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We report for the first time the successful use of fluconazole to treat cutaneous leishmaniasis due to Leishmania braziliensis. We used escalating doses from 5 to 8 mg/kg per day. At a dose of 5 mg/kg per day, 75% patients were cured, and at 8 mg/kg per day, the cure rate was 100%. Fluconazole was well tolerated.

Visceral and cutaneous leishmaniasis are major endemic diseases in northeast Brazil. The objective of the current study was to determine the species and geographic distribution of potential sand fly vectors of Leishmania in the state of Rio Grande do Norte. Sand flies were captured using CDC light traps in 30 municipalities distributed throughout the 8 geographic zones of the state. Twelve Lutzomyia species were identified. Lutzomyia longipalpis Lutz & Neiva was the most prevalent and accounted for 85.59% of the sand fly captured. The remaining species were distributed as follows: L. evandroi Costa Lima & Antunes (10.83%), L. oswaldoi Mangabeira (0.99%), L. sallesi Galvao & Coutinho (0.58%), L. intermedia Lutz & Neiva (0.53%), L. lenti Mangabeira (0.53%), L. migonei Franca (0.49%), L. walkeri Newstead (0.24%), L. goiana Martins, Falcao & Silva (0.15%), L. samueli Deane (0.04%), and L. capixaba Dias, Falcao, Silva & Martins (0.03%), and L. peresi Mangabeira (0.01%). L. longipalpis, which is known to be a vector of Leishmania chagasi Cunha & Chagas (L. donovani chagasi), was captured in 93% of municipalities distributed across all geographical areas of the state and its distribution was independent of obvious climatic and topographic parameters. It was identified in all municipalities where human visceral leishmaniasis had been reported. In contrast, climate and topography appeared to be important for other Lutzomyia species. For example, L. intermedia and L. migonei, which are known to transmit Leishmania braziliensis Viana, were geographically restricted. They were captured in municipalities where cases of cutaneous and mucosal leishmaniasis had been reported. The widespread distribution of L. longipalpis, its adaptation to peridomicillary settings, and its ability to transmit L. (d.) chagasi suggest that a large number of persons may be at risk of acquiring visceral leishmaniasis in the state of Rio Grande do Norte, Brazil.

The clinical manifestations of leishmaniasis depend on com­ plex interactions between the virulence characteristics of the infecting Leishmania species and the immune responses of its host. The result is a spectrum of disease ranging from localized skin lesions to diffuse involvement of the reticuloendothelial system. Human disease has traditionally been divided into three major clinical syndromes: visceral, cutaneous, and mucosal leishmaniasis; however, a number of variants exist. Further­ more, a single Leishmania species can produce more than one clinical syndrome, and each syndrome is caused by multiple species. The true incidence and prevalence of leishmaniasis is uncer­ tain because many cases go undiagnosed or unreported in areas where the infection is endemic. In 1993, the World Health Organization estimated that 350 million people worldwide were at risk for infection. The incidence of cutaneous leishmaniasis has been estimated to be 1.0-1.5 million cases per year, and

Preparative SDS-PAGE followed by electroelution was used to separate proteins of Leishmania chagasi promastigotes into 67 fractions. These fractions were tested for the ability to stimulate proliferation of peripheral blood mononuclear cells from healthy immune donors who were treated previously for visceral leishmaniasis and from nonimmune controls. The proliferative responses elicited by these proteins varied among individuals. The 69-kDa protein fraction contained a fragment with sequence similarity to the 70-kDa heat-shock protein. Fragments of the 46- and 41-kDa fractions had sequences not present in the National Biological Research Foundation data bank. These data suggest that a successful subunit vaccine may require multiple parasite antigens. The identification of antigens that elicit human T cell responses is an important step toward understanding the immunology of L. chagasi infection and ultimately in the development of a vaccine.

Patients from across the spectrum of clinical manifestations of Leishmania chagasi infection were evaluated for in vitro correlates of immunity. Peripheral blood mononuclear cells were assayed for parasite-specific lymphoproliferation, cytokine generation, and the capacity to activate autologous macrophages to kill intracellular amastigotes. Patients with acute kala-azar were generally unreactive in each of these assays. Children with subclinical infection demonstrated relatively low levels of proliferation and interferon-gamma production, but none went on to develop overt kala-azar during the study. Patients evaluated after therapy for kala-azar demonstrated yet higher levels of lymphoproliferation and cytokine generation and produced low but significant levels of cytokines in vitro in response to parasite antigens, but not during the activation of infected macrophages. Finally, peripheral blood mononuclear cells from adults with positive delayed-type hypersensitivity responses and no history of kala-azar showed the broadest reactivity in vitro. These patients' cells generated the largest amounts of activating cytokines in vitro during the activation of autologous macrophages to a leishmanicidal state.

Epidemiologic aspects of the relationship between infection with Leishmania chagasi and development of clinical visceral leishmaniasis (VL) were studied in all children < 11 years old in a defined, endemic, rural area of the state of Ceara in northeast Brazil. Antileishmanial antibodies were measured in the same subjects by ELISA on six occasions between May 1987 and August 1989. Seroconversion was documented during this period in 108 children, with a cumulative annual incidence of 4.6%. Twelve (11.1%) of these children developed VL. Age < 4 years, hematocrit < 33%, and living in the mountains predicted the development of clinically apparent VL after seroconversion. Despite a high percentage of dogs serologically positive in the region (38%), there was no increased risk of infection for children living in the same household with dogs. Since children in households with a prior case of VL had a threefold increased risk of infection, human-sandfly-human transmission might have been important.

To the Editor—We appreciate Drs Torres and Suarez's interest in our article, “High-Dose Oral Fluconazole Therapy Effective for Cutaneous Leishmaniasis Due to Leishmania (Vianna) braziliensis” [1]. They refer to evidence of Leishmania amazonensis isolated from human as well as domestic and wild reservoir hosts from the state of Ceara and suggest it is an important etiologic agent of cutaneous leishmaniasis in the region. Concerning human hosts, their statement is based on 2 publications [2, 3] that showed a single isolate of L. amazonensis from only 1 human case of cutaneous leishmaniasis. Both articles deal with the same parasite grown from a human skin biopsy sample in 1984. Because that event was so rare, the question as to whether it was an imported case remains. In respect to domestic and wild reservoirs of L. amazonensis in the state of Ceara, there is no proof of isolates of L. amazonensis from any reservoir or from sandflies. The data available for isolates from humans [4–7], from domestic and wild reservoir hosts [4, 6], and from sandflies [4, 6, 8, 9] support our statement: Leishmania (Viannia) braziliensisis is the only known agent of cutaneous leishmaniasis in the state of Ceara. In a large study of 272 human isolates from 39 different municipalities, all were characterized as L. braziliensis [5]. In another report [6], the author studied 354 isolates from humans, rodents, dogs, and sandflies; all were characterized as L. braziliensis. Furthermore, because the patients in our study were from several different endemic areas, the hypothesis that the response of our patients was due to aspecific clinical syndrome caused by L. braziliensis from a specific endemic area is not true. The lymphadenopathy described in L. braziliensis infection [5] has been documented in other regions of Brazil, and its detection depends on the moment patients seek medical attention and on a comprehensive physical examination because this lymphadenopathy is an early manifestation of infection and, as a rule, the lymphadenopathy is painless and abates as the ulcer progresses. There is evidence that 1 strain of L. braziliensis from 1 region may be genetically different from another strain from other regions [10], and it is possible that these strains may respond differently to therapy. Hence, it is critically important that fluconazole be tested in other areas where L. braziliensis and other species of Leishmania are endemic, keeping in mind that optimal weight-based dosing is very likely to be an important determinant of therapeutic success [1].

The epidemiological pattern of visceral leishmaniasis in north-eastern Brazil is changing. The disease was typically seen in rural, endemic areas, but is now occurring as an epidemic in the city of Natal where 316 cases have been reported since 1989; 49% were in children less than 5 years of age. The principle clinical and laboratory findings were weight loss, fever, hepato-splenomegaly, anaemia, leucopenia and hypergammaglobulinaemia. Elevated transaminases and hyperbilirubinaemia were also observed. The diagnosis was confirmed in 87% of cases by identifying amastigotes in aspirates from bone marrow or spleen. Five isolates were identified as Leishmania (L.) chagasi by isoenzyme analysis. The mortality rate was 9%; all deaths occurred during the first week in hospital. One person had concurrent human immunodeficiency virus infection. Among 210 household contacts and neighbours of patients from the endemic area examined for evidence of L. (L.) chagasi infection, 6 additional cases of visceral leishmaniasis were diagnosed. Thirtyeight percent of house-mates and neighbours gave a positive Montenegro skin test reaction, indicating prior subclinical infection.

Reprints or correspondence: Dr. Richard D. Pearson, Box 801379, Division of Geographic and International Medicine, Dept. of Medicine, University of Virginia Health System, Charlottesville, VA 22908 (rdp9g@virginia.edu). Clinical Infectious Diseases 2001; 33:1944–5 2001 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2001/3311-0022$03.00 Figure 1. Scattergram generated by an automated blood-cell analyzer for the patient with Plasmodium vivax malaria. The diagnosis of P. vivax malaria was confirmed by examination of Wright-Giemsa–stained blood smears. Black points, malaria organisms; orange points, neutrophils; blue points, lymphocytes; purple points, monocytes.

Little is known about the interrelationship between undernutrition and parasitic infections in areas of the world where both are prevalent. The associations between undernutrition and visceral leishmaniasis, an important protozoal disease, were assessed in a study of residents of an area in Brazil with endemic leishmaniasis. Mid-arm anthropometry was used to assess fat and muscle area. Children with visceral leishmaniasis came from large families (9.6 +/- 1.1 members vs. 6.8 +/- 0.7 members in neighborhood control families), and patient housemates had fat areas that were 78% (P less than .05) those of age- and sex-matched neighborhood controls. The children with visceral leishmaniasis who were studied four months or less after diagnosis had fat areas that were 66% (P less than .05) those of age- and sex-matched household controls or 41% (P less than .01) those of neighborhood controls and muscle areas that were 81% (P less than .025) those of household controls or 75% (P less than .05) those of of neighborhood controls. It is hypothesized, on the basis of these data and other findings, that undernutrition is associated with the development of clinically apparent visceral leishmaniasis and that the disease itself has a profound effect on nutritional status, resulting in loss of both muscle and fat, effects that possibly are mediated by interleukin-1 and/or other factors produced by Leishmania donovani-infected macrophages.

Axenically cultured Giardia lamblia trophozoites (2 x 10(5)) were inoculated by gavage into suckling mice. All mice three, seven, and 14 days old became infected, with the peak trophozoite count in the small bowel of 5.3 +/- 1.1 x 10(6) occurring seven days after inoculation of three-day-old mice. In addition to infecting each of 65 challenged mice, G. lamblia was able to complete its life cycle by encysting and, as cysts, to infect previously unchallenged animals. Control mice given culture medium alone, mice challenged with trophozoites when older than 14 days of age, and mothers of infected mice did not become infected. There was no difference in body weight between infected mice and control mice, nor were histopathologic changes in the small bowel noted at the time of peak infection. Infection was cleared in all mice by 17-21 days. Thus, axenically cultured G. lamblia trophozoites are capable of infecting and completing their life cycle in suckling mice. The susceptibility of mice to infection is remarkably age specific, and the infection is apparently without adverse effects on the murine host.