A Review of Leishmaniasis in Ecuador1

YOSHIHISA HASHIGUCHI~ & EDUARDO A. GC~MEZLANDIRES~

444

This article briefly reviews current knowledge about leishmaniasis in Ecuador- proceeding from 1920, when the first human case was described, to the present. Regarding basic conditions, it appears that 34 of Ecuador’s 20 provinces have endemic leishmaniasis. Nationally, over 4,000 cases were registered in the 1983- 1986 period. Of 260 cases cited in the literature from 1920 through 1987, 240 (92.3%) were said to involve cutaneous forms of the disease and 18 (6.9%) mucocutaneous ones. Only one case each of visceral and diffuse cutaneous leishmaniasis was re- ported in 1920-1987, and neither of these has been confirmed. Various Leishmania strains isolated by the authors from wild animals and man are currently being studied. To date, tests employing isoenzyme eIectrophoresis and monoclonal antibodies have identified some of the isolated strains as L. ama- zonensis and L. panamensis. At present it seems evident that a detailed study of leishmaniasis transmission in Ecuador is needed in order to develop a plan for future control of the disease. Survey work directed at identifying the particular Leishmania varieties prevalent in the country’s different endemic areas is also needed, as is research on the sandfly vec- tors and animal reservoirs of the disease.

eishmaniasis was first reported in ways been a rural disease. Therefore, pa- L Ecuador in 1920 by Valenzuela (I). tients are usually poorly educated; some However, until recently it has remained suffer benign infections that heal sponta- one of the least studied of Ecuador’s neously, while others with longer, more tropical diseases. For many years the chronic infections go to rural doctors who main research on the disease involved are unable to confirm the infections, pri- clinical diagnosis, which eventually pro- marily for lack of laboratory facilities, and duced some confirmed case reports. can only make clinical diagnoses. No well-organized medical registration One result is that many cases regis- system for leishmaniasis is available in tered as leishmaniasis may in fact be mis- Ecuador, a circumstance to which a vari- diagnosed cases of other problems such ety of factors have contributed. To begin as anthrax, bacterial abscess, leprosy, with, leishmaniasis in Ecuador, as in paracoccidioidomycosis, sporotrichosis, other South American countries, has al- skin cancer, or syphilis. Double counting also occurs. Some ‘Work on the review presented here was supported registered patients are sent to city labora- by a grant-in-aid for overseas scientific research from the Ministry of Education, Science, and Cul- tories to have suspected leishmaniasis ture of Japan (Grant Nos. 61041059, 62043055, confirmed, where they are often regis- 63041096). This article has previously been pub- tered again; and some positive cases are lished in Spanish in the Boletin de la Oficina Sanitaria then sent to hospitals that frequently lack Panamericuna, 108(4):296-307, 1990. aDepartment of Parasitology, Kochi Medical School, antimonials, but which are apt to register Nankoku City, Kochi 783yJapar-r. them a third time. Thus the same case aDeaartment of Trouical Medicine. Facultv of Medi- cine, Universidad Catdlica Santiago de duayaquil, may appear two or three times in statisti- Apartado 4671, Guayaquil, Ecuador. cal compilations.

64 Bulletin ofPAH0 25(1j, 1992 On the other hand, many other cases leishmaniasis was widespread in north- are never registered. A substantial share western South America (3). of those afflicted may never consult a As already noted, serious transmission doctor; instead they consult anyone with studies of leishmaniasis did not begin un- past experience of the disease about the til 1982 (4-6). Nevertheless, from 1920 medicine to be used, and buy it if it is onward significant clinical and therapeu- available. Such cases will never appear in tic research was conducted and a con- the statistics. Therefore, as in many other siderable amount of information was South and Central American countries, obtained. The following is a brief chrono- leishmaniasis statistics in Ecuador do not logic account of important events in this closely reflect the actual incidence of the history of leishmaniasis research: disease in the country, serving only to In 1920 Valenzuela described the first identify endemic foci or show where acci- recorded case, in a female patient with dental vector-human contacts have leishmanial ulcers on her forearm and occurred. thorax (1). In sum, since 1920 many clinical cases In 1924 Heinert reported the first case have been diagnosed, and various clini- of mucocutaneous leishmaniasis in one cal features of the disease have been dis- of his patients at the general hospital in cussed within the Ecuadorian medical Guayaquil(7). community; but until very recently the In 1928 Valenzuela reported a case of manner in which leishmaniasis was mucocutaneous leishmaniasis with os- transmitted, as well as the identity of its teoperiostitis, a diagnosis based on some reservoirs and vectors, remained un- X-ray films he had taken of the patient known. (8). This is the only record of this compli- cation in a leishmaniasis patient from HISTORICAL REVIEW Ecuador. In 1931 Trujillo reported a case of vis- It is at present unclear whether ceral leishmaniasis. The patient also had leishmaniasis evolved independently as a a single ulcer on his leg, from which no zoonosis in the Old and New Worlds. In amastigote forms were isolated (9). This the past the continents were linked, and was the first report of visceral leish- it is therefore difficult to hypothesize maniasis in Ecuador, although it appar- about the geographic origins of the dis- ently represented an incorrect diagnosis. ease. It is known, however, that the origi- Valenzuela reported a new type of mu- nal parasite has diverged, adapting to cocutaneous leishmaniasis causing laryn- different vectors and reservoirs in each geal ulcers, although no parasites were hemisphere. observed in smear specimens (10). According to Ala-Vedra, who sought In 1945 Carrera reported the first case evidence of leishmaniasis in old Ecua- of leishmaniasis from Ecuador’s Amazon dorian ceramics, the disease existed in region (II). Ecuador for hundreds or perhaps thou- In 1949 Leon reported a case of visceral sands of years before the arrival of Euro- leishmaniasis-in a three-year-old boy peans. The fact that some pre-Columbian from Esmeraldas Province. The patient’s ceramics appear to show typical leish- hepatic and splenic biopsies were re- mania1 lesions suggests that the disease ported positive (2). However, no other was prevalent in that era (2). Ceramics cases of visceral leishmaniasis have been from other Andean countries, such as reported from this or other areas of Ecua- Colombia and Peru, also suggest that dor to date.

Hashiguchi B G&ez Landires Leishmaniasis 65 In 1950 Rodriguez began the first tax- firmed vectors and reservoirs living in onomic studies of Ecuadorian sandflies. the area where the patients resided, after He described a new species, Phlebotomus observing local ecologic conditions, and camposi (12). made some recommendations for epi- In 1952 Ala-Vedra reported ceramic ev- demiologic surveillance and future con- idence pointing to pre-Columbian cases trol of the disease in Ecuador. of the disease. He also described and In 1954 Leon published an analysis on listed clinical aspects of the disease and probable factors causing or predisposing hypothesized about its transmission to the mucosal lesions of American mechanisms, vectors, and reservoirs. leishmaniases, and on the probable Several chemotherapeutic treatments for mechanisms disseminating the agent Ecuadorian leishmaniasis were first con- from the skin to the mucous membranes. sidered and compared in his text (2). In He also discussed the general clinical as- that same year Rodriguez conducted a re- pects of otic, rhinal, buccal, phar- view of available knowledge on sandfly yngolaryngeal, and ophthalmic (pal- taxonomy, especially regarding R camposi pebral) leishmaniasis found in the New (13, 14). World (29). In 1953 Rodriguez reported observa- In 1956 Rodriguez described a new tion of I? dysponetus in copula in Ecuador sandfly species, P guayasi, and included (25). In addition, Rodriguez and Aviles a modified checklist of Ecuadorian sand- made a bibliographic review of all known flies (20). I? guayasi was later found to be leishmanial cases in Ecuador, adding 29 synonymous with Lufzornyia serrarza. cases that they themselves had diag- In 1960 Arzube recorded the occur- nosed (16). They also evaluated Ecua- rence of R sallesi and I? cayannensis cayan- dorian leishmaniasis research on the nensis in Ecuador for the first time (21). parasite, clinical aspects of the disease, In 1961 Zerega described a case of dif- vector taxonomy, and histopathologic di- fuse cutaneous leishmaniasis in Ecuador. agnosis. They did not believe that the ce- The clinical, histopathologic, immu- ramic evidence was sufficient to suggest nologic, and parasitologic aspects of the pre-Columbian existence of leishmani- case received thorough study (22). No asis, emphasizing that the involvement subsequent Ecuadorian cases of this kind of indigenous American mammals as have been recorded. leishmanial reservoirs was a better argu- In 1962 Arzube published a tentative ment. Rodriguez also described a new plan for investigating leishmaniasis in sandfly species, I? leopoldoi, which is still Ecuador’s Esmeraldas Province. He considered a valid species under the clas- made vector and human case surveys in sification Brumptomyia leopoldoi (17). different areas of the department and In that same year Carrera reported concluded that control measures should seven cases of leishmaniasis from Suscal, include poisoning wild animal reservoirs Guayeturo, and Cochancay in Caiiar Pro- in their burrows (23). vince, 800-1,000 m above sea level on the In 1967 Leon presented a brief review Andean slopes (18). All the smear speci- of the cutaneous forms of leishmaniasis mens from the patients’ ulcerous lesions in children, based on the cases reported were positive for Leishmania amastigotes. from different areas of Ecuador (24). These cases were the first reported from In 1969 Rodriguez reported a new Ecuador’s Andean region. Carrera also focus of leishmaniasis in Los Bancos, a named a number of suspected but uncon- locale some 1,150 m above sea level in

66 Bulletin ofPAHO 25(2), 2992 Pichincha Province. He also made a brief Ecuador’s Amazon region, with special survey of local sandfly fauna and pre- reference to treatment of the patients. He sented some recommendations for con- followed up cases for a long period after trolling the disease (25). treatment, lending credibility to his con- In 1975 Leon modified the classification clusions (31). Also in 1984 Hashiguchi et of clinical forms of American cutaneous al. published the results of an epidem- leishmaniasis on the basis of personal ex- iologic survey on leishmaniasis per- perience and the published literature formed in September 1982 at the “Coop- G’6). erativa 23 de Febrero,” a newly In 1978 Tafur and de Tafur devised a established plantation in the Andean re- therapeutic assay for cutaneous leish- gion (32). The results indicated that maniasis, using metronidazole, in Los leishmaniasis transmission had been oc- Rfos Province (27). The preliminary re- curring in a diverse array of the planta- sults were good, but the treated patients tion’s working and living areas. In addi- were not followed for a long enough time tion, Young and Rogers provided a to establish whether permanent cures checklist of 49 sandfly species and sub- had been achieved. species found in Ecuador and made addi- In 1979 Leon and Leon published an tional comments on some species (33). In epidemiologic evaluation of nasal mu- their text, three closely related anthro- cocutaneous leishmaniasis. They pre- pophilic sandflies, Lu. amazonensis, Lu. sented information on the diverse clinical davisi, and Lu. daustrei, all occurring in aspects of this form of the disease and many parts of the Amazon Basin, are made recommendations for its treatment keyed and illustrated. (28). In 1985 Hashiguchi et al. published the In 1981 Calero and de Coronel carried results of studies done from 1982 to 1984 out an epidemiologic study of leish- with special reference to vectors and res- maniasis in a village on the Andean slope ervoirs (4-6). Among six anthropophilic where the disease was epidemic (29). species of sandflies examined, two spe- In 1982 Amunarriz made a careful cies (Lu. frapidoi and Lu. harfmanni) were study of human leishmaniasis cases in implicated for the first time as probable Ecuador’s Amazon region. He studied vectors of leishmaniasis in Ecuador. Also, the clinical forms and different treat- through examination of a considerable ments of the disease and undertook fol- number of wild mammals, three probable low-up studies lasting two years or more reservoirs of the disease were identified; (30). Also in 1982 the authors of the pre- these naturally infected animals were the sent article began research on leish- sloth Choloepus hofFmanni didacfyIus, the maniasis transmission in Ecuador. This squirrel Sciurus granafensis, and the kink- was the first attempt to determine the ajou Pofos paws. Some ecologic studies vectors and reservoirs in leishmaniasis- on the vector sandflies, such as their bit- endemic parts of the country. The re- ing behavior and activity cycles, were search was directed primarily at estab- also performed in leishmaniasis-endemic lishing some pilot endemic areas for areas and were related to climatic condi- studying leishmaniasis transmission with tions. Vertical sandfly distributions were special reference to reservoirs and also investigated at altitudes ranging vectors. from 350 m to 2,000 m above sea level In 1984 Amunarriz published an ab- along the road from Cochancay to stract of his research on leishmaniasis in Cuenca in Ocafia, Caiiar Province.

Hashiguchi & Gdmez lmdires Leishmaniasis 67 In 1986 Calero et al. reported two cases GEOGRAPHIC CASE of mucocutaneous leishmaniasis from DISTRIBUTION Ecuador’s Amazon region (34), and Fer- reti et al. demonstrated a case of gan- Leishmaniasis probably exists as a zoo- glionar leishmaniasis (35) that was thor- nosis in most parts of Ecuador’s tropical oughly investigated and confirmed. and subtropical humid forest. Analysis of In 1987 Hashiguchi et al. reported the the data registered at the National Insti- results of an epidemiologic survey of tute of Health and Tropical Medicine in leishmaniasis at different altitudes of Guayaquil and the results of our epidem- Ecuador’s endemic areas on the Andean iologic surveys indicate that there is a slope. These results suggested that the principal endemic area traversing Ecua- intensity of transmission was markedly dor from north to south and forming a influenced by the altitudes of human wide belt along the western slopes of the dwelling sites, as measured by natural in- Andes. The disease is also endemic along fection rates of sandflies with Leishmania the Pacific Coast and in Ecuador’s Ama- promastigotes at each site studied (36). zon region. In addition, a new type of That same year Mimori et al. examined leishmaniasis was recently observed in the relationship between the severity of the Andean highlands at altitudes of ulcerated lesions and immune responses 2,300-2,500 meters above sea level in the early stage of cutaneous leish- (39, 40). In all, 14 of Ecuador’s 20 pro- maniasis in Ecuador; their findings sug- vinces have leishmaniasis-endemic re- gested that the lesions’ severity was pro- gions, these 14 being Esmeraldas, portionally related to activation of both Pichincha, Manabi, Guayas, Los Rfos, the humoral and cell-mediated immune Bolivar, Caiiar, Azuay, El Oro, Loja, systems (37). Napo, Pastaza, Morona Santiago, and In 1989, for the first time in Ecuador, Zamora Chinchipe (Figure 1). Mimori et al. examined Leishmania organ- Regarding prevalence data, lack of an isms isolated from mammals and hu- adequate system for registering epidem- mans. They reported the presence of at iologic information and the total absence least two Leishmania species, L. ama- of a surveillance and control program has zonensis and L. panamensis, in the country meant that there are no statistical data on (38). the incidence or prevalence of human As the above indicates, from 1920 to leishmaniasis in Ecuador. From 1920 to 1981 Ecuadorian leishmaniasis research 1952 there were only a few reports of hu- involved only clinical case studies, man cases, the disease being little-known mostly of patients in city hospitals. Since in the country at that time. From 1953 to 1982, however, studies have been con- 1987 most leishmaniasis studies were ducted in leishmaniasis-endemic areas. performed on human cases coming to These latter have involved collection of health centers and general hospitals for both data and samples for analysis; most care, though a few epidemiologic surveys of these samples are currently being sub- were made in leishmaniasis-endemic jected to a variety of tests-including iso- areas (16, 25, 29-32, 36). enzyme electrophoresis, monoclonal an- In the course of preparing this article tibody binding and k-DNA probe we have compiled a partial statistical rec- examinations, experimental infection of ord in order to estimate the occurrence of laboratory animals, and other laboratory leishmaniasis cases in each endemic area studies. of the country. The cases included were

68 Bulletin ojPAH0 25(Z),2992 Top left photo: A case of Andean leishmaniasis in a six-year-old girl from Paute (Azuay Province, Ecuador). The subject, positive for Leishmania mexicana amastigotes, exhibits a superficial 1 Omm x 15mm lesion. Top right: A cutaneous leishmaniasis lesion with pronounced lymphadenitis on the left forearm of a male subject 19 years of age residing in Echandia (Bolivar Province). Four additional lesions on this subject’s left elbow are not shown. Bottom: A view of Echandia (Bolivar Province, Ecuador), a settlement in a Pacific lowland area endemic for leishmaniasis. (Photos by Y. Hashiguchi.)

Hashiguchi & Gbmn Landires Leishmaniasis 69 ,#.=-=-.; e : : * / 1 Lola* 1 Zsmcta

Figure 1. A map showing all of Ecuador’s 20 provinces except GalApagos. Asterisks denote depart- ments with endemic leishmaniasis.

diagnosed clinically and/or parasitolog- bly Esmeraldas, Pichincha, Manabf, Los ically, and were then registered at the Rios, and Guayas. Statistics Department of the National In- stitute of Health and Tropical Medicine CLINICAL CONSIDERATIONS and the Epidemiology Division Sub- secretariat (Section II) of the Ministry of Clinical forms of leishmaniasis found Health in Guayaquil (Table 1). Most of in Ecuador have been mainly limited to these cases had occurred in the provinces cutaneous and mucocutaneous ones. As situated along the Pacific lowlands and Table 2 shows, of 260 cases reported by western slopes of the Andes-most nota- type in the literature from 1920 through

70 Bullefin ofPAH0 25(l), 1991 Table 1. Leishmaniasis cases registered at the National Institute of Hygiene and Tropical Medicine and the Epidemiology Division Subsecretariat of the Ministry of Health of Ecuador, 1983-I 986. Years Province 1983 1984 1985 1986 Total Esmeraldas 220 270 295 307 1,092 Pichincha 150 110 210 215 685 Bolivar - - - 2 4" 24 Manabi 210 272 253 - 735 Los Rios 12 8 391 73 484 Guayas 142 156 240 140 678b Caiiar 95 - - 95" Azuay 12 29 70 52 163 El Oro 1 4 - - 5 Loja 5 22 - 1 28 Napo 7 5 12 17 41 Pastaza 7 11 9 6 33 Morona Santiago 11 - - 1 12 Zamora Chinchioe 2 4 17 23 Total 874 887 1,484 853 4,098 aFrom ourunpublisheddata. "Consistingpktly ofourdata (32, 36).

Table 2. Leishmaniasis cases reported by clinical disease form in principal Ecuadorian medical journals, 1920-l 987. CL = cutaneous leishmaniasis; MCL = mucocutaneous leishmaniasis; DCL = diffuse cutaneous leishmaniasis; VL = visceral leishmaniasis; M = male; F = female; ? = patient’s sex not cited. Clinicaldiseaseform and sex of patients Total CL MCL DCL VL cases Year reported M?FM?FMFMF Ref. nos. 1920 2 1 1 1,16 1922 1 1 7,16 1925 1 1 16 1928 2 2 8,16 1931 2 1 1 9,16 1945 1 1 1,16 1949 3 2 1 1,16 1951 1 1 16 1952 14 9 4 1 2 1953 39 16 10 10 3 16,18 1961 1 22 1969 28 16 10 2 25 1978 13 13 27 1981 10 5 5 29 1982 32 22 10 30,31 1984 15 7 8 32 1987 95 32 31 32 32 Total 260 93 76 71 8 10 1 1

Hashiguchi 8 Go’mez Landires Leishmaniasis 71 1987, 240 (92.3%) were cutaneous and 18 and reports of many cases presenting (6.9%) were mucocutaneous. various clinical features of the disease Only one case each of the diffuse cuta- have been published. Unfortunately, neous and visceral forms have been re- these reports have not been followed by ported to date, both of these reports be- field research in endemic areas. There- ing based on clinical diagnosis-without fore, much of the knowledge of Ecua- any parasitologic confirmation being pro- dorian leishmaniasis to date remains vided by examination of smear speci- largely speculative. mens or cultures. There is thus insuffi- The first studies dealing with cient evidence demonstrating the leishmaniasis transmission in Ecuador existence of these two forms in Ecuador, were done by Rodriguez in 1950-1956 and more detailed investigations are (12-15, 17, 20), and they were later fol- required. lowed by the contributions of Arzube (21) The case reported as visceral leish- and Young and Rogers (33)-all of these maniasis in 1949 by Leon (1) came from being taxonomic studies of Ecuadorian an area of Esmeraldas Province endemic sandflies (12-25, 17, 20, 21, 33). In all, 49 for the cutaneous form of the disease. To sandfly species and subspecies (includ- date, no other case of the visceral form ing seven new species) were recorded has been reported from this area. Since (33). In 1982 we began research to investi- the diagnosis was not confirmed by vis- gate the transmission mechanism of ceral biopsy and parasite isolation, it ap- leishmaniasis in endemic areas of Ecua- pears that the infection could have been dor, with special reference to vectors and the ordinary cutaneous form manifesting reservoirs; some of our data have already a visceral phase in an immunologically been published (4-6, 32). deficient patient. The case of diffuse cutaneous Vectors leishmaniasis was reported in 1961 by Zerega (22), who stated that the clinical, In 1982-1989 a survey of Ecuadorian immunologic, and histopathologic find- leishmaniasis vectors was performed in ings indicated this form of the disease. different endemic areas, and 13 man- Unfortunately; however, no information biting Lufzomyia species were collected was reported regarding the drug resis- using human bait (4, 6, 39, 40). Dissec- tance usually found in cases with this tion of the collected sandflies showed form, nor was any parasite isolation per- that four species, Lu. trapdoi, Lu. gomezi, formed for the purpose of obtaining a de- Lu. ayacuchensis, and Lu. hartmanni, were finitive diagnosis, though a biopsy speci- naturally infected with Leishrnania pro- men was positive for amastigotes. No mastigotes (4, 39, 40). The nine other col- further likely cases of diffuse cutaneous lected species, which have not yet been leishmaniasis have been reported in implicated in transmission, are Lu. pan- Ecuador to date. amensis, Lu. hirusta hirusta, Lu. shannoni, Lu. osornoi, Lu. nevesi, Lu. carrerai thula, TRANSMISSION STUDIES Lu. carrerai carrerai, Lu. yuilZi, and Lu. ser- rana. The first two of these have been im- Since the first diagnosed case of hu- plicated as vectors of leishmaniasis in man leishmaniasis was reported in Ecua- neighboring countries. In this vein, it dor, study of this disease has concen- should be noted that some of the other trated on clinical and therapeutic aspects, sandfly species previously reported in

72 Bulletin ojPAH0 25(l), 1991 Ecuador (i.e., Lu. flaviscutehata, Lu. olmeca PARASITE ISOLATIONS bicolor, Lu. ylephiletor, and Lu. paraensis) have been also implicated as vectors of Since 1920 many attempts have been the disease in other countries. made to isolate Leishmania from human With regard to the four Ecuadorian lesions in Ecuador. Until recently, these species in which infections were ob- yielded no positive results. However, served, Lu. trapidoi and Lu. gomezi have during 1982 and 1988 we were able to col- been implicated as vectors in other South lect a considerable number of Leishmania American countries, but detection of organisms from humans and wild mam- Leishmania promastigotes in Lu. hart- mals. The circumstances of these parasite manni and Lu. ayacuchensis represents the isolations have been described previ- first time these species have been impli- ously (5, 39, 40). cated as vectors of New World leish- For the first time in Ecuador, some of maniasis. our isolates were characterized by using isoenzyme electrophoresis and monoclo- Reservoirs nal antibodies. This process identified isolates from three wild animals as being A survey of Ecuadorian leishmaniasis L. amazonensis, as noted above. Another reservoirs was initiated in 1982, when the isolate, from the cutaneous lesion of a vector research was also done. Forty- human subject living in Santo Domingo eight wild mammals belonging to 12 spe- de 10s Colorados (Pichincha Province), cies and 12 genera were caught in two has been identified as L. panamensis (38); leishmaniasis-endemic areas, Naranjal and three other species of the parasite (L. (Guayas Province) and Ocaiia (Cafiar mexicana, L. braziliensis, and L. guyanensis) Province), and were examined for leish- have recently been isolated from Ecua- mania1 parasites (5). Three mammalian dorian patients with the disease (40, 41). species-the sloth ChoIoepus hoffmanni di- However, a number of remaining isolates dactylus (this species was misidentified as are currently under study, and some of Bradypus variegatus ephippiger in our origi- the parasites involved appear to be differ- nal text), the squirrel Sciurus granatensis, ent from the currently well-established and the kinkajou Potos flavus-tested pos- New World Leishmania species (38, 40). itive for the parasites, while the others- Didelphis marsupialis, Tamandua tetradac- DIAGNOSIS tyla, Sylvilagus braziliensis, Dasypus novem- cinctus, Proechimys semispinosus (Rattus Direct parasite detection using smears spinosus), Rattus rattus, Coendou bicolor, from ulcerous lesions or nodules is the Agouti paca, and Dasyprocta punctata- principal method used to diagnose yielded negative results. The isolates ob- leishmaniasis in Ecuador. However, such tained are still under study. More re- work has only been performed at a few cently, three wild animals, a specimen of Ecuadorian medical centers. Rural doc- Sciurus vulgaris from Palenque (Los Rfos tors rarely use this technique, and many Province) and specimens of Potos flavus cases of dermal lesions have therefore and T tetradactyla from Echeandia (Bolf- been treated for leishmaniasis without var Province), were found to be positive differential diagnosis when drugs are for the parasite; the organisms isolated available. Immunologic diagnosis has not from these animals have been identified been routinely performed in the country, as L. amazonensis (38). but skin testing (Montenegro’s test)

Hashiguchi B Gdmez Landires Leishmaniasis 73 using promastigote antigen prepared by many years prime attention was paid to the method of Reed et al. (42) has re- clinical and therapeutic aspects of the dis- cently been employed as a diagnostic tool ease; and aside from some sporadic at- at the National Institute of Health and tempts, research on leishmaniasis trans- Tropical Medicine in Guayaquil, with mission was ignored. It also seems good results. evident that a detailed study of leishmaniasis transmission is necessary in order to obtain enough information to TREATMENT develop a plan for future control of the disease. Antimonials are regularly used in Several Ecuadorian stocks of Leish- Ecuador to treat leishmaniasis patients. mania have already been isolated from Gulcantime@ (meglumine antimonate) animals and man. As noted above, exam- seems to be the most effective drug, ination of these isolates has shown that though Fuadin@ (stibophen B.P.) is prob- five Leishmania species-L. amazonensis, L. ably equally potent. RepodraP (stibo- mexicana, L. braziliensis, L. guyanensis, and phen) is also sometimes used in Ecuador L. panamensis-are in the country at pre- to treat leishmaniasis. Other drugs, such sent. Such survey work should be contin- as amphotericin B (Fungizone@), py- ued in order to further delineate the cau- rimethamine, and LampiP are used occa- sative agent or agents of leishmaniasis sionally, with some satisfactory results throughout the country. Work of this na- being reported. A few doctors in Ecuador ture should make special efforts to isolate have used MetronidazoP for leish- the parasite from vector sandflies. maniasis treatment and have reported The biology of the implicated vectors, some good results (27); however, this Lu. trapidoi, Lu. gomezi, Lu. ayacuchensis, drug may only be acting as an antiinflam- and Lu. hartmanni, should be extensively matory agent, since there is no known studied. Fortunately, progress we have biochemical mechanism that would qual- made in the laboratory rearing of sand- ify it as a curative agent (43). flies will permit us to investigate this in In general, therapeutic assays with a detail. correspondent follow-up of patients for a To date five wild animals (Choloepus h. long period have not as yet been done in didactylus, Potos jlavus, Sciurus granatensis, Ecuador. Amunarriz has published data S. vulgaris, and Tamandua tetradactyla) on a carefully designed therapeutic re- have been found naturally infected with search procedure using antimonials and Leishmania in Ecuador. Future studies five kinds of traditional Amazonian In- should be made to determine their true dian medicines (32). His information on and potential roles as reservoirs in all the effectiveness of the Indian treatments leishmaniasis-endemic areas. against leishmaniasis is noteworthy. However, it will be necessary to study Acknowledgments. We are grateful to more cases treated with Indian medicines Dr. Bryce C. Walton for his critical read- before any definitive conclusions can be ing of the manuscript. Thanks are also reached. extended to our Ecuadorian colleagues who have generously enabled us to use COMMENTS all available facilities at the National Insti- tute of Health and Tropical Medicine Review of past leishmaniasis research (NIHTM)-and especially to Dr. Vicenta in Ecuador reveals one clear fact: For V de Coronel, Dr. Guarberto Avalos Z.

74 BuIZetin ofPAH0 25(l), 2991 (Director, NIHTM), and the skillful staff ador. Rev Ecuat Hig Med Trap. 1952;8- at the NIHTM Library. 9:15-18. 14. Rodriguez JD. Notas adicionales sobre la REFERENCES especie ecuatoriana Pklebofomus (Pressafia) camposi Rodriguez, 1952. Rev Ecuaf Enfo- 1. Rodriguez JD. Lecciones de parasitologia ku- mol. 1953;1(2):91-96. mana: @nero Leishmania. 5th ed. Guaya- 15. Rodriguez JD. Observacibn de1 P dyspon- quik Universidad de GuayaquiI; 1974: efus Fairchild y Hertig, 1952, en copula. Rev 170-85. Ecuaf HigMed Pop. 1953;10:25-26. 2. Ala-Vedra JT. El botdn de Oriente en el 16. Rodriguez JD, Aviles F. Algunas observa- Ecuador. Paper presented at the IV Con- ciones sobre leishmaniasis cutaneo- greso de Medicina y I de Cirugia Ecu- mucosa en el Ecuador. Rev Ecuaf Hig Med atorianos, I. Jornada Pedilifrica Ecuaforiana. Trop. 1953;10:35-58. Guayaquil: Universidad de Guayaquil; 17. Rodriguez JD. Los Pklebofomus de1 Ecu- 1952:1-23. ador (Diptera, Psychodidae). Rev Ecuaf 3. Werner KJ, Barreto I? Leishmaniasis in Hig Med Trap. 1953;10:51-55. Colombia: a review. Am j Trap Med Hyg. 18. Carrera CT. Anotaciones sobre la 1981;30:751-61. leishmaniasis sel&tica americana o cut- 4. Hashiguchi Y, Gdmez EAL, de Coronel aneo-mucosa. Rev Ecuaf EnfomoI Parasifol. w et al. Natural infections with pro- 1953;1:76-90. mastigotes in man-biting species of sand 19. Le6n LA. La Leiskmania braziliensis Viana, flies in leishmaniasis-endemic areas of 1911 y las leishmaniasis otorrino-buco-far- !$LKVI;~ Am J Trop Med Hyg. 1985; ingolaringea y oft&lmica. Rev Ecuaf Enfo- ma1 Parasifol. 1954;2:15-28. 5. Hashiguchi Y, G6mez EAL, de Coronel 20. Rodriguez JD. Los Pklebofomus de1 Ecu- w et al. Leiskmania isolated from wild ador (Diptera, Psychodidae). Rev Ecuat mammals caught in endemic areas of Hig Med Trop. 1956;13:75-80. leishmaniasis in Ecuador. Trans R Sot Trop 21. Arzube MER. Los Pklebofomus de1 Ecu- Med Hyg. 1985;79:120-21. ador (relato de capturas no publicadas). 6. Hashiguchi Y, Gdmez EAL,, de Coronel Rev Ecuaf Hig Med Trop. 1960;17: 155-159. W, et al. Biting activity of two anthro- 22. Zerega E Sobre un case de leishmaniasis pophilic species of sandflies, Lufzomyia, in tegumentaria difusa. Rev Ecuaf Hig Med an endemic area of leishmaniasis in Trop. 1961;18:17-20. Ecuador. Ann Trop Med Parasifol. 23. Arzube MER. Plan tentativo de investiga- 1985;79:533-38. cidn de la leishmaniasis sudamericana en 7. Heinert JF. Un case de leishmaniasis cu- la Provincia de Esmeraldas, Ecuador. Rev taneomucosa. An Sot Med-Quir Guayas. Ecuaf Hig Med Trap. 1962; 19: 79-83. 1924;3:450-51. 24. Ledn LA. Leishmaniasis tegumentaria en 8. Valenzuela AJ. [Sobre leishmaniasis] en la 10s niiios. In: Reimpreso de komenaje R Aldo Sociedad Medico-Quinirgica de1 Guayas: Muggia, volumen jubilar. Quito: Editorial seccidn cientifica de agosto de 1928. An Universitaria; 1967: 1-31. Sot Med-Quir Guayas. 1931;11:410. 25. Rodriguez JD. Leishmaniasis muco cut- 9. Trujillo l? [Sobre leishmaniasis] en la anea en la Provincia de Pichincha. Rev Ec- Sociedad Mhdico-Qutirgica de1 Guayas: uaf Hig Med Trop. 1969;26:3-7. secci6n de1 14 de agosto de 1931. An Sot 26. Le6n LA. Formas clfnicas de la Med-Quir Guayas. 1931;11:410. leishmaniasis tegumentaria americana. 10. Valenzuela AJ. Leishmaniasis laringea. Pren Med Argenf. 1975;62:73. An Sot Med-Quir Guayas. 1931;11:287. 27. Tafur A, de Tafur C. Evaluacio’n ferapelifica 11. Carrera CT. Leishmaniasis cutaneo mu- de1 Metronidazol (Acromona) en la cosa. Rev Asoc Med Cuenca. 1945;6:23. leiskmaniasis cufanea. Guayaquil: Offset 12. Rodriguez JD. Los Pklebotomus de1 Ecu- ABAD; 1978:3-10. ador: 1, consideraciones generales. Rev 28. Le6n LA, Ledn R. Las rinopafias en la leisk- Ecuaf Hig Med Trap. 1950;7:1-10. maniasis fegumenfaria americana. Quito: Ed- 13. Rodriguez JD. Los Pklebofomus de1 Ecu- itorial Universitaria; 1979:1-16.

Hashiguchi & G6mezLandires Leishmaniusis 75 29. Calero G, de Coronel VV Estudio de la 37. Mimori T, Hashiguchi Y, Kawabata M, et leishmaniasis cutanea en un asentamiento al. The relationship between severity of agrfcola precordillerano. An Med Cir. ulcerated lesions and immune responses 1981;4:28-32. in the early stage of cutaneous leishman- 30. Amunarriz M. Leishmaniasis. In: Salud y iasis in Ecuador. Ann Trop Med Parasitol. enfermedad: patologia tropical en la regidn 1987;81:681-85. amazo’nica. Napo, Ecuador: Ediciones CIC- 38. Mimori T, Grimaldi Jr G, Kreutzer RD, et AME, Prefectura Apostolica de Aguarico; al. Identification of Leishmania isolates 1982:73-88. from humans and wild animals in Ecua- 31. Amunarriz M. Leishmaniasis en la region dor, using isoenzyme electrophoresis and amazdnica. Napo, Ecuador: Ediciones CIC- monoclonal antibodies. Am J Trop Med AME, Prefectura Apostolica de Aguarico; Hyg. 1989;40:156-60. 1984:1-35. 39. Hashiguchi Y. Studies on New World 32. Hashiguchi Y, de Coronel VV, Gomez leishmaniasis and its transmission, with par- EAL. An epidemiological study of ticular reference to Ecuador. Kochi, Japan: leishmaniasis in a plantation “Cooper- Kyowa Printing; 1987:1-174. (No 1). ativa 23 de Febrero” newly established in 40. Hashiguchi Y. Studies on New World Ecuador. jpn j Parasitol. 1984;33:393-401. leishmaniasis and its transmission, with par- 33. Young DC, Rogers TE. The phlebotomine ticular reference to Ecuador. Kochi, Japan: sand fly fauna (Diptera: Psychodidae) of Kyowa Printing; 1990:1-238. (No 2). Ecuador. JMed Entomol. 1984;21:597-611. 41. Armijos RX, Chico ME, Cruz ME, et al. 34. Calero G, Heinert JM, Martinez RL. Human cutaneous leishmaniasis in Ecua- Leishmaniasis cutaneo mucosa: reporte dor: identification of parasites by enzyme de dos cases de la amazonia ecuatoriana. electrophoresis. Am J Trop Med Hyg. Dermatol Ecuat. 1986;1:26-29. 1990;42:424-28. 35. Ferretti HZ, de Ferretti MIB, de Ramirez 42. Reed SG, Badaro R, Masur H, et al. Selec- B. Leishmaniasis ganglionar: reporte de tion of a skin test antigen for American un case. Dermatol Ecuat. 1986;1:30-34. visceral leishmaniasis. Am J Trop Med Hyg. 36. Hashiguchi Y, Gdmez EAL, de Coronel 1986;35:79-85. VV, et al. Leishmaniasis in different alti- 43. Walton BC, Paulson JE, Arjona MA, et al. tudes on Andean slope of Ecuador. ]pn J American cutaneous leishmaniasis. Trop Med Hyg. 1987;15:7-15. JAMA. 1974;228:1256-58.

76 Bulkfin ofPAH0 2.X1), 1991