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.engue is globally the most important mosquito-borne viral disease of humans, with a global burden of ∼100 million cases per annum (1, 2). Aedes aegypti mosquitoes are the primary mosquito vectors of dengue viruses (DENV), of which there are four virus types (DENV-1-4). Multiple factors influence the likelihood of infection and dissemination of DENV in Ae. aegypti and include the amplitude of daily temperature fluctuations (3), mean temperature (4), and the genotype of mosquito and virus (5), among others (6). The extrinsic incubation period (EIP), a critical determinant of vector competence (7,8), is widely accepted to be 7-14 d for DENV in Ae. aegypti, although a recent modeling analysis of historical DENV transmission data has suggested a wider range of 2-15 d at 30°C (9). A major caveat to many of these observations is that they stem from laboratory experiments with artificially generated virus-spiked blood meals and often in-bred colony mosquitoes.The temporal and virological variables associated with the transmission of DENV from a naturally infected human to a biting Ae. aegypti mosquito are poorly understood. Natural history studies of experimental DENV infection of small cohorts of human volunteers in the 1920s by Siler et al. (10,11), likely using DENV-4 (12), and subsequent studies by Simmons et al. (13), likely using DENV-1 (12), suggested that the window of time before the onset of clinical symptoms that DENV-1 or DENV-4 could be transmitted to Ae. aegypti mosquitoes was 6-18 h or 2 d, respectively (14). After fever onset, the duration of infectiousness was 4-5 d for DENV-1 and up to 2 d for DENV-4, with an EIP in the mosquito of 10 d or more. Consistent with this, mosquitobiting studies by Gubler et al. in the 1960s (15-18) collectively estimated that dengue cases were infectious for 4-5 d after illness onset (range, 2-12 d). The human viremia level required to infect Ae. aegypti mosquitoes is unknown, and therefore it is uncertain what percentage of symptomatic (or asymptomatic...

Calling in sick: impacts of fever on intra-urban human mobility

“…For dengue, infectiousness often lasts longer than fever. In experimental feeding studies, infection of mosquitoes was documented up to 2 days before [37] and 2 days after [38] the period of fever, which typically lasts between 2 and 7 days [32]. In a more recent study [39], at a given viremia level, dengue virus infected people with no detectable symptoms or whose symptoms had not yet begun were more infectious to mosquitoes than people who were bitten when they were symptomatic.…”

Invasiveness ofAedes aegyptiandAedes albopictusand Vectorial Capacity for Chikungunya Virus

“…With DENV, variation occurs in both interspecific and intraspecific serotype-specific ID 50 estimates. For example, the ID 50 for DENV-1 and DENV-2 was lower than for DENV-3 and DENV-4 in one study in Vietnam [36], and field populations of A. aegypti demonstrated lower vector competence for the American genotype of DENV-2 than the Southeast Asian genotype [37]. It has been shown that people with asymptomatic and presymptomatic DENV infections had an approximately 100-fold lower ID 50 and resulted in larger viral loads in infected mosquitoes, which was interpreted as increased transmission potential [38].…”

Crossing the scale from within-host infection dynamics to between-host transmission fitness: a discussion of current assumptions and knowledge

“…Figure 3 provides another example of a direct mapping from within-human pathogen load data to transmission for dengue infections. For each of the four dengue serotypes, the association between viraemia in dengue patients and the infectiousness of these patients to mosquitoes is shown ( figure 3; [46]). In acute infections, such as dengue, pathogen levels do not reach a defined steady state at which pathogen levels are more or less constant for an extended period.…”