Evaluation of the histopathological classifications of American cutaneous and mucocutaneous leishmaniasis

In order to evaluate the reliability of histopathological classifications of cutaneous and mucocutaneous leishmaniasis the authors compared the histopathological patterns of two biopsies taken simultaneously from the same patient, and classified the material according to Ridley et al. (1980), to Magalh?es et al. (1986a), and to a more simplified classification with only three patterns. Distinct histopathological aspects were observed in different lesions or even in the same lesion. The authors concluded that histopathological patterns do not represent a stage of tegumentary leishmaniasis, thus they can not be correlated with prognosis and therapeutical response as suggested in the literature.     

Constitutive nitric oxide synthase-like enzyme in two species involved in cutaneous and mucocutaneous leishmaniasis

Leishmania is an obligate intracellular parasite that primarily inhabits macrophages. The destruction of the parasite in the host cell is a fundamental mechanism for infection control. In addition, inhibition of the leishmanicidal activity of macrophages seems to be related to the ability of some species to inhibit the production of nitric oxide (NO) by depleting arginine. Some species of Leishmania have the ability to produce NO from a constitutive nitric oxide synthase-like enzyme (cNOS-like). However, the localization of cNOS-like in Leishmania has not been described before. As such, this study was designed to locate cNOS-like enzyme and NO production in promastigotes of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis. NO production was initially quantified by flow cytometry, which indicated a significant difference in NO production between L. (L.) amazonensis (GMFC = 92.17 +/− 4.6) and L. (V.) braziliensis (GMFC = 18.89 +/− 2.29) (P < 0.05). Analysis of cNOS expression by immunoblotting showed more expression in L. (L.) amazonensis versus L. (V.) braziliensis. Subsequently, cNOS-like immunolabeling was observed in promastigotes in regions near vesicles, the flagellar pocket and mitochondria, and small clusters of particles appeared to be fusing with vesicles suggestive of glycosomes, peroxisome-like-organelles that compartmentalize the glycolytic pathway in trypanosomatid parasites. In addition, confocal microscopy analysis demonstrated colocalization of cNOS-like and GAPDH, a specific marker for glycosomes. Thus, L. (L.) amazonensis produces greater amounts of NO than L. (V.) braziliensis, and both species present the cNOS-like enzyme inside glycosomes.     

Tumour necrosis factor alpha and mucocutaneous leishmaniasis

Allelic associations between polymorphisms at the tumour necrosis factor (TNF) locus within the major histocompatibility complex (MHC) and susceptibility to a range of autoimmune and infectious diseases have been established in humans. Among these is the severe and debilitating mucocutaneous form of leishmaniasis (MCL) caused by Leishmania braziliensis. This was preempted by the demonstration of high levels of circulating TNF-alpha in the sera of patients presenting with clinical mucocutaneous disease. Here, Jennie Blackwell looks at the implications this might have for the diagnosis and treatment of mucocutaneous disease, and the broader implications that the positive and negative immunomodulatory roles of TNF-alpha have in maintaining apparently detrimental alleles in the population.     

Note on the history of cutaneous leishmaniasis in the Mediterranean and Middle East area

There exist records of what seems to be cutaneous leishmaniasis at least as far back as 650 BC, and possibly much earlier in the Tigris/Euphrates basin. It was described by Avicenna in the 10th century AD, and was well-known in Aleppo and Baghdad by the 18th century AD. Cutaneous leishmaniasis due to Leishmania infantum may have occurred in Crete in the 18th century. Artificial transmission was effected in Algeria and Aleppo in the 18th century.     

Experimental canine mucocutaneous leishmaniasis (Leishmania braziliensis braziliensis)

Four mongrel dogs were intradermically inoculated with 3 x 10(6) Leishmania braziliensis braziliensis promastigotes. Three out of the four animals developed cutaneous lesions respectively 4, 7, and 8 months after. The fourth dog did not develop lesion at the inoculation site, but a mucosal ulcer was seen 16 months after the inoculum. Clinical, histopathological, and serological findings were similar to what is found in natural canine infection as well as in the human disease. These results suggest that dogs may be an useful model for L. b. braziliensis infection.     

Immunobiology of experimental cutaneous leishmaniasis

The study of the murine model of infection with Leishmania major is providing important insights into the understanding of the complex interactions between the host and intracellular pathogens. Using this model system, basic research is actively leading to the identification of host factors promoting or circumventing the development of immunity to L. major. Here, Geneviève Milon, Giuseppe Del Giudice and Jacques A. Louis review recent results related to the characterization of immunological host factors determining resistance and susceptibility to this parasite, and try to identify areas where further research is required for a better understanding of the complex events triggered by intracellular parasites within their hosts. Extrapolation to the human leishmaniases of the rapid advances made in this murine model of infection, should pave the way to the rational design of future immunoprophylactic and immunotherapeutic measures.     

Miltefosine for disseminated cutaneous leishmaniasis

Disseminated cutaneous leishmaniasis is a rare presentation characterized by hematogenous dissemination of the parasite that causes the appearance of multiple nodules and plaques in the skin of the whole body and even including the nasal mucous membrane. It differs from diffuse cutaneous leishmaniasis because the alteration in cellular immunity is lower and the lesions may have epidermal desquamation. On the other hand, diffuse cutaneous leishmaniasis presents nodular lesions and a specific anergy in the immune response directed against the parasite. This article describes the case of a Colombian patient with disseminated cutaneous leishmaniasis caused by L. (V) panamensis. The initial treatments with Glucantime and Amphotericin B failed, but his lesions healed after treatment with miltefosine.     

Immunologic memory in cutaneous leishmaniasis

Leishmania major infections induce solid immunity to reinfection. Experimental studies in mice indicate that the CD4+ T cells responsible for this immunity include two populations: parasite-dependent T effector cells and parasite-independent central memory T (Tcm) cells. While there currently is no vaccine for leishmaniasis, the existence of a long-lived population of Tcm cells that does not require the continued presence of live parasites suggests that a vaccine that expands these cells might be efficacious.     

Vectors of cutaneous leishmaniasis in north-central Venezuela

Abstract. An entomological survey was undertaken from January 1991 to February 1992 in El Ingenio, Miranda State, Venezuela, an endemic area of cutaneous leishmaniasis: prevalence of 10.7 cases per 100,000 inhabitants.
A total of 4863 female sandflies (Phlebotominae) of fourteen species were collected in Shannon traps, then dissected and examined for leishmanial infections.
Lutzomyia ovallesi (85.4%) and Lu. gomezl (11.2%) were the predominant anthropophilic species of sandfly. Fifty-one (1.19%) Lu. ovallesi and two(0.47%) Lu. gomezi had natural infection with Leishmania promastigotes. Identification of the parasites was done by using the polymerase chain reaction (PCR) and DNA hybridization. Two isolates from Lu. gomezi and forty-nine from Lu. ovallesi were typed as Leishmania braziliensis and three of the latter reacted with Le. mexicana also. This is the first report of Lu. gomezi with parasites typed as Le. braziliensis.
We concluded that Lu. ovallesi is the primary vector of cutaneous leishmaniasis in the north-central area of Venezuela and Lu. gomezi should be regarded as an additional vector.     

Concordance of leishmaniasis cutaneous tests in Tunisia

A cross sectional study aimed to evaluate the effect of antigenic preparation (Leishmania infantum versus Leishmania major) and dose of leishmania antigens (5 x 10(6) versus 2.5 x 10(6) parasites in the same volume) on the reproducibility of delayed type hypersensitivity leishmania skin test. Results showed that among 34 individuals involved from visceral leishmaniasis endemic area. 26 (76.5%) had a positif Leishmania infantum leishmania (L-L. infantum) test and 27 (79.4%) to Leishmania major leishmania (L-L. major). Mean size of cutaneous reaction was 5.94 +/- 2.86 mm for L-L. infantum and 5.41 +/- 3.23 mm for L-L. major, with a significant positive linear association (p < 10-3). Intra-class correlation coefficient was 0.80 (CI95% = [0.64-0.93]) and concordance Kappa (kappa) was 0.57 (CI95% = [0.40-0.74]). Among 153 individuals from zoonotic cutaneous leishmaniasis. 92.9% revealed a positive test for both types of leishmanin (L-L. major full dose versus L-L. major half dose). Mean size of cutaneous reaction was 12.61 +/- 4.65 mm for the reference test and 11.30 +/- 3.95 mm for diluted one, with a positive linear association (p < 10-3). Intra-class correlation coefficient was 0.78 (IC95% = [0.71-0.84]) and concordance Kappa (kappa) was 0.82 (IC95% = [0.73-0.91]). These results demonstrate a limited effect of leishmania antigenic variation and antigen dose on the reproducibility of delayed type hypersensitivity induced by the leishmanin test.     

Detection of amastigotes in cutaneous and mucocutaneous leishmaniasis using the immunoperoxidase method, using polyclonal antibody: sensibility and specificity compared with conventional methods of diagnosis

The indirect immunoperoxidase method was evaluated in 265 biopsies with the purpose of increasing the sensitivity of the diagnostic histopathology of tegumentary lesions caused by subspecies of the Leishmania braziliensis complex. A diagnosis of leishmaniasis was established by parasitological methods (181) or clinical criteria (12) in 193 patients (72.8%). In the latter group of confirmed cases standard histochemistry and immunoperoxidase were compared with direct examination of tissue scraping and culture of lesion aspirates. The detection and localization of amastigotes was more efficient using the immunoperoxidase method (61.3%) than conventional histopathology with hematoxilin and eosin (34.6%) or direct examination of tissue scraping (43.9%). However, culture of lesion aspirates was the most sensitive procedure (89.8%). The efficiency of the immunoperoxidase method was greater in recent lesions, being positive in 75% of cases with less than 3 months evolution, while 55.6%, 37.5%, and 21.1% of cases with lesion evolution of 3-5.9, 6-11, and 12 months or greater, respectively, were positive. The combined use of the direct examination of lesion scraping and immunoperoxidase applied to histological sections of the biopsy from the lesion border allowed an etiologic diagnosis of 72% of confirmed cases. Cross-reactivity was observed with Paracoccidioides braziliensis but not with Mycobacterium leprae, Sporothrix schenckii, or Histoplasma capsulatum.     

Immunologic responsiveness in American cutaneous leishmaniasis lesions

American cutaneous leishmaniasis is a disease of skin and mucous membranes in which T lymphocytes reactive to Leishmania (Viannia) braziliensis are thought to contribute to protective immunity. To characterize the nature of the T cell inflammatory infiltrate in American cutaneous leishmaniasis lesions, immunohistochemistry with mAb that define T cell subpopulations and in situ hybridization to detect mRNA coding for IFN-gamma were performed. In both localized cutaneous (LCL) and mucocutaneous (MCL) lesions, we observed a predominance of T memory (CD4+CD45RO+) as compared to T naive cells (CD+CD45RA+). The percentages of cells containing IFN-gamma mRNA were equivalent in both LCL and MCL lesions. T cells were extracted from LCL and MCL lesions and analysis indicated that T cells from both lesions had been stimulated by L. (V.) braziliensis in vivo and gave equivalent proliferative responses in vitro. The present data suggest that T memory cells, which are likely to elaborate IFN-gamma, are components of DTH response to L. (V.) braziliensis and participate in the pathogenesis of both LCL and MCL lesions.     

Effects of ultraviolet B irradiation on cutaneous leishmaniasis

Protection against many infectious diseases is mediated by cellular immunity in the competent host. Ultraviolet (UV) radiation, a component of sunlight, is a potent suppressor of cell-mediated immune responses. Suzanne Holmes Giannini discusses the possible relevance of ambient levels of UVB to pathogenesis and immunity in infectious diseases, with special reference to cutaneous leishmaniasis.