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PubMed1998

Geographic distribution and clinical description of leishmaniasis cases in Peru.

Studies were conducted from 1986 through 1993 to further define the geographic distribution and relative importance of different species of Leishmania as a cause of leishmaniasis in Peru. Patients with a clinical diagnosis of cutaneous and/or mucosal or diffuse cutaneous leishmaniasis were enrolled at the Naval Medical Research Institute Detachment (NAMRID) Laboratory in Lima, the Tropical Disease Clinic at San Marcos University Daniel A. Carrión, the Central Military Hospital, and a Ministry of Health hospital in Cusco, Peru. Clinical features, lesion aspirates, and biopsy tissue were obtained from each patient. All specimens were collected and assayed separately, including multiple specimens from some of the same patients for Leishmania parasites by inoculating aliquots of either aspirates or biopsy tissue suspensions onto Senekji's blood agar medium. Stocks of Leishmania isolates were used to prepare promastigotes to produce extracts for identifying the Leishmania species by the cellulose acetate electrophoresis enzyme technique. A total of 351 isolates of Leishmania were obtained from 350 patients who were infected primarily in the low and high jungle of at least 15 different Departments of Peru. Of the 351 isolates, 79% were identified as L. (V.) braziliensis, 7% as L. (V.) guyanensis, 10% as L. (V.) peruviana, 2% as L. (V.) lainsoni, and 1.7% as L. (L.) amazonensis. The clinical form of disease varied depending on the species of Leishmania, with L. (V.) braziliensis being associated most frequently with cutaneous, mucosal ulcers and mixed cutaneous and mucosal disease, and L. (V) peruviana, L. (V.) guyanensis, L. (V.) lainsoni with cutaneous lesions. Leishmania (L.) amazonensis was isolated from six patients, three with cutaneous lesions, one with mucosal lesions, and two with diffuse cutaneous lesions. Among all of the leishmaniasis cases, males were affected more frequently, and cases occurred among patients less than 10 to more than 51 years of age. These data further defined the geographic distribution and the relative frequency of Leishmania species associated with different clinical forms of leishmaniasis in Peru.

Adolescent↗

PubMed1985

In situ characterization of the cellular immune response in American cutaneous leishmaniasis.

American cutaneous leishmaniasis is a spectrum of granulomatous disease caused by related species of an intracellular parasite. The host response in localized cutaneous leishmaniasis (LCL) is effective in that few organisms can be found in tissue lesions. In contrast, diffuse cutaneous leishmaniasis (DCL) patients mount a poor response with numerous parasites present in multiple skin lesions. Immunopathological correlates were sought in LCL and DCL with immunoperoxidase techniques using monoclonal antibodies directed against T lymphocyte subpopulations and interleukin-2 in tissue lesions. Both LCL and DCL granulomas showed a mixture of T lymphocyte subpopulations with the ratio of helper:suppressor phenotypes less than one. This ratio and localization of cells is more similar to the ineffective lepromatous leprosy granuloma than the effective tuberculoid leprosy granuloma. In contrast, interleukin-2 was identified in equivalent numbers of cells in LCL and tuberculoid leprosy, an order of magnitude greater than DCL and lepromatous leprosy lesions. Cells expressing Tac, the receptor for interleukin-2, were present in approximately equal numbers in all disorders. The immunological effectiveness of granulomas appear to related less to the numbers and location of T cell phenotypes than to the functional aspects of these cells, particularly the ability to generate lymphokines.

Granuloma↗

PubMed1998

T cell responses to crude and defined leishmanial antigens in patients from the lower Amazon region of Brazil infected with different species of Leishmania of the subgenera Leishmania and Viannia.

Amazonian localized cutaneous leishmaniasis (LCL) is caused by parasites of the subgenera Leishmania and Viannia. Respectively, these parasites may cause diffuse cutaneous leishmaniasis (DCL) and mucocutaneous leishmaniasis (MCL). This, together with differing skin test responses, suggests some species-specificity in cell mediated immunity. In this study, T cell responses (proliferative and interferon-gamma) to crude and defined antigens were examined in paired samples pre and post chemotherapy. Untreated L. (L.) amazonensis LCL patients showed lower responses to crude leishmanial antigens than the L. (V.) spp. group. L. (V.) braziliensis antigen was a more potent stimulator of T cell responses than L. (L.) amazonensis antigen in all patient groups. Few positive responses were seen to the L. (L.) amazonensis glycoprotein GP46. A substantial proportion of LCL patients did respond to the L. (L.) pifanoi amastigote antigens A2, and the surface membrane glycoprotein P8. DCL patients were poor responders to all leishmanial antigens, except GP46. In contrast, MCL patients were good responders to all antigens except GP46 and A2. A significant rise in the response to P8 and A2 antigen was seen post treatment across all LCL and MCL patients, indicating that these antigens might provide suitable vaccine candidates.

Adult↗

PubMed1997

Leishmania aethiopica derived from diffuse leishmaniasis patients preferentially induce mRNA for interleukin-10 while those from localized leishmaniasis patients induce interferon-gamma.

Exposure of peripheral blood mononuclear cells to promastigotes of Leishmania aethiopica derived from patients with the self-limiting, localized form of the disease (local cutaneous leishmaniasis; LCL) preferentially induced mRNA for interferon (IFN)-gamma but little for interleukin (IL)-10. In contrast, stimulation of the same cells with promastigotes derived from patients with the persistent, disseminated form of the disease (diffuse cutaneous leishmaniasis; DCL) stimulated the expression of IL-10 rather than IFN-gamma. In general, parasites derived from LCL patients induced more expression of other cytokines tested, including IL-4, IL-6, and transforming growth factor-beta, although tumor necrosis factor-alpha was equivalent in cultures stimulated with LCL or DCL promastigotes. The results suggest that the antigen-specific immunosuppression observed in DCL patients and the resulting clinical picture could in part be due to the properties of the infecting parasite to induce more IL-10 than IFN-gamma.

Animals↗

PubMed1989

Profile of human T cell response to leishmanial antigens. Analysis by immunoblotting.

Control and resolution of leishmanial infection depends primarily on T cell-mediated immune mechanisms. The nature of the leishmanial antigens involved in eliciting T cell immunity is unknown. We have examined the pattern of peripheral blood lymphocyte responses in patients with active, healed, or subclinical leishmanial infection to fractionated leishmanial antigens using a T cell immunoblotting method in which nitrocellulose-bound leishmanial antigen, resolved by one or two dimensional electrophoresis, are incorporated into lymphocyte cultures. The proliferative and IFN-gamma responses of cells from patients with healed mucosal or cutaneous leishmaniasis were remarkably heterogeneous and occurred to as many as 50-70 distinct antigens. In contrast, responses from subjects with active, nonhealing, diffuse cutaneous leishmaniasis were either absent or present to only a small number of antigens. Control and resolution of leishmaniasis, and resistance to reinfection, is therefore associated with a T cell response to a large and diverse pool of parasite antigens. The method of T cell immunoblotting appears to offer a powerful, rapid, and relatively simple approach to the identification of antigens involved in eliciting a T cell response in human leishmaniasis.

Antigens, Protozoan↗

PubMed1998

[Immunopathology of American tegumentary leishmaniasis].

The complex cell mediated immune response in parasitic diseases can be evaluated in different body compartments. In the present work we describe the results of studies of peripheral blood lymphocytes and the cutaneous lesions in the three clinical forms of tegumentary leishmaniasis. These clinical forms, that constitute a clinical, histological and immunological spectrum, are: localized cutaneous leishmaniasis (LCL), diffuse cutaneous (DCL9, and the intermediate forms that include mucous and verrocous leishmaniasis (MCL). The overall results suggest that the cytokine pattern of lymphocytes in the blood and lesions of LCL, the self-limiting form of the disease, is T-helper type 1. This leads to the cure of the lesions in these patients, either spontaneously or after appropriate therapy. The disseminated disease in DCL patients is resistant to chemotherapy, and is characterized by a Th2 cytokine pattern, with a an absence of IL-2 AND ifn-gamma production when the lymphocytes are specifically stimulated by leishmanial antigen. This is probably why these patients are unable to control the infection, and allows the cutaneous dissemination of the parasite. The intermediate MCL form is characterized by destructive lesions of the oral and nasopahryngeal mucosas, with a tendency to the chronicity of the infection. The cytokine pattern of MCL patients is a mixture of Type 1 and Type 2 responses. This may be responsible for the progression of the disease in these patients, as it is possible that when both types of cytokines are produced, the Type 2 responses can predominate over the Type 1 and the disease is maintained in a chronic, although activated, state. The examination of the cutaneous lesions demonstrated that the epidermis in the DCL lesions is deficient in ICAM-1 accessory signals and MHC-II expression by keratinocytes, and presents a variable number of Langerhans cells. In MCL lesions, the expression of ICAM-1 and MHC-II is elevated, and Langerhans cells are absent in the damaged epithelium. The epidermis of LCL lesions show ICAM-1 in patches and MHC uniformly expressed by keratinocytes. DCL lesions are characterized by low CD4/CD8 and memory/naive T cell ratios, low numbers of T gamma delta cells, and an apparent defect in the expression of LFA-1 directional receptors. The cytokine patterns are Th1 and Th2, with the latter predominating. MCL granulomas manifest high CD4/CD8 and memory/naive Tcel ratios, low numbers of T gamma delta, a high coefficients of cellular adhesion, with a mixed Th1/Th2 cytokine pattern. LCL granulomas are characterized by a normal CD4/CD8 ratio, a high memory/naive cell ratio, numerous groups of T gamma delta, a high expression of directional receptors, and Th1/Th0 cytokine patterns. We discuss the results in the context of the immunological effects, both in immunotherapy and immunoprophylasis, of the combined vaccine of BCG plus promastigotes of Leishmania. In immunotherapy we demonstrate that the combined vaccine simulates a Th1 response in LCL patients. As an immunoprophylactic vaccine in healthy individuals from an endemic area of leishmaniasis, it stimulates a Th1 response (positivity in the Montenegro cutaneous reactions, proliferative responses in vitro and production of IFN-gamma), with a low specific antibody response. This demonstrates that the combined vaccine is potentially useful both in the treatment of LCL patients, as well as being potentially protective applied as immunoprophylaxis in the control of leishmaniasis.

Animals↗

PubMedDate not supplied

Comparison of parasitological and immunological methods in the diagnosis of leishmaniasis in Ethiopia.

The sensitivity and specificity of parasite demonstration methods (smear, culture and histology) and serological assays (enzyme-linked immunosorbent assay [ELISA], direct agglutination test and immunoblot) were compared in the diagnosis of leishmaniasis in Ethiopia. Culture was found to be the most sensitive diagnostic method, followed by ELISA, for the diagnosis of cutaneous leishmaniasis (CL). When the clinical type of CL was taken into consideration, serological and parasitological methods were equally good for the diagnosis of diffuse cutaneous leishmaniasis. Overall, the serological assays were not sensitive enough to diagnose all the parasitologically confirmed cases of localized cutaneous leishmaniasis. Both groups of diagnostic methods performed equally well in the diagnosis of visceral leishmaniasis patients. In cases of CL where clinical diagnosis was a problem and histology could not give a definitive diagnosis due to the absence of demonstrable parasites, one of the serological assays, preferably ELISA, was very useful in establishing the final diagnosis.

Adolescent↗

PubMed1986

Cutaneous leishmaniasis in Ethiopia: I. Lymphocyte transformation and antibody titre.

The Ethiopian cutaneous leishmaniasis (ECL) caused by Leishmania aethiopica manifests itself in two different forms: The self-healing localized form (LCL) and the non-self-healing diffuse cutaneous leishmaniasis (DCL). In patients suffering from these two forms of ECL, the Leishmania antigen induced in-vitro lymphocyte response and the Leishmania specific antibody titres were investigated. Whole promastigotes and a soluble fraction thereof were used as antigens and antibody titres were determined by a newly developed enzyme-immunosorbent assay (ELISA). Mononuclear cells from the majority of patients but not from healthy donors proliferated in response to soluble Leishmania antigen. In contrast, whole promastigotes induced a proliferation in both patients and controls. Only DCL-cases failed to proliferate in response to both leishmanial antigens. On the average, sera from DCL-patients contained higher titres of Leishmania specific antibodies than those from LCL-patients. One practical implication of these results is that lymphocyte proliferation in combination with specific antibody titre can be used as a reliable diagnostic tool in ECL.

Adolescent↗

PubMed1993

Histocompatibility antigens in Egyptians with cutaneous leishmaniasis: a preliminary study.

The frequency of human leucocytic antigens (HLA) were studied in 27 patients with cutaneous leishmaniasis to evaluate the role of HLA antigens as genetic markers in the pathogenesis of this protozoal skin infection. A significant statistical association was observed between HLA-A11, -B5 and -B7 antigens and diffuse cutaneous leishmaniasis. In conclusion, study of immune response genes could be of value to understand the pathogenic mechanisms responsible for cutaneous leishmaniasis.

Adult↗

PubMed2005

TGF-beta-associated enhanced susceptibility to leishmaniasis following intramuscular vaccination of mice with Leishmania amazonensis antigens.

Leishmania amazonensis and Leishmania braziliensis are the main causal agents of anergic diffuse cutaneous leishmaniasis and hyperergic mucosal leishmaniasis in man, respectively. In this work we demonstrate that intramuscular vaccination of BALB/c mice with whole antigens of L. amazonensis (LaAg) but not L. braziliensis (LbAg) results in increased susceptibility to cutaneous leishmaniasis. LaAg vaccination resulted in an increased capacity of the draining lymph nodes to produce IL-10 and TGF-beta during antigen recall responses. In vitro cultivation with LaAg but not LbAg induced increased apoptosis of CD8+ T cells. Following infection with L. amazonensis, LaAg-vaccinated mice produced significantly more TGF-beta and a higher serum IgG1/IgG2a antibody ratio compared with LbAg-vaccinated and non-vaccinated animals. The association of TGF-beta with enhanced susceptibility to infection was confirmed in mice co-vaccinated with LaAg and neutralizing anti-TGF-beta antibodies. Upon parasite challenge, these animals developed much smaller lesion sizes and parasite burdens, comparable with non-vaccinated controls. The disease-promoting effect of LaAg vaccination is not a general event, as in contrast to BALB/c, the disease outcome in C57Bl/6 mice was unaltered. Together, these findings indicate that species-specific components of L. amazonensis activate overt TGF-beta production that predisposes more susceptible individuals to aggravated disease following vaccination.

Animals↗

PubMed2004

Differential interferon- gamma production characterizes the cytokine responses to Leishmania and Mycobacterium leprae antigens in concomitant mucocutaneous leishmaniasis and lepromatous leprosy.

BACKGROUND: Tegumentary leishmaniasis and leprosy display similar spectra of disease phenotypes, which are dependent on cell-mediated immunity to specific antigens. Diffuse cutaneous leishmaniasis and lepromatous leprosy represent the anergic end of the spectrum, whereas mucocutaneous leishmaniasis and tuberculoid leprosy are associated with marked antigen-specific cellular immune response. METHODS: We characterized and compared the cell-mediated response to Leishmania and Mycobacterium leprae antigens in a patient with an intriguing association of mucocutaneous leishmaniasis with lepromatous leprosy, which are at opposite ends of the immunopathological spectra of these diseases. This was done by performance of skin tests and by assessment of the cell proliferation and cytokine production of peripheral blood mononuclear cells (PBMCs). RESULTS: Strong skin-test reactions and PBMC proliferation were observed in response to Leishmania antigens but not to M. leprae antigens. The stimulation of PBMCs with Leishmania and M. leprae antigens induced comparable levels of tumor necrosis factor- alpha , interleukin-5, and interleukin-10. However, the interferon- gamma response to Leishmania antigens was remarkably high, and that to M. leprae antigens was almost nil. CONCLUSIONS: We found that concomitant leprosy and tegumentary leishmaniasis can produce opposite polar forms associated, respectively, with absent or exaggerated cell-mediated immune responses to each pathogen. This suggests that independent mechanisms influence the clinical outcome of each infection. Moreover, interferon- gamma appears to play a major role in the clinical expression of these intracellular infections.

Animals↗

PubMed2004

Disseminated cutaneous leishmaniasis after visceral disease in a patient with AIDS.

Leishmaniasis is emerging as a common and serious opportunistic disease for patients with HIV infection. Almost all cases of HIV-Leishmania coinfection have been described in Mediterranean countries and they occur with various clinical presentations, ranging from typical visceral forms to asymptomatic or atypical cases, including cutaneous and mucocutaneous leishmaniasis. Pentavalent antimony compounds have been the mainstays of antileishmanial therapy for half a century and new lipid formulations of amphotericin B seem reliable, but the most effective treatment remains unknown. We describe a patient who was HIV infected and an intravenous drug user, with an unusual disseminated cutaneous leishmaniasis, after an initial visceral disease and after a 13-month maintenance treatment with liposomal amphotericin. The severe concurrent immunosuppression probably played an essential role in leading to this atypical cutaneous form, characterized by diffuse, nonulcerated, nonscabby maculopapular lesions.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

The value of a direct agglutination test in the diagnosis of cutaneous and visceral leishmaniasis in Ethiopia.

The usefulness and sensitivity of a direct agglutination test (DAT) in the diagnosis of cutaneous leishmaniasis due to Leishmania aethiopica infection has been investigated. Formalin-fixed, trypsin-treated and Coomassie blue-stained Leishmania promastigotes of various origins were used as antigens. L. major, L. donovani, L. aethiopica but not L. tropica antigen preparations were able to distinguish sera from individuals infected with Leishmania from sera of uninfected controls, although the titres of sera from patients with localized cutaneous leishmaniasis were low. Comparable results were obtained when the same sera were tested using freshly prepared antigen or antigen stored for 10 months at 4 degrees C. The assay was also used to monitor improvement of disease status following treatment of diffuse cutaneous leishmaniasis patients, and it was found to correlate well with the changing clinical status of the patients.

Adolescent↗

PubMed1990

Histocompatibility (HLA) antigens in Egyptians with two parasitic skin diseases (scabies and leishmaniasis).

The frequency of human leucocytic antigens (HLA) were studied in 62 patients with scabies and 27 patients with cutaneous leishmaniasis to evaluate the role of HLA antigens as genetic markers in the pathogenesis of these parasitic skin diseases. A significant statistical association was proved between HLA-A11 antigen and scabies and between HLA-A11, -B5 and -B7 antigens and diffuse cutaneous leishmaniasis.

Adolescent↗

PubMed2006

Miltefosine: oral treatment of leishmaniasis.

The well-known problems of classic treatment of the leishmaniases with pentavalent antimony (reduced efficacy), difficulties of administration and increasing frequency and severity of adverse events have stimulated the search for new drugs to treat these diseases. Other injectable, oral and topical drugs have not been consistently effective, especially in the modern World. Beginning in 1998, Indian researchers conducted several trials with hexadecylphosphocholine (miltefosine) in patients with visceral leishmaniasis, and in 1999, clinical studies were initiated in Colombia for cutaneous disease. More than 2500 patients have been treated, including patients with diffuse cutaneous leishmaniasis, mucosal disease and patients coinfected with HIV. Cure rates between 91 and 100% were reached with a dose of 2.5 mg/kg/day for 28 days, with no difference between treatment-naive and relapsing patients. Mild gastrointestinal events were present in 35-60% of patients and 10-20% had mild transaminase and creatinine elevations. Miltefosine has potent leishmanicidal activity as a consequence of its interference in parasite metabolic pathways and the induction of apoptosis. Miltefosine is the first effective and safe oral agent with the potential to treat all major clinical presentations of leishmaniasis.

Administration, Oral↗

PubMed1979

Induction of delayed-type sensitivity to Leishmania parasite in a case of leishmaniasis cutanea diffusa with BCG and cord-factor (Trehalose-6-6' dimycolate).

The delayed hypersensitivity against the leishmania parasite was restored to a patient who had suffered from diffuse cutaneous leishmaniasis (DCL) for 26 years, by the application of an ointment containing heat-killed and lyophilized BCG and cord-factor (trehalose-6-6'-dimycolate) after stripping the affected and adjacent areas with scotch-tape.

BCG Vaccine↗

PubMed1988

Serological patterns and specificity in American cutaneous leishmaniasis.

Sera from diverse clinical forms of American cutaneous leishmaniasis show remarkably different patterns of reactivity to Leishmania mexicana and L. braziliensis after absorption with these two species of Leishmania. The enhanced species specificity of absorbed sera was confirmed by reactions with well characterized reference strains. The use of pairs of enriched polyclonal sera from mucocutaneous and diffuse cutaneous leishmaniasis permits the preliminary classification of isolates in the L. mexicana or L. braziliensis complexes by a simple, inexpensive, and quantitative immunoassay.

Animals↗

PubMed1983

Leishmaniasis in Brazil: XX. Prevalence of "enzootic rodent leishmaniasis" (Leishmania mexicana amazonensis), and apparent absence of "pian bois" (Le. braziliensis guyanensis), in plantations of introduced tree species and in other non-climax forests in eastern Amazônia.

In Amazonian Brazil most human leishmaniasis is due to Leishmania braziliensis s.l. and is acquired during the clearing of primary climax forest. One of the largest deforestation projects has taken place on the JARI property where plantations of exotic tree species are grown for paper pulp. The ability of the regional leishmaniasis enzootics to invade plantations was investigated. CDC light-trap catches indicated the phletobomine vectors of Le. b. guyanensis (causing "pian bois" in man) to be very scarce in JARI plantations compared to native-forest controls. It is concluded (drawing on other observations) that the vectors of "pian bois" are unlikely to thrive in any secondary forest. In contrast, catches from mammal traps and rodent-baited (Disney) traps demonstrated the presence in JARI plantations of infected Proechimys guyannensis and large populations of Lutzomyia flaviscutellata, respectively the major rodent reservoir and sandfly vector of Le. mexicana amazonensis. Alone amongst the local vectors of human cutaneous leishmaniasis, Lu. flaviscutellata is adapted to non-climax forests (primary or secondary, natural or man-made; synopsis given). It is predicted that the public health importance of Le. m. amazonensis is unlikely to diminish following the development of Amazônia. This is worrying because ca. 30% of Le. m. amazonensis infections in man cause highly-disfiguring, incurable "diffuse cutaneous leishmaniasis".

Animals↗