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PubMedDate not supplied

The clinical and immunological spectrum of American cutaneous leishmaniasis.

American cutaneous leishmaniasis is characterized by a spectrum of clinical manifestations. These include localized, often self-healing single lesions, intermediate forms which frequently produce mucosal lesions and often show exaggerated delayed-type hypersensitivity (DTH), and the rare diffuse cutaneous leishmaniasis in which no reaction of protective cell-mediated immunity or DTH can be demonstrated. Clinical, pathological and immunological studies have begun to unravel some of the mechanisms associated with different disease manifestations, dependent on complex interactions between the host immune response, measured in terms of indices including lymphocyte subsets and lymphokines in vitro and within active lesions, and different species of Leishmania.

Animals↗

PubMed2002

Divergent expression of inflammatory dermal chemokines in cutaneous leishmaniasis.

Human leishmaniasis is caused by protozoan Leishmania (L.) parasites and comprises a heterogeneous group of clinical appearances ranging from visceral to cutaneous leishmaniasis. In the New World, L. mexicana mediates American cutaneous leishmaniasis, one of the most common forms of this disease. Two different disease progressions can be observed: (i) self-healing localized cutaneous leishmaniasis (LCL) and (ii) progressive diffuse cutaneous leishmaniasis (DCL). These different forms are associated with a T helper 1 (Th1) or Th2 response, respectively, and are additionally characterized by opposing dermal chemokine profiles. Lesions of LCL show high expression of CCL2/MCP-1, CXCL9/MIG, CXCL10/IP-10 and only low amounts of CCL3/MIP-1alpha. In contrast, lesions of chronic DCL are dominated by the expression of CCL3/MIP-1alpha. This finding implies that CCL2/MCP-1 contributes to the healing process. Indeed, CCL2/MCP-1 induces leishmanicidal activities in human monocytes in contrast to CCL3/MIP-1alpha. This effect is enhanced by interferon-gamma and abrogated by interleukin-4. In the murine model of leishmaniasis, the impact of CCL2/MCP-1 is well documented. Normally resistant mice become susceptible for Leishmania infections if CCR2, the receptor for CCL2/MCP-1, is knocked out. Based on this evidence, we propose that tissue specific expression of these small molecules actively regulates cell traffic and tissue localization of effector cells and, additionally, has direct immunological effects.

Animals↗

PubMed2003

Variations in the serum levels of soluble CD23, nitric oxide and IgE across the spectrum of American cutaneous leishmaniasis.

Serum IgE levels and the expression of low affinity receptor for IgE (Fc epsilon RII/CD23) are increased in cutaneous leishmaniasis. The ligation of CD23 receptor by IgE-anti-IgE immune complexes results in nitric oxide (NO) production, which is a critical leishmanicidal factor. Human monocytes/macrophages express Fc epsilon RII/CD23 after activation with IFN-gamma and IL-4. In the present study, we assessed the relationship between NO, total and Leishmania-specific IgE and soluble CD23 across the clinical spectrum of American cutaneous leishmaniasis (ACL). Sixty-nine ACL patients and 22 endemic controls were studied. NO concentration was estimated using the Greiss method. Soluble CD23, total IgE and anti-Leishmania IgE levels were measured using ELISA. Soluble CD23 was increased in the four patient groups (0.001<P<0.05) compared by the Mann-Whitney test to healthy subjects, particularly in mucocutaneous leishmaniasis (MCL) and diffuse cutaneous leishmaniasis (DCL) patients. Total IgE levels were higher in ACL patients (P<0.0001). Anti-Leishmania IgE showed a similar tendency, where MCL and DCL patients had greater levels. All patients groups, except intermediate or chronic cutaneous leishmaniasis (ICL) patients, showed elevated levels of NO(2)(-)/NO(3)(-) compared to healthy individuals (0.001<P<0.01). Interestingly, ICL patients did not produce significant levels of NO(2)(-)/NO(3)(-). ACL patients showed a significant positive correlation between soluble CD23 and anti-Leishmania IgE. DCL patients showed a positive correlation between both parameters. Overall results suggest that sCD23, IgE and NO may play different roles across the ACL spectrum.

Adult↗

PubMed1987

In situ characterization of the cutaneous immune response in Ethiopian cutaneous leishmaniasis.

Cryostat sections from 10 patients with localized cutaneous leishmaniasis (LCL) and eight patients with diffuse cutaneous leishmaniasis (DCL) from Ethiopia were studied with immunofluorescence methods for the phenotypic characterization of cells in the lesions. Higher numbers of Leu 2+ and Leu 3+ cells (P less than 0.005) were found in LCL than in DCL, while the Leu 3a + b/Leu 2a ratios were the same. No differences were found in the numbers of transferrin receptor, HLA-DR, and HLA-DQ expressing cells in the granulomas. Significantly (P less than 0.0001) lower numbers of IL-2 receptors expressing (Tac+) cells were found in DCL than LCL lesions, suggesting interference in the activation of the T cells. IL-2-containing cells were absent in DCL and were found in LCL lesions. Epidermal keratinocytes above the LCL but not the DCL lesions expressed HLA-DR (but not HLA-DQ) antigen, suggesting a lower gamma-interferon production in the DCL granulomas. The number of Langerhans' cells (Leu 6+) was higher in the epidermis of DCL (P less than 0.005) than in LCL, while a lower number of Leu 6+ cells were seen in the dermal lesions (P less than 0.001). These observations could account for some of the mechanisms responsible for the disturbed immunostimulation and immunoregulation observed in the lesions of DCL.

Ethiopia↗

PubMedDate not supplied

Seroepidemiological studies of cutaneous leishmaniasis in the Campeche state of México.

Seroepidemiological studies of cutaneous leishmaniasis were carried out in 169 individuals in a rural area of the Campeche state of México. Fifty showed cutaneous lesions suggestive of leishmaniasis, 70% were parasite positive and 96% skin test positive. An overall 40% positivity to skin test with Montenegro's antigen was found. Most of the affected individuals were males from 11 to 30 years-old. Antibodies were determined by immunofluorescent antibody test (IFA) and by Western blot. Two antigen preparations were used, one from a Leishmania mexicana strain which produced localized cutaneous leishmaniasis (LCL) and the other from a diffuse cutaneous leishmaniasis (DCL). In the general population from the area of study 19% gave positive IFA tests with DCL antigen and 20% with LCL antigen while for the patients 67% gave positive IFA tests with DCL and 71% with LCL. By Western blot analysis most of the patients recognized more antigens in the DCL than in the LCL strain. In the DCL strain 78% of patients recognized a 105 kDa, 34% a 139 kDa, 28% a 117 kDa and 26% a 205 kDa MW antigen. In the LCL strain 40% of patients recognized a 205 kDa and 22% a 175 kDa antigens.

Adult↗

PubMed1983

Late metastatic Leishmaniasis in the mouse. A model for mucocutaneous disease.

BALB/c, C57B1/6 and (BALB/c x C57B1/6)F1 mice all proved susceptible to infection by a strain of Leishmania isolated from a Central Brazilian with espundia. The course of disease differed markedly between BALB/c and C57B1/6 mice. BALB/c mice suffered from a rapidly progressive and widely metastatic, but non-ulcerative, disease resembling diffuse cutaneous leishmaniasis. In contrast, C57B1/6 mice initially contained parasite multiplication effectively and appeared clinically cured. However, the parasite could persistently be cultured up to about 1 year post-infection. At that time, the parasite load in the infected footpad increased and a patent disease developed characterized by distinctive ulcerative metastases with destruction of soft-tissue in the nasal region similar to the one observed in espundia. Development of disease in both strains of mice was associated with depression of cell-mediated immunity as monitored by delayed-type hypersensitivity in vivo and lymphocyte transformation in vitro. Thus, our study suggests that diffuse cutaneous leishmaniasis and espundia can be caused by the same strain of parasite, and that the particular clinical expression in the individual mouse is determined by the host response.

Animals↗

PubMedDate not supplied

Evaluation of the direct agglutination test (DAT) using freeze-dried antigen for the detection of anti-Leishmania antibodies in stored sera from various patient groups in Ethiopia.

Tests on a panel of 421 serum samples from Ethiopia and 11 from Europe with the direct agglutination test (DAT) and freeze-dried antigen (Leishmania donovani 1S) showed that a cut-off titre of 1:200 or 1:400 could be employed. Using a cut-off titre of 1:400, 181 (88.3%) of 205 serum samples from visceral leishmaniasis (VL) patients tested positive, as did 5 (13.9%) of 36 sera from patients with localized cutaneous leishmaniasis, 5 (71.4%) sera from 7 patients with diffuse cutaneous leishmaniasis and 8 (89.9%) sera from 9 HIV-positive VL patients. We also found that 19 (57.6%) sera from 33 treated VL patients were still positive in the DAT at 1.5 to 5 years after treatment.

Agglutination Tests↗

PubMed1998

[Disseminated cutaneous leishmaniasis revealing human immunodeficiency virus infection].

BACKGROUND: Unlike visceral leishmaniasis, cutaneous leishmaniasis is uncommonly described in patients with human immunodeficiency virus infection. Diffuse cutaneous forms due to Leishmania infantum are always accompanied by visceral parasite infection. CASE REPORT: We report a case of cutaneous leishmaniasis without visceral extension which was the inaugural sign of immunodeficiency virus infection. Polymerase chain reaction amplification of the genome was used to identify Leishmania infantum. Pentamidine (2 injections at the dose of 4 mg/kg, separated by one week) followed by maintenance therapy at the same dose every two weeks was given. Clinical cure was obtained after the initial injections and the intracellular parasite infestation had disappeared at the histology control. DISCUSSION: This case was unusual in that it was the inaugural sign of HIV infection. In addition, it is the first reported case of diffuse cutaneous leishmaniasis without visceral extension of Leishmania infantum in an HIV-infected patient. As no therapeutic consensus has been established, pentamidine would appear to be interesting for this population which also requires pneumocystosis prophylaxy.

AIDS-Related Opportunistic Infections↗

PubMed1984

Observations on local heat treatment for cutaneous leishmaniasis.

Local heat treatment was tested and found effective in three patients with diffuse cutaneous leishmaniasis (DCL), a form of disease poorly responsive to the usual chemotherapy. A water bath that circulated water through a pad wrapped around the lesion provided a temperature of 39 degrees C to 41 degrees C for a cumulative time of at least 20 hours, over a period of several days. In the DCL patients beneficial effect of heat treatment was documented by pre- and post-treatment biopsies and cultures. Several other patients with ordinary cutaneous leishmaniasis did not respond to the same form of treatment. It was concluded that different strains and/or species of leishmanial parasites vary in their sensitivity to elevated temperature. While local heat treatment may be curative in certain cases of cutaneous leishmaniasis, such therapy is still experimental and should be monitored by quantitative parasitological studies to document its usefulness.

Adolescent↗

PubMed1987

Electron microscopical studies on cutaneous leishmaniasis in Ethiopia. II. Parasite and host cell differences between the localized and the diffuse form.

The ultrastructure of Leishmania aethiopica parasites and their host cells was investigated in lesions of 7 patients suffering from diffuse cutaneous leishmaniasis (DCL) and in lesions of 4 patients with localized cutaneous leishmaniasis (LCL). The appearance of host cells and parasites varied considerably in both disease forms. Host cell variations occurred especially in the number of cytoplasmic vesicles, the size of the parasitophorous vacuoles, and the number of amastigotes per parasitophorous vacuole. Differences concerned the occurrence of a special macrophage-type in DCL-lesions which was characterized by an electron-translucent cytoplasm and a low degree of parasitization, larger parasitophorous vacuoles with higher numbers of amastigotes per vacuole in infected macrophages from DCL-patients, and the number of electron dense granules in host cell vacuoles of DCL-patients. The parasites inducing DCL and LCL significantly differed in size and membrane structure: Amastigotes had a length of 2.27 +/- 0.48 micron and a width of 1.77 +/- 0.40 micron in DCL-lesions, and 1.92 +/- 0.40 micron and 1.48 +/- 0.32 micron in LCL-lesions. Promastigotes obtained from DCL-patients revealed 2078 +/- 308 integral membrane particles (IMP)/micron2 and 892 +/- 246 IMP/micron2 on the P- and E-fracture faces of plasma membranes, while the corresponding values of LCL-derived promastigotes amounted to 1690 +/- 376 IMP/micron2 and 652 +/- 274 IMP/micron2, respectively.

Animals↗

PubMed2004

Disseminated cutaneous leishmaniasis due to Leishmania guyanensis: case of a patient with 425 lesions.

Disseminated cutaneous leishmaniasis is characterized by the presence of a large (> or =10) number of lesions at several anatomic sites (head, limbs, and trunk). Most of the lesions are small, papular, and appear simultaneously with or secondarily to one or several ulcerated lesions of localized cutaneous leishmaniasis. We report the first case of disseminated cutaneous leishmaniasis in French Guiana. It concerns a 24-year-old woman who tested negative for human immunodeficiency virus (HIV). The disease began with three lesions that became ulcerated. One week later, multiple papulo-nodular lesions appeared. We counted a total of 425 lesions. Leishmania were observed in the lesions. The species involved was L. guyanensis, which has never been described in a case of disseminated cutaneous leishmaniasis. The patient was rapidly cured by a single course of pentamidine. Disseminated cutaneous leishmaniasis should be distinguished from other types of leishmaniasis with multiple lesions. These include anergic diffuse cutaneous leishmaniasis, post-kala-azar leishmaniasis, and leishmaniasis associated with HIV infection.

Adult↗

PubMed2002

Expression of inducible nitric oxide synthase in skin lesions of patients with american cutaneous leishmaniasis.

Cytokine-inducible (or type 2) nitric oxide synthase (iNOS) is indispensable for the resolution of Leishmania major or Leishmania donovani infections in mice. In contrast, little is known about the expression and function of iNOS in human leishmaniasis. Here, we show by immunohistological analysis of skin biopsies from Mexican patients with local (LCL) or diffuse (DCL) cutaneous leishmaniasis that the expression of iNOS was most prominent in LCL lesions with small numbers of parasites whereas lesions with a high parasite burden (LCL or DCL) contained considerably fewer iNOS-positive cells. This is the first study to suggest an antileishmanial function of iNOS in human Leishmania infections in vivo.

Animals↗

PubMed2000

Monocyte chemotactic protein-1 stimulates the killing of leishmania major by human monocytes, acts synergistically with IFN-gamma and is antagonized by IL-4.

We recently demonstrated that monocyte chemotactic protein-1 (MCP-1) is strongly expressed in lesions of patients with self-healing localized cutaneous leishmaniasis (LCL) whereas it is scarce in those of chronic diffuse cutaneous leishmaniasis (DCL). This finding indicated that MCP-1 may contribute to the healing process. In the present study, we analyzed the capacity of MCP-1 to trigger leishmanicidal activities. The results show that MCP-1 directly stimulates the elimination of intracellular Leishmania parasites by human monocytes, a potential that correlates with the induction of reactive oxygen intermediates. Release of NO was not detected. To understand the cross-talk between the chemokine and T cell-associated cytokines, we studied the influence of the Th1 cytokine IFN-gamma and the Th2 cytokine IL-4 on MCP-1-mediated activation of human monocytes. The data demonstrate that IFN-gamma and MCP-1 synergistically activate monocytes to clear intracellular parasites, whereas IL-4 abrogates the effect of MCP-1. Furthermore, IL-4 inhibits MCP-1 expression by infected monocytes, a finding that may explain the lack of MCP-1 in chronic lesions. The data suggest a novel model for macrophage activation in cutaneous leishmaniasis. In lesions of LCL, the synergistic action of MCP-1 and IFN-gamma may stimulate the killing of parasites by macrophages and promote healing, whereas the presence of IL-4 in DCL lesions may favor the suppression of MCP-1 and, together with the lack of IFN-gamma, the progression of disease.

Animals↗

PubMed1993

Mucocutaneous leishmaniasis: a clinicopathologic classification.

BACKGROUND: Leishmaniasis, a chronic parasitic disease transmitted by Phlebotomus sandflies, affects millions of patients. Mucocutaneous leishmaniasis caused by Leishmania brasiliensis is endemic in much of South America. OBJECTIVE: Our purpose was to develop a system for staging mucocutaneous leishmaniasis on the basis of clinical, histopathologic, epidemiologic, and immunologic criteria. METHODS: Seventy-five Bolivian patients with mucocutaneous leishmaniasis were evaluated by history and physical examination; cutaneous, mucosal, and bone marrow biopsy specimens; and immunologic assessment. RESULTS: Mucocutaneous leishmaniasis may progress through three clinical stages: (1) the primary or cutaneous, (2) the cicatricial, and (3) the secondary or mucocutaneous stages. The primary stage can be further subdivided into three phases: lymphoplasmocytic, tuberculoid, and diffuse cutaneous phases. The secondary stage can also be subdivided into three phases: edematous, granulomatous proliferative, and granulomatous necrotizing stages. CONCLUSION: A classification or staging system enhances the ability to evaluate patients with mucocutaneous leishmaniasis and determine more accurately their prognosis and treatment.

Adult↗

PubMedDate not supplied

[Disseminated cutaneous leishmaniasis due to Leishmania viannia braziliensis in the state of Maranhão, Brazil].

The authors describe a case of a patient from Barreirinhas, MA with disseminated cutaneous leishmaniasis, who presented 58 lesions spread all over his body, with many different aspects, but ulcerative lesions were predominant. They discuss the difficulty of laboratory diagnosis in the beginning of the investigation and its therapeutics implications. The parasite isolated was identified as Leishmania viannia braziliensis using monoclonal antibodies in the fluorescent antibody test. This form of the disease is different from the diffuse cutaneous leishmaniasis found in Maranhão, due to Leishmania (Leishmania) amazonensis which is responsible for most of the cases of cutaneous leishmaniasis in our state. The possible mechanisms of lesions dissemination are discussed.

Adult↗

PubMed1993

Serum levels of tumor necrosis factor in patients with American cutaneous leishmaniasis.

The purpose of this study was to evaluate serum levels of TNF-alpha in patients with either of the three clinical forms of American cutaneous leishmaniasis. The 86 patients examined were classified as having either the localized (LCL: 22 patients), mucocutaneous (MCL: 45 patients), or the rare diffuse (DCL: 19 patients) form of the disease. Our results show a significant increase in the mean level of TNF-alpha in the three groups of patients when compared to controls. MCL patients produce significantly higher levels of TNF-alpha than DCL patients. The proportion of individuals positive for serum TNF-alpha was significantly higher in both MCL and DCL patients than in the controls. No significant differences were found in the level of TNF-alpha when compared between before and after cure of 12 patients with MCL. There were no significant correlations between the level of TNF-alpha and the skin test diameter. The results will be discussed in terms of the pathogenesis of the disease in its different clinical forms.

Adolescent↗

PubMed1983

Characterization of the cellular immune response in American cutaneous leishmaniasis.

The in vitro and in vivo cellular immune reactivity of 49 patients with American cutaneous leishmaniasis (ACL) was evaluated using mitogens and parasite antigens. Patients were examined before treatment and were classified on the basis of clinical and histopathological criteria as suffering localized cutaneous leishmaniasis (LCL, 32 patients) or mucocutaneous leishmaniasis (MCL, 11 patients). A small group (6 patients) of treated diffuse cutaneous leishmaniasis (DCL) patients was also examined. The lymphocyte proliferative responses to PHA were significantly lower than those of controls (87 individuals, from either endemic or nonendemic zones) in LCL, and particularly MCL. Con A responses were, however, effectively normal in these patients. Both in vivo and in vitro cellular immune responses to leishmanial antigens were significantly greater in MCL and LCL patients than in the controls, the intensity of the reactions being by far the greatest in MCL. DCL patients demonstrated a complete absence of specific immune responsiveness both in vivo and in vitro. The significance of these results in the mechanisms leading to the resolution of the infection or production of pathologic lesions is discussed.

Adolescent↗

PubMed2004

Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review.

The wide variety of Leishmania species responsible for human American cutaneous leishmaniasis combined with the immune mechanisms of the host results in a large spectrum of clinical, histopathological, and immunopathological manifestations. At the middle of this spectrum are the most frequent cases of localized cutaneous leishmaniasis (LCL) caused by members of the subgenera Leishmania and Viannia, which respond well to conventional therapy. The two pathogenicity extremes of the spectrum generally recognized are represented at the hypersensitivity pole by mucocutaneous leishmaniasis (MCL) and at the hyposensitivity pole by anergic diffuse cutaneous leishmaniasis (ADCL). Following the present study on the clinical, histopathological and immunopathological features of cutaneous leishmaniasis in Amazonian Brazil, we propose the use of the term "borderline disseminated cutaneous leishmaniasis" for the disseminated form of the disease, due to parasites of the subgenera Leishmania and Viannia, which might be regarded as intermediate between LCL and the extreme pathogenicity poles MCL and ADCL.

Animals↗