Integrating Epidemiological and Molecular Approaches to Study the Transmission and Treatment of Giardia lamblia
Batni, Sweta R.
Giardia lamblia, a eukaryotic intestinal parasite, is one of the major causes of diarrheal disease, giardiasis, worldwide. The pathophysiological complications of Giardia infections include small intestinal barrier dysfunction and decreased intestinal surface area. These factors can in turn result in small intestinal malabsorption and contribute to undernutrition of the infected host.Undernutrition is an especially important concern for children under five as this is a period of critical childhood growth and development. However, our understanding of the global childhood morbidity associated with Giardia infections is limited as observational studies addressing the association between G. lamblia infection and undernutrition in children, measured either as anthropometric indicators of growth [weight-for-age (WAZ), weight-for-height (WHZ), height-for-age (HAZ)], or by decreases in serum micronutrient (vitamins and minerals) levels, have been inconclusive.Thus, in Part I of the research presented here, we performed two different systematic reviews and meta-analyses pooling individual epidemiological studies to obtain summary estimates of the overall qualitative and quantitative effects of G. lamblia infection and growth (Chapter 3) and micronutrient malnutrition (Chapter 4).We found that Giardia infection, with or without diarrhea, was statistically significantly associated with mild and moderate growth deficits (WAZ WHZ, and HAZ > -2 SD). Infection was also significantly negatively associated with decreased levels of serum zinc and iron. However, infection did not increase the odds of either severe growth deficits (WAZ, WHZ, or HAZ -2 SD). Infection was also significantly negatively associated with decreased levels of serum zinc and iron. However, infection did not increase the odds of either severe growth deficits (WAZ, WHZ, or HAZCurrent anti-Giardia treatments are recommended to treat symptomatic giardiasis given limited tolerance and the potential for harsh side effects. Additional concerns such as high rates of clinical resistance and treatment failures raise the development of new therapeutics against Giardia to a high priority. In Part II of the research presented here (Chapter 6), we describe a bottom up approach to rational drug development using Surface Plasmon Resonance (SPR) as a tool to identify small molecule compounds targeting putative methyltransferase enzymes in Giardia.
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