Asymptomatic humans transmit dengue virus to mosquitoes

Abstract

Three-quarters of the estimated 390 million dengue virus (DENV) infections each year are clinically inapparent. People with inapparent dengue virus infections are generally considered dead-end hosts for transmission because they do not reach sufficiently high viremia levels to infect mosquitoes. Here, we show that, despite their lower average level of viremia, asymptomatic people can be infectious to mosquitoes. Moreover, at a given level of viremia, DENV-infected people with no detectable symptoms or before the onset of symptoms are significantly more infectious to mosquitoes than people with symptomatic infections. Because DENV viremic people without clinical symptoms may be exposed to more mosquitoes through their undisrupted daily routines than sick people and represent the bulk of DENV infections, our data indicate that they have the potential to contribute significantly more to virus transmission to mosquitoes than previously recognized.

Keywords: Aedes aegypti; Cambodia; dengue; human-to-mosquito transmission; mosquito experimental infection.

Fig. 1.

Profiles of plasma viremia and infectiousness by day of illness. Plasma viremia expressed as DENV cDNA copy number per milliliter (A) and percentage of infected mosquitoes following direct (B) and indirect feeding (C) are shown as a function of day of illness for presymptomatic/symptomatic participants. Day 0 is the onset of clinical symptoms. Each dot corresponds to an individual participant and is color-coded by DENV serotype. A, B, and C include 163, 142, and 144 participants who developed symptoms, respectively. In A, solid lines indicate the quadratic regression and dotted lines represent the SE of regression parameter estimates. In B and C, the size of the dots is proportional to the number of mosquitoes tested per participant.

Fig. 2.

Dose–response profiles by disease category. The percentage of infected mosquitoes is shown as a function of viremia (measured as cDNA copies per milliliter of plasma) for each study participant involved in direct (A) and indirect (B) mosquito feedings. Solid symbols represent positive viremia levels. Open symbols correspond to undetectable viremia levels in five participants that resulted in mosquito infection. The size of the dot is proportional to the number of mosquitoes tested per participant (direct feeding: mean, 10.0; median, 9; IQR, 5–14; indirect feeding: mean, 8.8; median, 7; IQR, 5–11). A includes 8 asymptomatic, 37 presymptomatic, and 117 symptomatic participants. B includes 10 asymptomatic, 41 presymptomatic, and 120 symptomatic participants. Curves are logistic regressions of the data (excluding participants with undetectable viremia). The minimum adequate model for direct feedings explained 34.2% of the variation in the proportion of mosquitoes infected, and disease category alone accounted for 8% of the overall variation. For the indirect feedings, the percentage of variation explained by the model was 37.4% and 7.8% for disease category alone.