Dengue Infection and Miscarriage: A Prospective Case Control Study

Dengue is the most prevalent mosquito-borne infection with two billion of the world's population at risk and 100 million infections every year. Dengue is increasingly important due to expansion in the vector's range, increased population density in endemic areas from urbanisation, social and environment change. Miscarriage and stillbirth is associated with dengue when the illness is severe. Dengue can also be transmitted directly from the ill mother through the placenta to the fetus in later pregnancy with variable effect to the fetus. However, dengue infection is asymptomatic to mild only in almost 90% of cases and up to 20% of pregnancies miscarry. Little is known if dengue infection in early pregnancy particularly when it is asymptomatic or mild has an effect on miscarriage. Our study explored the relationship between dengue and miscarriage by looking at recent infection rates amongst women who had miscarried and those whose pregnancies were healthy in an area were dengue is common. Our study finds a positive association between recent dengue infection and miscarriage. This finding may be important in explaining some of the miscarriages in areas where dengue is common. It is also relevant to newly pregnant women from non-dengue travelling to dengue endemic areas

Specific IgM and IgG responses in primary and secondary dengue virus infections determined by enzyme-linked immunosorbent assay

IgM- and IgG-capture ELISAs are widely used as diagnostic tests for confirmation of dengue virus infection. The positive rate of anti-dengue IgM and IgG detection was examined in primary and secondary dengue virus infections in the setting of a provincial hospital using IgM- and IgG-capture ELISAs. Disease day 1 was defined as the day of onset of symptoms. In total, 232 plasma samples were collected from 106 confirmed dengue cases consisting of 12 primary and 94 secondary infections. In primary infection, anti-dengue IgM was detected in 4 out of 5 samples collected on disease day 5 and in all the 21 samples collected on disease day 6 or later. Specific IgG was detected in 2 out of 5 samples collected on day 12, and in 5 out of 6 samples collected on disease days 13–15, but was not detected in samples collected on disease day 10 or earlier. In secondary infection, IgM was not detected in the samples on disease days 2 and 3, but detected in 20 out of 79 samples collected on days 4–6, in 44 out of 65 on disease days 7–11 and in 40 out of 51 samples on disease days 12–14. In contrast, specific IgG was detected in 21 out of 60 samples on disease days 4 and 5, in 13 out of 19 on disease day 6, in 62 out of 65 on disease days 7–11 and in all the samples collected on disease day 12 or later. The result indicate that seroconversion rates of IgM and IgG are different between primary and secondary infections, and suggest that detection of specific IgM and IgG is necessary for determining dengue virus infection and for differentiating primary and secondary dengue infections

Estimation of Dengue Virus IgM Persistence Using Regression Analysis ▿

Dengue virus IgM persistence was estimated using follow-up sera from 98 patients (60 with primary infections and 38 with secondary infections) whose first-specimen IgM index was strongly positive, suggesting recent disease onset. Regression analysis of the follow-up IgM index versus days between samples yielded a trend line that reached the cut-point index (1.10) at 179 days for the primary infection group and 139 days for the secondary infection group. This difference reflected significantly higher first-sample IgM indices in primary infections than in secondary infections rather than differences in IgM decay rates

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