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Pathogenesis of leptospirosis pulmonary hemorrhage syndrome in humans

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Croda, Júlio Henrique Rosa
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo. [2009]. 152 f.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina
Defense date:
Examining board members:
Duarte, Maria Irma Seixas; Capelozzi, Vera Luiza; Lancellotti, Carmen Lucia Penteado; Nicodemo, Antonio Carlos; Salomão, Reinaldo
Advisor: Duarte, Maria Irma Seixas
Field of knowledge: Health Sciences - Medicine
Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS; Biblioteca Digital de Teses e Dissertações - USP
Location: Universidade de São Paulo. Biblioteca Central da Faculdade de Medicina; FM W4.DB8 SP.USP FM-2 2008; C954pa

Leptospirosis is a zoonotic disease that is a cause of high morbidity and mortality in humans and is an important public health problem. Caused by bacteria of Leptospira genus, this disease presents diverse clinical manifestations and is especially important in developing countries. Leptospirosis pulmonary hemorrhage syndrome is the major cause of death in patients with the severe form of leptospirosis. The pathogenic mechanisms of this syndrome are unknown. With the purpose of identifying these pathogenic mechanisms, 30 necropsies (pulmonary samples) from patients with leptospirosis pulmonary hemorrhage syndrome and seven controls were evaluated. . To determine whether the immune system is involved, histology and immunohistochemistry (IgM, IgG, IgA, and C3) experiments were performed on lung tissue samples, as well sera measurements of autoantibodies (against the basal membrane and anti-cardiolipin) were performed in leptospirosis patients with and without pulmonary hemorrhage syndrome (in paired samples) and in healthy donors from a blood bank. We found that patients with leptospirosis pulmonary hemorrhage syndrome differed from control pulmonary hemorrhage patients in several features: the presence of moderate to high levels of macrophages in the alveolar space (77% versus 29%, respectively; p = 0.02), the presence of the focal hyaline membrane on alveolar surface (100% versus 0%; p < 0.01), extensive necrosis and regeneration of pneumocyte II cells (100% versus 0%; p < 0.01) and the presence of plasma cells in the alveolar septum (77% versus 29%, respectively; p =0.02). No statistically significant differences were observed in the number of other cells in the alveolar septae. Intact leptospires were rarely detected. Leptospiral antigen was not correlated with the intensity of the lesions... (AU)