Viruses transmitted by mosquitoes (arboviruses) continue to be a major threat to public health. This project studied the mechanisms that drive arbovirus transmission, using dengue virus in Thailand as a case study. All four serotypes of dengue virus have circulated endemically in Thailand for decades. We used historic serotype distributions and measures of antigenicity from novel cartographic methods to reconstruct the changing immune profile of the population. Further, we used detailed data on the historical genetic make-up of viruses that circulated in the country by sequencing isolates from each dengue serotype for each year over 50 years from the country. We then used measures of human behaviours (mixing patterns and mobility) obtained from mobile phone and questionnaire data as well as mosquito distributions to develop an integrative analytical framework that can bring together these different datasets and explore the consistency of different hypotheses of viral spread. This project allowed valuable insights into long-term drivers of virus spread with key implications for public health. Finally, as the peak of the COVID-19 pandemic occurred during the middle of the project, we quickly expanded our project to also include understanding SARS-CoV-2 burden and spread. In such a way we were able to support the French government on their COVID-19 response.
Our project found that the specific virus that infects an individual determines their future infection and disease risk. This means that an individual’s first dengue infection (or vaccine) in life determines their immune response to that pathogen and is important to consider as we start vaccinating young individuals around the world who won’t have seen dengue before. We further quantified the underlying risk of infection for different arboviruses, which is useful as we look to target interventions in the most appropriate way possible.
We used new mathematical models applied to geolocated dengue genomes to quantify the respective roles of human mobility, local immunity and mosquito levels in spreading the virus. We showed that those involved in transmission (often children) moved around less than adults, limited the short term movement of the virus. However, the occasional long distance movement by infected individuals was sufficient to result in long range virus movement in the medium term, although rarely between countries.
Our study also helped identify an immune correlate of protection for chikungunya virus, another arbovirus transmitted by the same mosquitoes. These findings have helped lead to the licensure of the first chikungunya vaccine through an unusual route that relies on immune correlates, rather than traditional large vaccine trials.
