Immunological and Viral Determinants of Dengue Severity in Hospitalized Adults in Ha Noi, Viet Nam

Abstract

BackgroundThe 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 Findings158 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.ConclusionDengue 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.

Detection of Dengue Virus Nonstructural Protein 1 (NS1) by Using ELISA as a Useful Laboratory Diagnostic Method for Dengue Virus Infection of International Travelers

“…NS1 antigen positive rates were at high levels on days 1-5 and days 6-10. While some investigators found higher detection rates in primary infection as compared to secondary infection, [31][32][33] others found no difference in NS1 detection rates between primary and secondary infection 13,34,35 or higher detection rates in secondary as compared to primary infection. 36 Magnitude and kinetics of NS1 also varied with infecting serotype and viremia clearance.…”

Viral kinetics of primary dengue virus infection in non-human primates: A systematic review and individual pooled analysis

“…Nisalak et al found DENV-3 to be associated with severe outbreaks of dengue in hospitalized cases in Bangkok, Thailand [15]. Fox et al found time to undetectable DENV-2 NS1 protein to be significantly longer than DENV-1 [26]. Extended durations of viremia for DENV-2 and -3 may be the cause of the increased severity of these infections and may be the reason sylvatic DENV-2 is the only serotype to have emerged in Africa from southeast Asia.…”

“…Studies in humans have found that higher peak viremia titers were positively associated with more severe disease [21, 22, 33]; however the evidence for an association between the magnitude and duration of viremia remains inconclusive. Vaughn et al found the time from peak viremia to clearance was more rapid in DHF cases than in DF cases [22], while Fox et al found no difference in rate of clearance between DHF and DF [26]. …”

Liposome-Mediated Delivery of Iminosugars Enhances Efficacy against Dengue Virus In Vivo

“…In humans, however, the immunopathogenic reaction, rather than the viral load directly (15), is hypothesized to be responsible for the clinical manifestations of severe dengue. Thus, differential triggering of the inflammatory cascade (in particular tumor necrosis factor alpha [TNF-␣] in the ADE mouse model) may explain increased survival in NB-DNJ PERL-treated mice.…”