A new approach to dengue fatal cases diagnosis: NS1 antigen capture in tissues

Abstract/Background

Dengue is the most important arthropod borne viral disease worldwide in termsof morbidity and mortality and is caused by any of the four serotypes ofdengue virus (DENV-1 to 4). Brazil is responsible for approximately80% of dengue cases in the Americas, and since the introduction ofdengue in 1986, a total of 5,944,270 cases have been reported including21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect manycell types and cause diverse clinical and pathological effects. The goal ofthe study was to investigate the usefulness of NS1 capture tests as analternative tool to detect DENV in tissue specimens from previouslyconfirmed 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 testsfor NS1 antigen capture: first generation Dengue Early ELISA (PanBioDiagnostics), Platelia NS1 (BioRad Laboratories) and the rapid test NS1 AgStrip (BioRad Laboratories). The overall dengue fatal case diagnosis basedon the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 AgStrip 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 theNS1 Ag Strip, and the differences in the sensitivities were statisticallysignificant (p<0.05). The NS1 Ag Strip was the mostsensitive 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 ELISAassays.

Conclusions/Significance

This study shows the DENV NS1 capture assay as a rapid and valuable approachto postmortem dengue confirmation. With an increasing number of DHF andfatal cases, the availability of new approaches useful for casesconfirmation plays an important tool for the disease surveillance.