Immunological and viral determinants of dengue severity in hospitalized adults in Ha Noi, Viet Nam

Abstract

Background: The relationships between the infecting dengue serotype, primary and secondary infection, viremia and dengue severity remain unclear. This cross-sectional study examined these interactions in adult patients hospitalized with dengue in Ha Noi.

Methods and findings: 158 patients were enrolled between September 16 and November 11, 2008. Quantitative RT-PCR, serology and NS1 detection were used to confirm dengue infection, determine the serotype and plasma viral RNA concentration, and categorize infections as primary or secondary. 130 (82%) were laboratory confirmed. Serology was consistent with primary and secondary infection in 34% and 61%, respectively. The infecting serotype was DENV-1 in 42 (32%), DENV-2 in 39 (30%) and unknown in 49 (38%). Secondary infection was more common in DENV-2 infections (79%) compared to DENV-1 (36%, p<0.001). The proportion that developed dengue haemorrhagic fever (DHF) was 32% for secondary infection compared to 18% for primary infection (p = 0.14), and 26% for DENV-1 compared to 28% for DENV-2. The time until NS1 and plasma viral RNA were undetectable was shorter for DENV-2 compared to DENV-1 (p≤0.001) and plasma viral RNA concentration on day 5 was higher for DENV-1 (p = 0.03). Plasma viral RNA concentration was higher in secondary infection on day 5 of illness (p = 0.046). We didn't find an association between plasma viral RNA concentration and clinical severity.

Conclusion: Dengue is emerging as a major public health problem in Ha Noi. DENV-1 and DENV-2 were the prevalent serotypes with similar numbers and clinical presentation. Secondary infection may be more common amongst DENV-2 than DENV-1 infections because DENV-2 infections resulted in lower plasma viral RNA concentrations and viral RNA concentrations were higher in secondary infection. The drivers of dengue emergence in northern Viet Nam need to be elucidated and public health measures instituted.

Figure 1. Daily platelet and haematocrit measurements in DF and DHF patients.

The number of DF (94 in total) and DHF patients (36 in total) assessed each day is shown above or below each box. Haematocrits were assessed on at least 4 days for 125 of 130 confirmed dengue patients.

Figure 2. NS1 measurements in DF and DHF patients stratified by serotype and primary versus secondary infection.

Plasma samples collected daily during admission and at follow-up from DF (pink) and DHF (blue) patients were tested by NS1 ELISA and results presented as OD₄₅₀ sample/OD₄₅₀ cutoff control.

Figure 3. Viral RNA concentration in DF and DHF patients stratified by serotype and primary versus secondary infection.

Plasma samples collected daily during admission from DF (pink) and DHF (blue) patients were tested by RT-PCR for viral RNA and results expressed as Log10 cDNA equivalents/ml of plasma.