A retrospective survey of dengue virus infection in fatal cases from an epidemic in Brazil
Introduction
Dengue infection is the most prevalent arthropod-borne viral disease in subtropical and tropical regions of the world (Halstead, 1980). All four of the dengue virus serotypes (genus Flavivirus, family Flaviviridae) consist of a single positive-strand RNA surrounded by an icosahedral nucleocapsid (Hammon et al., 1960). Dengue virus infection causes either a relatively mild disease, known as classic dengue fever (DF) or a more severe form, dengue hemorrhagic fever (DHF), a fulminating illness characterized by hemorrhagic manifestations and plasma leakage, which may progress to dengue shock syndrome (DSS) and death (Halstead, 1988). The virus can infect many cell types from the vascular, muscular and hematological systems causing diverse clinical and pathological signs (Seneviratne et al., 2006).
Studies of specimens from patients presenting DHF/DSS revealed the presence of viral antigens or RNA in diverse tissues including liver, spleen, brain, lymph node, thymus, kidney, lung, heart, bone marrow and skin and mainly in mononuclear phagocytic cells (Bhamarapravati et al., 1967, Bhoopat et al., 1996, Boonpucknavig et al., 1979, Hall et al., 1991, Miagostovich et al., 1997, Yoskan and Bhamarapravati, 1983). The purpose of the present study was to investigate by different diagnostic approaches dengue virus in human tissue specimens from fatal cases during a large-scale dengue fever epidemic in 2002 in the State of Rio de Janeiro, Brazil.
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Study population
The human tissue specimens examined included liver (n = 28), lung (n = 14), spleen (n = 16), brain (n = 11), kidney (n = 5), bone marrow (n = 1) and heart (n = 2) obtained from 29 patients presenting with acute febrile illness with two or more of the following clinical manifestations: headache, retrobulbar pain, myalgia, arthralgia, rash and hemorrhage. All samples were received refrigerated and separately from private and public hospitals in the metropolitan area of Rio de Janeiro city and stored at −70 °C
Results
The combination of four methods provided diagnostic confirmation of DENV-3 infection in 26 (89.6%) out of the 29 suspected fatal cases. As demonstrated in Table 1, the use of only one diagnostic tool provided positive results in 9/26 cases (34.6%), only one case determined by immunohistochemistry (3.8%), and in 8/26 patients diagnosis was confirmed by real-time RT-PCR (30.8%). In the other 17/26 cases (65.4%), infection was detected by at least two different diagnostic approaches.
A total of 77
Discussion
During 2002, a total of 813,104 dengue cases were notified in Brazil, mainly in the southeastern and northeastern regions (Nogueira et al., 2007). This number corresponded to 80% of all the reported dengue cases in the Americas (Nogueira et al., 2007). The introduction of DENV-3 into Rio de Janeiro in 2000 placed the region at high risk of a new epidemic involving this serotype, since the emergence of a new serotype into a susceptible population with high mosquito densities may produce a
Conflicts of interest statement
The authors have no conflicts of interest concerning the work reported in this paper.
Acknowledgments
The research described in this publication was made possible by support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (grant no. 501564/03-9) and FAPERJ (grant no. E-26/152490/2002). The authors are grateful to the Program for Technological Development in Tools for Health-PDTIS-FIOCRUZ for the use of their facilities. J.M.G.A. received a fellowship from CNPq.
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