Rural campaign to diagnose and treat mucocutaneous leishmaniasis in Bolivia

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1 Rurl cmpign to dignose nd tret mucocutneous leishmnisis in Bolivi J.-P. Dedet,1 R. Melogno,2 F. Crdens,3 L. Vld,4 C. Dvid,5 V. Fernndez,6 M. E. Torrez,5 L. Dimier-Dvid,5 P. Lyevre,5 & M.E. VillreI7 Mucocutneous leishmnisis (MCL) is endemic in the tropicl Amzonin lowlnds of Bolivi, n re tht regulrly receives influxes of migrtory popultions. In these new griculturl development res, cmpign to dignose nd tret the disese ws crried out between 1989 nd 1992, in order to provide direct ccess to MCL tretment in the endemic res t stndrd equivlent to tht offered in the urbn centres in Bolivi. The cmpign led to the cretion of decentrlized locl centres for dignosis nd tretment of the disese. A cmpign to inform the popultion bout leishmnisis ws lso undertken nd courses were run to educte medicl nd prmedicl personnel. As result of the cmpign, 3285 cses of leishmnisis were dignosed, including 2152 cutneous nd 326 mucosl forms. Also, totl of 1888 cses were treted, 1677 of which were cutneous nd 211, mucosl. Introduction Mucocutneous leishmnisis (MCL) cused by Leishmni brziliensis Vinn, 1911 (1) occurs in two stges: primry cutneous lesion, followed (in some cses) by secondry mucosl involvement, often resulting in severe fcil deformities (2). MCL is endemic in numerous countries of South nd Centrl Americ (3, 4) nd is the predominnt form of leishmnisis in Bolivi, where it extends to the mjority of the tropicl Amzonin lowlnds, including the Yungs nd the Cordiller Oriente region (5, 6). These regions re coloniztion zones where high-ltitude popultions regulrly migrte, ejected from the Anden highlnds by the low productivity I Co-Director, Instituto Bolivino de Biologi de Altur, L Pz, Bolivi. Present ddress: Lbortoire d'ecologie Medicle et Pthologie Prsitire, Fculte de M6decine de Montpellier, Universite de Montpellier 1, 163, rue Auguste-Broussonet, Montpellier, Frnce. Requests for reprints should be sent to Professor Dedet t this ddress. 2 Director, Progrmm de Asentmientos Humnos, L Pz, Bolivi. 3 Chief, Dermtology Deprtment, Hospitl de Clinics, Universidd Myor de Sn Andres, L Pz, Bolivi. 4 Professor, Dermtology Deprtment, Hospitl de Clinics, Universidd Myor de Sn Andres, L Pz, Bolivi. 5 Scientist, Instituto Bolivino de Biologi de Altur, L Pz, Bolivi. 6 Executive Director, Progrmm de Asentmientos Humnos, L Pz, Bolivi. 7 Physicin, Dermtology Deprtment, Hospitl de Clinics, Universidd Myor de Sn Andres, L Pz, Bolivi. Reprint No of the lnd, the ending of mining ctivities following the fll in metl prices, nd govemment policy of reloction. The rrivl of new popultions in these griculturl development res produces rich nd vried pttem of tropicl diseses, in which MCL predomintes. Methods for controlling leishmnisis re generlly limited nd depend on the epidemiologicl type of the disese nd the nturl life-cycle of the corresponding prsite species (7-9). In this respect, MCL is one of the most unfvourble types, since it is wild zoonosis of sylvtic regions whose nturl reservoirs remin unknown; moreover, it occurs in mediclly underequipped res inhbited by poor popultions. The present rticle reports one intervention strtegy ginst MCL: the Dignosis nd Tretment of MCL, Rurl Cmpign (DTLRC), which hs been crried out in Bolivi in the Yungs, Alto Beni, nd Beni regions since August Mterils nd methods The problem nd dopted strtegy MCL is endemic in Bolivi, where retrospective study recently reported tht totl of 4058 cses hd been reported between 1975 nd 1991, of which 739 hd mucosl involvement (5). The isoltes obtined from cutneous s well s mucosl lesions hve consistently been chrcterized s L. brziliensis (10, 11). With 1-3% prevlence of MCL, Yungs nd Alto Beni re the regions tht hve the highest endemicity (5). Bulletin of the World Helth Orgniztion, 1995, 73 (3): World Helth Orgniztion

2 J.P. Dedet et l. Despite this epidemiologicl sitution, the people ffected remin untreted for the following resons: lck of recognition of the severity of the mucosl involvement; their low economic sttus; lck of helth fcilities in the endemic res; nd the high cost of therpy. The mucosl lesions, in prticulr, need prolonged tretment using pentvlent ntimony compounds or mphotericin B, under constnt medicl cre. The low economic sttus of those infected with MCL nd the lck of informtion combine to prevent them from trvelling to L Pz nd Snt Cruz, the only plces in Bolivi where, before DTLRC begn, the necessry tretment ws vilble. Thus ffected individuls hve tended to remin in the endemic zones, llowing their mucosl lesions to progress until they hd destroyed lrge prt of the fce, common sight in Bolivi (12). The bsic objective of DTLRC ws to provide direct ccess to proper tretment for the ffected popultion inside the endemic res. Locl centres for the dignosis nd tretment of MCL were set up. Moreover, cmpign ws initited to inform the popultion bout DTLRC nd educte medicl nd prmedicl personnel bout the condition; lso, ctive cse detection ws undertken. Orgniztions involved DTLRC ws privte inititive run by nongovernmentl orgniztions (NGOs) in the endemic zones where leishmnisis hs been prevlent for mny yers Ṫhe promotion nd coordintion of the cmpign ws the responsibility of the Bolivin NGO, Progrmm de Asentmientos Humnos. The following lso took prt in the cmpign: Sn Borj nd Rurrenbque prishes; the Assocition for Rurl Coopertion in Afric nd Ltin Americ (ACRA); Medecins sns Frontieres (MSF); nd the Helth District of Yungs Lrecj (Tropicl). Two public or semipublic orgniztions collborted in plnning the cmpign nd in the scientific nd technicl supervision of its opertions: the Instituto Bolivino de Biologi de Altur nd the Dermtology Deprtment, Hospitl of Clinics, L Pz. Territoril extent of the cmpign Alto Beni (Deprtment of L Pz) nd prt of the Deprtment of Beni (Rurrenbque-Yucumo-Sn Borj regions) were covered by the August December 1990 cmpign (Fig. 1). Alto Beni is situted t the foot of the Andes (ltitude: m), while Beni lies in the plin. This zone extends between Srri nd Covendo (west to est) nd between Rurrenbque nd Crnvi (north to south) nd encompsses pproximtely 2400 km2. It is covered by tropicl rin forest. The popultion consists of colonists who moved there bout 25 yers go nd is estimted to comprise pproximtely fmilies ( persons) who, fter clering initilly forested lnd, hve engged in griculture. In this sme zone there live lso two tribl groups: the Chimnes (c persons) nd the Mosetenes (c persons). Although the opertionl re is crossed by single, unsphlted rod nd by vrious rivers, its uneven topogrphy mkes penetrtion difficult nd the mjority of settlements hve to be visited on foot. In , the DTLRC extended its opertions to Yungs (L Pz Deprtment) (Fig. 1). This re consists of high ( m), nrrow, nd steep- Fig. 1. Mp showing the re covered by the cmpign, GUAN *Dignosis nd tretment centres * Helth centres involved BENI SAN BORJA EL PALMAR RI A HO QUIQUtBE TIN YUCOMO COVENDO <) ~~~~LAASUTA ~CBBA Desjeux P. Leishmniose cutnee et cutn6o-muqueuse m6ricine. Etude de 113 cs observes en Bofivie. Thesis, Pris, LA PAZ*0 AHLUM N trupana c 340 WHO Bulletin OMS. Vol

3 Dignosis nd tretment of mucocutneous leishmnisis in Bolivi sided Anden vlleys oriented north to south. The vegettion vries with ltitude nd is tropicl up to 1500 m. Yungs hs been colonized for more thn 300 yers nd hs popultion of bout inhbitnts, who live dispersed or grouped in smll urbn centres. Even though it hs more uneven topogrphy thn Beni nd Alto Beni, Yungs is more ccessible thnks to its better infrstructure. Prcticl orgniztion of the cmpign Sector division. The Beni nd Alto Beni zone ws divided into six sectors, centred in one of the following loclities: Sn Borj, Rurrenbque, Specho, Srri, Covendo, nd El Plmr (Fig. 1). Ech sector ws under the responsibility of one of the executive orgniztions. A mp of the cmpign zone (scle, 1:300) ws mde nd census of the popultion ws crried out. In the Yungs zone, the sector division estblished by the Ministry of Public Helth ws dopted, which corresponded to six new sectors. Dignosis nd tretment centres. Three specific centres for dignosis nd tretment of MCL were creted in 1989, in Rurrenbque, Sn Borj, nd Specho. Two new centres were subsequently dded: the first used the infrstructures of n existing hospitl (Coroico) nd the second ws totlly new (El Plmr). The objectives of these centres were to provide direct dignosis nd dequte tretment for MCL ptients in the endemic re. Ech centre hd smll lbortory equipped with microscope, centrifuge, spectrophotometer, nd wter-bth, s well s disposbles nd bsic regents needed for prsitologicl dignosis (smers stined by Giems nd sometimes biopsies) nd for crrying out the tests indicted for the follow-up of the tretment (hemogrms, urine nlysis, nd determintion of ure, cretinine, trnsminses, lkline phosphtse, nd serum potssium levels). Ech centre ws equipped with 8-10 hospitl beds to permit tretment of MCL ptients with intrvenous infusions of mphotericin B under strict medicl supervision. Also, ech centre gurnteed to distribute drugs (including pentvlent ntimony compounds) for the mbultory tretment of cutneous leishmnisis nd to follow up ptients. They lso functioned s the opertionl centres for cse detection nd collected epidemiologicl dt on leishmnisis for their prticulr re. Trining of personnel. Courses nd workshops were held regulrly, ltemtely in L Pz nd in the endemic zones, to trin the medicl nd prmedicl personnel prticipting in the cmpign. Their im ws to updte the knowledge of the prticipnts in ll spects of MCL, prticulrly its epidemiology, clinicl fetures nd evolution, dignosis, nd tretment. A bsic objective ws lso to instruct the prticipnts on orgnizing meetings to educte the public bout the disese. Over the period August 1989 to December 1990, totl of 10 trining courses of dys' durtion were held, ech being structured ccording to the ctegory of the prticipnts (physicins, nurses, or lbortory technicins). After hving been trined, the prticipnts orgnized 37 courses (lsting 1-3 dys) to instruct helth uxiliries nd those responsible for populr helth eduction, who in tum gve informtion tlks to the public. Over the following 2 yers of the cmpign, 11 courses were held for helth professionls in 1991 nd seven in 1992, while 24 nd 12 courses, respectively, were held for uxiliries. The totl number of individuls trined by DTLRC ws 832, including physicins, nurses, lbortory technicins nd uxiliries. Teching mterils. Adequte teching mteril ws creted t the outset of DTLRC, s outlined below. * A technicl mnul ws produced for the helth professionls intervening in the cmpign. Illustrtive plcrds were prepred nd these were used to summon the popultion to informtion meetings (Fig. 2). * The teching mteril to inform the public during site visits included series of posters nd sets of slides, which described the nturl history of leishmnisis, its clinicl evolution, nd the therpeutic nd prophylctic options. * Illustrted clendrs were widely distributed to the popultion in the cmpign re nd specific bulletins were produced for ptients under tretment. * During the second yer of the cmpign, regulr rdio progrmmes in three lnguges (Spnish, Aymr nd Quechu) were brodcst for the generl public. Results Informtion cmpign Ech sector ws visited by personnel from the prticipting orgniztions who provided informtion to the public: generl meetings were held fter they hd been nnounced on posters nd rdio progrmmes, nd door-do-door individul visits were lso mde. The rel impct of the cmpign is difficult to evlute. No ssessment ws mde for the popultion covered. However, during the third yer of the cmpign, there were indictions tht it hd hd n WHO Bulletin OMS. Vol

4 J.P. Dedet et l. Fig. 2. A ptient stnding in front of poster used to nnounce the informtion meetings during the cmpign. impct t the locl level: in prticulr, mny ptients presented spontneously to the dignosis nd tretment centres. It is estimted tht bout 80% of the popultion living in the endemic res re wre of leishmnisis nd know where to present if they re infected. Moreover, the cmpign lso hd ntionl impct, s evidenced by the requests mde by vrious deprtments in the country to be included in DTLRC ctivities. Detection of cses The detection of cses ws both ctive nd pssive. Cses were detected directly during the cmpign visits nd informtion meetings held in the settlements, the infected ptients being sent to the relevnt dignosis nd tretment centre for dignostic confirmtion. The number of infected ptients who spontneously presented to the centres incresed regulrly; however, in compiling the results, the type 342 of detection ws not differentited, since the cmpign's objective ws to rech the mximum number of infected persons. In cses of cutneous leishmnisis, the dignosis ws mde on the bsis of the clinicl spect of the lesions. Evidence of prsites on Giems-stined smers ws sought. Becuse of the low positivity rtes with mucosl cses (13), the dignosis ws bsed on both n nterior cutneous lesion nd the presence of grnulomtous nd/or ulcertive lesions of the nsl nd/or buccl mucose (14). Between August 1989 nd December 1990 the cmpign resulted in the detection of totl of 849 cses of MCL, of which 492 were cutneous nd 105 mucosl forms (Tble 1). The remining 252 cses were "intermedite" (i.e., ptients hd scr indictive of cutneous leishmnisis, but without ny current mucosl involvement). Inclusion of only ctive cses (cutneous + mucosl) gives n nnul incidence of 0.96 per 100 in Alto Beni/Beni. During 1991, totl of 1432 cses of MCL were detected, of which 787 were cutneous, 115 mucosl, nd 530 intermedite (Tble 1). Considering gin only the ctive cses, the nnul incidence for Alto Beni/Beni/Yungs ws 0.64 per 100. In 1992, totl of 1004 cses were detected, corresponding to 873 cutneous, 106 mucosl, nd only 25 intermedite (Tble 1) (nnul incidence, 0.70 per 100). Tretment of cses Bsed on published dt (15, 16) nd the experience cquired t the Hospitl de Clinics, L Pz, the therpeutic schemes outlined below were defined. * Cutneous forms were treted using intrmusculr injections of meglumine ntimonite (dose, 20 mg Sb kg-'.dy-') for 20 dys (17). The tretment ws mbultory, the ptient ttending dily for n injection t the MCL centre for dignosis nd tretment. If distnce prevented the dily return of the ptient to such centre, the complete tretment ws delegted to helth centre closer to his/her home. In this cse, Tble 1: Number of cses of mucocutneous mnlsis detected by DTLRC in Bolivi, leish- No. of cses: Cutneous Mucosl Intermedite Totl Totl DTLRC = Dignosis nd Tretment of MCL, Rurl Cmpign. WHO Bulletin OMS. Vol

5 Dignosis nd tretment of mucocutneous leishmnisis in Bolivi the control of the tretment ws under the responsibility of the locl helth centre, which returned the empty mpoules to DTLRC t the end of the tretment. * Ptients ffected with mucosl forms of MCL were hospitlized, nd fter hemtologicl nd renl function tests hd been crried out, were treted with mphotericin B dissolved in 500 ml of 5% glucose solution, to which ws dded 1 mg dexmethsone. The solution ws infused intrvenously over 6-8 hours. For dults, the dose of mphotericin B ws progressively incresed up to 50 mg, by perfusion; three doses were dministered per week-the complete tretment consisting of 45 doses (2.25 g mphotericin B). * In intermedite forms, conservtive pproch ws dopted. Ptients were recommended to consult one of the MCL centres once yer for exmintion. Over the period August 1989 to December 1990, the totl number of cses treted ws 356, of which 298 were cutneous nd 58 mucosl (Tble 2). During 1991 the number of cses treted reched 695, of which 629 were cutneous nd 66 mucosl. During 1992, the number of cses treted ws 837, of which 750 were cutneous nd 87 mucosl (Tble 2). The increse in the number of mucosl cses treted reflects the slow estblishment of mphotericin B tretment under field conditions. Also, the regulr increse in the proportion of treted ptients per detected cse (Tble 2) provides n dditionl mesure of the benefit of the cmpign. Tble 2: Number of cses of mucocutneous mnisis treted by DTLRC in Bolivi, leish- No. of cses treted: Cutneous Mucosl (88.8)b 13 (50.0) (54.3) 45 (57.0) (79.9) 66 (57.4) (85.9) 87 (82.1) Totl (77.9) 211 (64.7) DTLRC = Dignosis nd Tretment of MCL, Rurl Cmpign. b Figures in prentheses re percent of the number of cses detected. The efficiency of the tretments cn be considered to hve been good in both cutneous nd mucosl forms (Tble 3), confirming the vlidity of the dignosis. In both forms of the disese, the follow-up of the ptients ws excellent, with the proportion of ptients lost to tretment being no greter thn 1.4% (cutneous cses). Tretment of the cutneous form ws interrupted becuse of side-effects in 4.1% of cses; filure of the stndrd series of meglumine ntimonite occurred in only 1.3% of cses, ll of whom received second course. Further rectivtion occurred in only 0.7% of cses. For the mucosl form, interruption of mphotericin B tretment ws more frequent (10.4% of cses), but the proportion of filures nd further rectivtion ws low (0.5%). The totl quntities of drugs used by DTLRC were mpoules of meglumine ntimonite nd mpoules of mphotericin B. Tble 3: Results of the tretment of cutneous nd mucosl cses of leishmnisis by DTLRC in Bolivi, Yer/form of leishmnisis No. of cses treted No. of interrupted tretments No. of cses cured No. of tretment filures No. of rectivted tretments No. of uncontrolled ptients 1989 Cutneous Mucosl Cutneous Mucosl Cutneous Mucosl Cutneous Mucosl Totl Cutneous Mucosl DTLRC = Dignosis nd Tretment of MCL, Rurl Cmpign. WHO Bulletin OMS. Vol

6 J.P. Dedet et l. Evlution of the cmpign From the beginning of the cmpign, evlution meetings were held regulrly, t centrl nd locl levels, with the prticiption of the orgnizing bodies. Over the period August 1989 to December 1990, eight evlution meetings were held (two t centrl level nd one in ech cmpign sector). In 1991 nd 1992, three generl meetings nd six locl meetings per sector were orgnized nnully. Discussion The DTLRC cmpign, run over the period in the L Pz nd Beni Deprtments of Bolivi, is n intervention strtegy tht could be extended to other countries. Also, lthough its strtegy ws directed towrds prticulr disese tht is difficult to control, its design is suitble for solving generl public helth problems. The objective of DTLRC ws not to control leishmnisis in the res where it operted, since this would hve been impossible for wild zoonosis in tropicl rin forest re, mintined through unknown sylvtic reservoirs. Insted, n intervention strtegy ws developed, bsed on public eduction. The informtion provided by DTLRC focused on the nture of the disese, its trnsmission modlities, the risk of mucosl involvement, nd erly tretment s mens of preventing fcil mutiltions. The cmpign lso provided trining for helth professionls in the endemic res, including physicins, nurses, lbortory technicins, nd helth uxiliries. As result of the cmpign, 3285 cses of leishmnisis were detected of which 1888 were treted, (1677 cutneous nd 211 mucosl forms). The tretments were dispensed in the endemic zone, using medicl nd lbortory stndrds similr to those vilble in L Pz nd Snt Cruz, the two urbn centres in Bolivi where leishmnisis tretment is vilble. The low proportion of mucosl cses treted ws relted to the lck of hospitl fcilities in the dignosis nd tretment centres. The efficcy of the tretments ws good, with high cure rtes for both forms. The coverge nd response of those covered by the cmpign, prticulrly in terms of complince with tretment, depended on the popultion ctegories: coverge ws optimum mong the colonists but ws low mong the ntive Chimnes nd Mosetenes popultions. DTLRC hd twofold impct on the popultion: t the individul level, it incresed understnding bout leishmnisis nd the need for erly dignosis nd complince with tretment. Also, the cmpign 344 lerted helth uthorities in Bolivi to the problems posed by leishmnisis nd prompted them to tke ction; precise sttistics bout MCL were obtined for n re where they were previously nonexistent. The intrinsic wekness of the cmpign is tht it ws privtely run nd supported finncilly by foreign donor nd not tken over by the officil Bolivin helth structures. DTLRC should be continued nd MCL should be considered by the ntionl uthorities in Bolivi to be mjor helth problem in the settled res. Officil bodies should ssume responsibility for the cmpign nd it should be extended to other endemic res not previously covered (Frnz Tmyo, Iturrlde nd Vc Diez provinces), s well s to other diseses, such s tuberculosis nd intestinl prsitosis. Acknowledgements The cmpign ws finnced by PL 480-USAID Bolivi. We re especilly grteful to Mr C. Brockmn nd Dr R. Zumrn, PL 480-USAID; nd Mr P. Hrtenberger nd Dr J. Kuritsky, USAID, Bolivi. All personnel of the prticipting orgniztions who cted to ensure the success of DTLRC re thnked. The Instituto Bolivino de Biologi de Altur (IBBA) receives finncil support from the French Ministry of Foreign Affirs, the Bolivin Ministry of Public Helth, nd the University Myor de Sn Andr6s, L Pz. Dr R.N. Dvidson is thnked for revising the mnuscript. Resume ' Cmpgne rurle de dignostic et de tritement de l leishmniose cutn6omuqueuse en Bolivie L leishmniose cutn6o-muqueuse (LCM) est end6mique dns les terres bsses mzoniennes de Bolivie, vers lesquelles migrent regulierement les popultions ltiplniques. Zoonose sylvtique suvge dont les r6servoirs demeurent inconnus, l LCM repr6sente un importnt probleme de snte publique pour ces popultions implnt6es, qui m6connissent l mldie et s'instllent dns des r6gions m6diclement sous-6quip6es. Dns ce contexte epid6miologique defvorble, les uteurs rpportent un exemple de strtegie d'intervention mise en plce l'inititive d'orgnistions non gouvernementles: l cmpgne rurle de dignostic et tritement de l LCM, qui 6t6 developpee prtir d'out 1989 dns les regions boliviennes des Yungs, de I'Alto B6ni et du Beni. WHO Bulletin OMS. Vol

7 Dignosis nd tretment of mucocutneous leishmnisis in Bolivi L'objectif principl 6tit d'ssurer un depistge mssif de I'ffection, vec dignostic precoce et tritement dns des conditions equivlentes celles rencontr6es dns les centres urbins de l Pz et Snt Cruz, et ce directement dns les zones d'end6mie. L decentrlistion ex6cutive de l cmpgne ete ssur6e grce l cretion de 5 centres locux de dignostic et de tritement, bse opertionnelle pour l'enqu6te de d6pistge dns le secteur. L cmpgne 6glement permis l formtion du personnel m6dicl et prmedicl exergnt dns l zone (832 professionnels de l snt6 form6s) et une informtion de l popultion vivnt dns l zone. Durnt trois ns et demi de cmpgne, 3285 cs de LCM ont ete detect6s, dont 2152 cs cutnes, 326 cs muqueux et 807 cs intermediires. L'incidence nnuelle de l LCM dns les zones couvertes pr l cmpgne etit comprise entre 0,64 et 0,96 pour 100 suivnt l'nnee. Prmi les cs d6tectes, un totl de 1888 personnes ont 6t6 trit6es (soit 57,5% des cs detectes) dont 1677 cutn6s et 211 cs muqueux. L'efficcite des tritements et6 bonne. L'impct de l cmpgne et6 importnt, tnt u niveu locl, sur les popultions expos6es, qu'u niveu ntionl. References 1. Vinn G. [A novel species of Leishmni: preliminry note]. Brsil M6dico, 1911, 25: 411 (in Portuguese). 2. Mrsden PD. Mucosl leishmnisis ("Espundi" Escomel, 1991). Trnsctions of the Royl Society of Tropicl Medicine nd Hygiene, 1986, 80: Dedet JP. Leishmni et leishmnioses du continent m6ricin. Annles de l'institut Psteurl- Actulit6s, 1993, 4: Shw JJ, Linson R. 7. Ecology nd epidemiology: New World. In: Peters W, Killick-Kendrick R, eds. The leishmnises in biology nd medicine. New York, Acdemic Press, 1987: Dvid C et l. Fifteen yers of cutneous nd mucocutneous leishmnisis in Bolivi: retrospective study. Trnsctions of the Royl Society of Tropicl Medicine nd Hygiene, 1993, 87: Torrez Espejo M et l. Epidemiologie de l leishmniose tegumentire en Bolivie. 1. Description des zones d'etude et frequence de l mldie. Annles de l Societ6 belge de M6decine tropicle, 1989, 69: Mrinkelle CJ. The control of leishmnises. Bulletin of the World Helth Orgniztion, 1980, 58: Sf'jnov VM. Leishmnisis control. Bulletin of the World Helth Orgniztion, 1971, 44: Control of the leishmnises. Report of WHO Expert Committee. Genev, World Helth Orgniztion, 1990 (WHO Technicl Report Series, No. 793). 10. Desjeux P et l. Les Leishmni de Bolivie. I. Leishmni brziliensis Vinn 1911 dns les d6prtements de L Pz et du Beni. Premiers isolements de souches d'origine humine. Crct6ristion enzymtique. In: Rioux JA, ed. Leishmni. Txonomie et phylogen6se. Applictions 6co- 6pid6miologiques. Montpellier, I.M.E.E.E., 1986: Revollo S et l. Isoenzyme chrcteriztion of Leishmni brziliensis brziliensis isoltes obtined from Bolivin nd Peruvin ptients. Trnsctions of the Royl Society of Tropicl Medicine nd Hygiene, 1992, 86: Wlton BC, Vlverde L. Rcil differences in espundi. Annls of tropicl medicine nd prsitology, 1979, 73: Dimier-Dvid L et l. Prsitologicl dignosis of mucocutneous leishmnisis due to Leishmni b. brziliensis in Bolivi. Revist d Sociedd Brsileir de Medicin Tropicl, 1991, 24: Dimier-Dvid L et l. Prticulrit6s 6pidemiologiques, cliniques et biologiques de l leishmniose cutneo-muqueuse en Bolivie d'pres un echntillon de 221 mldes. Bulletin de l Soci6t6 de Pthologie exotique, 1993, 86: Frnke ED et l. Efficcy nd toxicity of sodium stibogluconte for mucosl leishmnisis. Annls of internl medicine, 1990, 113: Mrsden PD et l. High continuous ntimony therpy in two ptients with unresponsive mucosl leishmnisis. Americn journl of tropicl medicine nd hygiene, 1985, 34: Herwldt BI, Bermn JD. Recommendtions for treting leishmnisis with sodium stibogluconte (Pentostm) nd review of pertinent clinicl studies. Americn journl of tropicl medicine nd hygiene, 1992, 46: WHO Bulletin OMS. Vol