Acute visceral leishmaniasis is associated with an antigen-specific immunosuppression of mononuclear cells as evidenced by defective in vitro production of interferon gamma. We evaluated treatment with recombinant human interferon gamma in combination with conventional pentavalent antimony therapy in patients with visceral leishmaniasis. Six of eight patients with visceral leishmaniasis (mean duration, 17 months) that had been unresponsive to multiple courses of pentavalent antimony responded to treatment with recombinant human interferon gamma (100 to 400 micrograms per square meter of body-surface area per day) in addition to pentavalent antimony (20 mg per kilogram of body weight per day) for 10 to 40 days. The other two patients improved initially but then relapsed and required treatment with amphotericin B. Eight of nine additional patients with previously untreated severe visceral leishmaniasis were also successfully treated with the combination of interferon gamma and pentavalent antimony. The 14 patients who responded to this regimen had marked improvement in symptoms and in measures of anemia and leukopenia, as well as weight gain, a decrease in spleen size, and an absence or reduction of leishmanias in splenic aspirates. These patients had no recurrence of illness after a mean (+/- SE) follow-up of 8 +/- 1 months. Fever was the only major side effect of interferon gamma. We conclude that the combination of interferon gamma and pentavalent antimony is effective in treating seriously ill patients with refractory or previously untreated visceral leishmaniasis.
High tumor necrosis factor-alpha (TNF alpha) levels were present in the serum of 24 of 28 active visceral leishmaniasis (VL) patients (142.9 +/- 113.9 pg/ml, mean +/- SD), whereas levels were not elevated in 26 of 30 patients with cryptic leishmanial infection (16 asymptomatic, 4 with self-healing subclinical infection, and 10 posttreatment VL cases). Serum TNF alpha levels were also not elevated in 15 normal volunteers (11.3 +/- 15.6 pg/ml) and in 10 patients with tegumentary leishmaniasis (19.1 +/- 10.8 pg/ml). Leishmanial infection of human monocyte-derived macrophages enhanced the basal TNF alpha production by these cells, and this effect was further potentiated by treatment with recombinant interferon-gamma. After effective treatment of VL patients, serum TNF alpha levels dropped rapidly (129 +/- 112 vs. 9 +/- 13 pg/ml in 10 days), even before clinical parameters such as spleen size or parasitism, white blood cell count, or levels of hemoglobin returned to normal values. On the other hand, patients unresponsive to treatment remained with elevated levels (276 +/- 69 vs. 155 +/- 71 pg/ml in 10 days). Thus, serum TNF alpha levels in VL patients are a good parameter to monitor in determining host response to therapy.
Twenty-four patients with acute visceral leishmaniasis and leukopenia (< 1500 neutrophils/mm3) due to Leishmania chagasi were studied, 4 in an open-label pilot study and 20 in a double-blind, placebo-controlled trial. Patients received granulocyte-macrophage colony-stimulating factor (GM-CSF), 5 micrograms/kg daily, or placebo for 10 days, plus 10-20 mg/kg pentavalent antimony daily for 20 days. In GM-CSF recipients, neutrophil counts increased threefold and fourfold over baseline at 5 and 10 days, respectively, and were significantly higher than those in placebo recipients (P < .02). Eosinophil and monocyte counts were significantly increase in GM-CSF recipients at 10 days (P < or = .03). Secondary infections occurred in 3 GM-CSF and in 8 placebo recipients (P = .04). All patients had complete resolution of their leishmaniasis at 3 months. Few adverse events were recorded. GM-CSF, 5 micrograms/kg daily for 10 days, was safe, rapidly reversed neutropenia, and reduced the number of secondary infections in patients with leishmaniasis.
The efficacy of GM-CSF was investigated in 20 neutropenic patients (< 1500 neutrophils/microliters) with acute visceral leishmaniasis due to Leishmania chagasi. Patients were randomized to receive either GM-CSF, 5 micrograms/kg daily (intravenously or subcutaneously), or placebo for ten days, in combination with pentavalent antimony, 10-20 mg/kg daily for 20 days. Neutrophil counts were significantly greater on days 5 and 10 of treatment in the GM-CSF group compared with the placebo group (p < 0.02). Eosinophil and monocyte counts were also significantly increased in the GM-CSF group at day 10 (p < or = 0.03). Interestingly, at day 30, platelet counts were significantly increased in the GM-CSF group on days 5 and 10 (p = 0.04 and 0.02, respectively). Patients in the GM-CSF group experienced fewer secondary bacterial or viral infections than placebo patients. Infections occurred in only three patients given GM-CSF compared with eight patients given placebo (p < 0.04). All patients had complete resolution of disease symptoms at three months. Few adverse events were recorded. GM-CSF given subcutaneously at a dose of 5 micrograms/kg daily for ten days was well tolerated, reversed neutropenia rapidly and reduced the number of secondary infections in patients with leishmaniasis.
Apesar de ser uma doença imunoprevenível, o tétano desponta como uma patologia com altas taxas de letalidade em países em desenvolvimento. No Brasil, mesmo com a ampla cobertura vacinal, a doença ainda é um grave problema de saúde pública por causar óbito de milhares de pacientes. Diante disso, esse estudo analisou o perfil clínico-epidemiológico dos casos de tétano internados em hospital de referência, em Salvador/Bahia, de 2006 a 2018. Trata-se de estudo epidemiológico, de caráter retrospectivo, baseado na revisão de prontuários médicos de paciente internados e diagnosticados com tétano. Os casos foram identificados através da pesquisa do banco de dados do referido hospital e do Setor de Vigilância Epidemiológica. Foram notificados 137 casos com suspeita de tétano, sendo 132 confirmados. Destes, 83% era do gênero masculino, solteiros (62%), da raça parda (39%), com média de idade de 42,5±18,3 anos, com esquema vacinal incompleto (72%). Em relação ao desfecho apresentado, 21% dos pacientes foram a óbito, 3% foram transferidos e 62% receberam alta hospitalar. As sintomatologias mais frequentes foram trismo (84%) e espasmo muscular generalizado (69,7%). O perfil epidemiológico de pacientes acometidos pelo tétano foi de adultos, do sexo masculino, solteiros, pardos, trabalhadores rurais, com esquema vacinal incompleto, baixa escolaridade, que tiveram longa permanência hospitalar Palavras-chaves: Tétano, Epidemiologia, Diagnóstico clínico, Saúde Pública.
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 eosinophils 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.
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