Contributions from the silent majority dominate dengue virus transmission

Abstract

Despite estimates that, each year, as many as 300 million dengue virus (DENV) infections result in either no perceptible symptoms (asymptomatic) or symptoms that are sufficiently mild to go undetected by surveillance systems (inapparent), it has been assumed that these infections contribute little to onward transmission. However, recent blood-feeding experiments with Aedes aegypti mosquitoes showed that people with asymptomatic and pre-symptomatic DENV infections are capable of infecting mosquitoes. To place those findings into context, we used models of within-host viral dynamics and human demographic projections to (1) quantify the net infectiousness of individuals across the spectrum of DENV infection severity and (2) estimate the fraction of transmission attributable to people with different severities of disease. Our results indicate that net infectiousness of people with asymptomatic infections is 80% (median) that of people with apparent or inapparent symptomatic infections (95% credible interval (CI): 0–146%). Due to their numerical prominence in the infectious reservoir, clinically inapparent infections in total could account for 84% (CI: 82–86%) of DENV transmission. Of infections that ultimately result in any level of symptoms, we estimate that 24% (95% CI: 0–79%) of onward transmission results from mosquitoes biting individuals during the pre-symptomatic phase of their infection. Only 1% (95% CI: 0.8–1.1%) of DENV transmission is attributable to people with clinically detected infections after they have developed symptoms. These findings emphasize the need to (1) reorient current practices for outbreak response to adoption of pre-emptive strategies that account for contributions of undetected infections and (2) apply methodologies that account for undetected infections in surveillance programs, when assessing intervention impact, and when modeling mosquito-borne virus transmission.

Under-the-Radar Dengue Virus Infections in Natural Populations of Aedes aegypti Mosquitoes

“…The absence of an index human DENV4 case does not preclude the possibility that DENV4 was transmitted locally. Up to 88% of primary DENV infections are asymptomatic, with DENV4 being widely understood to cause primarily subclinical infections (14,15). Importantly, clinically inapparent infections could contribute to 84% of DENV transmission events through mosquitoes, so the threat of local transmission cannot be ruled out (14).…”

“…Up to 88% of primary DENV infections are asymptomatic, with DENV4 being widely understood to cause primarily subclinical infections (14,15). Importantly, clinically inapparent infections could contribute to 84% of DENV transmission events through mosquitoes, so the threat of local transmission cannot be ruled out (14). However, it is noteworthy that DENV4 was detected in adult female mosquitoes reared from wild-captured eggs, implicating transovarial transmission (TOT) in local A. aegypti as has been shown for DENV1 in Key West, FL (16).…”

Detection of dengue virus type 2 of Indian origin in acute febrile patients in rural Kenya

“…However, as asymptomatic people were not included in this study, the true level of infections remains to be determined. The subclinical infections enable the silent transmission and may constitute the majority of the infections in an non-outbreak situation [49,50]. The unrecognition of dengue due to lack of diagnostic testing is likely to lead to underestimates of its impact to the public health.…”

Human Mobility and the Global Spread of Infectious Diseases: A Focus on Air Travel

“…Interestingly, there is emerging evidence that individuals infected with dengue virus who are asymptomatic or presymptomatic (and presumably have lower levels of viremia) are still able to infect competent mosquito vectors. Such individuals may be more prone to traveling given their lack of symptoms, and are likely contributing to global dengue virus transmission [63,64].…”