Case Report: Diffuse Cutaneous Leishmaniasis by Leishmania infantum in a Patient Undergoing Immunosuppressive Therapy: Risk Status in an Endemic Mediterranean Area.

This case report highlights the risk of severe cutaneous leishmaniasis (CL) by Leishmania infantum in patients undergoing immunosuppressant therapy who either live in an endemic area or are visiting in the transmission season. The case patient, resident in Majorca (Balearic Islands), presented 12 disseminated erythematous skin lesions, 1-6 cm in diameter, located on the scalp, cheek, umbilical region, and lower extremities 8 years after undergoing anti-tumor necrosis factor (TNF) therapy. Parasite presence in peripheral blood and high levels of specific antibodies were also observed, indicating a possible risk of CL shifting toward a visceral infection. However, once CL was diagnosed, anti-TNF therapy was discontinued and liposomal amphotericin B was administered, resulting in a complete healing of lesions, no Leishmania DNA detection in blood, and an important serological decrease in antibodies. The lack of data on the supposed epidemiological association between leishmaniasis and immunosuppressive therapy highlights the importance of implementing surveillance systems in endemic areas. No obvious relationship was found based on the data provided by the Balearic Islands Epidemiological System, in contrast with data reported in nearby endemic areas. This indicates that if the suspected association is to be clarified, greater efforts are needed to report information about concomitant diseases and therapies in leishmaniasis patients.

Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis.

Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8⁺ T cells following infection with the intracellular parasite Leishmania, CD8⁺ T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8⁺ T cells from lesions exhibited a cytolytic phenotype. To determine if CD8⁺ T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8⁺ T cells. In mice with severe pathology, we visualized CD8⁺ T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8⁺ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8⁺ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.

Diffuse skin spread of HIV-associated visceral leishmaniasis: cumbersome diagnostic and therapeutic issues.

An infrequent and atypical case report of HIV-associated visceral leishmaniasis complicated by a diffuse, aspecific maculo-papular cutaneous involvement was characterized by a prolonged course, and a lack of response to repeated attack/maintenance cycles performed with liposomal amphotericin B, despite a satisfactory immune response maintained thanks to a concurrent, potent combination antiretroviral treatment. Only a very prolonged administration of the older i.v. pentamidine isethionate together with oral paromomycin led to a slow, but complete cure of both visceral leishmaniasis and its related skin dissemination, in absence of adverse events and long-term disease relapses.

[Disseminated cutaneous leishmaniasis secondary to lymphoedema: two cases]. / Leishmaniose cutanée disséminée sur lymphoedème: deux cas.

BACKGROUND: Dissemination of cutaneous leishmaniasis may take various forms: satellite papules, sporotrichoid nodules and widespread papulonodular lesions (disseminated cutaneous leishmaniasis). We describe a particular clinical form of dissemination in two patients with erysipelas secondary to lymphoedema. PATIENTS AND METHODS: Case 1. A 75-year-old man with diabetes consulted for erysipelas of the leg secondary to lymphoedema. The site of entry was an infected cutaneous leishmaniasis lesion. The initial outcome was favourable under intravenous penicillin G treatment. Twelve days later, some fifty papulonodular lesions appeared and were strictly limited to the erythematous erysipelas plaque. PCR screening of papulonodular lesion smears for Leishman bodies was positive. Histological examination of skin biopsy samples showed lobular panniculitis. Case 2. A 64-year-old woman with diabetes presented erysipelas in the right upper limb secondary to lymphoedema scattered with multiple erythematous, infiltrated, papular lesions in a setting of cutaneous leishmaniasis lesions. PCR analysis of smears taken from the secondary nodular lesions demonstrated the presence of leishmaniasis, while histological analysis of biopsy samples revealed panniculitis. DISCUSSION: Disseminated cutaneous leishmaniasis is characterized by the appearance of multiple (>10) pleomorphic lesions on two or more noncontiguous areas of the body. Our two patients presented certain features of disseminated cutaneous leishmaniasis. However, they were unusual in terms of the strict localisation of nodular lesions to the erysipelas plaque. This particular aspect suggests haemolymphatic dissemination of the protozoan infection from the initial lesion as a result of local factors.

An unusual presentation of post-kala-azar dermal leishmaniasis.

An atypical presentation of post-kala-azar dermal leishmaniasis is reported to highlight the importance of suspecting dermatosis in patients from areas endemic for kala-azar.

Successful treatment with miltefosine of disseminated cutaneous leishmaniasis in a severely immunocompromised patient infected with HIV-1.

We describe here a case of disseminated cutaneous leishmaniasis due to Leishmania major in a severely immunocompromised patient from Burkino Faso, Africa, who is infected with human immunodeficiency virus-1. The skin lesions failed to respond to full treatment courses of amphotericin B, sodium stibogluconate, and liposomal amphotericin B but were successfully treated with miltefosine, an alkylphosphocholine analogue.

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.

Impaired expression of inflammatory cytokines and chemokines at early stages of infection with Leishmania amazonensis.

Infection of mice with Leishmania major results in disease progression or resolution, largely depending on the genetic backgrounds of the mouse strains. Infection with Leishmania amazonensis, on the other hand, causes progressive cutaneous lesions in most inbred strains of mice. We hypothesized that deficient activation of early immune responses contributes to the pathogenesis in L. amazonensis-infected mice. To distinguish early molecular events that determine the outcome of Leishmania infections, we examined cytokine gene expression in C57BL/6 mice infected with either L. amazonensis or L. major (a healing model). After 2 to 4 weeks, L. amazonensis-infected mice had significantly delayed and depressed expression of inflammatory cytokines (interleukin-12 [IL-12], gamma interferon, IL-1 alpha, IL-1 beta), CC chemokines (CC chemokine ligand 3 [CCL3]/macrophage inflammatory protein 1 alpha [MIP-1 alpha], CCL4/MIP-1 beta, CCL5/RANTES, MIP-2), and chemokine receptors (CCR1, CCR2, CCR5) in foot tissues and draining lymph nodes compared to the expression in L. major-infected controls. These findings correlated with defective T-cell responsiveness to parasite stimulation in vivo and in vitro. Adoptive transfer of L. amazonensis-specific Th1 cells prior to infection overcame the immune defects of the animals, leading to complete control of the disease. Studies with gene knockout mice suggested that IL-10, but not IL-4, contributed partially to compromised immunity in L. amazonensis-infected hosts. The data suggest that there is impairment in multiple immune functions at early stages of infection with L. amazonensis parasites and provide a compelling rationale to explore immune augmentation as an intervention in American cutaneous leishmaniasis.

A leishmaniose tegumentar sob a perspectiva do paciente: resultado de uma prática educativa / Cutaneous leishmaniasis under the patient's perspective: an educational practice result

Foi realizado um estudo descritivo empregando a metodologia qualitativa entre portadores de leishmaniose tegumentar visando identificar a representatação que a doença tem para o seu portador, antes e depois do tratamento e intervenção educacional. O estudo foi realizado de setembro de 2000 a março de 2001 no Estado do Paraná, Brasil. Para a coleta dos dados foi realizada a entrevista semi-estruturada, sendo que os membros foram analisados pela técnica do discurso do sujeito coletivo. Foram destacadas as idéias centrais relacionadas com a etiologia da leishmaniose, sua transmissão/prevenção, gravidade, estigma, dificuldades do tratamento, sentimentos frente à doença e validade da educação em saúde.este estudo evidenciou que o acompanhamento dos pacientes e as medidas educacionais são de fundamental importãncia para que o grupo social assuma um maior controle sobre sua saúde, auxiliando sobremaneira no enfrentamento da doença e seu tratamento.

A descriptive study was carried out among cutaneous leishmaniasis patients using the qualitative methodology, aiming to identify the role that the disease has to its suffers both before and after treatment and educational intervention. The study was carried out from September 2000 to March 2001 in the state of Paraná, Brazil...

Genetic variability within the species Leishmania aethiopica does not correlate with clinical variations of cutaneous leishmaniasis.

Leishmania aethiopica infections in man result in a spectrum of diseases from LCL to DCL. These clinical manifestations have been attributed to genetic differences within the host or the parasites. In this study two different PCR-based methods were used to elucidate genetic variation within the species L. aethiopica. Inter- and intra-specific variations were detected in the ITS of the ribosomal operon in different strains and species of Leishmania, using a PCR-RFLP approach, and by a PCR fingerprinting technique that used single non-specific primers to amplify polymorphic regions of the genomic DNA. Both methods revealed genetic heterogeneity among ten L. aethiopica isolates examined. Unrooted distance trees separated the ten strains into two different genetic groups. This subdivision was correlated to the geographical origin of the isolates rather than to the clinical manifestation of the disease.

Post-kala-azar dermal leishmaniasis.

Post-kala-azar dermal leishmaniasis is a dermatosis which was described during the first quarter of this century. Most cases reported are from the Indian subcontinent and certain parts of Africa. The disease generally follows an attack of kala-azar, usually a few months to several years after the visceral disease has healed. The clinical picture is variable. In this report, we present a case of post-kala-azar dermal leishmaniasis in a 5-year-old Iranian boy who presented with multiple, asymptomatic, erythematous papules on his trunk and extremities and a brownish, figurate discoloration on his lower extremities, 4 years after an attack of kala-azar which was completely cured. Histopathological examination of one of the biopsied papules revealed multiple Leishman bodies. The patient was successfully treated with a pentavalent antimonial compound.

Leishmaniose tegumentar americana / Mucocutaneous leishmaniasis

A Leishmaniose tegumentar americana é uma afecçäo com comportamento endêmico e tem sua importância epidemiológica alicerçada na incidência e nos diferentes quadros clínicos graves conhecidos que, se näo diagnosticados ou diagnosticados incorretamente, podem evoluir determinando severas mutilaçöes. Milhares de pessoas säo atingidas por essa parasitose a cada ano, com repercussäo na saúde pública de muitas populaçöes. Segundo a O.M.S., calcula-se que 350 milhöes de pessoas estäo expostas ao risco de contrair a doença e que é de 12 milhöes o número atual de infectados. A enfermidade predomina nas regiöes tropicais e subtropicais em desenvolvimento. Assim, o cirurgiäo-dentista tem papel importante no diagnóstico e no encaminhamento do paciente para o tratamento médico

[Disseminated cutaneous leishmaniasis in a case of an immunodepressed woman]. / Leishmaniose cutanée disséminée chez une immunodéprimée.

The authors report a case of Leishmania major leishmaniasis which occurred in a female kidney transplant recipient. In contrast with visceral leishmaniasis, disseminated cutaneous leishmaniasis seems to be exceptional in immunodepressed patients.

Leishamaniose tegumentar no estado de Goiás: análise dos dados epidemiológicos, clínicos e imunopatológicos de infecçåo humana, registrados de 1965 a 1984 / Tegumentary leishmaniosis in Goiás

Uma análise de 565 casos de leishmaniose tegumentar registrados em Goiânia-Go, Brasil, de 1965 a 1984, mostrou 379 (67,08 por cento) casos de pacientes autóctones, 171 (30,37 por cento) alóctones, e 15 pacientes de procedência duvidosa. Estes casos foram distribuídos por critério geográfico, bem como epidemiológico, clínico e imunopatológico. Os casos autóctones foram predominantemente das mesorregioes do Alto Araguaia-Tocantins e Goiânia, cujas microrregioes Alto Tocantins e Mato Grosso de Goiás respectivamente, contribuiram juntas com 45,09 por cento que foram relacionadas às condiçoes fitoecológicas, e ao desenvolvimento de atividades agropastoris naquelas áreas. O estudo clínico de pacientes autoctones, mostrou 43,00 por cento da forma cutanea; 55,94 por cento forma cutaneo-mucosa e 1,06 por cento aparentemente forma mucosa; somente 89 casos (54,60 por cento) tiveram lesao unica de pele; 34 casos (34,35 por cento) de 2 a 5 e 18 casos (11,04 por cento) tiveram acima de 5 lesoes. O paciente mais jovem afetado era uma criança de 1 ano e o mais velho tinha 83 anos de idade. Os pacientes acima de 20 anos de idade, apresentaram lesoes multiplas mais frequentes. A duraçåo da doença em relaçåo às lesoes única e múltiplas, mostrou mais lesoes únicas observadas de um a três (1 a 3) meses (39,32 por cento). A duraçåo da doença em relaçåo à clínica, demonstrou forma cutânea de 1 a 24 meses; cutâneo-mucosa de 2 a 60 meses. Em 212 pacientes com forma cutâneo-mucosa, a lesåo metastática foi distribuida em relaçåo ao intervalo de tempo, entre lesåo primária de iniciaçåo e a lesåo mucosa; em cutåneo-mucosa concomitante primária 7 casos; concomitante secundária com intervalo de 2 a 6 meses, 3 casos; metastática precoce com 6 a 12 meses, 65 casos e por último a metastática clássica, com 24 a 60 meses ou mais com 127 casos. Os aspectos epidemiológicos disponíveis såo muito pobres, mas é relevante o conhecimento de algumas espécies de vetores de várias áreas, bem como o descobrimento de novas espécies de Leishmanis patogênica para o homem e a constataçåo da espundia por esta espécie e por L. m. amazonensis. Análise imunopatológica en relaçåo às formas clínicas foi baseada no índice parasitêmico, constituiçåo do infiltrado celular, presença de células multinucleares, tendência à granulomas, necrose, fibrose e sinais de hipersensibilidade e periendovasculites, os quais quando associados com análise do perfil da imunidade celular e humoral såo muito importantes para o estudo evolutivo e terapêutico adequado do leishmaniótico.

Novo meio líquido autoclavável, isento de sangue, para isolamento primário de Leishmanias de lesöes tegumentares: I-sua potencialidade no estudo da biologia dos tripanosomatídeos / A new autoclavable culture medium, devoid of blood for isolation of Leishmania from skin lesions: I - its potentiality in the study of the biology of Trypanosomidae

Novo meio, inicialmente denominado, BHYMI (Brain-heart-yeast-meat infusion) logo Rq., constante basicamente de extrato de cérebro, extrado de coraçäo, estrato de carne, extrato de levedura, mais glicose, cloreto de sódio e água, é meio monofásico de baixo custo, disponível no comércio ou facilmente preparado com matérias primas locais, no laboratório, de fácil esterilizaçäo, claro, facilitando a coleta e contagem dos organismos cultivados; foi usado, inicialmente, como a fase líquida dos meios difásicos NNN ou Ducrey, logo como meio de cultura único (exclusivo) para cultivo de leishmanias. É capaz de isolar primariamente leishmania de lesöes, em proporçäo bastante razoáveis, manter cepas isoladas e de funcionar mesmo após ser guardado por 12 meses à temperatura ambiente, como líquido ou por mais tempo quando liofilizado. Seu pH ótimo é de 7.4 a 7.6. Quando enriquecido com soro fetal bovino (S.F.B) na proporçäo de 5, 10, 20 e/ou 30 pôr cento potencia o crescimento das cepas de leishmanias e permite o cultivo de Trypanossomas sp; usado em temperatura mais elevada condiciona o aparecimento de formas amastigotas dos tripanosomatídeos. Quando associado a soro de pato e/ou na presença de cloridrato de tetraciclina estimula a metaciclogenese do Trypanosoma cruzi. Associado ao sangue (Plasma e/ou soro) de galinha estimula a transformaçäo de promastigota de leishmania sp para amastigota em temperatura adequada (35º C). Enriquecido com carväo de sangue de feto bovino, de bovino adulto e de pato ("Charcoal" - sangue dissecado pelo calor lento e permanente, desidratado ou näo, previamente, a vácuo, e moído finamente, para se transformar em pó) - permite o crescimento exuberante de Trypanosomatídeos e mantém os atributos que soros e plasmas frescos ou conservados conferem ao meio, sendo muito bom para manutençäo e crescimento de Trypanosoma cruzi. Este meio pode ser usado como difásico sendo incorporado à peptona ou ágar, como base, tendo como meio líquido o próprio meio, soros consevados de boi, SFB ou soro de pato, meio 199, meio de Grace ou suplemento líquido de Hanks, dependendo da finalidade do cultivo. A associaçäo de extrato de flebotomíneos ou de triatomíneos ao meio permitiu também crescimento aumentado das leishmanias