Forms Of Cutaneous Leishmaniasis Research Articles

CD26 expression on CD4+ T cells in patients with cutaneous leishmaniasis

Surrogate marker(s) of protection in human leishmaniasis is not well defined. In this study, T helper 1 (Th1) and Th2 cytokine profiles and CD26 expression on CD4(+) T cells in peripheral blood mononuclear cells of patients with healing or non-healing forms of cutaneous leishmaniasis (CL) stimulated with Leishmania antigens were assessed. The level of interferon (IFN)-gamma production was significantly higher in patients with healing or non-healing forms of CL than in healthy controls, but it was not significantly different between the two patient groups. The level of interleukin-5 production was significantly higher in patients with the non-healing form of CL than in the two other groups. There was a significant increase in the level of CD26 expression on CD4(+) T cells in patients with healing (P < 0.001) or non-healing (P = 0.025) forms of CL compared with the control group, but no significant difference was seen between the two patient groups. A weak positive correlation was seen between IFN-gamma production and CD26 expression on CD4(+) T cells of patients with the healing form of lesion (r = 0.54, P = 0.008), but this correlation was not observed in patients with the non-healing form of CL (r = 0.53, P = 0.078). Surface CD26 is not correlated with the clinical manifestation of CL or IFN-gamma production. Therefore, CD26 is not a surrogate marker for IFN-gamma production in CL.

Anatomo-clinical features of an erysipeloid form of cutaneous leismaniasis in Tunisia

The erysipeloid form of cutaneous leishmaniasis is considered as an unusual and rare clinical presentation in Tunisia. Our prospective study on 4 observations, aimed at examining the clinical, histological and progressive features of the "erysipeloid" form of cutaneous leishmaniasis. Our patients were 3 females and one male more than 62 years old. Their cutaneous leishmaniasis was clinically characterised by an infiltrated and extensive plaque which was localised on the face covering the nose and cheeks looking like erysipelas. The treatment was intramuscular meglumine antimoniate (Glucantime) in three cases and metronidazole in one case. A regression without scar was noticed in all the cases. On the histological examination, we observed an intense epidermic and constant hyperplasia with presence of amastigotes in 3 cases. Our study shows the lesional polymorphism of the old word cutaneous leishmaniasis in our region. The "erysipeloid" form of cutaneous leishmaniasis is a rare clinical presentation which generally affects women. If the clinical aspect is very meaningful, the histological aspect is meaningful but not specific.

Immunity and immunosuppression in experimental visceral leishmaniasis.

Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL)-2, interferon (IFN)-gamma, and IL-12, the latter in a mechanism independent of IFN-gamma and linked to transforming growth factor (TGF)-beta production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-beta as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

Leishmania mexicana mexicana: Genetic Heterogeneity of Mexican Isolates Revealed by Restriction Length Polymorphism Analysis of Kinetoplast DNA

Berzunza-Cruz, M., Bricaire, G., Zuluoaga Romero, S., Pérez-Becker, R., Saavedra-Lira, E., Pérez-Montfort, R., Crippa-Rossi, M., Velasco-Castrejón, O., and Becker, I. 2000. Leishmania mexicana mexicana: Genetic heterogeneity of mexican isolates revealed by restriction length polymorphism analysis of kinetoplast DNA. Experimental Parasitology95, 277–284. Leishmania mexicana mexicana isolates from 23 patients with localized, diffuse, and an atypical “pseudodiffuse” form of cutaneous leishmaniasis were obtained in various endemic regions of Mexico. Restriction fragment length polymorphism analysis of kinetoplast DNA was done with nine different endonucleases in addition to an in vitro growth pattern analysis. We found that the 23 L. mexicana mexicana isolates could be consistently classified into six groups, according to the endonuclease digestion patterns obtained with HaeIII, HpaII, and MseI. Whereas localized cutaneous leishmaniasis isolates could have any of five patterns, diffuse cutaneous leishmaniasis showed only two patterns and pseudodiffuse cutaneous leishmaniasis consistently showed only one pattern. Thus, a clear correlation among digestion pattern, clinical disease, and geographical localization was obtained for the pseudodiffuse cutaneous leishmaniasis group. Additionally, the L. mexicana mexicana isolates could be differentiated into fast- and slow-growing groups. Diffuse cutaneous leishmaniasis isolates were found to be fast growing, whereas localized cutaneous leishmaniasis isolates fell into both categories. In contrast, all pseudo diffuse cutaneous leishmaniasis isolates were slow growing. Here we report the first study in which distinct and persistent genotypic characteristics of kinetoplast DNA heterogeneity within the L. mexicana mexicana species could be directly correlated with clinical disease and its growth behavior, suggesting that a distinctive restriction pattern could have important biological implications. Additionally, this study sheds new light on the biological significance of parasite kinetoplast DNA, since the heterogeneity seems not to be random but to form a distinct pattern.

Leishmania:Amastigotes Synthesize Conserved Secretory Acid Phosphatases during Human Infection

Ellis, S. L., Shakarian, A. M., and Dwyer, D. M., 1998.Leishmania:Amastigotes synthesize conserved secretory acid phosphatases during human infection.Experimental Parasitology89, 161–168.Leishmania donovaniis the major causative agent of Old World human visceral leishmaniasis (VL).In vitro, both promastigotes and axenic amastigotes ofL. donovaniconstitutively secrete soluble acid phosphatases (SAcPs), which contain conserved antigenic epitopes. These SAcPs are the most abundant and best characterized secretory proteins of this parasite. The aim of this study was to determine whether this enzyme was produced by intracellular amastigotes during the course of human infection. To that end, sera from acutely infected leishmaniasis patients were tested for anti-SAcP antibodies usingL. donovanipromastigote culture supernatants. Our results showed that VL patient sera from different endemic foci immunoprecipitated parasite SAcP enzyme activity. Further, these VL patient sera recognized the 110- and 130-kDa SAcPs in both Western blots and radioimmunoprecipitation assays. Results of tunicamycin experiments demonstrated that VL patient anti-SAcP antibodies were directed against the polypeptide backbone of the parasite SAcPs. In addition, both radiolabeledL. donovaniSAcPs and native enzyme activities were immunoprecipitated by sera from patients with various forms of cutaneous leishmaniasis. Together, these studies demonstrate thatLeishmaniaamastigotes produce SAcPs during the course of human infections.

Activity of Pentostam (Sodium stibogluconate) against Cutaneous Leishmaniasis in Mice Treated with Neutralizing Anti-Interferon-γ Antibody

Studies with Leishmania donovani in the mouse have demonstrated that an intact T cell compartment is required for effective anti-leishmanial therapy using pentavalent antimony compounds such as Pentostam (sodium stibogluconate), suggesting that the in vivo efficacy of drug treatment is at least partially immune-based. Similarly, Leishmania-infected, immunodeficient human patients including those with acquired immunodeficiency syndrome (AIDS) generally relapse following therapy with antimonials. However, sodium stibogluconate is directly parasiticidal in vitro, in the absence of T cells or T cell products. Using a model of a cutaneous form of leishmaniasis, in which susceptible BALB/c mice were infected with Leishmania major, we investigated whether the antileishmanial activity of the drug demonstrated a requirement for interferon-gamma (IFN-gamma), a cytokine produced during a T helper cell type 1 (Th1) immune response and known to contribute to resistance to infection, and whether drug therapy affected the nature of the antileishmanial response. Lesion development was suppressed in mice treated from the onset of infection with sodium stibogluconate alone, and in animals treated with sodium stibogluconate plus a neutralizing anti-IFN-gamma antibody, and tissue parasite burdens were approximately 10,000-fold less at the end of therapy in both groups compared with controls. Lesion development was similarly suppressed in mice with established lesions treated with either sodium stibogluconate alone, or sodium stibogluconate plus anti-IFN-gamma antibody. The production of IFN-gamma by cells from infected animals was somewhat increased immediately following therapy with sodium stibogluconate, an effect that was not long-lasting, while interleukin-4 (IL-4) production was not affected by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Leishmaniasis and itraconazole: a controlled clinical trial on cutaneous subtypes

Ten patients each with the nodular and ulcerative forms of cutaneous leishmaniasis were selected by clinical and pathological criteria. Capsule itraconazole was given in a daily dose of 4 mg per kg body weight (max. 200 mg) for 6 weeks. Six patients (60.0%) of the nodular and nine patients (90.0%) of the ulcerative subgroups were cured by strict clinical and parasitological criteria. No major adverse effects were noted. Review after 6 months revealed no recurrences. In another ten patients (control group) not receiving any drug, the lesions showed no significant change except for one patient demonstrating spontaneous remission. Thus, itraconazole has a promising antileishmanial potential in India.

Andean leishmaniasis in Ecuador caused by infection with Leishmania mexicana and L. major-like parasites.

Between 1986 and 1988, epidemiologic studies were carried out in a small rural community in an Andean region of Ecuador, where cutaneous leishmaniasis is highly endemic. A total of 25 human cases, positive for Leishmania parasites by culture and/or smear, were examined. Fourteen of the cases were in infants less than one year of age, suggesting intradomiciliary transmission of the disease. Clinically, many of these cases were similar to descriptions of "uta," a form of cutaneous leishmaniasis which occurs in Andean regions of Peru and is reported caused by L. peruviana. Of the 11 positive cultures obtained from human cases in the present study, eight were identified by molecular characterization as L. mexicana and three were identified as L. major-like. Two additional isolates of L. mexicana were also made from an infected dog and from a sand fly, Lutzomyia ayacuchensis, living in the region, thus implicating the latter species as possible reservoir and vector, respectively, of L. mexicana in this highland community. The significance and validity of recent isolates of L. major-like parasites from the New World are also discussed.

Generation of species-specific DNA probes for Leishmania aethiopica

We report here the cloning of kinetoplast DNA (kDNA) sequences from Leishmania aethiopica in order to develop a specific and sensitive method for the identification of the parasite. Analysis of the cloned kDNA sequences showed different taxonomic specificities demonstrating sequence diversity within the kinetoplast DNA. Cloned whole minicircle hybridized with all Old World Leishmania species tested. Some cloned fragments of minicircle kDNA hybridized with Leishmania species causing cutaneous leishmaniasis in the Old World, but not with the viscerotropic species. Two L. aethiopica-specific clones were found. These clones hybridized with all L. aethiopica isolates tested, but did not react with other Leishmania species. The nucleotide sequence of the L. aethiopica-specific R3 clone is presented. Clones hybridizing with only some of the L. aethiopica isolates were also identified, although none of them showed specificity only for isolates causing localized (LCL) or diffuse (DCL) form of cutaneous leishmaniasis in Ethiopia.

Cutaneous leishmaniasis: relative role of T cell subsets.

Leishmanias are protozoan parasites which are transmitted to their mammalian host by the bite of a sandfly vector (1). Upon entering the host, the flagellated promastigote form of the parasite which is injected by the sandfly is phagocytized by mononuclear phagocytic cells in which it transforms into the aflagellate amastigote form. Following infection of man by Leishmania several different forms of disease can ensue which depend upon the species of Leishmania carried by the sandfly. For example, a cutaneous form of leishmaniasis can be caused by L. major, L. mexicana or L. braziliensis a mucocutaneous form by L. braziliensis and a visceral form by L. donovani In addition, a spectrum of clinical manifestations can be observed in patients suffering from each of these forms of the disease which suggests that the pathologic changes observed in leishmaniasis are due to both the species of the infecting parasite and to the host response to the parasite.KeywordsCutaneous LeishmaniasisSurface PhenotypeLesion ProgressionCell Deficient MouseMajor Histocompatibility AntigenThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Chemotherapy of Experimental Leishmania enriettii Infection

ConclusionsThere is a parallelism between the chemotherapeutic results observed by us(5) in the cutaneous L. brasiliensis infection of mice, and those obtained in the cutaneous guinea pig (L. enriettii) leishmaniasis.According to results so far obtained, cutaneous infection of the guinea pig with L. enriettii has the drug sensitivity of cutaneous L. brasiliensis infection, which is not affected by Pentostam, tartar emetic and hydroxy-stilbamidine. Glucantime treatment gave prompt therapeutic results. It is likely that the higher effect of Glucantime depends on its great tolerance and on the large amounts of pentavalent antimonials which can be given in this form. The L. enriettii infection, not contagious for man, represents under these conditions a useful method of searching for new therapeutic agents effective against the human form of cutaneous leishmaniasis. Both these cutaneous infections have a different drug sensitivity than L. donovani; whether this difference depends on the specific drug sensitiv...

AMERICAN LEISHMANIASIS

On a recent trip to Peru to study verruga peruana, I saw some cases of cutaneous leishmaniasis and discussed this subject with numerous Peruvian colleagues. Following my visit to Sao Paulo, Brazil, in 1929, I realized that there was a form of cutaneous leishmaniasis which occurs mainly in the forest regions of the Americas, extending from Mexico to the northern part of Argentina. 1 This disease has been observed in every country of South America except Chile, though by far the greatest number of cases are found in the tropical forests of Brazil, Peru and Bolivia. The type of leishmaniasis in question differs clinically from oriental sore in that it affects the mucous membranes of the nose and throat in perhaps 20 per cent of the cases and as a result may cause permanent and often severe deformity. The investigations of Noguchi, in 1925, by agglutination tests apparently showed that