Epidemiological Risk Factors Associated with High Global Frequency of Inapparent Dengue Virus Infections

Abstract

Dengue is a major international public health concern, and the number of outbreaks has escalated greatly. Human migration and international trade and travel are constantly introducing new vectors and pathogens into novel geographic areas. Of particular interest is the extent to which dengue virus (DENV) infections are subclinical or inapparent. Not only may such infections contribute to the global spread of DENV by human migration, but also seroprevalence rates in naïve populations may be initially high despite minimal numbers of detectable clinical cases. As the probability of severe disease is increased in secondary infections, populations may thus be primed, with serious public health consequences following introduction of a new serotype. In addition, pre-existing immunity from inapparent infections may affect vaccine uptake, and the ratio of clinically apparent to inapparent infection could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable, but “inapparent” was the major outcome of infection in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent infection rates. However, one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year, strongly supporting an important role for short-term heterotypic immunity in determining the outcome of infection. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is urgently needed. Inapparent infections need to be considered for their impact on disease severity, transmission dynamics, and vaccine efficacy and uptake.

Quantifying the added value of climate information in a spatio-temporal dengue model

“…This may occur irrespective of the circulating serotype as homotypic immunity is believed to be life-long (Sabin, 1952) and heterotypic immunity is estimated to last from 3 months to a year (Reich et al, 2013;Sabin, 1952). The latter may not prevent infection, but rather reduce clinical disease (Endy et al, 2011;Grange et al, 2014;Sabin, 1952). Additionally, heavy rains can "wash-out" mosquito breeding sites, resulting in short-term population crashes.…”

“…The small temporal decline has been linked to a reduced estimated force of infection and the changing demography (reduced birth and death rates) may have contributed to this ). However, there exist no extensive data on seroprevalence and the majority of infections are inapparent with no clinical presentation (Grange et al, 2014).…”

Asymptomatic humans transmit dengue virus to mosquitoes

“…"Asymptomatic" refers to a confirmed DENV infection in the complete absence of reported or detected symptoms. Inapparent human DENV infections are a potentially important component of the overall burden of dengue because they can serve as a previously unrecognized source of mosquito infection (12). Epidemic transmission of DENV associated with low viremia levels and mild illness has been reported (13).…”

“…An estimated 300 million of the total 390 million DENV infections per year are clinically inapparent or mildly symptomatic, i.e., no illness that disrupted a person's daily routine (1). Following Grange et al (12), we use "inapparent" or "subclinical" interchangeably to denote infections confirmed by virus detection or seroconversion, but with insufficient symptoms to be detected by existing surveillance systems and health care providers. "Asymptomatic" refers to a confirmed DENV infection in the complete absence of reported or detected symptoms.…”

La dengue, maladie complexe

“…Un individu peut donc potentiellement déve-lopper quatre infections à la dengue. Entre 50 et 80 % des infections à la dengue sont cependant asymptomatiques (Grange et al, 2014). Ce différentiel de vulnérabilité individuelle dépend de nombreux facteurs tels que la géné-tique, l'immunité ou encore l'âge (Huy et al, 2013).…”