Helminths and metabolic outcomes in rural and urban Uganda.
Sanya, Richard Edwin
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Background: Inflammation plays an important role in the development and progression of metabolic disorders such as type 2 diabetes, obesity, dyslipidaemia and atherosclerosis. Helminths modulate human immune responses as a survival mechanism and this may have both detrimental and beneficial effects on the host. This PhD addresses the hypothesis that owing to their immunomodulatory properties, helminths may influence inflammatory processes involved in the aetiology and progression of metabolic disorders. The main objective was to understand the impact of helminth infection on metabolic health in humans. Methods: In a cluster-randomised trial conducted in 26 rural island fishing communities in Lake Victoria, Uganda, the effects of four years of community-wide intensive versus standard anthelminthic treatment on metabolic outcomes (insulin resistance, fasting blood glucose, fasting blood lipids, blood pressure, body mass index, waist and hip circumference) were investigated. Also, observational associations between helminth infection and metabolic outcomes were assessed. Using data from the trial and data from a contemporaneous cross-sectional study conducted in urban sub-wards of Entebbe municipality, Wakiso district, Uganda, rural-urban differences in metabolic parameters and the particular role of helminths in any observed differences were investigated. Lastly, using a multiplex immunoassay, differences in inflammatory markers in selected individuals living in the rural and urban setting were explored. Results: In the trial, there was some evidence that the intensive anthelminthic intervention resulted in higher mean LDL-cholesterol compared to standard intervention. Lower LDL-cholesterol levels were observed in S. mansoni and Strongyloides infected participants compared with the uninfected. S. mansoni infection was associated with lower total cholesterol levels. Participants with moderate to heavy S. mansoni infection had lower triglycerides, LDL-cholesterol and diastolic blood pressure levels. For the rural-urban comparisons, urban residents had lower mean fasting glucose and insulin resistance but higher blood pressure. Current helminth infection did not explain the observed rural-urban differences. On combining multiple inflammatory markers using principal component analysis, individuals in the rural and urban setting had different inflammatory profiles. Conclusions: Helminth infections may have some metabolic benefits such as induction of a favourable lipid profile in humans. Environmental factors related to rural and urban living influence metabolic outcomes. It is important to understand the underlying mechanisms of the potential metabolic benefits of helminths to humans and of rural-urban differences in metabolic and inflammatory processes with a view to using this knowledge to develop new approaches to manage metabolic diseases.