An agent-based model of dengue virus transmission shows how uncertainty about breakthrough infections influences vaccination impact projections.

Prophylactic vaccination is a powerful tool for reducing the burden of infectious diseases, due to a combination of direct protection of vaccinees and indirect protection of others via herd immunity. Computational models play an important role in devising strategies for vaccination by making projections of its impacts on public health. Such projections are subject to uncertainty about numerous factors, however. For example, many vaccine efficacy trials focus on measuring protection against disease rather than protection against infection, leaving the extent of breakthrough infections (i.e., disease ameliorated but infection unimpeded) among vaccinees unknown. Our goal in this study was to quantify the extent to which uncertainty about breakthrough infections results in uncertainty about vaccination impact, with a focus on vaccines for dengue. To realistically account for the many forms of heterogeneity in dengue virus (DENV) transmission, which could have implications for the dynamics of indirect protection, we used a stochastic, agent-based model for DENV transmission informed by more than a decade of empirical studies in the city of Iquitos, Peru. Following 20 years of routine vaccination of nine-year-old children at 80% coverage, projections of the proportion of disease episodes averted varied by a factor of 1.76 (95% CI: 1.54-2.06) across the range of uncertainty about breakthrough infections. This was equivalent to the range of vaccination impact projected across a range of uncertainty about vaccine efficacy of 0.268 (95% CI: 0.210-0.329). Until uncertainty about breakthrough infections can be addressed empirically, our results demonstrate the importance of accounting for it in models of vaccination impact.

Time-varying, serotype-specific force of infection of dengue virus.

Infectious disease models play a key role in public health planning. These models rely on accurate estimates of key transmission parameters such as the force of infection (FoI), which is the per-capita risk of a susceptible person being infected. The FoI captures the fundamental dynamics of transmission and is crucial for gauging control efforts, such as identifying vaccination targets. Dengue virus (DENV) is a mosquito-borne, multiserotype pathogen that currently infects ∼390 million people a year. Existing estimates of the DENV FoI are inaccurate because they rely on the unrealistic assumption that risk is constant over time. Dengue models are thus unreliable for designing vaccine deployment strategies. Here, we present to our knowledge the first time-varying (daily), serotype-specific estimates of DENV FoIs using a spline-based fitting procedure designed to examine a 12-y, longitudinal DENV serological dataset from Iquitos, Peru (11,703 individuals, 38,416 samples, and 22,301 serotype-specific DENV infections from 1999 to 2010). The yearly DENV FoI varied markedly across time and serotypes (0-0.33), as did daily basic reproductive numbers (0.49-4.72). During specific time periods, the FoI fluctuations correlated across serotypes, indicating that different DENV serotypes shared common transmission drivers. The marked variation in transmission intensity that we detected indicates that intervention targets based on one-time estimates of the FoI could underestimate the level of effort needed to prevent disease. Our description of dengue virus transmission dynamics is unprecedented in detail, providing a basis for understanding the persistence of this rapidly emerging pathogen and improving disease prevention programs.

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

Pathogens inflict a wide variety of disease manifestations on their hosts, yet the impacts of disease on the behaviour of infected hosts are rarely studied empirically and are seldom accounted for in mathematical models of transmission dynamics. We explored the potential impacts of one of the most common disease manifestations, fever, on a key determinant of pathogen transmission, host mobility, in residents of the Amazonian city of Iquitos, Peru. We did so by comparing two groups of febrile individuals (dengue-positive and dengue-negative) with an afebrile control group. A retrospective, semi-structured interview allowed us to quantify multiple aspects of mobility during the two-week period preceding each interview. We fitted nested models of each aspect of mobility to data from interviews and compared models using likelihood ratio tests to determine whether there were statistically distinguishable differences in mobility attributable to fever or its aetiology. Compared with afebrile individuals, febrile study participants spent more time at home, visited fewer locations, and, in some cases, visited locations closer to home and spent less time at certain types of locations. These multifaceted impacts are consistent with the possibility that disease-mediated changes in host mobility generate dynamic and complex changes in host contact network structure.

House-to-house human movement drives dengue virus transmission.

Dengue is a mosquito-borne disease of growing global health importance. Prevention efforts focus on mosquito control, with limited success. New insights into the spatiotemporal drivers of dengue dynamics are needed to design improved disease-prevention strategies. Given the restricted range of movement of the primary mosquito vector, Aedes aegypti, local human movements may be an important driver of dengue virus (DENV) amplification and spread. Using contact-site cluster investigations in a case-control design, we demonstrate that, at an individual level, risk for human infection is defined by visits to places where contact with infected mosquitoes is likely, independent of distance from the home. Our data indicate that house-to-house human movements underlie spatial patterns of DENV incidence, causing marked heterogeneity in transmission rates. At a collective level, transmission appears to be shaped by social connections because routine movements among the same places, such as the homes of family and friends, are often similar for the infected individual and their contacts. Thus, routine, house-to-house human movements do play a key role in spread of this vector-borne pathogen at fine spatial scales. This finding has important implications for dengue prevention, challenging the appropriateness of current approaches to vector control. We argue that reexamination of existing paradigms regarding the spatiotemporal dynamics of DENV and other vector-borne pathogens, especially the importance of human movement, will lead to improvements in disease prevention.

Reduced risk of disease during postsecondary dengue virus infections.

BACKGROUND: Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1-4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission. METHODS: DENV infections before and during the study period were determined by analysis of serial serum samples with virus neutralization tests. Third and fourth infections were classified as postsecondary infections. Dengue fever cases were detected by door-to-door surveillance for acute febrile illness. RESULTS: Among susceptible participants, 39% (420/1077) and 53% (1595/2997) seroconverted to DENV-3 and DENV-4, respectively. Disease was detected in 7% of DENV-3 infections and 10% of DENV-4 infections. Disease during postsecondary infections was reduced by 93% for DENV-3 and 64% for DENV-4, compared with primary and secondary infections. Despite lower disease rates, postsecondary infections constituted a significant proportion of apparent infections (14% [for DENV-3 infections], 45% [for DENV-4 infections]). CONCLUSIONS: Preexisting heterotypic antibodies markedly reduced but did not eliminate the risk of disease in this study population. These results improve understanding of how preinfection history can be associated with dengue outcomes and DENV transmission dynamics.

Using the Health Belief Model to Predict Pre-Travel Health Decisions among U.S.-Based Travelers.

International travelers are at increased risk of infectious disease, but almost half of Americans traveling to lower- and middle-income countries seek no health information before traveling. The Health Belief Model (HBM) can help evaluate decisions by categorizing behaviors into five categories: susceptibility, severity, benefits, barriers, and self-efficacy. This study sought to use the HBM to elucidate what may influence an individual to make certain pre-travel health decisions. We surveyed 604 participants who had recently traveled to an at-risk country. Participants were subset into nested groups: full population, sought any health information, and visited a clinic or health care provider (HCP). Survey questions were categorized according to the HBM, assembled into a priori models, and analyzed in each group using logistic regression with three main outcome variables: "Sought any pre-travel health information," "Visited clinic or HCP," and "Received vaccine." Of the 604 participants, 333 (55%) sought any health information, 245 (41% of total) reported visiting an HCP, and 166 (27% of total) reported receiving a vaccine before traveling. Models containing variables from the susceptibility and benefits categories were most successful in predicting all three outcomes; susceptibility was a more relevant consideration in information seeking and seeing a provider than vaccination, whereas benefits was relevant for all outcomes. Our results emphasize the importance of an individual's perceived susceptibility to disease and perceived benefit of interventions in predicting pre-travel health behaviors. Understanding this interaction can help shape how HCPs and public health entities can encourage health care seeking and vaccine uptake in travelers.

Model-based estimates of chikungunya epidemiological parameters and outbreak risk from varied data types.

Assessing the factors responsible for differences in outbreak severity for the same pathogen is a challenging task, since outbreak data are often incomplete and may vary in type across outbreaks (e.g., daily case counts, serology, cases per household). We propose that outbreaks described with varied data types can be directly compared by using those data to estimate a common set of epidemiological parameters. To demonstrate this for chikungunya virus (CHIKV), we developed a realistic model of CHIKV transmission, along with a Bayesian inference method that accommodates any type of outbreak data that can be simulated. The inference method makes use of the fact that all data types arise from the same transmission process, which is simulated by the model. We applied these tools to data from three real-world outbreaks of CHIKV in Italy, Cambodia, and Bangladesh to estimate nine model parameters. We found that these populations differed in several parameters, including pre-existing immunity and house-to-house differences in mosquito activity. These differences resulted in posterior predictions of local CHIKV transmission risk that varied nearly fourfold: 16% in Italy, 28% in Cambodia, and 62% in Bangladesh. Our inference method and model can be applied to improve understanding of the epidemiology of CHIKV and other pathogens for which outbreaks are described with varied data types.

Inapparent infections shape the transmission heterogeneity of dengue.

Transmission heterogeneity, whereby a disproportionate fraction of pathogen transmission events result from a small number of individuals or geographic locations, is an inherent property of many, if not most, infectious disease systems. For vector-borne diseases, transmission heterogeneity is inferred from the distribution of the number of vectors per host, which could lead to significant bias in situations where vector abundance and transmission risk at the household do not correlate, as is the case with dengue virus (DENV). We used data from a contact tracing study to quantify the distribution of DENV acute infections within human activity spaces (AS), the collection of residential locations an individual routinely visits, and quantified measures of virus transmission heterogeneity from two consecutive dengue outbreaks (DENV-4 and DENV-2) that occurred in the city of Iquitos, Peru. Negative-binomial distributions and Pareto fractions showed evidence of strong overdispersion in the number of DENV infections by AS and identified super-spreading units (SSUs): i.e. AS where most infections occurred. Approximately 8% of AS were identified as SSUs, contributing to more than 50% of DENV infections. SSU occurrence was associated more with DENV-2 infection than with DENV-4, a predominance of inapparent infections (74% of all infections), households with high Aedes aegypti mosquito abundance, and high host susceptibility to the circulating DENV serotype. Marked heterogeneity in dengue case distribution, and the role of inapparent infections in defining it, highlight major challenges faced by reactive interventions if those transmission units contributing the most to transmission are not identified, prioritized, and effectively treated.

Quantifying heterogeneities in arbovirus transmission: Description of the rationale and methodology for a prospective longitudinal study of dengue and Zika virus transmission in Iquitos, Peru (2014-2019).

Current knowledge of dengue virus (DENV) transmission provides only a partial understanding of a complex and dynamic system yielding a public health track record that has more failures than successes. An important part of the problem is that the foundation for contemporary interventions includes a series of longstanding, but untested, assumptions based on a relatively small portion of the human population; i.e., people who are convenient to study because they manifest clinically apparent disease. Approaching dengue from the perspective of people with overt illness has produced an extensive body of useful literature. It has not, however, fully embraced heterogeneities in virus transmission dynamics that are increasingly recognized as key information still missing in the struggle to control the most important insect-transmitted viral infection of humans. Only in the last 20 years have there been significant efforts to carry out comprehensive longitudinal dengue studies. This manuscript provides the rationale and comprehensive, integrated description of the methodology for a five-year longitudinal cohort study based in the tropical city of Iquitos, in the heart of the Peruvian Amazon. Primary data collection for this study was completed in 2019. Although some manuscripts have been published to date, our principal objective here is to support subsequent publications by describing in detail the structure, methodology, and significance of a specific research program. Our project was designed to study people across the entire continuum of disease, with the ultimate goal of quantifying heterogeneities in human variables that affect DENV transmission dynamics and prevention. Because our study design is applicable to other Aedes transmitted viruses, we used it to gain insights into Zika virus (ZIKV) transmission when during the project period ZIKV was introduced and circulated in Iquitos. Our prospective contact cluster investigation design was initiated by detecttion of a person with a symptomatic DENV infection and then followed that person's immediate contacts. This allowed us to monitor individuals at high risk of DENV infection, including people with clinically inapparent and mild infections that are otherwise difficult to detect. We aimed to fill knowledge gaps by defining the contribution to DENV transmission dynamics of (1) the understudied majority of DENV-infected people with inapparent and mild infections and (2) epidemiological, entomological, and socio-behavioral sources of heterogeneity. By accounting for factors underlying variation in each person's contribution to transmission we sought to better determine the type and extent of effort needed to better prevent virus transmission and disease.

Microsatellite-based parentage analysis of Aedes aegypti (Diptera: Culicidae) using nonlethal DNA sampling.

To track Aedes aegypti (L.) egg-laying behavior in the field in Iquitos, Peru, we developed methods for 1) sampling DNA from live mosquitoes and 2) high through-put parentage analysis using microsatellite markers. We were able to amplify DNA extracted from a single hind leg, but not from the pupal exuvia. Removal of a leg from teneral females caused no significant changes in female behavioral or life history traits (e.g., longevity, blood feeding frequency, fecundity, egg hatch rate, gonotrophic cycle length, or oviposition behavior). Using a panel of nine microsatellite markers and an exclusion-based software program, we matched offspring to parental pairs in 10 Ae. aegypti test families in which parents originated from natural development sites in Iquitos. By mating known individuals in the laboratory, retaining the male, sampling the female's DNA before release, and collecting offspring in the field, the technique we developed can be used to genotype large numbers of Ae. aegypti, reconstruct family relationships, and track the egg-laying behavior of individual Ae. aegypti in nature.

Surveying Health-Related Knowledge, Attitudes, and Behaviors of U.S.-Based Residents Traveling Internationally to Visit Friends and Relatives.

U.S. residents traveling internationally to regions with increased risk of infectious diseases infrequently seek pretravel health care. First- and second-generation immigrants traveling to their countries of origin and visiting friends and relatives (VFRs) have increased risk of certain infectious diseases and are more likely to participate in high-risk activities. In an online survey of 994 U.S. residents with two foreign-born parents who went on at least one international trip to an at-risk country (defined as having a typhoid vaccine recommendation) in the prior 3 years, respondents were questioned about their international travel over the previous 3 years and their knowledge and individual risk of disease. Participants reported infrequently seeking pretravel health information (32% of trips) or consulting a healthcare provider before their trips (15% of trips). Participants reported seeking pretravel health information less often for VFR trips home (22%) than to other regions (30%). Perceived risk of disease was directly associated with seeking pretravel health information (82% for the highest and 13% for the lowest perceived risk), consulting a healthcare provider (55% for the highest and 5% for the lowest perceived risk), and reporting travel-associated illness (54% for the highest and 10% for the lowest perceived risk). Respondents were generally knowledgeable about cholera, hepatitis B, malaria, and rabies but had low knowledge of hepatitis A and typhoid. Understanding where VFR travelers lack understanding of disease transmission and which travelers are ideal targets for interventions has the potential to shape physician recommendations and public health strategy in this vulnerable population.

Shifting priorities in vector biology to improve control of vector-borne disease.

Vector control remains the primary measure available to prevent pathogen transmission for the most devastating vector-borne diseases (VBDs): malaria, dengue, trypanosomiasis, filariasis, leishmaniasis, and Chagas disease. Current control strategies, however, are proving insufficient and the remarkable advances in the molecular biology of disease vectors over the last two decades have yet to result in tangible tools that effectively reduce VBD incidence. Here we argue that vector biologists must fundamentally shift their approach to VBD research. We propose an agenda highlighting the most critical avenues to improve the effectiveness of vector control. Research priorities must be diversified to support simultaneous development of multiple, alternative control strategies. Knowledge across relevant diseases and disciplines should be better integrated and disease prevention efforts extended beyond the academic sector to involve private industry, ministries of health, and local communities. To obtain information of more immediate significance to public health, the research focus must shift from laboratory models to natural pathogen-transmission systems. Identification and characterization of heterogeneities inherent to VBD systems should be prioritized to allow development of local, adaptive control strategies that efficiently make use of limited resources. Importantly, increased involvement of disease-endemic country (DEC) scientists, institutes, and communities will be key to enhance and sustain the fight against VBD.

Usefulness of commercially available GPS data-loggers for tracking human movement and exposure to dengue virus.

BACKGROUND: Our understanding of the effects of human movement on dengue virus spread remains limited in part due to the lack of precise tools to monitor the time-dependent location of individuals. We determined the utility of a new, commercially available, GPS data-logger for long-term tracking of human movements in Iquitos, Peru. We conducted a series of evaluations focused on GPS device attributes key to reliable use and accuracy. GPS observations from two participants were later compared with semi-structured interview data to assess the usefulness of GPS technology to track individual mobility patterns. RESULTS: Positional point and line accuracy were 4.4 and 10.3 m, respectively. GPS wearing mode increased spatial point error by 6.9 m. Units were worn on a neck-strap by a carpenter and a moto-taxi driver for 14-16 days. The application of a clustering algorithm (I-cluster) to the raw GPS positional data allowed the identification of locations visited by each participant together with the frequency and duration of each visit. The carpenter moved less and spent more time in more fixed locations than the moto-taxi driver, who visited more locations for a shorter period of time. GPS and participants' interviews concordantly identified 6 common locations, whereas GPS alone identified 4 locations and participants alone identified 10 locations. Most (80%) of the locations identified by participants alone were places reported as visited for less than 30 minutes. CONCLUSION: The present study demonstrates the feasibility of a novel, commercially available GPS data-logger for long-term tracking of humans and shows the potential of these units to quantify mobility patterns in relationship with dengue virus transmission risk in a tropical urban environment. Cost, battery life, size, programmability and ease of wear are unprecedented from previously tested units, proving the usefulness of GPS-dataloggers for linking movement of individuals and transmission risk of dengue virus and other infectious agents, particularly in resource-poor settings.

Estimating the impact of city-wide Aedes aegypti population control: An observational study in Iquitos, Peru.

During the last 50 years, the geographic range of the mosquito Aedes aegypti has increased dramatically, in parallel with a sharp increase in the disease burden from the viruses it transmits, including Zika, chikungunya, and dengue. There is a growing consensus that vector control is essential to prevent Aedes-borne diseases, even as effective vaccines become available. What remains unclear is how effective vector control is across broad operational scales because the data and the analytical tools necessary to isolate the effect of vector-oriented interventions have not been available. We developed a statistical framework to model Ae. aegypti abundance over space and time and applied it to explore the impact of citywide vector control conducted by the Ministry of Health (MoH) in Iquitos, Peru, over a 12-year period. Citywide interventions involved multiple rounds of intradomicile insecticide space spray over large portions of urban Iquitos (up to 40% of all residences) in response to dengue outbreaks. Our model captured significant levels of spatial, temporal, and spatio-temporal variation in Ae. aegypti abundance within and between years and across the city. We estimated the shape of the relationship between the coverage of neighborhood-level vector control and reductions in female Ae. aegypti abundance; i.e., the dose-response curve. The dose-response curve, with its associated uncertainties, can be used to gauge the necessary spraying effort required to achieve a desired effect and is a critical tool currently absent from vector control programs. We found that with complete neighborhood coverage MoH intra-domicile space spray would decrease Ae. aegypti abundance on average by 67% in the treated neighborhood. Our framework can be directly translated to other interventions in other locations with geolocated mosquito abundance data. Results from our analysis can be used to inform future vector-control applications in Ae. aegypti endemic areas globally.

The genetic structure of Aedes aegypti populations is driven by boat traffic in the Peruvian Amazon.

In the Americas, as in much of the rest of the world, the dengue virus vector Aedes aegypti is found in close association with human habitations, often leading to high population densities of mosquitoes in urban settings. In the Peruvian Amazon, this vector has been expanding to rural communities over the last 10-15 years, but to date, the population genetic structure of Ae. aegypti in this region has not been characterized. To investigate the relationship between Ae. aegypti gene flow and human transportation networks, we characterized mosquito population structure using a panel of 8 microsatellite markers and linked results to various potential mechanisms for long-distance dispersal. Adult and immature Ae. aegypti (>20 individuals per site) were collected from Iquitos city and from six neighboring riverine communities, i.e., Nauta, Indiana, Mazan, Barrio Florida, Tamshiaco, and Aucayo. FST statistics indicate significant, but low to moderate differentiation for the majority of study site pairs. Population structure of Ae. aegypti is not correlated with the geographic distance between towns, suggesting that human transportation networks provide a reasonable explanation for the high levels of population mixing. Our results indicate that Ae. aegypti gene flow among sub-populations is greatest between locations with heavy boat traffic, such as Iquitos-Tamshiaco and Iquitos-Indiana-Mazan, and lowest between locations with little or no boat/road traffic between them such as Barrio Florida-Iquitos. Bayesian clustering analysis showed ancestral admixture among three genetic clusters; no single cluster was exclusive to any site. Our results are consistent with the hypothesis that human transportation networks, particularly riverways, are responsible for the geographic spread of Ae. aegypti in the Peruvian Amazon. Our findings are applicable to other regions of the world characterized by networks of urban islands connected by fluvial transport routes.

The relationship between entomological indicators of Aedes aegypti abundance and dengue virus infection.

Routine entomological monitoring data are used to quantify the abundance of Ae. aegypti. The public health utility of these indicators is based on the assumption that greater mosquito abundance increases the risk of human DENV transmission, and therefore reducing exposure to the vector decreases incidence of infection. Entomological survey data from two longitudinal cohort studies in Iquitos, Peru, linked with 8,153 paired serological samples taken approximately six months apart were analyzed. Indicators of Ae. aegypti density were calculated from cross-sectional and longitudinal entomological data collected over a 12-month period for larval, pupal and adult Ae. aegypti. Log binomial models were used to estimate risk ratios (RR) to measure the association between Ae. aegypti abundance and the six-month risk of DENV seroconversion. RRs estimated using cross-sectional entomological data were compared to RRs estimated using longitudinal data. Higher cross-sectional Ae. aegypti densities were not associated with an increased risk of DENV seroconversion. Use of longitudinal entomological data resulted in RRs ranging from 1.01 (95% CI: 1.01, 1.02) to 1.30 (95% CI: 1.17, 1.46) for adult stage density estimates and RRs ranging from 1.21 (95% CI: 1.07, 1.37) to 1.75 (95% CI: 1.23, 2.5) for categorical immature indices. Ae. aegypti densities calculated from longitudinal entomological data were associated with DENV seroconversion, whereas those measured cross-sectionally were not. Ae. aegypti indicators calculated from cross-sectional surveillance, as is common practice, have limited public health utility in detecting areas or populations at high risk of DENV infection.

Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru.

BACKGROUND: Nearly half of the world's population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region. METHODOLOGY/PRINCIPAL FINDINGS: We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%-65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1-17.7). CONCLUSIONS/SIGNIFICANCE: Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.

Socially structured human movement shapes dengue transmission despite the diffusive effect of mosquito dispersal.

For sexually and directly transmitted infectious diseases, social connections influence transmission because they determine contact between individuals. For pathogens that are indirectly transmitted by arthropod vectors, the movement of the vectors is thought to diminish the role of social connections. Results from a recent study of mosquito-borne dengue virus (DENV), however, indicate that human movement alone can explain significant spatial variation in urban transmission rates. Because movement patterns are structured by social ties, this result suggests that social proximity may be a good predictor of infection risk for DENV and other pathogens transmitted by the mosquito Aedes aegypti. Here we investigated the effect of socially structured movement on DENV transmission using a spatially explicit, agent-based transmission model. When individual movements overlap to a high degree within social groups we were able to recreate infection patterns similar to those detected in dengue-endemic, northeastern Peru. Our results are consistent with the hypothesis that social proximity drives fine-scale heterogeneity in DENV transmission rates, a result that was robust to the influence of mosquito dispersal. This heterogeneity in transmission caused by socially structured movements appeared to be hidden by the diffusive effect of mosquito dispersal in aggregated infection dynamics, which implies this heterogeneity could be present and active in real dengue systems without being easily noticed. Accounting for socially determined, overlapping human movements could substantially improve the efficiency and efficacy of dengue surveillance and disease prevention programs as well as result in more accurate estimates of important epidemiological quantities, such as R0.

Determinants of heterogeneous blood feeding patterns by Aedes aegypti in Iquitos, Peru.

BACKGROUND: Heterogeneous mosquito biting results in different individuals in a population receiving an uneven number of bites. This is a feature of many vector-borne disease systems that, if understood, could guide preventative control efforts toward individuals who are expected to contribute most to pathogen transmission. We aimed to characterize factors determining biting patterns of Aedes aegypti, the principal mosquito vector of dengue virus. METHODOLOGY/PRINCIPAL FINDINGS: Engorged female Ae. aegypti and human cheek swabs were collected from 19 houses in Iquitos, Peru. We recorded the body size, age, and sex of 275 consenting residents. Movement in and out of the house over a week (time in house) and mosquito abundance were recorded on eight separate occasions in each household over twelve months. We identified the individuals bitten by 96 engorged mosquitoes over this period by amplifying specific human microsatellite markers in mosquito blood meals and human cheek swabs. Using a multinomial model assuming a saturating relationship (power), we found that, relative to other residents of a home, an individual's likelihood of being bitten in the home was directly proportional to time spent in their home and body surface area (p<0.05). A linear function fit the relationship equally well (ΔAIC<1). CONCLUSIONS/SIGNIFICANCE: Our results indicate that larger people and those who spend more time at home are more likely to receive Ae. aegypti bites in their homes than other household residents. These findings are consistent with the idea that measurable characteristics of individuals can inform predictions of the extent to which different people will be bitten. This has implications for an improved understanding of heterogeneity in different people's contributions to pathogen transmission, and enhanced interventions that include the people and places that contribute most to pathogen amplification and spread.