Enteric infections in Rwandan children under 5 years

Abstract

Infectious diarrhea is a main cause of illness and death among children in poor countries, and enteric infections may also cause stunting as a result of impaired uptake of nutrients. This thesis investigated a broad range of enteric pathogens among children under five in Rwanda, focusing on their role in diarrhea, the rates of pathogen acquisition and clearance, and the potential impact of IFNL4 and FUT2 genetic variants on infection susceptibility. The findings in Paper I show high infection rates among 794 Rwandan children with Shigella and ETEC as the primary causes of diarrhea, while rotavirus was no longer the predominant etiology. However, as shown in Paper II, rotavirus remains an important cause of diarrhea despite vaccination since 2012. The longitudinal cohort study of 120 children described in Paper II also shows that new enteric infections occur very frequently, indicating heavy exposure, particularly in rural areas, but also that most infections are cleared within one month. Genetic variation in the IFNL4 gene has recently been associated with the rate of diarrhea in a study from Mali, but Paper III did not identify any significant association between the rs12979860 genotypes and any of a broad range of enteric pathogens. Paper IV showed that ‘non-secretors’ with a FUT2 stop codon variant had a lower frequency of rotavirus but identified no association with other pathogens. The results show that Rwandan children were heavily exposed to enteric pathogens, that this exposure was greater among children in rural areas, that Shigella, ETEC, and rotavirus were the main causes of diarrhea, and that children with inactivated FUT2 (non-secretors) were less susceptible for rotavirus. The findings suggest that reducing exposure by improving living conditions should be a main priority to improve childhood health and growth in Rwanda.