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.

Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort

“…Once recovery occurs from a DENV infection by any given serotype, the patient gains permanent homologous and transient heterologous immunity. In humans, if a subsequent heterologous infection occurs, the risk of developing severe dengue increases; these results were corroborated in a recent study demonstrating that in a narrow range of preexisting anti-DENV antibodies, the hazard of severe disease was significantly increased [2,3,14,15].…”

Natural Products with Potential to Treat RNA Virus Pathogens Including SARS-CoV-2

“…Dengue is the most prevalent mosquito-borne viral disease in the world. 41 The dengue virus consists of four serotypes, which introduces considerable complication in the disease and its clinical course. Infection with one serotype does not confer immunity to another serotype.…”

“…Rather, infection with a different serotype can create an antibody-dependent enhancement of the disease. This makes it very difficult to develop a universal vaccine for all the Dengue serotypes 41 and makes imperative the development of small-molecule therapeutics.…”

Evolution, heterogeneity and global dispersal of cosmopolitan genotype of Dengue virus type 2

“…According to empirical data, the highest pooled mortality rate has been reported during DENV-2 outbreaks 10 . Studies have also shown that DENV-2 causes more severe secondary infections than other serotypes 11 , 12 . These evidences indicate an important role played by DENV-2 in dengue epidemiology and global health burden.…”