Aspects of disease burden and risk factors for bacterial disease in low- and middle-income countries

Bacterial infections cause substantial morbidity and mortality, particularly in low- and middle-income countries. Strained healthcare systems, limited access to clean water, and fragmented hygiene and sanitary infrastructure increase risk of disease transmission. However, effective vaccines have been developed and can be deployed strategically to prevent disease. This thesis sets out to measure aspects of cholera and typhoid disease burden and to evaluate how natural infection and WASH affect disease risk in endemic settings. The analyses are performed on historical datasets of clinical studies of cholera and typhoid vaccines that were conducted in Bangladesh and India, respectively. Using a vaccine probe analytical approach, I assessed whether there was evidence of cholera in diarrhoeal cases that tested negative for cholera by conventional faecal culture and provided evidence that cholera cultures are highly sensitive. Secondly, I developed a clinical definition for typhoid fever that satisfied the criteria of being predictive of culture-confirmed typhoid fever and being protected against by an effective typhoid vaccine. Thirdly, I measured the degree to which natural typhoid protected against a subsequent typhoid fever episode and found little evidence for the development of natural immunity. Finally, I evaluated which components of household WASH in a typhoid endemic setting were associated with reduction of typhoid risk and asked whether WASH and vaccine interventions acted synergistically to control typhoid