Subclinical or asymptomatic infection is documented in individuals living in endemic areas for leishmaniasis suggesting that the development of an appropriate immune response can control parasite replication and maintain tissue integrity. A low morbidity indicates that intrinsic factors could favor resistance to Leishmania infection. Herein, leishmanial T-cell responses induced in subjects with low susceptibility to leishmaniasis as asymptomatic subjects were compared to those observed in cured cutaneous leishmaniasis (CCL) patients, who controlled the disease after antimonial therapy. All of them have shown maintenance of specific long-term immune responses characterized by expansion of higher proportions of CD4+ as compared to CD8+ Leishmania reactive T-lymphocytes. Asymptomatic subjects had lower indexes of in vitro Leishmania induced lymphoproliferative responses and interferon-gamma (IFN-gamma) production in comparison to CCL patients. On the other hand, interleukin (IL-10) production was much higher in asymptomatics than in CCL, while no differences in IL-5 levels were found. In conclusion, long lived T-cell responses achieved by asymptomatic individuals differed from those who had developed symptomatic leishmaniasis in terms of intensity of lymphocyte activation (proliferation or IFN-gamma) and regulatory mechanisms (IL-10). The absence of the disease in asymptomatics could be explained by their intrinsic ability to create a balance between immunoregulatory (IL-10) and effector cytokines (IFN-gamma), leading to parasite destruction without producing skin tissue damage. The establishment of profiles of cell-mediated immune responses associated with resistance against Leishmania infection is likely to make new inroads into understanding the long-lived immune protection against the disease.

Trata-se de um estudo epidemiológico descritivo com o objetivo de avaliar a ocorrência de miíases humanas em áreas urbanas de quatro municípios do Estado do Rio de Janeiro. Foram analisados 71 pacientes que procuraram espontaneamente o atendimento em Postos de Saúde, no período de outubro de 1999 a outubro de 2003. Maior prevalência da doença foi encontrada em adultos e idosos acima de 51 anos (42,3%) e em menores de 10 anos (33,8%). Do total dos casos estudados, 62% incluíam-se no nível sócio-econômico baixo; 60,6% eram do sexo masculino e 33,8% dos indivíduos infestados, sem profissão. Nos casos analisados as espécies bioagentes foram Cochliomyia hominivorax (Coquerel, 1858); Dermatobia hominis (Linnaeus Jr, 1781) e Cochliomyia macellaria (Fabricius, 1775). Os resultados apontam para a associação da doença com as condições de vida e de higiene dos pacientes, sinalizando para a necessidade de atenção mais específica à saúde dos grupos mais vulneráveis.

This was a descriptive epidemiological study with the aim of evaluating the occurrence of human myiasis in urban areas of four municipalities in the State of Rio de Janeiro. Seventy-one patients who spontaneously sought attendance at primary healthcare units between October 1999 and October 2003 were examined. The disease was more prevalent among adults, including in individuals more than 51 years old (42.3%), and among children less than 10 years old (33.8%). From all the cases studied, 62% were of low socioeconomic level; 60.6% were male; and 33.8% of the infested individuals were unemployed. In the cases analyzed, the bioagent species were Cochliomyia hominivorax (Coquerel, 1858), Dermatobia hominis (Linnaeus Jr, 1781) and Cochliomyia macellaria (Fabricius, 1775). The results point towards an association between the disease and the patients’ living and hygiene conditions. This indicates the need for more specific healthcare among more vulnerable groups.

Apesar de utilizado há mais de meio século no tratamento da leishmaniose, o antimônio apresenta ainda problemas quanto a sua toxicidade e dose ideal. Doses baixas têm se mostrado tão eficazes quanto doses altas. Neste trabalho, apresentamos o resultado do emprego de uma ampola de antimoniato de meglumina intramuscular, em dias alternados, até a cura clínica, numa série de 40 casos. A dose total utilizada, por paciente, variou de 1.822,5 a 12.150mg de antimônio pentavalente e o tempo de tratamento de 3 a 10 semanas com eficácia de 86%. Dos 40 pacientes estudados, 36 ainda estão em acompanhamento, com um tempo médio de 10,7 ± 7 meses e média de 9 meses. Não houve recidivas nem lesões mucosas. O esquema utilizado foi bem tolerado, de fácil aplicação, eficácia comparável ao esquema oficialmente preconizado pela OMS, mostrando-se como valiosa alternativa para os casos com potencial toxicidade ao antimônio ou cuja aplicação de injeções diárias represente um obstáculo ao tratamento.

Despite more than half a century of use in leishmaniasis, antimony therapy still presents serious problems concerning dosage and toxicity. Low and high doses have been shown to be equally effective. In this paper, the feasibility of injecting one ampoule of meglumine antimoniate intramuscularly every other day until clinical cure is demonstrated, while studying a series of 40 cutaneous leishmaniasis cases. Total dose used varied from 1,822.5 to 12,150mg of pentavalent antimony and total time of treatment varied from 3 to 10 weeks, with 86% efficacy. Thirty-six out of the 40 patients are still on follow-up with a mean time of 10.7 ± 7 months and a median of 9 months. No relapse or mucosal lesions have been noted so far. The schedule showed good tolerance and easy application and its efficacy was comparable to the officially recommended WHO schedule. Therefore, such a schedule represents a valuable alternative for the cases with high toxicicity to antimony or daily injections are an obstacle to the treatment.

São relatados dois casos de leishmaniose mucocutânea resistentes ao tratamento. Depois das terapêuticas iniciais (antimônio, anfotericina B e/ou pentamidina), os pacientes receberam um esquema alternativo: uma ampola de antimoniato de meglumina (405mg de antimônio pentavalnte [Sb v]) por via intramuscular, três vezes por semana até a cura completa das lesões. Um paciente recebeu um total de 30 ampolas durante 10 semanas e o outro, 36 ampolas durante 12 semanas. Ambos permanecem clinicamente curados até um ano após o tratamento.

Two mucocutaneous leishmaniasis cases resistant to therapy are reported here. After the failure of initial therapies (antimony, amphotericin B and/or pentamidine) patients received a low-dose schedule: one ampoule of meglumine antimoniate (405mg of pentavalent antimony [Sb v]) by intramuscular injection, three times a week until complete healing of the lesions. One patient was cured with a total of 30 ampoules in 10 weeks and the other received 36 ampoules in 12 weeks. Both remain clinically cured after one year of follow-up.

Paniculite eosinofílica pode ser desencadeada por muitos fatores; aqui os autores descrevem a síndrome em conseqüência de injeções intramusculares de compostos de antimônio para tratamento de leishmaniose tegumentar americana em três pacientes. Todos eles desenvolveram lesões em placa, profundamente infiltradas, no local da injeção antimonial. A histopatologia mostrou acentuado infiltrado inflamatório da hipoderme com numerosos eosinófilos. O estudo imunológico não demonstrou imunoglobulinas ou frações do complemento nas lesões. O diagnóstico final foi de paniculite eosinofílica ocorrendo como efeito colateral da terapia antimonial. O mecanismo patogênico dessa paniculite não pôde ser definido. As hipóteses sugeridas foram de lesão induzida por fenômeno físico - a pressão exercida pelo volume do líquido injetado - ou de uma reação alérgica ao antimônio.

Eosinophilic panniculitis may be induced by several triggering factors and this syndrome is described here following the intramuscular injection of antimonial compounds for treatment of American muco-cutaneous leishmaniasis. Three patients, treated with intramuscular injections of pentavalent antimony (Glucantime®) were studied through clinical examination, histopathology and immunologic methods. The three patients developed deep infiltrated plaques at the site of antimony injection. Histopathology disclosed a prominent inflammatory infiltrate of the subcutaneous fat with numerous eosinophils. Immunologic studies could not detect immunoglobulins or complement fractions in the lesions. The final diagnosis was eosinophilic panniculitis occurring as a side-effect of antimonial therapy. The pathogenesis was not clear and it is suggested that the disease could be induced by a physical factor such as pressure or an immunological reaction to antimony.

Cutaneous biopsies (n = 94) obtained from 88 patients with American tegumentary leishmaniasis were studied by conventional and immunohistochemical techniques. Specimens were distributed as active lesions of cutaneous leishmaniasis (n = 53) (Group I), cicatricial lesions of cutaneous leishmaniasis (n = 35) (Group II) and suggestive scars of healed mucosal leishmaniasis patients (n = 6) (Group III). In addition, active cutaneous lesions of other etiology (n = 24) (Group C1) and cutaneous scars not related to leishmaniasis (n = 10) (Group C2) were also included in the protocol. Amastigotes in Group I biopsies were detected by routine histopathological exam (30.2%), imprint (28.2%), culture (43.4%), immunofluorescence (41.4%) and immunoperoxidase (58.5%) techniques; and by the five methods together (79.3%). In Group II, 5.7% of cultures were positive. Leishmanial antigen was also seen in the cytoplasm of macrophages and giant cells (cellular pattern), vessel walls (vascular pattern) and dermal nerves (neural pattern). Positive reaction was detected in 49 (92.5%), 20 (57%) and 4 (67%) biopsies of Groups I, II and III, respectively. Antigen persistency in cicatricial tissue may be related to immunoprotection or, on the contrary, to the development of late lesions. We suggest that the cellular, vascular and neural patterns could be applied in the immunodiagnosis of active and cicatricial lesions in which leishmaniasis is suspected.

A resposta de pacientes com leishmaniose ao tratamento antimonial pode variar em função de fatores como a cepa do parasito envolvido, estado imunológico do paciente e a forma clínica da doença. Os esquemas terapêuticos com antimônio pentavalente (Sb5+) têm sido frequentemente modificados quanto à dose e duração da terapia. Os efeitos colaterais observados com o uso de 20 mg/kg/dia de Sb5+ durante quatro semanas (dose recomendada para o tratamento da forma mucosa) são mais acentuados em pacientes idosos, os mais afetados pela forma mucosa (espundia) da doença. Nossa experiência demonstra que a forma cutânea ocorrendo no Rio de Janeiro responde muito bem ao tratamento com a dose de 5 mg/kg/dia de Sb5+ durante 30 ou 45 dias. Neste estudo foi obtida elevada eficácia (91,4%) com o mesmo regime terapêutico em 36 pacientes com espundia (que evoluem, contudo, com lesão crônica menos destrutiva do que o observado em outras áreas endêmicas) procedentes desta região. Os efeitos colaterais foram reduzidos, não havendo também qualquer resistência ao emprego de doses maiores nos casos que não responderam ao tratamento inicial.

Response to treatment with antimonial drugs varies considerably depending on the parasite strain involved, immune status of the patient and clinical form of the disease. Therapeutic regimens with this first line drug have been frequently modified both, in dose and duration of therapy. A regimen of 20 mg/kg/day of pentavalent antimony (Sb5+) during four weeks without an upper limit on the daily dose is currently recommended for mucosal disease ("espundia"). Side-effects with this dose are more marked in elderly patients, more commonly affected by this form of leishmaniasis. According to our experience, leishmaniasis in Rio de Janeiro responds well to antimony and, in cutaneous disease, high cure rates are obtained with 5 mg/kg/day of Sb5+ during 30 to 45-days. In this study a high rate of cure (91.4%) employing this dose was achieved in 36 patients with mild disease in this same geographic region. Side-effects were reduced and no antimony refractoriness was noted with subsequent use of larger dose in patients that failed to respond to initial schedule.