My research aims to improve understanding of the epidemiological factors and population processes shaping infectious disease spread in human and animal populations. A key practical focus is the analysis and optimisation of intervention strategies aimed at reducing transmission or disease burden. Much of my work is applied, informing disease control policy-making by public and global health institutions.
With recent advances in data availability (both epidemiological and molecular) and affordable high-performance computing, mathematical models of infectious disease spread now offer the potential to provide predictive, quantitative analyses of alternative disease control and treatment strategies, as well as qualitative insight into the complex non-linear processes shaping pathogen replication and evolution. An important strand of my research program is therefore to develop the statistical and mathematical tools necessary for such increasingly sophisticated models to be rigorously tested and validated against epidemiological, molecular and experimental data. The breadth of my research interests reflects my belief that comparative analyses of different host-pathogen systems can provide powerful insights into the population processes common to many infectious diseases, while highlighting how key differences in disease biology, route of transmission or host population structure determine observed differences in patterns of infection.
A major research interest throughout my career has been on developing mathematical models of the geographic spread of newly emergent pathogens - such as BSE/vCJD, foot and mouth disease, SARS and MERS, pandemic influenza, Ebola and ZIka - to examine containment and mitigation strategies. Much of this work has been undertaken in collaboration with colleagues in my department and external institutions - most notably public health partners such as the World Health Organization [WHO], the US Centers of Disease Control and Prevention and Public Health England. These partnerships have been vital in facilitating the results of my work being used to inform policy. Building on our earlier work, I and my colleagues founded the MRC Centre for Outbreak Analysis and Modelling in 2008 to consolidate and enhance our work on emerging infections and its translation to public health policy-making.
A second major current personal research interest is the epidemilogy and control of major mosquito-borne diseases, notably malaria (working with Azra Ghani) and 'flaviviruses' - a family of viruses which includes dengue, yellow fever and Zika. The work of my group on these viruses includes assessment of disease burden, understanding how transmission intensity varies geographically and seasonally, and modelling the optimal use of current and novel interventions.
Use of Wolbachia as a novel vector control measure
One strand of my recent work has examined the potential public health benefits of Wolbachia, a novel biological control to reduce the ability of Aedes aegypti mosquitoes to transmit dengue. Collaborating with Christl Donnelly and with the Eliminate Dengue initiative which is developing Wolbachia, we have estimated the potential impact of Wolbachia on dengue transmission and are now studying spatial spread of Wolbachia after initial release. This work is informing the design of the first large scale trials of Wolbachia and measure its impact on dengue transmission. The first such trials are likely to start in Colombia and Indonesia, with studies in Vietnam and Brazil starting soon after.
Potential impact of dengue vaccine Use
Recently been published in Science, my research on the Sanofi vaccine (in collaboration with colleagues at the University of Florida and Johns Hopkins University) examined the benefits and risks associated with large-scale roll-out immunisation programmes using this vaccine. Our analysis showed that the the complex efficacy trends seen in the clinical trials of the vaccine was consitent with the hypothesis that the vaccine acted akin to a silent (i.e. non-symptomatic) natural infection - priming the immune system of people who have never had dengue (and thus potentially increasing their risk of experience severe dengue infection in future), but boosting the immunity of those who experienced dengue before being vaccinated (thus dramatically reducing their risk of experiencing severe dengue disease in future). Our analysis showed that this means use of the vaccine can substantially reduce dengue case numbers when used in high transmission intensity settings, but might increase the numbers of hospitalised dengue cases if used in low transmission intensity settings where most children being vaccinated have not yet been infected with dengue. My work informed and supports the recommendations of the WHO Scientific Advisory Group of Experts [SAGE] on Immunization on use of this vaccine.
In ongoing work, I and my collaborators are currently analysing historical dengue serosurvey and surveillance data to generate global maps which indicate where use of the vaccine will give public health benefits and where it may pose risks. Examples of the former include high transmission intensity countries such as the Philippines, while examples of the latter include low transmission areas such as Singapore and Queensland, Australia. However, many countries - such as Brazil, Colombia and Malaysia - have substanial variation in transmission intensity from district to district which means that vaccination roll-out decisions will need to be made at the subnational level. For example, vaccine use could reduce dengue case numbers by a quarter in northern Brazil, but may have negative outcomes if used in the much lower transmission intensity areas of southern Brazil. This highlights the importance of clear and careful comunication with policy-makers and the public regarding the likely impact of use of this vaccine in different settings.
et al., 2016, Unraveling the drivers of MERS-CoV transmission., Proc Natl Acad Sci U S A, Vol:113, Pages:9081-9086
et al., 2016, Countering the Zika epidemic in Latin America, Science, Vol:353, ISSN:0036-8075, Pages:353-354
et al., 2016, Estimating Dengue Transmission Intensity from Case-Notification Data from Multiple Countries, PLOS Neglected Tropical Diseases, Vol:10, ISSN:1935-2735
et al., 2016, Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance, PLOS Computational Biology, Vol:12, ISSN:1553-734X
et al., 2015, The role of rapid diagnostics in managing Ebola epidemics, Nature, Vol:528, ISSN:0028-0836, Pages:S109-S116
et al., 2015, Assessing the epidemiological effect of wolbachia for dengue control, Lancet Infectious Diseases, Vol:15, ISSN:1473-3099, Pages:862-866