Utility of IgM/IgG ratio and IgG avidity for distinguishing primary and secondary dengue virus infections using sera collected more than 30 days after disease onset

Dengue virus (DV) IgM/IgG ratio and IgG avidity value (AV) can reliably distinguish between primary and secondary DV infections using sera collected within 30 days of disease onset, but little is known about their efficacies using sera collected >30 days after onset. To investigate this issue, we analyzed specimens submitted to our reference laboratory for DV antibody testing. We first classified patients as having primary (n = 55) or secondary (n = 58) infections based on seroconversion patterns in a comparison of two sera collected <30 days apart. We then evaluated IgM/IgG ratios and IgG AVs of the second specimens by using receiver operating characteristic curve analysis. The IgM/IgG ratio that best discriminated primary from secondary infection was 1.32; 95% of 55 primary infections exhibited ratios of >1.32, whereas 93% of 58 secondary infections exhibited ratios of ≤1.32. The discriminatory AV was 0.39; 95% of 41 primary infections exhibited AVs of ≤0.39, whereas 95% of 38 secondary infections exhibited AVs of >0.39. We then evaluated the IgM/IgG ratios and AV for primary-infection patients whose second serum samples were collected ≥30 days after the first serum samples; only 56% of 27 sera exhibited ratios of >1.32, whereas 81% of 21 sera exhibited AVs of ≤0.39. Assuming that the first specimens were collected within a week after symptoms appeared, these findings indicate that IgG AV is superior to the IgM/IgG ratio for distinguishing primary from secondary DV infections when using samples collected more than 5 weeks after disease onset.