Host and viral features of human dengue cases shape the population of infected and infectious Aedes aegypti mosquitoes

Abstract

Dengue is the most prevalent arboviral disease of humans. The host and virus variables associated with dengue virus (DENV) transmission from symptomatic dengue cases (n = 208) to Aedes aegypti mosquitoes during 407 independent exposure events was defined. The 50% mosquito infectious dose for each of DENV-1-4 ranged from 6.29 to 7.52 log10 RNA copies/mL of plasma. Increasing day of illness, declining viremia, and rising antibody titers were independently associated with reduced risk of DENV transmission. High early DENV plasma viremia levels in patients were a marker of the duration of human infectiousness, and blood meals containing high concentrations of DENV were positively associated with the prevalence of infectious mosquitoes 14 d after blood feeding. Ambulatory dengue cases had lower viremia levels compared with hospitalized dengue cases but nonetheless at levels predicted to be infectious to mosquitoes. These data define serotype-specific viremia levels that vaccines or drugs must inhibit to prevent DENV transmission.

Keywords: entomology; infectious disease; virology.

Fig. 1.

Profile of DENV transmission from 208 hospitalized dengue cases to Ae. aegypti mosquitoes by fever day and virus serotype. (Left) Patients’ longitudinal plasma viremia profiles according to fever day (gray lines) with a LOESS scatterplot smoother (blue lines) and stratified by virus serotype. The day of defervescence is assigned fever day = 0 for all patients. (Right) Scatterplots of the proportion of mosquitoes with DENV-infected abdomens 12 d after blood-feeding by fever day at the time of mosquito exposure. The graphs also show the estimated associations (blue lines) with pointwise 95% confidence intervals (gray-shaded areas) based on marginal logistic regression.

Fig. 2.

Dose–response scatterplots of plasma viremia vs. the proportion of mosquitoes with DENV-infected abdomens after feeding on 208 hospitalized dengue patients. Each dot point shows the proportion of all mosquitoes that took a blood meal during an exposure event and had DENV-infected abdomens 12 d later vs. the corresponding plasma viremia in the patient at the time of mosquito exposure, stratified by serotype. The graphs show the estimated associations (blue lines) with pointwise 95% confidence intervals (gray shaded areas) based on marginal logistic regression. Serotype-specific associations between the odds of abdomen infection and viremia were DENV1: OR 3.93 (95% CI 2.89–5.33; P < 0.001), DENV2: OR 5.48 (95% CI 3.81–7.90; P < 0.001), DENV3: OR 2.61 (95% CI 1.48–4.58; P < 0.001), and DENV4: OR 2.30 (95% CI 1.65–3.21; P < 0.001) per +1 log10-copies/mL increase in viremia.

Fig. 3.

Dose–response scatterplots of plasma viremia vs. the proportion of mosquitoes with infectious saliva after feeding on 72 hospitalized dengue patients. Each dot point shows the proportion of all mosquitoes that took a blood meal during an exposure event and had saliva containing infectious DENV 14 d after blood-feeding vs. the corresponding patient’s plasma viremia at the time of exposure, stratified by serotype. Each dot represents one mosquito exposure, and the size of the dot is proportional to the number of mosquitoes assessed (ranging from 2 to 17). Serotype-specific associations between the odds of saliva positivity and viremia were DENV1: OR 1.47 (95% CI 0.96–2.711; P = 0.08), DENV2: OR 2.53 (95% CI 1.75–3.65; P < 0.0001), DENV3: OR 1.69 (95% CI 1.09–2.60; P = 0.02) and DENV4: OR 2.77 (95% CI 1.68–4.55; P < 0.0001) per +1 log10 copies/mL increase in viremia.