Abstract
/Background Dengue is the most important arthropod borne viral disease worldwide in terms of morbidity and mortality and is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Brazil is responsible for approximately 80% of dengue cases in the Americas, and since the introduction of dengue in 1986, a total of 5,944,270 cases have been reported including 21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many cell types and cause diverse clinical and pathological effects. The goal of the study was to investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from previously confirmed dengue fatal cases (n = 23) that occurred in 2002 in Brazil. Methodology/Principal Findings A total of 74 tissue specimens were available: liver (n = 23), lung (n = 14), kidney (n = 04), brain (n = 10), heart (n = 02), skin (n = 01), spleen (n = 15), thymus (n = 03) and lymph nodes (n = 02). We evaluated three tests for NS1 antigen capture: first generation Dengue Early ELISA (PanBio Diagnostics), Platelia NS1 (BioRad Laboratories) and the rapid test NS1 Ag Strip (BioRad Laboratories). The overall dengue fatal case diagnosis based on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag Strip was 34.7% (08/23), 60.8% (14/23) and 91.3% (21/23), respectively. The Dengue Early ELISA detected NS1 in 22.9% (17/74) of the specimens analyzed and the Platelia NS1 in 45.9% (34/74). The highest sensitivity (78.3%; 58/74) was achieved by the NS1 Ag Strip, and the differences in the sensitivities were statistically significant (p<0.05). The NS1 Ag Strip was the most sensitive in liver (91.3%; 21/23), lung (71.4%; 10/14), kidney (100%; 4/4), brain (80%; 8/10), spleen (66.6%, 10/15) and thymus (100%, 3/3) when compared to the other two ELISA assays. Conclusions/Significance This study shows the DENV NS1 capture assay as a rapid and valuable approach to postmortem dengue confirmation. With an increasing number of DHF and fatal cases, the availability of new approaches useful for cases confirmation plays an important tool for the disease surveillance.
Highlights
Dengue virus (DENV) infection is recognized as one of the most important mosquito borne human infections in the 21th century
With an increasing number of Dengue Hemorrhagic fever (DHF) and fatal cases, the availability of new approaches useful for cases confirmation plays an important role for the disease surveillance
The diagnosis of fatal cases in frozen and fixed tissues from autopsies can be determined by techniques such as viral RT-PCR, in situ hybridization, viral proteins detection by immunohistochemistry and NS3 specific immunostaining
Summary
Dengue virus (DENV) infection is recognized as one of the most important mosquito borne human infections in the 21th century. In Brazil, the disease is an important public health problem associated with explosive epidemics and since DENV introduction in 1986 [3], a total of 5,944,270 cases were reported including 21,596 DHF and 874 fatal cases. A number of studies have shown previously that the DENV nonstructural 1 (NS1) antigen, a highly conserved glycoprotein produced in both membrane-associated and secreted forms, is abundant in the serum of patients in the early phase of infection [5,6,7,8,9] and it is useful in the diagnosis of dengue infection [8,10,11,12,13]. An evaluation of the three NS1 tests for early diagnosis of dengue in Brazil was performed previously [14]
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