Dengue virus transmission and case management for improved disease control.

Dengue is the major arboviral disease in humans and is primarily transmitted through Aedes aegypti mosquitoes' bites. Better understanding of dengue virus (DENY) transmission and case management is needed to reduce morbidity and mortality. This thesis aimed to bridge existing knowledge gaps by investigating three main topics: The factors associated with human-to-mosquito DENV transmission remains poorly understood. We conducted the Ae. aegypti-feeding experiments on 208 laboratory-confirmed dengue patients: Plasma viremia levels were positively associated with DENV transmission, while illness day and antibody titers were independently correlated with a reduced risk of DENV transmission to mosquitoes. Physicians attending to dengue patients at outpatient clinics are ideally placed to communicate measures to limit DENV transmission in and around households. We explored knowledge, attitudes and practices of 50 physicians and 49 patients/caregivers on DENY transmission and prevention using semi-structured questionnaires. Both physicians and patients had an incomplete understanding of DENY transmission, leading to their inadequate attitudes and preventative practices. We measured the effectiveness of a 13% DEET-based repellent ·on febrile dengue patients compared to matched healthy controls (n=19 experiments). The repellent provided ~ 1 hour of Ae. aegypti repellency and no difference in protection between patients and controls, suggesting that while providing some benefit, duration of protection was limited and needed fi'equent reapplication. Early diagnosis and proper management are a prerequisite for reducing dengue mortality. We retrospectively described 55 fatal dengue cases at the Hospital for Tropical Diseases between 2008 and 2012. Females were predominant in study population (68%). Majority of patients (91 %) hospitalized with dengue shock syndrome. Other complications included respiratory distress (100%); severe bleeding (85%); severe liver involvement (76%); and renal failure (64%). The findings described manifestations associated with fatal outcome and identified knowledge gaps in dengue management. Overall, this thesis provided new insights into DENY transmission and clinical features of fatal dengue. The results also identified issues for public health that need improvement, e.g. opportunities for physicians to contribute more to public health by educating deng~e-affected families to perform relevant vector control.