Defining empirical management of acute febrile illness in Myanmar

Fever is a common presenting symptom in primary care in low- and middle- income countries (LMICs). Non-malaria pathogens are now responsible in most cases after a decline of malaria in previously malaria endemic regions of Myanmar. It is important to provide appropriate treatment to those patients after malaria is ruled out by rapid tests or microscopy. The overall aim of this thesis is to improve management of acute non-malaria febrile illness in Myanmar. Empirical treatment strategies with selected antibiotics were devised and their cost-effectiveness was evaluated using a decision tree modelling approach. A systematic review on infectious neglected tropical diseases (NTDs) was conducted to collate all reports of NTDs in Myanmar (Chapter 2). The review identified diseases (rickettsial infection and leptospirosis) commonly associated with acute fever and this finding partly informed selection of antibiotics for empirical treatment. A cost- effectiveness analysis of empirical treatment showed empirical treatments being cost- saving and C-reactive protein (CRP) guided empirical treatments being highly cost- effective compared to current practice of care in rural Myanmar (Chapter 3). Alongside this, antibiotic use for acute febrile illness was also explored from the prescriber's perspective by secondary analysis of the data derived from a clinical trial (Chapter 4) and the user's perspective by public engagement activities (Chapter 6). The secondary data analysis found a substantial variation of antibiotic prescription among primary care doctors for acute febrile illness and the variation remained after accounting for patients' clinical presentations and CRP test results. Widespread environmental distribution of Burkholderia pseudomallei, the causal organism of melioidosis, which commonly presents as community acquired pneumonia and sepsis, was confirmed by a large nationwide study (Chapter 5). In conclusion, this thesis uses a multifaceted approach to improve management of acute febrile illness in Myanmar. Findings from this thesis point towards an empirical antibiotic treatment strategy as a potential approach for management of non-malaria febrile illness in rural Myanmar which could be evaluated in field trials.