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Cross-serotype interactions and disease outcome prediction of dengue infections in Vietnam.

ABSTRACT: Dengue pathogenesis is extremely complex. Dengue infections are thought to induce life-long immunity from homologous challenges as well as a multi-factorial heterologous risk enhancement. Here, we use the data collected from a prospective cohort study of dengue infections in schoolchildren in Vietnam to disentangle how serotype interactions modulate clinical disease risk in the year following serum collection. We use multinomial logistic regression to correlate the yearly neutralizing antibody measurements obtained with each infecting serotype in all dengue clinical cases collected over the course of 6 years (2004-2009). This allowed us to extrapolate a fully discretised matrix of serotype interactions, revealing clear signals of increased risk of clinical illness in individuals primed with a previous dengue infection. The sequences of infections which produced a higher risk of dengue fever upon secondary infection are: DEN1 followed by DEN2; DEN1 followed by DEN4; DEN2 followed by DEN3; and DEN4 followed by DEN3. We also used this longitudinal data to train a machine learning algorithm on antibody titre differences between consecutive years to unveil asymptomatic dengue infections and estimate asymptomatic infection to clinical case ratios over time, allowing for a better characterisation of the population's past exposure to different serotypes.

SUBMITTER: Aguas R

PROVIDER: S-EPMC6598999 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionDengue hemorrhagic fever is caused by four serotypes of dengue viruses transmitted by mosquitoes. In Vietnam, dengue outbreaks occur every year, and all four serotypes have been found circulating with the dominant one varying over time. However, in 2017 an unusual dengue fever outbreak occurred in the North of Vietnam, predominantly caused by DENV1 (92%) and DENV2 (7.3%). The objective of the present study was to obtain and characterize the full-length genome sequence of seven DENV2 strains in 2017 epidemic.Materials and methodsWhole-genome sequencing of seven DENV2 isolates from the 2017 outbreak were obtained using the Illumina MiSeq next generation sequencer system. Complete genome sequences were then analyzed to find out genetic variants and genetic relationships between these DENV2 with other strains that circulated in Vietnam previously and other regions of the world.ResultsThe complete genome sequence of seven DENV2 isolates in the 2017 dengue outbreak comprised 10,696 nucleotides with an open reading frame coding for 3392 amino acids. The genome analysis showed only a small number of amino acid changes which were obtained in all genes, in which a few amino acids substitutions were distributed over the positions such as G156 (NS1), V106 (NS2A), and L258/T260 (NS5). The phylogenetic analysis revealed that the DENV2 isolates in the 2017 outbreak were most closely related to the dengue virus from India in 2006, suggesting that the causative virus originated from the DENV2 that caused dengue hemorrhagic fever in 2006 in India.ConclusionThe first complete genome sequences of seven DENV2 isolates in the 2017 dengue outbreak in Northern Vietnam were successfully obtained. The genetic and phylogenetic data indicated that these DENV2 isolates were not causative virus circulating in Vietnam previously but originated from India in 2006. These data are emerging and providing valuable information for the management and surveillance of dengue in Vietnam.

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Cross-serotype interactions and disease outcome prediction of dengue infections in Vietnam.

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