Dengue virus (DENV) is the most prevalent arthropod-borne virus worldwide, infecting as many as 100,000 people each year. The primary vector, Aedes aegypti, is a highly anthropophilic urban mosquito that has been shown distribute bites heterogeneously in a population. Targeting this vector is currently the only form of control available for DENV prevention, and mathematical models are often used to identify efficacious control strategies. Therefore it is essential to understand the complex interaction between mosquito and human populations, and incorporate these interactions into comprehensive models of virus transmission. I conducted two studies to identify heterogeneities in mosquito and human populations in Iquitos, Peru, and used the results to parameterize a model of DENV transmission that could identify efficacious targeted vector control and vaccination strategies.
First, to identify geographic heterogeneities in transmission of DENV, I conducted local and global spatial analyses of seroconversion data collected in eight geographic zones of Iquitos during a longitudinal cohort study from 1999–2005. Global clustering (case-control Ripley's K statistic) appeared at radii of ∼200–800 m. Local analyses (Kuldorf spatial scan statistic) identified eight DENV-1 and 15 DENV-3 clusters from 1999–2003. The number of seroconversions per cluster ranged from 3–34 with radii from zero (a single household) to 750 m; 65% of clusters had radii >100 m. Spatial heterogeneity was detected during the interepidemic period of DENV-1 and DENV-2 transmission (prior to 2001). Cumulative seroprevalence of the invading epidemic DENV-3 was spatially similar to preexisting DENV-1 and DENV-2 seroprevalence, indicating geographic heterogeneities in transmission.
Second, to identify heterogeneous feeding patterns of Ae. aegypti in households in Iquitos, I enrolled 19 houses into a study which involved collecting mosquitoes and identifying the individuals from whom they had recently fed. Ten microsatellite markers were used to obtain DNA profiles from mosquito blood meals. Participants were interviewed to obtain anthropomorphic measurements and daily activity schedules each week that mosquitoes were collected. Young children (<18 yo) received a fewer than expected number of bites and there was no difference between males and females. Time spent in the house did not confound the relationship between biting and age. Using a generalized linear mixed regression model, proportional body surface area, daily temperature range and household mosquito abundance were the best predictors of the proportion of bites an individual received.
Finally, I used the results obtained from the previous two studies to expand on the general susceptible-exposed-infected/susceptible-exposed-infected-recovered model of dengue virus transmission. Creating eight identical equations (one for each zone), the model included varying mosquito and human population sizes by zone, with movement between zones. Four human populations were incorporated, using the assumption of heterogeneity by age identified in study 2 as well as the hypothesis that 20% of the population is responsible for 80% of infections. Using this model, I was able to recreate the invasion of DENV-3 into Iquitos, and test various strategies for vector control (larval and adult) as well as vaccination strategies, should one become available. Results indicate that targeting vector control could increase efficacy of intervention programs, and that once a vaccine is available, strategies for distribution will vary depending on the history of DENV transmission in the region.
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|Advisor:||Scott, Thomas W.|
|Commitee:||Reisen, William K., Smith, David L.|
|School:||University of California, Davis|
|School Location:||United States -- California|
|Source:||DAI-B 74/07(E), Dissertation Abstracts International|
|Subjects:||Entomology, Public health|
|Keywords:||Aedes aegypti, Dengue virus, Heterogeneity, Mathematical model, Vector control|
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