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New aspects on cutaneous leishmaniasis.

Cutaneous Leishmaniasis today is still a persistent health problem in most parts of the world even in the nonendemic countries. In the first part of this work the general aspects of the disease are considered such as, the organism, the reservoir, the insect vector and the mode of transmission. Epidemiological data including the author's personal observations follow. The traditional clinical classification is mentioned as well as the "new aspects" of the clinical classification by the author as results from his histological investigation. The main points of this classification could be summarized as follows: a) The histologically characterized as granulomatous phase of this disease corresponds clinically to the papular-nodular ulcerated lesions (Acute Leishmaniasis). b) The histologically microtuberculoid phase corresponds clinically to chronic cutaneous Leishmaniasis. c) The Lupus vulgaris-like histological picture, corresponds clinically to the recidivans or late form of Cutaneous Leishmaniasis. This classification is conventional with several clinical criteria. Furthermore, immunology treatment and control of this disease are discussed.

Age Factors↗

Murine epidermal Langerhans cells are potent stimulators of an antigen-specific T cell response to Leishmania major, the cause of cutaneous leishmaniasis.

Cutaneous leishmaniasis is initiated by the bite of an infected sandfly and inoculation of Leishmania major parasites into the mammalian skin. Macrophages are known to play a central role in the course of infection because they are the prime host cells and function as antigen-presenting cells (APC) for induction of the cell-mediated immune response. However, in addition to macrophages in the dermis, the skin contains epidermal Langerhans cells (LC) which can present antigen (Ag) to T cells. Therefore, using a murine model of cutaneous leishmaniasis, we analyzed the ability of epidermal cells to induce a T cell response to L.major. The results demonstrated that freshly isolated LC, but not cultured LC, are highly active in presenting L.major Ag in vitro to T cells from primed mice and to a L.major-specific T cell clone. Furthermore, freshly isolated LC had the ability to retain L.major Ag in immunogenic form for at least 2 days. Their efficiency was much greater than that of irradiated spleen cells, a standard population of APC. LC stimulated both T cell proliferation and production of the lymphokines interleukin (IL)-2 and IL-4. The response was Ag specific and could be induced by lysate of L.major parasites and by live organisms. The data suggest that epidermal LC are important APC in cutaneous leishmaniasis. They may perform a critical function by capturing L.major Ag in the skin and presenting it either to quiescent T cells circulating through the draining lymph node or locally to T effector cells infiltrating the cutaneous lesion.

Animals↗

Conventional scraping versus fine needle aspiration cytology in the diagnosis of cutaneous leishmaniasis.

Cutaneous leishmaniasis is an endemic parasitic disease, the diagnosis of which is important for its successful management. Whereas conventional scraping is a technique widely employed for detecting the parasite, fine needle aspiration cytology (FNAC) is used rarely. The value of these two techniques for confirming the clinical diagnosis was compared prospectively in 46 cases. The study indicated that both methods are comparable if performed by trained individuals. However, FNAC is easier to perform and repeat and takes less time to demonstrate the organism. Therefore, FNAC is recommended as the method of choice in confirming the clinical suspicion of cutaneous leishmaniasis in endemic areas.

Adolescent↗

[Occupational medicine aspects of cutaneous leishmaniasis].

Cutaneous Leishmaniasis as an Occupational Disease We report 2 cases of cutaneous leishmaniasis with special regard to its significance for occupational health. Preventive measures are discussed as well as the difficulties in clarifying the diagnosis and therapeutic possibilities.

Dermatitis, Occupational↗

Expression of inducible nitric oxide synthase in human cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is an infectious disease caused by Leishmania parasite. The expression of inducible nitric oxide synthase (iNOS) and generation of nitric oxide in response to IFN-gamma and TNF-alpha is important in control of infection. The aim of the study was to determine the expression of iNOS in the lesions of Leishmania tropica, and whether there was a correlation between the level of expression and the duration of the disease. Punch biopsy was performed from patients (n = 29) and iNOS immunohistochemical staining was applied. Expression of iNOS protein was detected 82.8% of patients. There was a strong expression with the duration of the disease less than 6 months (p < 0.002). These findings demonstrate that iNOS has a role in L. tropica especially during the early stages of the infection.

Adolescent↗

Increased DNA damage and oxidative stress in patients with cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a chronic infectious and granulomatous disease caused by the Leishmania parasite that invades the skin. Reactive oxygen and nitrogen species (ROS and RNS) produced during an inflammatory response are an important part of host-defense strategies of organisms to kill the parasite. However, it is not well known whether these intermediates cause DNA damage in CL patients. We investigated the effect of Leishmania infection on basal levels of DNA strand breaks and on the oxidative/anti-oxidative status of patients with CL, and compared the data with those of healthy subjects. Twenty-five CL patients and 19 age- and sex-matched control subjects were enrolled in the study. We used the single-cell gel electrophoresis (also called comet assay) to measure DNA strand breaks in peripheral blood mononuclear leukocytes. Plasma protein carbonyl (PC), malondialdehyde (MDA) and total peroxide (TP) concentrations were measured to determine oxidative status and total anti-oxidative response (TAR) in plasma was measured to determine anti-oxidative status. The mean values of DNA damage and MDA and TP concentrations were significantly higher in CL patients than in the control group (p<0.001, p<0.01 and p<0.001, respectively). PC levels were also higher in patients, but this was not statistically significant (p>0.05). There was a significantly positive correlation between plasma MDA and DNA damage (r=0.524, p<0.01), and a negative correlation between TAR and TP levels (r=-0.790, p<0.001) in the patient group. These findings support the notion that ROS and RNS produced by the organism as a defense strategy may amplify the leishmanicidal activity in patients with CL. However, these intermediates not only cause the killing of the parasite but also induce oxidative damage in non-infected cells. Therefore, these patients must be treated urgently to counteract the oxidative DNA damage.

Adolescent↗

The contribution of the Fas/FasL apoptotic pathway in ulcer formation during Leishmania major-induced cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL), caused by the intracellular protozoan Leishmania major, is characterized by lesion formation and ulceration at the site of infection. The mechanism of ulcer formation during CL is not fully understood. The expression of Fas and FasL and the levels of apoptosis in skin biopsies and in restimulated blood mononuclear cells from patients with 1 to 7 months of L. major-induced CL were analyzed using immunohistochemistry and fluorescence-activated cell sorting analysis. The levels of soluble Fas and FasL were also analyzed by enzyme-linked immunosorbent assay. A substantial number of apoptotic keratinocytes were observed mainly in the superficial epidermis of morphologically active and healing CL skin samples. Fas expression was increased on epidermis in active CL, whereas Fas expression was similar in healing and healthy epidermis. FasL-expressing macrophages and T cells were found in subepidermal infiltrate, mainly in active disease. When CL peripheral blood mononuclear cells were restimulated with L. major, Fas was up-regulated on effector T cells, and high levels of sFasL were secreted. Supernatants from restimulated cultures induced apoptosis in human keratinocytes (HaCaT), possibly through Fas/FasL interactions. Our results indicate that FasL-expressing effector T cells and macrophages may act to induce apoptosis and ulcer formation in Fas-expressing keratinocytes during L. major infection.

Animals↗

Antigen presentation by epidermal Langerhans cells in experimental cutaneous leishmaniasis.

Cutaneous leishmaniasis is a disease induced by intradermal injection of leishmania promastigotes. Since the first cells the parasite encounters are those of the skin, the involvement of this organ in the early immune response might be relevant to the outcome of the disease. In this study we examined the ability of epidermal langerhans cells (LC) to become infected in vivo and to function as antigen presenting cells during the early hours of infection with Leishmania major. Our experiments showed that LC from mice injected with parasites can present antigen to a leishmania-specific T cell line when LC are obtained as early as four h after infection. The stimulation was specific, since LC from leishmania injected mice did not present antigen to an ovalbumin-specific T cell line nor did LC from ovalbumin-injected mice present antigen to the leishmania specific T cell line. Despite the ability of epidermal LC cells to present antigen, no parasites were detected in the epidermis, suggesting that these cells are not directly involved in establishing an infection.

Animals↗

[Cutaneous leishmaniasis].

Cutaneous leishmaniasis in its various forms is a frequent disorder in some parts of the world. It can represent an exotic souvenir for the traveller. Four main types of the disease are recognized. They have different prognoses of evolution. The parasite species, the animal reservoir and the geoclimatic environment influence the nature of human leishmaniasis.

Climate↗

The clinical picture of six Egyptian cases of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a skin disease encountered in the East Mediterranean Region including Egypt. In this paper, it was intended to throw some light on the clinical picture of six parasitologically proven human CL. Also, the results of treating three cases of them with Pontostam or Cryosurgery. The whole results were discussed.

Adult↗

The adjuvant effects of IL-12 and BCG on autoclaved Leishmania major vaccine in experimental cutaneous leishmaniasis.

Cutaneous leishmaniasis is a universal disease causing skin ulceration and deformity. A reliable vaccine remains to be a possible practical means of control. The amastigotes multiply intracellulary in macrophages provoking a cell-mediated type of immune response. IL-12 is the central cytokine of CMI. It is produced by sensitized macrophages, stimulates both Th1 and NK cells to secrete IFN-gamma which in turn activates the intracellular killing of Leishmania in macrophages via increased oxygen radicals. This work aimed mainly at studying the adjuvant effect of IL-12 on autoclaved L. major (ALM) vaccine, compared to that of BCG in L. major infection. The material included five groups of Swiss albino mice; the test group infected after receiving ALM+IL-12, a non-infected control group, and three other control groups infected after receiving ALM+BCG, IL-12 alone and BCG alone L. major was cultured to provide promastigotes for vaccine and infection. The measured parameters included the lesion size, type and progress; the parasite density and the level of IFN-gamma in serum. The results showed that the best protection against challenge infection was obtained by ALM + IL-12 followed by ALM + BCG. The former is recommended for use as a vaccine with regards to its proved efficacy and known safety.

Adjuvants, Immunologic↗

[Cutaneous leishmaniasis].

Cutaneous leishmaniasis is endemic in certain tropical and sub-tropical regions, and is sometimes encountered as an imported disease in Norway. The disease is characterized by chronic and painless, but often disfiguring, ulcers that regress after some months to years, leaving atrophic scars. Diagnosis is established by demonstrating amastigote Leishmania bodies by microscopy of Giemsa-stained smears from the periphery of the lesions. This report presents six cases seen in our department in the course of the last 14 years.

Adolescent↗

Early surgical treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis, treated or untreated, is known to leave disfiguring scars. These scars are usually on exposed parts, for which plastic surgery may be required. The present work deals with the treatment of cutaneous leishmaniasis using surgical techniques from the onset. In 20 patients, 35 lesions were excised down to the deep fascia. To cover the resulting defect, subcuticular sutures were used in 7 small lesions. Dufourmental (LLL flap) and Limberg flaps were used in 23 lesions of moderate size. Free grafting was resorted to in five large lesions. Using these techniques, morbidity was reduced and cosmetic results were satisfactory.

Adolescent↗

Evaluation of T cells, B cells and Ig. in tissues of human cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a granulomatous skin disease. The healing of the CL. lesions is attributed to the delayed immunity developed against the amastigotes of the parasite. However, in some cases in spite of the development of strong delayed hypersensitivity CL. lesions failed to heal. In this paper, it was intended to assess the role of immunity in the lesions of human cutaneous leishmaniasis. The results showed that the helper cells predominated the suppressor ones, the mean percentage of B lymphocytes was 25 and the immunoglobulins particularly the IgG were demonstrated by being positively stained. On the other hand, the complement (C3) was within the normal range.

B-Lymphocytes↗

Resistance to macrophage-mediated killing as a factor influencing the pathogenesis of chronic cutaneous leishmaniasis.

Cutaneous leishmaniasis can be either a spontaneously healing or chronic disease, depending upon the strain of parasite and the immunological status of the host. We have investigated parasite factors responsible for the variable pathogenesis observed in leishmanial infections by testing the sensitivity of several leishmanial strains to intracellular killing in lymphokine (LK) activated mouse macrophages. Significant microbicidal activity against Leishmania tropica, a strain which heals in C57BL/6 (B6) mice, was found. In contrast, a strain (Maria) which has previously been shown to induce chronic nonhealing cutaneous lesions in B6 mice was resistant to killing in activated macrophages. This resistance to killing was observed in macrophages activated by LK obtained from either Bacille Calmette-Guérin-, L. tropica, or the Maria strain infected mice. The inability of LK activated macrophages to kill the Maria strain was shown not to be due to parasite induced inhibition of killing mechanisms, since Maria strain infected, LK treated macrophages exhibited tumoricidial activity similar to uninfected macrophages. Furthermore, LK activated macrophages simultaneously infected with the Maria strain and another intracellular pathogen, Toxoplasma gondii, killed Toxoplasma, but not the Maria strain. Temperature was also found to significantly influence the multiplication and killing of Leishmania parasites. As would be expected from their cutaneous nature, L. tropica and Maria strain parasites multiplied better at 35 degrees C than at 37 degrees C. Also consistent with the failure of cutaneous strains to visceralize in immunocompetent mice was the observation that the killing of leishmanial parasites was enhanced at the higher temperature. Thus, the temperature dependent growth capacity and sensitivity to killing of a given leishmanial strain in macrophages may be important factors influencing the pathogenesis of cutaneous leishmaniasis.

Animals↗

Think cutaneous leishmaniasis.

Cutaneous leishmaniasis is now seen in non-endemic areas, especially in travellers to and troops serving in the Middle East. It was a common problem among American troops returning from the Gulf war. This article presents the clinical manifestations, the laboratory findings and the treatment options for this disease.

Administration, Cutaneous↗

Topical chemotherapy of cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) is one of the most important causes of chronic ulcerative skin lesions. The disease is endemic in many parts of the world, presenting a range of clinical forms - acute, chronic, recurrent and diffuse(1). Several species of Leishmania are involved, including L. major, L. tropica and L. aethiopica in the Old World, and several members of the L. braziliensis and L. mexicana complexes in the New World. Some forms of the disease produce only mild, self-limited lesions, while at the other extreme are the destructive mucocutaneous forms caused by L. braziliensis and L. panamensis(1-7). In all cases, chemotherapy tends to be difficult - often requiring prolonged parenteral administration of toxic drugs such as pentavalent antimonials or amphotericin B. Such drugs are also expensive and relatively inefficient in the sense that much of the active ingredient is excreted by the patient before reaching its target. Consequently, there is renewed interest in the development of active formulations suitable for topical application directly onto the lesions.

Journal Article↗