Nonstructural protein NS1: giving a new structure to dengue diagnosis.

In a recent article (6), Wang et al. reported an extensive evaluation of NS1 antigen and compared it with real-time PCR, an IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA), and a hemagglutination inhibition assay for diagnosis of dengue virus infection. The authors reported MAC-ELISA positivity for 46 (92%) out of 50 samples positive for dengue virus by real-time PCR (RT-PCR). However, the literature suggests (5) that viremia in dengue lasts for less than 5 days and that the IgM antibody response takes 5 to 10 days to develop in cases of primary dengue virus infection and 4 to 5 days in cases of secondary dengue virus infection (2, 5). Hence, at a particular time postinfection, it is unlikely that the results for both of these tests will be positive. The authors report that they were able to detect viral RNA up to 8 days postinfection. However, this also does not explain the overlap period, as it does not explain why RT-PCR positivity was observed in only 1 out of 100 dengue virus IgM-positive samples. It is important to know in how many cases the virus genome could be detected until day 8 out of the 50 samples that were positive by real-time PCR. It would also be valuable to know whether the same patient’s blood was drawn for 8 consecutive days and checked for viremia and, if so, whether the virus was detectable. The authors mention that they were able to detect NS1 antigen up to 14 days from the onset of fever. Previous studies (1, 3) have reported that NS1 antigen is positive for 9 days postinfection in cases of primary dengue and up to 5 days postinfection in cases of secondary dengue. We have also evaluated and compared NS1 with IgM for diagnosis of acute dengue virus infection in 87 patients. NS1 antigen had a sensitivity of 71 to 100% when used for patients who had a fever for 3 days. We suggest that NS1 antigen should be considered the test of choice for patients presenting with a history of fever of up to 3 days of duration. On day 4, a combination of MAC-ELISA and an NS1 antigen test would increase the sensitivity of diagnosis. We found that detection of NS1 antigen was not useful beyond day 4 of fever. We also compared both of these diagnostic modalities with conventional RT-PCR for 40 samples from patients with acute dengue. The results for the NS1 test were positive for an additional 15 samples which were negative by conventional RT-PCR (4). It is important to know that NS1 testing is also available as a strip test and also as a dengue duo test (NS1/IgM/IgG), which has further increased the sensitivity of detection.