A* STAR Programme - Combining pathogen genetic and epidemiological information using computationally intensive Bayesian methods.

Infectious diseases exert a major and growing burden on human health. The pathogens (viruses, bacteria and other microorganisms) that cause them are dynamic in at least two senses. The first is epidemiological – they spread from person to person, violating the assumptions of ‘classical’ epidemiology. The second is genetic – they are constantly evolving. The interactions between these two types of dynamics is poorly understood, but is believed to be very important for key challenges such as the emergence of antimicrobial resistance, which requires evolutionary pressure together with sufficient transmission routes. This doctoral project will consider the integration of epidemiological and genetic information through mathematical / computer modelling and statistics, applied to data on salmonella, and extended to antimicrobial resistance if successful. These models can then be applied for transmission routes of viral agents too.

Singapore is in an endemic region for many tropical infectious diseases as well infections that are epidemic in temperate regions, such as influenza. Due to the high density of travel to this entrepôt, Singapore is particularly at risk of importation, and subsequent establishment, of pathogens from other parts of the world. In the last two decades, Singapore has experienced outbreaks of Nipah virus, SARS, pandemic influenza, Chikungunya, Zika virus and Group B Streptococcus, and the links with South East Asia, East Asia and the Middle East puts Singapore at risk of emerging infectious diseases such as avian influenza, MERS-CoV, and multidrug resistant tuberculosis. This risk is exemplified by the recent Zika Virus outbreak, facilitated by the lack of herd immunity and the endemicity of the mosquito species that carries the virus. Large outbreaks in Brazil have caused concern as they have revealed hitherto unknown clinical consequences. In particular, infections are thought to harm the foetus with 1% of infections in early pregnancies resulting in gross defects of the brain. Singapore is experiencing its first outbreak starting in August 2016 with 428 reported cases, as of 28 October 2016. The virus in Singapore appears to be related to Asian variants (unpublished data). We do not know whether this strain will cause congenital defects or why the outbreak happened when it did. It is expected that Zika will establish itself in the local population of people and mosquitoes and constitute an on-going threat over years to come. We thus have an on-going effort with the national environmental
agency (NEA) to study Zika collected field isolates from human and mosquitos. We plan to refine tests for detecting infection and to study the virus in order to understand its evolution and transmission. This involves work on human and mosquito samples in laboratories, deploying novel ground breaking methods to detect and characterize the virus’ genes. A large component of our work involves computational work, developing tools to analyze different aspects of the virus, like Bayesian methods for epidemiological analysis of transmission based models. This on-going effort with the NEA will also involve surveillance sequencing of thousands of food-borne bacterial pathogens over the next 5 years.

http://www.singaporeastar.manchester.ac.uk/projects/