es Cutaneous Leishmaniasis Due to Leishmania infantum Case Reports and Literature Review Pascal del Giudice, MD; Pierre Marty, MD; Jean Philippe Lacour, MD; Christophe Perrin, MD; Francine Pratlong, MD: Hervé Haas, MD; Pierre Dellamonica, MD; Yves Le Fichoux, MD Background: Lcishmania infantum recently has been identified as a possible agent of cutaneous leishmaniasis (CL). This species has been isolated from cutaneous le sions of patients from the Mediterranean Basin. How- ‘ever, tle is known about the clinical, biological, of thers peutic features of this newly recognized CL, Observations: Six patients aged 9 months to 85 years in southeastern France were found to have autochthon- ‘ous leishmaniasis, Parasitological identification showed that the agent was L infantum, zymodemes Montpel- lier-1 for 2 patients and Montpellier-24 for 1 patient. Five patients who underwent testing with « Western blot as- say were found to have antibodies against 4 antigens with, molecular masses of 18, 21, 23, and 31 kd. Five patients N-methylglucamine,and 1 patient was successfully treated, with topical paromomycin sulfate. No patient had vi ceral disease at diagnosis or alter follow-up. Conelustons: Recent data provide increasing evidence that infantum is an important agent of CL. In southwestern Europe, this species is the only agent that has long been fdenufied from autochthonous CL. Leishmania infantum should be considered an agent of CL in areas in which vis- ceral leishmaniasis is endemic. Western blot assay could bea useful test for the diagnosis, but precise parasitologi- ification is important to having a better knowl edge ofthe disease. The relationships between CL and the visceral disease have to be explored, cal were successfully treai -d with local injections of Arch Dermatol, 1998;134:193-198 From the Departments of Infections Diseases (Dr del Gin Parastology-Mycology (Drs Marty and Le Fichow) Dermatology (Dr Lacou), and Pathology (Dr Perrin), Centre Hospitalier Universitaire de ‘Nice; Centre Hospitalier Inter ‘Communal de FrejusSaint Raphacl (Drs del Giudice Haas, and Dellamonic); and Laboratoire dEcologie Medicale Pathologie Parasitire (Dr Pratlong), Montpelier, France OST CASES of cutaneous leishmaniasis (CL) in the Mediterranean Ba- sin are caused by 2 Leishmania species: Leishmania major and Leishmania tropica.: Leishmania infantum, the causative agent of visceral leishmaniasis (VL), was consid- cred to cause only systemic disease. In 1080, Rioux et al identified L infantum in 2 pe tients with CL. The responsibility of Lin- Jantum asa agent of CL recently has been ‘confirmed in several countries ofthe Medi- terranean Basin. Although the visceral form. of L infantum leishmaniasis is well known, the cutaneous form has been poorly de- scribed. Visceral leishmaniasis is endemic im southern France, but CL is tare atd oc- ccurs sporadically.” We studied the clinical, biological, and therapeutic features of 6 pa- tients with CL contracted in this region. Ls CLINICAL MANIFESTATIONS The main characteristics ofthe patients are summarized in Table ¥. The lesions oc- (©1908 American Med jamanetwork.comy by a UFBA User on 10/10/2022 curred in apparently healthy individuals. No patient took immunosuppressive drugs, but patients 1, 2, and 3 used der- mocorticoid ointments before the diagno- sis as treatment, which resulted in det ‘oration ofthe lesions in2 patients Patient 5 was pregnant at the time of diagnosts The face was the most alfected site. The most usual clinical presentation was a chronic, symptomless, erythematous or lupoid papule (4 patients) (Figure 1, Figure 2, and Figure 3). Patient | presented with an ulcerative lesion, and patient 4 had an infiltrative leston (igure 4). No regional Iymphadenop- athy or clinical signs of visceral invalve- ‘ment were detected. DIAGNOSIS, PARASITOLOGICAL IDENTIFICATION, AND HISTOLOGY Microscopic examination of smears showed the presence of amastigotes in le- sions from 5 patients, The identified para- es belonged to the L infantum com- plex, 2ymodemes Montpellier (MON)-1 (2 patients) and MON-24 (1 patient). West- erm blot analysis of serum samples from Association, All rights reserved.PATIENTS AND METHODS Beuveen January 1986 and December 1995, 6 pa- tients with autochthonous CL were investigated at Nice University Hospital, Nice, France (throughout this article, autochthonous CL will refer to CL ac quired locally) ll paiens lived in southern France (lpes-Maritimesand Var counties) and had not trav led during the past 3 years. The ease of patient 1 was reported previowsly.*Clinical datawere recorded. Ae pirateor skin biopsy specimens were smeared, fixed, Stained (May-Grinvtald-Giemsa), examined fr Leish- ‘mania, and cultured in Nicolle-Novy-MacNeal me- dium, After isolation, organisms were explored for typing by isoenzyme electrophoresis atthe Labora Loire dEcologie Medicale et Pathologie Parasitaire, Montpelier, France.?® The biopsy specimens were fixed in Bouin liq- uid and processed in the usual manner, Sections were stained with hematoxylin-cosin-safran, Giemsa, pe- Fiodicacid-Schiffreagent,Grocott-Gomoni and Zichl- Neelsen. Serum samples were tested for indirect hao- rescent antibody assay with promastigote antigens of L infantum and for Western blot assay.” The Mon- tenegeo test (leishmanin test) used antigens pro- vided by the Istituto Superiore di Sanita, Rome, ltaly A positive test result was defined by the presence of palpable induration of 5 mm or greater at 48 hours, There were no atempis to locate parasites in the vis ‘cera of bone marrow. 5 patients showed the simultaneous presence of antibod- les against 4 antigens with molecular masses of 18, 21, 23, and 31 ke Histological examination showed that the lestons pre dominated in the dermis, There was a massive, diffuse infiltrate throughout the dermis without a grenz zone. The infiltrate was composed predominantly of hist ceytesand lymphocytes. Eosinophils and neutrophils were rare, and plasma cells were seen occasionally. Focally, the dermis was necrotic. In patients, the histiocytes con- tained Leishmania species that were apparent with he- rmatoxylin-cosin and Giemsa stains. When numerous, the parasites were also seen extracellularly. The kinetoplast was rarely detected with Giemsa stain. The microorgan- isms were readily differentiated from Histoplasma cap- sulatum and other small fungi by the negativity of peri- odie acid-Schiff and Grocott-Gomori stains. Minimal changes were observed in the epidermis: slight hyper- keratosis with parakeratosis and moderate acanthosis. In 2 patients, Leishman bodies were seen in the epidermal cells. TREATMENT AND OUTCOME Four patients were treated with a single local injection of meglumine antimoniate (1 mL/em). Patient 5 had a second injection 15 days later because of suspicion of in- complete healing, Patient 6 was treated with topical paro- momycin for 10 days but showed local ieritation a few days later. All patients were cured within 10 days to L month, No visceral involvement was clinically detected during long-term follow-up, which is ongoing, Less} —_ Leishmanta infantum isthe causative agent of Mediterrs- nea VL." Visceral leishinaniasis fs endemic in south- cen France, where reservoirs are domestic dogs and vec- tors are mainly Phlchotomus perniciosus and Phlebotomus ariasi” The isolation of L infantum in CL. from ou pa- fents (southeastern France) and previous reports from the region of the Pyrences-Orientales (southwestern France) confim that this species isthe only agent of spo- radic autochthonous CL in France."*"°"* Leishmania infantum has long been considered ex- clusively tobe an agent of VI, and L major and L.trpica to be the only agents of CL the Meditertancan Basin. However, i 1980, Riou etal first isolated L infantum from eutancous lesions. Later, L infantum was identified sn CL in patients from other countries inthe Mediterrs- nnean Basin: Spain,” lly." Algeria? Morocco,” Tun sia," Malta," Cyprus," and Greece” Leishmania infantum has been isolated and ident fied from approximately 100 patients with cutaneous le sons, however, lew eases of | infantum cutaneous eish- maniasis (LICL) are well documented. Most reports provide only aparastologial identification, ut no cini- Cal, biological, or therapeutic data have been provided fd litle is known about these aspects." In reviewing the lterature we found only 11 previous patients with ‘Table 1. Pain Characteristics of the Patlents* Patten sex) We ot Clea! Diagnostic Montenegro Westen Distt, No." Age, Leslons Location size, mm Form Delay TestReslls IFAT lot Examinallon Paras Treatment outcome 7 MSG 1 Ehov 20 Uke amo M0 CMON A Mure 2 FB 1 heck «10 Papule «6 mo ND te +} ND Muar 3 FB Mose 10 Papua, Smo = ND) gue Cure(t0) 1 km 10 4 F851 Chook 90.40 Infra amo} MD} + MONA Mg 5 F221 haak 15x10 Papua 2y Mo MONA NM glue Cure (t m0) 1 how 10 6 mmo 6 face 5.10 Papula Smo |= NDAD} = + ND. Topical «Cue 1 okm 10 Farorarycn “WAT ndeats inde fuorescent antibody est +, poste, - negative ND, no data MON, Monge, and NM pu, oalN-metyllcaine. (©1908 American Med jamanetwork.comy by a UFBA User on 10/10/2022 Association, All rights reserved.Figure 3. Pzpuos sion of te cheek patent) documented LICL in 6 publications and the initial reports by Rioux and colleagues,*!*"" providing at least clinical, biological, histological, or therapeutic in- formation, PARASITOLOGICAL IDENTIFICATION Six zymodemes have been isolated from CL in tmmuno- ‘competent hosts: MON-11, MON-24, MON-29, MON- 33, MON-78, and MON-111 The reservoirs ofthese der- motropic zymodemes are not identified, and, regarding vectors, only L infantum MON-24 has been isolated from P ariasi®* and Phlebotomus perfiliewi> Some 2y- modemes have been found in VL and CL in tmmuno- ‘competent hosts: MON-1, MON-34, and MON-80. GEOGRAPHICAL DISTRIBUTION AND EPIDEMIOLOGY Leishmania infantum cutaneous leishmaniasis is present in the Mediterranean Basin in 2 distinctive areas. (1) In northern Africa, different Leishmania species are tespon- sible for CL. Leishmania infantum and L major are pres- ‘entin Algeria,” whereas L infantum, L major, and L tropica are found in Tunisia and Moroceo." Leishmania ma- {jor and L tropiea are present in the arid zone of northern Sahara, but L infantum is observed in the northern part fof these countries, in the subhumid bioclim: which is a region endemic for VL."*"* (2) Howev southwestern Europe, including Spain, Italy, Maita, Figure 4. fate sin (pati 4). Cyprus, and France, L infantum is the only species that hhas long been identified in patients with autochthonous VL, mucocutaneous lesions,” and CL. Itis likely that L {infantum is the agent of CL in Portugal since the dermo- tropic zymodeme MON-24 has been isolated from P. In contrast to the rare reports of LICL, CL has been known for many years in the different countries of the Mediterranean Basin.*"** However, the difficulty in in- Lerpretation of earlier reports is that identifications of the parasite were not as precise as they are now. The inc dence of LICLis variable in each focus. In France before 1075, fewer than 40 patients with CL had been re- ported." During 1986 and 1987, a survey of patients with leishmaniasis found 4 with autochthonous CL, Whereas VL was diagnosed in 95 patients in the same pe” riod.* In the counties we studied, the finding of 6 pa- lents in 10 years is equivalent to 4 rate of 0.5 cases per million population per year, whereas the rate of VL is es- mated to be 10 per million In 1985, Rioux etal iden- Lied L infantum from 21 patients with CL in the Pyrenees- Orientales,”' which represents the most important series of isolation of L infantum from CL. In Spain or ltaly, CL, hhas been diagnosed in hundreds of patients for years in different foci" The incidence of LICL in northern Alrica is difficult o assess because ofthe presence of other species of Leishmania, The most important series of pre sumptive LICL was reported by Belazzoug et al,” with 114 cases from northern Algeria supposedly due to Lin- ‘fantum MON-24 Is likely thatthe tre incidence of LICL, (©1908 American Med jamanetwork.comy by a UFBA User on 10/10/2022 Association, All rights reserved.is underestimated because of the undetected oF wnre- ported cases, because small lesions are not considered to bea priority for medical care, and because of the lack of precise knowledge of L infantum in patients with CL Most foct show an enzymatic polymorphism. In southern France, 5 zymodemes have been identified in patients with CL: MON-1, MON-11, MON-24, MON- 29, and MON-33.*!" In Italy, despite an enzymatic poly- morphism, L infantum MON-24 is responsible for about 70% of the cases of CL.” In countriesin which alow poly. morphism has been observed, its difficult to draw con- clusions because of the small number of strains studied, Leishmania infantum cutaneous leishmaniasis sa spo- radie disease that has been deseribed in most patients in foci where the visceral disease is endemic. The L infan- ‘um complex has a wide geographic distribution, extend- ing in the Old World from northeastern China tothe west- ‘ern Mediterranean Basin and from southern Europe to [Alvica,’ Therefore, LICL is expected to exist in these re- ‘gions, In the New World the agent of VL is Leishmania ‘hagasi. Most authors agree to consider L chagasi iden- tical to L infantum." The finding of L chagast in a cuta- neous lesion was first recognized by Oliveira Neto et ab? in Brazil. Later, Lchagasi was identified in patients with CL from Honduras,” El Salvador," and other foci of Cen- tral America.""” Zeledon et al" reported an outbreak of 200 patients with CL attributed to L infantum in Costa Rica. Therefore, there is increasing evidence that LICL is present in the Americas, (CLINICAL FEATURES All age groups are represented within a range of 9 months to8 years," but mostly children are affected in north- cern Alrica.® The male-to-female ratio is 1. The initial le sion is a small erythematous papule that slowly in- cereases in size to form a nodule or a plaque that may’ uleerate and become crusted, The most usual clinica ture is a single lesion that consists of small, crusty ul- cers surrounded by a notable erythematous reaction oF nonulcerated papules that, when ulcerated, are recov- ‘ered with a discrete crust.” Lesions are located on the face (80%), are generally unique oF few in number (1- 3),!* and are symptomless. The medium diameter is 10 mm, but it varies from a few to 30 mL. The delay before diagnosis varies from 1 month to 2 years, with a mean ‘of 3 to 6 months. The relatively long period before di- ‘agnosis is due to the progressive and symptomless evo- lution of the lesions. The diagnosis is usually made in autumn or winter in Europe because patients are con- laminated in summer, the period of activity of phlebot- ‘omine sandilies, The lesions may show a polymorphism in their clink- cal features, They are composed of a variable degree of elementary clinical lesions: papule, erythema, uleer- ation, or infiltration. The elinical aspect results in the pre- dominance oF the association of these elementary com- pounds. According to the intial description proposed by Rioux et al,! itis possible to distinguish 4 main clinical forms (Table 2): papulous, impetiginold, ulcerative, and infiltrative. These clinical characteristics ate those of a localized CL (LCL). Data are limited to show a correla- Table 2, Clinical Forms of Localized Cutaneous Lelshmaniases Due to Leishmania infantum ound, eeabe, wal-ercumecrba sons wth need vistas border nds paruamtous tase Lasions may be covered wth anoxia or ‘rycen erst ands varie degre ‘Small chose round erythamatous oped puro nada nonce lasions, 20 10 fim in ameter Som leone may be fxm by the calecene of mile smal pape dened erythematous infitatd plane. xyhmatousrorinlrated plage, wih scaling and ‘upereial erosons and cust Papas tion between the zymodeme and the clinical feature Draining regional lymph nodes and solitary subcutane- ous nodules representing lymphatic dissemination have not been reported. Results of the general physical ex- amination are normal, untreated, the lesions usually persist longer than 1 year.!? Sometimes they persist for 3 years, but sponta- neous healing occurs, leaving a flat atrophie scar." Rioux, etal" reported 2 episodes of LICL in the same patient due to 2 different zymodemes that occurred 3 years apart. The absence of protective immunity alter the first infec lion suggests that there is no crossover immunity b ‘ween 2 different 2ymodemes. However, the authors tated that the rapid healing of the second infection suggested that the first infection gave partial immunity." Leishmania infantum cutaneous leishmaniasis shares ‘most clinical and biological features with LCL due to L. major and L tropica, the concurrent species in the Medi {erranean Basin, Belazzoug et ab consider that LICL may be clinically distinguished from LCL due to L major, which produces larger and multiple lesions with a heavy crust and unaesthetic scars. However, the only way to differ- entiate the diseases is by isolation and identification of the parasite DIAGNosIS As for other patients with CL, the diagnosis is based on the demonstration of the parasite in smears or in skin bi- opsy specimens." In patients with LICL, direct examina- lion of smears is difficult because the parasites are ust- ally rare; however, it remains the most sensitive technique for the diagnosis of CL. Specimens from bi- opsy oF aspirate may be cultured on Nicolle-Novy- MacNeal blood agar. The growth of promastigotes al- lows subsequent species identification by means of fsoenzyme analysis. However, culturing Leishmania spe- cies from LICL in conventional blood-agar medium has proved difficult." Unconventional semisolid blood- ‘agar medium? and an in vive method using inbred ham- sters treated with cortisone" have been used to solve these difficulties. Identification of the Leishmania species by use of diagnostic DNA probe has been proposed. Re- sults of the Montenegro test usually become positive af- ter 2 months but provide litle information."° Classic rological tests (indirect fluorescent antibody test, enzyme- (©1908 American Med jamanetwork.comy by a UFBA User on 10/10/2022 Association, All rights reserved.linked immunosorbent assay, and direct agglutination) do not provide determinant informations." When these antibodies are present, the titers ate usually low. Marty ‘etal’ recently reported that the Western blot analysis from patients with VL due to L infantum showed the si- mulianeous presence of antibodies against 4 antigens with molecular masses of 18, 21, 23, and 31 kd. This Western blot assay used in 5 of our patients also showed the presence of antibodies against these 4 anti- gens. Therefore, i these results are confirmed by larger studies, the Western blot assay could be a useful diag- nostic test for VL or CL. However, this technique, using promastigotes derived from culture of strains of Linfan- uum MON-L, cannot distinguish between dermotropic strains and viscerotropic strains, Studies are ongoing to determine whether this Western blot is specific to L infantum, The histological pattern of LICL ts similar to that of other LCLs, However, the finding of parasites in the epidermis has been exceptionally reported.” In our pa- tients, the transepithelial elimination of Leishmania or- _ganisins was seen in histiocytes in patients with exocy- losis and in epidermal cells, The significance of the phenomenon isnot clear. Some authors suggest that Leish- mania organisms can be differentiated [rom Histoplasma ‘capsulatum using hematoxylin-cosin-safran staining sec- tionsalone." In our 4 patients, the clear-capsule-like zone around individual organisms, given asa histological clue for H capsulatum, was a constant feature of Leishman bod- les. Therefore, in our experience, special stains were nec- cessaty in all cases for distinguishing Leishmania organ- isms from Histoplasma organisms and other small fang. THERAPY systemic therapy with meglumine antimoniate or sibo- gluconate sodium has been efficient in all patients with presumptive LICL.” However, our opinion is that sys- temic therapy is not indicated for patients with lesions usually of limited size that heal spontaneously. Local thera- peutics is a more attractive approach. Local injection of meglumine antimoniate has been used successfully as in ‘our patients."® There ate isolated reports of other sys- temic of local therapy being used in patients with pre: sumptive LICL, but data are limited. After therapy, the lesions heal slowly within 10 days to 1 month, leaving a depressed, atrophic sear.!°"" LICL IN HUMAN IMMUNODEFICIENCY ‘VIRUS-SEROPOSITIVE PATIENTS, Hundreds of eases of VL have been reported from south- ‘ern Europe in human immunodeficiency virus-infected, patients." In contrast, cutaneous lesions have been re- ported rarely in these patients.""” Ithas been suggested that immunocompromised patients tend to develop VL rather than LCL. Some cutaneous lesions have been re- ported in patients with VL and seem to be related to sec- ‘ondary cutaneous location of parasites due to the dis- semination of the Leishmania species." Apparent primitive LCL has been reported rarely, and only a single ‘case has been proved to be due to L infantum." In none of these patientshas a secondary visceral localization been proved. RELATIONSHIPS WITH VL Manson-Bahr” suggested in 1955 that in some patients, a primary skin lesion could occur at the site of the sand. fly bit, with lymphatic spread of the parasites to the r gional glands and eventually to the viscera. Its likely that this hypothetic cutaneous lesion, called leishmani- coma in some textbooks oF reports, has been assimilated to LICL* However, this hypothesis seems to be excep- tional. No documented ease of LICL has been compli- cated by a visceral disease in an immunocompetent pa- tient. The only report ofa possible LICL that has preceded VL.was of child who had Vi 4 months after CL." How- ever, the parasites had not been identified, and it has been shown that the same patient may be infected with dif- ferent zymodemes a few months apart. The reason some zymodemes may cause either cuta- neous lesions or visceral disease and others may cause both cutaneous and visceral disease is unclear. It has been sug- gested that the zymodeme type might affeet the clinical re- sponse."* Another hypothesis is that the host immune re- sponse affects the elinical response. The different tropisia observed in immunocompetent hosts is not observed in pa tients with human immunodeficiency virus infeetion in whom VL may be eaused by dermotropic zymodemes in the absence of cutancous lesions.“ It has been proposed that the immunodeficieney related to human immunod ficiency virus infection favors the dissemination of para- sites that are normally dermotropic:* Immunosuppres- sion with corticosteroids in hamsters provokes Viseeralization of dermotropic Leishmania species. tn 1957, André etal” reported the case of a newborn who had VL alter exsanguinotransfusion from a donor with LCL, Localized CL suggests a strong, specific, cell- mediated response, demonstrated by Montenegro test- ing, and VL is characterized by the absence of cell- mediated immunity."* Our patients confirm that L infantum isa causative agent of CL in the Mediterranean Basin. ts responsibility in CL from other areas where VI is endemie may be suspected. Our opinion is that CL in ‘many patients is undetected because of the poor knowl edge of the disease. Identification of the parasites iso- lated from CL. from these regions is necessary for a bei ter understanding of the disease and to elucidate its relationships with the visceral form. Accepted for publication July 9, 1997. We thank all collaborators from the hospital and the university departments and all dermatologists who re- {ferred to us patients suspected of having CL, especially Alice ‘Adda, MD; Gilles Rostain, MD; Denis Simon, MD: Chris- tian Boissy, MD; Bernard Marcelet, MD; Joanna Kubar, MD, PAD, Jean Francois Quaranta, MD; Alain Lelievre, MD; Yves Pinier, MD; and Thierry Tartarin. We thank Dr Gramiccia Marina (Istituto Superiore di Sanita, Rome, Italy) for pro- viding the leishmanin Corresponding author: Pascal del Giudice, MD, Ho- pital V'Archet, Serv. des Maladies Infecicuses, Route de St Antoine de Ginestiere, BP 3079 Nice Cedex, France. (©1908 American Med jamanetwork.comy by a UFBA User on 10/10/2022 Association, All rights reserved.Es} 1. Paron RO ine Suse nil perm tis De 106252 2. Roa Lanett 6, Mazon. ero, Pang Laimana int e- i 190, pet Baton d Orit aoc ropoe ines miu de dee soucasisokes das ks Pyne Orarnes. CA Sances ‘ead Sie 20-701-708 ‘eal, Toppa, Bruker Danis M Geni M.Leshaiasin Fane, Lanes 19882204 Mary, Pang aro Alés A, LeFchou.. Leishman intamya _aTMOW 2s une son cui ccna cia halen ie Fane) Pras 10061175178 Fou A Lane 6, Sees E, Paton F, asin P Peres Taxonomy ot Listmania ws ot ones: suoesons ora ew casicaon Aan Pas- Sot Hum Con. 19085. 11-125. 6. Prag F, Ose JP. Mary Pea Leshan-huan imancdecin) vi ‘us couicon fe Modteranan basi: Somaya chaactizion of 100 isos ofthe Lashmana infu complex. Jct 10851723286, 1. 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Premera contagion du Bouton det en Fac, Bul Acad Med {az083 106201 Gracin, radon, ob, Lehman intarumsans aaa n gett tutus keisha i Aba ein (a. Tare Sac Tp Med Ay. ‘0073285257 ati S, Marl A, Grad Leishmania in Tuscany (ta), a ra fis ofa racoded humana Trane Soc Trp Med Hy, 108.75238- ut BalazougS, Arma Xhoga A, Bold, abe Dera0 Lachaise tuned nore Algire,Bul Sc Pathol xt 1085, 78815422, {amiesM, Grdon Sst into elena eso of alan femetape strane tL intr eeu. Tee So Trop Med yg ta876 mn Geral Osa. Liman infantum the atop get ot Ameean ver eshenanass (AVL? Mem st Osvaldo rz 18722: 47- Mu (iva MP, rina, Maren Paseo RS, March CA Meo Prat ee caneaseshranin a duce by Laisa doo van capa Mr st Osa Cuz 1985303309 Panes Paren Mariza el Lami donvan a cil art ‘feuaneosfehnanase Hone. Lancet 101317 57-8 aly PC, Kesar RD, MeMhow rat, Gam A Nava FA, Cutaens ish ania ew of cases sn tional nutes fH, Cp net Dis too 020-07 (ster, Chul J, Hons LO, etal American cuaneus shania onparsone tee satan stboglicrteteamarsehedukes An.Toped ig, THs 86-0. alu WR Mean 18, Garon OM, t a Sty antago t= gluons tray of Anereancuaneouskichnanass, Lancet 887.213. © ZaldanR.Hdsgo Vise A Uriel tne eihanasisin 4 amir gon of potest Costa Re, Tne Soe Top Med 19 eras. ton AX, Mab, Farah 5, hagssan HT Hisoptooy of eutaenus leihmanas Arcb armatal 96693 306401. SalignanU, Cosel. Mcoscope flea between cuanous his- toplasrasis ana thai JC Pao. 08623560 Seal Vala Ga abi. Cites banasie in aeqegmu- aetine pene. Tans So rp Med 108038 38630, Sepia M Matto 8, Dowie , tal Demanoduar and vcr eshman- side to Laishman int ith ae soreyne pte: eprotacase invoking patent wih AIDS. cn et is 1096227607 Daun Peas PF sta Leishmaniasis pasoingasademsaryosts- Mo eapion ADS. 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