Ana Cristina R. Saldanha

Leishmaniose visceral no estado do Maranhão, Brasil: a evolução de uma epidemia

Os autores fazem um breve relato da evolucao historica da leishmaniose visceral no Estado do Maranhao, Brasil, avaliando as possiveis causas da expansao da referida doenca no Estado, assim como as medidas de controle adotadas pelo Ministerio da Saude objetivando a diminuicao da incidencia da mesma.

Cura espontânea da leishmaniose causada por Leishmania Viannia Braziliensis em lesões cutâneas

In field clinics in the communities of Três Braços and Corte de Pedra, Bahia, we have attended 1.416 patients with tegumentary leishmaniasis in fourteen years, the predominant species in transmission is Leishmania Viannia brasi liensis (LVB). Because of the danger of metastasis with this infection treatment was routinely recommended with Glucan-time. However sixteen patients refused injection therapy and six women were pregnant when seen and not treated. All patients were followed up in our clinic. All these patients closed their skin ulcers although one subsequently relapsed. Patients were followed up for variable periods (four to twelve years), after the diagnosis. In nine patients (40.9%) of the cohort, the time to healing after initiation of the lesion was calculated as six months of evolution. At twelve months, nineteen patients (86.3%) had complete healing of their lesions. In three patients an active lesion was present for longer than one year. The determinants of this variable natural evolution of human LVB lesion remains completely unknown. It is difficult for us to understand and compare the effects of therapeutic agents in mucocutaneous leishmaniasis.Os autores relatam que durante 14 anos de trabalho clinico em campo, realizado nas comunidades de Tres Bracos e Corte de Pedra, Bahia, acompanharam 1.416 pacientes portadores de Leishmaniose Tegumentar Americana, cuja especie envolvida na transmissao, e predominantemente a Leishmania Viannia brasilienses. A terapeutica utilizada rotineiramente nos casos e o antimoniato-N-metilglucamina (Glucantime). Contudo, 16 pacientes do sexo masculino recusaram-se a utilizar a medicacao e 6 do sexo feminino encontravam-se em periodo gestacional, portanto nao utilizaram o medicamento. Estes pacientes foram acompanhados por um periodo entre 4 a 12 anos, a partir do diagnostico. Observou-se que em 9 pacientes (40,9%) desta casuistica, o tempo de cicatrizacâo apos o aparecimento da lesao, pode ser calculado em 6 meses de evolucao. Quando se eleva a observacao para 12 meses, temos que 19 pacientes (86,3%) cicatrizaram suas lesoes neste periodo. Em 3 casos (13,6%) as lesoes permaneceram ativas por mais de 12 meses. Conclui-se que os determinantes da cicatrizacâo natural das lesoes produzidas por Leishmania Viannia Braziliensis permanecem desconhecidos, dificultando para nos entendermos e compararmos aos efeitos das drogas utilizadas no tratamento da leishmaniose tegumentar.

Estado atual da leishmaniose cutânea difusa (LCD) no Estado do Maranhão: II. aspectos epidemiológicos, clínico-evolutivos

Os Autores fazem um estudo retrospectivo e prospectivo de 6 pacientes portadores de leishmaniose cutânea difusa, observados no Estado do Maranhao a partir de 1974. Os casos abordados sao oriundos de diversas regioes do estado, observando-se em todos eles o envolvimento da leishmania (Leishmania) amazonensis, sendo que 5 (84%) dos pacientes apresentaram inicio de doenca na 1a decada de vida. Em todos os pacientes envolvidos no estudo, houve relato de lesao inicial nodular unica, que, posteriormente, em periodo variavel de tempo, disseminou-se adquirindo outros aspectos. Evolutivamente apresentaram multiplas lesoes nodulares e ulceradas, intradermorreacao de Montenegro(-) e refratariedade aos esquemas terapeuticos utilizados ate ao presente momento.

Arginase I, Polyamine and Prostaglandin E2 Pathways Suppress the Inflammatory Response and Contribute to Diffuse Cutaneous Leishmaniasis

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of tegumentary leishmaniasis. The molecular mechanisms underlying DCL pathogenesis remain unclear, and there is no efficient treatment available. This study investigated the systemic and in situ expression of the inflammatory response that might contribute to suppression in DCL. The plasma levels of arginase I, ornithine decarboxylase (ODC), transforming growth factor β (TGF-β), and prostaglandin E2 (PGE2) were higher in patients with DCL, compared with patients with localized cutaneous leishmaniasis (LCL) or with controls from an area of endemicity. In situ transcriptomic analyses reinforced the association between arginase I expression and enzymes involved in prostaglandin and polyamine synthesis. Immunohistochemistry confirmed that arginase I, ODC, and cyclooxygenase2 expression was higher in lesion biopsy specimens from patients with DCL than in those from patients with LCL. Inhibition of arginase I or ODC abrogates L. amazonensis replication in infected human macrophages. Our data implicate arginase I, ODC, PGE2, and TGF-β in the failure to mount an efficient immune response and suggest perspectives in the development of new strategies for therapeutic intervention for patients with DCL.

Cromoblastomicose produzida por Fonsecaea pedrosoi no Estado do Maranhão. I - aspectos clínicos, epidemiológicos e evolutivos

The aim of this study was to observe the clinical and of epidemiological behavior of chromoblastomycosis in the State of Maranhao. A retrospective and prospective study ofl 3 cases was performed at the infectious diseases section of the Hospital dos Servidores do Estado do Maranhao, from November, 1988 to July, 1991. In the investigation a protocol record was used with a view to further analysis. A higher prevalence betweem 50 and 60 years of age (46.1%) and in male patients (92.3%) was noted. Twelve patients (92.3%) were from Maranhao State, and 10 of them (76.9%) came from the Western Microregion of the State of Maranhao. Regarding occupation, 92.3 % were landworkers, and most of them presented the lesions on the lower limbs (84.6%) of a vegetant warty aspect, brown in color with itching. Histopathological exammination diagnosed chromomycosis in 100% of the cases. Culture was performed in 11 cases, and Fonsecaea pedrosoi isolated in 9 of them. Treatment with 5-fluorocytosine resulted in a good evolutive response. This study indicates the existence of a probable endemic area of chromomycosis in hinterland of Maranhao (Western Microregion) that hither to unknown.

Chemokines and chemokine receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) includes different clinical manifestations displaying diverse intensities of dermal inflammatory infiltrate. Diffuse CL (DCL) cases are hyporesponsive, and lesions show very few lymphocytes and a predominance of macrophages. In contrast, localized CL (LCL) cases are responsive to leishmanial antigen, and lesions exhibit granulocytes and mononuclear cell infiltration in the early phases, changing to a pattern with numerous lymphocytes and macrophages later in the lesion. Therefore, different chemokines may affect the predominance of cell infiltration in distinct clinical manifestations. In lesions from LCL patients, we examined by flow cytometry the presence of different chemokines and their receptors in T cells, and we verified a higher expression of CXCR3 in the early stages of LCL (less than 30 days of infection) and a higher expression of CCR4 in the late stages of disease (more than 60 days of infection). We also observed a higher frequency of T cells producing IL-10 in the late stage of LCL. Using immunohistochemistry, we observed a higher expression of CCL7, CCL17 in lesions from late LCL, as well as CCR4 suggesting a preferential recruitment of regulatory T cells in the late LCL. Comparing lesions from LCL and DCL patients, we observed a higher frequency of CCL7 in DCL lesions. These results point out the importance of the chemokines, defining the different types of cells recruited to the site of the infection, which could be related to the outcome of infection as well as the clinical form observed.

DIFFUSE CUTANEOUS LEISHMANIASIS WITH ATYPICAL ASPECTS

A 16‐year‐old man had long‐standing diffuse cutaneous leishmaniasis with the following characteristics: diffuse infiltrated lesions rich in amastigotes, absence of mucosal involvement, and lack of parasite‐specific cell‐mediated immune response. In situ identification of Leishmania mexicana amazonensis was achieved by the use of monoclonal antibodies. Clinically, as an atypical finding there was deep and extensive ulceration in the lower limbs. Histologically, an atypical characteristic was the presence of a high number of eos‐inophils in the infiltrate predominantly in the ulcerated lesion. Ultrastructurally, parasitized and lysed eosinophils with dispersion of their granules were seen in the vicinity of parasitized or lysed macrophages.

Leishmaniose cutânea disseminada produzida por Leishmania viannia braziliensis no Estado do Maranhão - Brasil

Os autores relatam o caso de um paciente procedente do Municipio de Barreirinhas, MA, portador de leishmaniose cutânea disseminada, que apresentava 58 lesoes distribuidas pelo corpo, sob os mais variados aspectos com predominância da lesao ulcerada. Discutem a dificuldade do diagnostico laboratorial na fase inicial da investigacao e suas implicacoes com a terapeutica. O parasita isolado e caracterizado pela tecnica de anticorpos monoclonais foi a Leishmania viannia braziliensis. Esta forma da doenca e diferente da leishmaniose cutânea difusa, encontrada no Maranhao, cujo agente etiologico e a Leishmania (Leishmania) amazonensis, responsavel pela grande maioria dos casos de leishmaniose tegumentar naquele Estado. Os possiveis mecanismos de disseminacao das lesoes sao tambem discutidos neste trabalho.

Spontaneous regional healing of extensive skin lesions in diffuse cutaneous Leishmaniasis (DCL).

The authors report a case of diffuse cutaneous leishmaniasis, with longstanding evolution and presenting with diffuse infiltrated lesions rich in amastigotes in the absence of mucosal involvement. In situ characterization with monoclonal antibodies revealed Leishmania amazonensis. Large regional lesions have presented spontaneous healing without specific therapy. Considering that DCL presents with a defect in the cellular immune response, this fact demonstrate that this patient may develop a regional cellular immune response enough to destroy the parasites and to produce clearing of some lesions.

Diabetes Mellitus Associated with Pentamidine Isethionate in Diffuse Cutaneous Leishmaniasis

The authors report a case of a male patient from Bacabal, MA with diffuse cutaneous leishmaniasis (DCL), for at least nine years, with 168 lesions on his body. These were tumour-like nodules with some ulceration. He used pentavalent antimonial (glucantime) and an association of gamma interferon plus glucantime with improvement of the lesions but relapsed later. Recently, pentamidine isethionate (pentacarinat) was given a dosage of 4mg/kg/weight/day on alternate days for 20 applications. After 3 months a similar course of 10 application was given 2 times. Later he developed diabetic signs with weight loss of 10kg, polydypsia, polyuria and xerostomia. The lower limbs lesions showed signs of activity. Blood glucose levels normalised and remain like this at moment. Attention is drawn to the fact that pentamidine isethionate should be used as a therapy option with care, obeying rigorous laboratory controls including a glucose tolerance test.