Biased efficacy estimates in phase-III dengue vaccine trials due to heterogeneous exposure and differential detectability of primary infections across trial arms.

Vaccine efficacy (VE) estimates are crucial for assessing the suitability of dengue vaccine candidates for public health implementation, but efficacy trials are subject to a known bias to estimate VE toward the null if heterogeneous exposure is not accounted for in the analysis of trial data. In light of many well-characterized sources of heterogeneity in dengue virus (DENV) transmission, our goal was to estimate the potential magnitude of this bias in VE estimates for a hypothetical dengue vaccine. To ensure that we realistically modeled heterogeneous exposure, we simulated city-wide DENV transmission and vaccine trial protocols using an agent-based model calibrated with entomological and epidemiological data from long-term field studies in Iquitos, Peru. By simulating a vaccine with a true VE of 0.8 in 1,000 replicate trials each designed to attain 90% power, we found that conventional methods underestimated VE by as much as 21% due to heterogeneous exposure. Accounting for the number of exposures in the vaccine and placebo arms eliminated this bias completely, and the more realistic option of including a frailty term to model exposure as a random effect reduced this bias partially. We also discovered a distinct bias in VE estimates away from the null due to lower detectability of primary DENV infections among seronegative individuals in the vaccinated group. This difference in detectability resulted from our assumption that primary infections in vaccinees who are seronegative at baseline resemble secondary infections, which experience a shorter window of detectable viremia due to a quicker immune response. This resulted in an artefactual finding that VE estimates for the seronegative group were approximately 1% greater than for the seropositive group. Simulation models of vaccine trials that account for these factors can be used to anticipate the extent of bias in field trials and to aid in their interpretation

Modeling the Spread of the Zika Virus at the 2016 Olympics

The Zika Virus is an arbovirus that is spread by mosquitoes of the \emph{Aedes} genus and causes mild fever-like symptoms. It is strongly associated with microcephaly, a condition that affects development of fetal brains. With the recent emergence of Zika in Brazil, we develop an agent-based model to track mosquitoes and humans throughout the 2016 Olympics in Rio de Janeiro to investigate how the Olympics might affect the spread of the virus. There are many unknowns regarding the spread and prevalence of Zika, with approximately 80\% of infected individuals unaware of their infectious status. We therefore discuss results of experiments where several unknown parameters were varied, including the rate at which mosquitoes successfully bite humans, the percentage of initially infected mosquitoes, and the sizes of the human and mosquito populations. From these experiments, we make initial predictions regarding effective control measures for the spread of Zika

The Evolution of Entomological Research with Focus on Emerging and Re-emerging Mosquito-Borne Infections in the Philippines

This paper presented previous and current research efforts for medically important mosquitoes that serve as vectors of emerging and re-emerging diseases in the Philippines, in light of identifying the research gap that exists in the field of public health entomology in the country. This extensive review of the past and current research studies with regard to medical entomology and vector control also attempted to provide proper direction and insights for effective implementation of the country’s vector control programs. All research studies conducted in the Philippines from 1958 up to the present that are related to the paper’s interest and are available on Philippines’ Department of Science and Technology and RITM databases were tracked. Results from this analysis imply that studies on public health entomology in the Philippines have evolved and have gone through various stages of development over time. However, the magnitude of research on medically important mosquitoes in the country is still insufficient for it to contribute comprehensively to integrated methods of vector management and totally eliminate mosquito-borne infections in the Philippines. It is recommended for researchers to work on the continuity of vector researches and explore further the diversity of the entomological aspects of the control of vector-borne diseases

New Cost-Benefit of Brazilian Technology for Vector Surveillance Using Trapping System

The recent introduction of chikungunya and Zika virus and their subsequent dispersion in the Americas have encouraged the use of novel technologies for adult Aedes surveillance to improve vector control. In Brazil, two platforms for surveillance of eggs and gravid Aedes aegypti have been developed. First, it consists of using data of sampling of eggs in ovitraps associated with GIS technologies to monitor Aedes spp. populations. Although effective, it is not realistic to use in a large-scale epidemic scenario as it requires a large amount of human resources for field and laboratory activities. Second, it consists of trapping female Ae. aegypti citywide at fine spatial and temporal scales for vector surveillance (MI-Aedes) to detect high Aedes infestation areas using a GIS environment and the identification of arbovirus-infected trapped mosquitoes by RT-PCR (MI-Virus platforms). Such integration of continuous vector surveillance and targeting vector control in hotspot areas is cost-effective (less than US$ 1.00/person/year), and it has been shown to reduce mosquito population and prevent dengue transmission. The main advantage of the MI-Aedes platform over traditional mosquito surveillance is the integration of continuous vector monitoring coupled with an information technology platform for near real-time data collection, analysis, and decision-making. The technologies also provide data to model the role of climate on the vector population dynamics

Roadmap for the Introduction of a New Dengue Vaccine

Dengue remains the most common vector-transmitted disease in the world despite enormous prevention and control efforts by endemic countries and regions. Today, after decades of research, public health programs contemplate as part of the intervention to control the disease, a safe and effective vaccine against dengue. In this chapter, we review general principles for developing a safe and efficacious vaccine against dengue virus, the current vaccine candidates approved and under research, and the roadmap for the introduction of a new dengue vaccine, based on the procedures, carried out by Mexico, for the licensure and eventual adoption of CYD-TDV vaccine, which concluded with Mexico becoming the first country in the world to grant licensure to a Dengue vaccine in December of 2015. Finally, we discuss the rationale for the adoption of dengue vaccines a public health policy and the paradigm shift required for the efficient adoption of vaccines in low- and middle-income countries

A review: Aedes-borne arboviral infections, controls and Wolbachia-based strategies

Arthropod-borne viruses (Arboviruses) continue to generate significant health and economic burdens for people living in endemic regions. Of these viruses, some of the most important (e.g., dengue, Zika, chikungunya, and yellow fever virus), are transmitted mainly by Aedes mosquitoes. Over the years, viral infection control has targeted vector population reduction and inhibition of arboviral replication and transmission. This control includes the vector control methods which are classified into chemical, environmental, and biological methods. Some of these control methods may be largely experimental (both field and laboratory investigations) or widely practised. Perceptively, one of the biological methods of vector control, in particular, Wolbachia-based control, shows a promising control strategy for eradicating Aedes-borne arboviruses. This can either be through the artificial introduction of Wolbachia, a naturally present bacterium that impedes viral growth in mosquitoes into heterologous Aedes aegypti mosquito vectors (vectors that are not natural hosts of Wolbachia) thereby limiting arboviral transmission or via Aedes albopictus mosquitoes, which naturally harbour Wolbachia infection. These strategies are potentially undermined by the tendency of mosquitoes to lose Wolbachia infection in unfavourable weather conditions (e.g., high temperature) and the inhibitory competitive dynamics among co-circulating Wolbachia strains. The main objective of this review was to critically appraise published articles on vector control strategies and specifically highlight the use of Wolbachia-based control to suppress vector population growth or disrupt viral transmission. We retrieved studies on the control strategies for arboviral transmissions via arthropod vectors and discussed the use of Wolbachia control strategies for eradicating arboviral diseases to identify literature gaps that will be instrumental in developing models to estimate the impact of these control strategies and, in essence, the use of different Wolbachia strains and feature