David P. Durham

The Interactive Roles of Aedes aegypti Super-Production and Human Density in Dengue Transmission

Background A. aegypti production and human density may vary considerably in dengue endemic areas. Understanding how interactions between these factors influence the risk of transmission could improve the effectiveness of the allocation of vector control resources. To evaluate the combined impacts of variation in A. aegypti production and human density we integrated field data with simulation modeling. Methodology/Principal Findings Using data from seven censuses of A. aegypti pupae (2007–2009) and from demographic surveys, we developed an agent-based transmission model of the dengue transmission cycle across houses in 16 dengue-endemic urban ‘patches’ (1–3 city blocks each) of Armenia, Colombia. Our field data showed that 92% of pupae concentrated in only 5% of houses, defined as super-producers. Average secondary infections (R0) depended on infrequent, but highly explosive transmission events. These super-spreading events occurred almost exclusively when the introduced infectious person infected mosquitoes that were produced in super-productive containers. Increased human density favored R0, and when the likelihood of human introduction of virus was incorporated into risk, a strong interaction arose between vector production and human density. Simulated intervention of super-productive containers was substantially more effective in reducing dengue risk at higher human densities. Significance/Conclusions These results show significant interactions between human population density and the natural regulatory pattern of A. aegypti in the dynamics of dengue transmission. The large epidemiological significance of super-productive containers suggests that they have the potential to influence dengue viral adaptation to mosquitoes. Human population density plays a major role in dengue transmission, due to its potential impact on human-A. aegypti contact, both within a persons home and when visiting others. The large variation in population density within typical dengue endemic cities suggests that it should be a major consideration in dengue control policy.

Dengue dynamics and vaccine cost-effectiveness in Brazil

Recent Phase 2b dengue vaccine trials have demonstrated the safety of the vaccine and estimated the vaccine efficacy with further trials underway. In anticipation of vaccine roll-out, cost-effectiveness analysis of potential vaccination policies that quantify the dynamics of disease transmission are fundamental to the optimal allocation of available doses. We developed a dengue transmission and vaccination model and calculated, for a range of vaccination costs and willingness-to-pay thresholds, the level of vaccination coverage necessary to sustain herd-immunity, the price at which vaccination is cost-effective and is cost-saving, and the sensitivity of our results to parameter uncertainty. We compared two vaccine efficacy scenarios, one a more optimistic scenario and another based on the recent lower-than-expected efficacy from the latest clinical trials. We found that herd-immunity may be achieved by vaccinating 82% (95% CI 58-100%) of the population at a vaccine efficacy of 70%. At this efficacy, vaccination may be cost-effective for vaccination costs up to US

National- and state-level impact and cost-effectiveness of nonavalent HPV vaccination in the United States

534 (95% CI

Quantifying transmission of clostridium difficile within and outside healthcare settings

369-1008) per vaccinated individual and cost-saving up to

The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States

204 (95% CI

Deriving behavior model parameters from survey data: Self-protective behavior adoption during the 2009–2010 Influenza A(H1N1) pandemic

39-678). At the latest clinical trial estimates of an average of 30% vaccine efficacy, vaccination may be cost-effective and cost-saving at costs of up to

Country- and age-specific optimal allocation of dengue vaccines

237 (95% CI

Evaluating the effectiveness of localized control strategies to curtail chikungunya.

159-512) and

Spatial and Temporal Clustering of Chikungunya Virus Transmission in Dominica

93 (95% CI

Potential effectiveness of long-acting injectable pre-exposure prophylaxis for HIV prevention in men who have sex with men: a modelling study

15-368), respectively. Our model provides an assessment of the cost-effectiveness of dengue vaccination in Brazil and incorporates the effect of herd immunity into dengue vaccination cost-effectiveness. Our results demonstrate that at the relatively low vaccine efficacy from the recent Phase 2b dengue vaccine trials, age-targeted vaccination may still be cost-effective provided the total vaccination cost is sufficiently low.