Patients with acute kala azar are generally nonreactive in a number of immunologic assays, including T cell proliferation and generation of macrophage-activating cytokines, principally IFN-'y, in response to leishmania antigens in vitro. To test for potential immunosuppressive factors, a series of T cell lines and clones were established from patients with acute kala azar, from patients after chemotherapy for kala azar, and from skin test-positive adults from the same endemic region. Although CD4+ T cell lines and clones could be readily established from the skin test-positive adults, lines and clones from acute or treated patients were heavily biased in expression of CD8+. The CD8 + cells from acute patients did not themselves release cytokines in response to leishmania antigens in vitro, but markedly affected the cytokine profile of peripheral blood mononuclear cells isolated 1 yr later after recovery. Addition of the CD8 + cells caused inhibition of lymphoproliferation and IFN-y release, with augmentation of IL-6 and IL-10 release. The inhibitory effects of the CD8+ cells could be partially abrogated by antibodies to IL-10 but not by antibodies to IL4. Analysis of four patients with acute kala azar demonstrated release of IL-10 that could not be demonstrated in supernatants from asymptomatic skin test-positive individuals. Generation of IL-10 may contribute to the profound suppression of IFN--y release that occurs during kala azar due to Leishmania chagasi. (J. Clin. Invest. 1993. 92:2626-2632.) Key words: leishmania -interleukin-10 * kala azar * interferon-'y -immunosuppression

Patients from across the spectrum of clinical manifestations of Leishmania chagasi infection were evaluated for in vitro correlates of immunity. Peripheral blood mononuclear cells were assayed for parasite-specific lymphoproliferation, cytokine generation, and the capacity to activate autologous macrophages to kill intracellular amastigotes. Patients with acute kala-azar were generally unreactive in each of these assays. Children with subclinical infection demonstrated relatively low levels of proliferation and interferon-gamma production, but none went on to develop overt kala-azar during the study. Patients evaluated after therapy for kala-azar demonstrated yet higher levels of lymphoproliferation and cytokine generation and produced low but significant levels of cytokines in vitro in response to parasite antigens, but not during the activation of infected macrophages. Finally, peripheral blood mononuclear cells from adults with positive delayed-type hypersensitivity responses and no history of kala-azar showed the broadest reactivity in vitro. These patients' cells generated the largest amounts of activating cytokines in vitro during the activation of autologous macrophages to a leishmanicidal state.

Abstract. Dengue remains a problem in Brazil, and a substantial number of cases that progress to death are not diagnosed by health services. We evaluated the impact of a protocol adopted by the Coroner's Office Rocha Furtado (CO-RF) for the detection of unreported deaths from dengue in Brazil. We evaluated prospectively cases of deaths referred to the CO-RF with suspicion of dengue and those referred with other diagnosis in which the pathologists suspected dengue as the cause of death. Biological material was collected from all bodies autopsied, for which the suspected cause of death was dengue, between January 2011 and December 2012. Of the 214 bodies autopsied, 134 (62.6%) tested positive for dengue; of these cases, 121 were classified as dengue according to the World Health Organization's case definition (1997 or 2009, as appropriate). Thus, CO-RF detected 90 deaths from dengue, which were not suspected during disease progression. This CO-RF protocol, through a combined effort of the surveillance and laboratory teams, increased the detection of fatal dengue cases by 5-fold. This is the largest series of autopsies performed in cases of death related to dengue in the world to date.

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Em algumas áreas endêmicas de leishmaniose tegumentar(LT) causada por Leishmania (Viannia) braziliensis existem evidências de transmissão domiciliar, e de que cães infectados estariam associados a casos humanos de LT. Neste trabalho, são apresentados os resultados de um estudo realizado na Serra de Baturité, no Ceará, em 1993, quando foram investigadas as evidências de transmissão domiciliar e a associação entre LT humana e infecção canina. Casos humanos de LT foram indivíduos que apresentavam úlceras de bordas elevadas, arredondadas, de diâmetro > 5 mm, duração > 15 dias e uma Reação de Montenegro positiva. Cães soropositivos foram aqueles que apresentavam uma prova de imunofluorescência indireta positiva. A idade foi dividida em dois estratos, de 1 a 10 e 11 a 89 anos. A incidência de LT não estava associada ao sexo (Razão de Incidência (RI) = 1,21; IC 95%: 0,86 - 1,72) e nem à idade (RI = 1,38; IC 95%: 0,97 - 1,96). Para os indivíduos que conviviam com um ou mais cães soropositivos, a incidência de LT humana foi 45% mais elevada (RI = 1,45; IC 95%: 1,02 - 2,06) depois de ajustar para o sexo, e 48% (RI = 1,48%; IC 95%: 1,04 - 2,10) depois de ajustar para idade. Considerando-se o risco domiciliar, a incidência de LT humana foi duas vezes mais elevada (RI = 2,01; IC 95%:1,32 - 3,06) nos domicílios que possuíam um ou mais cães soropositivos. Conclui-se que os indivíduos foram acometidos de LT independente do sexo e da idade e que os casos humanos estavam associados à presença de cães infectados. Portanto, estes resultados suportam a hipótese de transmissão domiciliar da leishmaniose tegumentar na Serra de Baturité, no Ceará.

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Meniscal transection rather than resection promotes more severe pain and structural damage in mice. Administration of opioids, cyclooxygenase and nitric oxide (NO) synthase inhibitors provide analgesia in this model. Careful description of the structures damaged is crucial when reporting experimental osteoarthritis (OA).

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