Spatial epidemiology of Plasmodium knowlesi in Sabah, Malaysia.

Since identification of a large number of human infections in 2004, the zoonotic malaria species Plasmodium knowlesi is currently the main cause of human malaria in Malaysian Borneo. Carried by long and pig-tailed macaques, deforestation and associated environmental and population changes have been hypothesised to be the main drivers of this emergence. This thesis aims to describe the epidemiology of P. knowlesi in Northern Sabah, Malaysia at a range of spatial scales and evaluate how environmental change and behaviour affect human infection risks. Satellite-based and aerial remote sensing technologies were utilised with GPS tracking and field surveys to characterise dynamic interactions between the environment, human, macaque and mosquito populations (Chapter 4). A retrospective analysis of reported P. knowlesi cases found marked spatial heterogeneity in village-level P. knowlesi incidence, with village-level numbers of cases positively associated with both forest cover and forest loss in surrounding areas (Chapter 5). To explore how these people used these environments, mobility patterns and resource utilisation were mapped using GPS tracking devices; these data were integrated with predictions of mosquito biting rates to estimate individual and location-specific exposure risks (Chapter 6). Additional surveys were conducted in households and villages of symptomatic cases and within case study communities to evaluate levels of infection and exposure within the wider population. These identified a substantial proportion of asymptomatic infections not detected by hospital-based surveillance systems (Chapter 7) and found positive associations between knowlesi sero-positivity and environmental factors at a fine spatial scale (Chapter 8). Results from these studies were used to design an ecologically-stratified cross-sectional survey across four districts in Northern Sabah; this study was used to identify individual and environmental variables associated with exposure and infection risk across a wider geographical area (Chapter 9). Together, these studies indicate a wide distribution of P. knowlesi infection and exposure in demographic groups underrepresented in clinical reports and highlight the role of local environmental change in P. knowlesi risk. Further research is needed to refine diagnostic methods and understand the longer-term impacts of ecological changes on disease dynamics.