Abstract
dc:description.abstractMosquito-borne viruses such as dengue and chikungunya viruses continue to cause a substantial burden on public health globally. After decades with few tools to tackle the spread of these viruses, new interventions are becoming available. The release of Wolbachia infected mosquitoes has been shown to reduce the incidence of dengue infection. In addition, the first chikungunya vaccines will soon be licensed. However, we currently have a poor understanding of the underlying transmission dynamics of both chikungunya and dengue, and whether these dynamics differ across spatial scales. This means the potential impact of these interventions is unknown. In this thesis, I tackle critical knowledge gaps in our understanding of the transmission dynamics of dengue and chikungunya viruses across different spatial scales. I also provide estimations of the impact of new interventions, providing an avenue to their future widespread use. This thesis brings together high quality data from cohort studies, seroprevalence studies and disease surveillance systems, with sophisticated analytical approaches to answer public health relevant questions. In the first part of my thesis, I work with data from a long running cohort study in Kamphaeng Phet province, Thailand. I used serological data from the study to explore the underlying spatial heterogeneity in dengue virus infection. I found that, in that province, dengue was transmitted consistently from one year to another with a very high rate of infection compared to other places where dengue is found. There additionally was very little spatial variation in terms of force of transmission. I showed that only around 1\% of all infections get detected by disease surveillance systems, highlighting the significant hidden burden of infection from the virus. I also explored potential drivers for transmission in these settings and found that most variation in protection against dengue was at the household level and that door screens had a significant protective effect. In the second part of my thesis, I present the results from a large Wolbachia release project in Rio de Janeiro, Brazil, where millions of Wolbachia infected mosquitoes were released in part of the city. Underlying heterogeneity in where and when cases of dengue and chikungunya were detected had complicated the efforts to understand the impact of the release program. I developed a spatially-explicit analytical approach that characterises the underlying spatial distribution of dengue and chikungunya cases within the city and estimates the impact of the release program on incidence. I showed that despite only intermediate levels of introgression in the city, there was a significant reduction in the incidence of both viruses. In the third section of the thesis, I estimate the global burden of chikungunya virus. I conducted a literature review to identify countries that have local transmission of chikungunya. Then, based on a series of seroprevalence studies across 26 countries, I developed serocatalytic models that estimated the history of infection in epidemic and endemic settings. I show that 113 countries have experienced chikungunya transmission. In a subset of 11 countries, the virus circulates endemically. I estimate that there are 26 million annual infections and 19,000 annual deaths globally, with the greatest burden in the WHO regions of Southeast Asia, Africa and the Americas. The first chikungunya vaccines are currently being licensed. In the last part of the thesis, I develop a simulation-based method to critically assess the impact of different vaccination strategies for chikungunya. In particular, I assess the potential use of a vaccine stockpile in epidemic countries, as is used for other pathogens such as cholera and Ebola. For each country where chikungunya circulates, I present country-specific estimates of infections, cases and deaths averted for different vaccination campaign scenarios. This thesis contributes to the current landscape of infectious diseases epidemiology by exploring the dynamics of transmission for dengue and chikungunya, whose burdens are one of the current biggest public health challenges. It has been written during a critical period of time where vaccines are about to be commercially available and there is an urgent need for better understanding of both pathogens dynamics. Finally, it introduced a wide range of model frameworks that can be applied and built upon to refine our knowledge about arboviral diseases. Much of my work has been conducted in close collaboration with organisations such as the Gavi Alliance, CEPI and the World Mosquito Program. This close relationship with key international bodies involved in the rollout of interventions maximises the impact of my findings.
Degree
thesis:*- Name dc:type.qualificationname
- Doctor of Philosophy (PhD)
- Level dc:type.qualificationlevel
- Doctoral
- Grantor dc:publisher.institution
- University of Cambridge
- Year dc:date.issued
- 2023
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Ribeiro dos Santos, Gabriel
- Advisor dc:contributor.advisor
-
- Salje, Henrik
Subjects
dc:subject × 9Rights
dc:rightsIdentifiers
dc:identifier.*- Author Identifier
- 0000-0003-4668-8755
- OAI identifier oai:identifier
- oai:www.repository.cam.ac.uk:1810/366236