inspection the difference is clear. Sometimes there is involvement of the skeleton.

Without treatment, secondary widespread lesions form

CLINICAL PRESENTATIONChronic inflammation of the bones of the fingers (dactylitis) should be distinguished from the more acute dactylitis seen in sickle cell anaemia. Since the general availability of penicillin, occasionally mild forms of yaws are seen with only one or just a few small lesions, a few papules or limited hyperkeratosis. It is not known whether the pathogen has a reduced sensitivity to penicillin.

CLINICAL PRESENTATIONLate-onset framboesia occurs in 10% of patients (after > 5 years). Characteristic of this condition are sporadic gummata in the skin; deep crater-like ulcers, which later heal with the formation of scars covered by a thin skin. Treponemes are very rare here and the lesions are therefore not particularly infectious. Contracture of the affected limb may occur. Joints may stiffen and chronic osteitis and periostitis can lead to bent legs (sabre tibiae).

After years without treatment, larger problems may developGangosaSabre Tibia

CLINICAL PRESENTATIONSecondary lesions occur in framboesia:Nodules : mainly around joints. Hard nodules, loose from the skin and the deep tissue on the extensor side of elbows, wrists, trochanters, ankles and sacrum. Gangosa : a rapid tissue loss from the nose, palate and upper lip, caused by a gumma in this area.

CLINICAL PRESENTATIONGoundou : swelling of the nose and upper jaw bones due to inflammation of the bones of the nose (osteitis). Gumma : a subcutaneous gumma can manifest itself as a cold abscess.

Endemic syphilis (bejel) is usually found in dry, hot climates (mainly in West Africa)

Endemic syphilis starts with primary white ulcers in the mouth and can end up like late yaws

Pinta is primarily found in arid climates in Central and South America

Pinta starts out similar to yaws but can eventually lead to hyperpigmentation or depigmentation

DIFFERENTIAL DIAGNOSISNodules : onchocerciasisGangosa : espundia (mucocutaneous leishmaniasis), deep mycosis (e.g. blastomycosis), leprosy and noma (= cancrum oris associated with, among other things, malnutrition, caused by infection with Borrelia sp. and fusobacteria).Goundou : fungal infection rhinoentomo phthoromycosis

What do we understand about the pathogenesis of these diseases? Not much

These diseases can be diagnosed in two ways Dark field microscopySerological Tests

DIAGNOSISDirect detection : material taken from skin lesion dark-field examination or fluorescent antibody staining and microscopic examination

Serodiagnosis :Treponemal antibodies (FTA-ABS, TP-PA)Nontreponemal antibodies (VDRL, RPR)

TREATMENTUp to 1980 PAM (procaine penicillin in oil with 2% aluminium monostearate) was recommended as the treatment of preference, but now benzathine penicillin is the treatment of choice. In patients over 10 years of age, a single IM injection of 2.4 million units of benzathine penicillin is sufficient. Half the dose should be used in younger children. In the early stages this produces fairly spectacular results. All individuals who have been in contact with the patient should also be treated.

Benzathine penicillin is the main drug of choice for treatment

TREATMENTIt is probably best to treat the late stage with repeated injections (3 injections at weekly intervals). Doxycycline can be used for one week as an alternative. Erythromycin is less active and chloramphenicol should not be used. In certain areas the eradication of framboesia has been followed by an increase in venereal syphilis.

Between 1950 and 1970, WHO and UNICEF led a campaign to treat people in 46 countries

It worked, but these diseases now receive little attention

PREVENTIONPrinciples of a vertical programme :There is no vaccine.The reservoir is exclusively human.There are no intermediate hosts.Penicillin is effective and there is no resistance.

INDONESIARADEN KODIJAT was born on September 16, 1890, at Muntilan, a village of Magelang Regency in the Residency of Kodu, some 40 kilometers from Djogjakarta in Central Java. The son of a government clerk, he was six years old when his father died and his uncle, a government teacher, took over his care.

INDONESIAQualifying for study at the only institute of higher learning for Indonesians at that time, he entered "Stovia" Medical School (School tot Opleiding van Indische Artsen) at Djakarta in 1908.

INDONESIADr. KODIJATs great work to eradicate yaws began in March 1930, when he was posted to Kediri in eastern Central Java as Residency Health Officer (a Residency is the administrative unit next in size to a Province). With this new scope for application of his ideas he was able to develop community-wide control methods that both cured the afflicted and prevented recurrence of this highly contagious disease. For 20 years prior to this time sporadic attempts had been made in Indonesia to treat yaws, but the endemic problem remained.

INDONESIAAfter charting the epidemiology of the disease Dr. KODIJAT initiated the first experiments with mass treatment. This was followed by careful checking of the entire population in the treated districts and further administration of the arsenical compounds where indicated. Meticulous and repeated examinations and careful records established the soundness of this system of control; it was adopted by doctors elsewhere in Indonesia and endorsed by the Far Eastern Intergovernmental Conference on Rural Hygiene at Bandung in 1937.

INDONESIAThe scope of this work expanded rapidlyBeginning with 250,000 examinations and 33,000 treatments in 1950, the campaign that Dr. KODIJAT directed examined 14 million Indonesians in 1955 and that year treated 1.2 million yaws cases. Recognition of Dr. KODIJATs scientific accomplishment came in the form of an invitation from WHO, in 1952, to serve as a member of the Expert Advisory Panel on Venereal Infections and Treponematosis (including yaws). WHO later gave international attention to his methods for treatment and control in its technical publications.

INDONESIAPada tahun 1995/1996 yang lalu ditemukan 244 penderita di 6 propinsi, yang meliputi 74 kabupaten daerah penanggulangan, sedangkan pada tahun 1996/1997 ditemukan 337 penderita di 7 propinsi dan meliputi 55 kabupaten daerah penanggulangan. Angka prevalensi tertinggi terdapat di Propinsi Irian Jaya yaitu sebesar 17 per 100.000 penduduk. Kenaikan jumlah kasus ini disebabkan oleh karena bersamaan dengan pelaksanaan PIN (Pekan Imunisasi Nasional) yang dapat menjangkau daerah sulit yang selama ini tidak terjangkau. Petugas PIN sekaligus dibekali obat Framboesia untuk menjangkau daerah sulit tersebut.

ReferencesAntel, George M., et al. The Endemic Treponematoses. Microbes and Infection 4.1 (January 2002): 83-94.Desrosiers, Daniel C. and Radolf, Justin D. Treponema pallidum, the stealth pathogen, changes, but how? Molecular Microbiology 72.5 (May 2009): 1081-1086.McCarrick, Jack , Yaws and Other Endemic TreponematosesPerine, Peter L. Handbook of Endemic Treponematoses : Yaws, Endemic Syphilis, and Pinta. Geneva: World Health Organization ;, 1984. Print.Schell, Ronald F., and Daniel M. Musher. Pathogenesis and Immunology of Treponemal Infection. New York: M. Dekker, c1983. Print.Yaws: A forgotten disease. World Health Organization., January 2007. http://www.who.int/mediacentre/factsheets/fs316/en/index.html

**