Rotavirus Diarrhea Reinfection and its Outcome on Weight and Hospitalization-Duration Among Children in Ghana: A Randomized, Double-Blinded, Placebo-Controlled Trial

Abstract

Background Rotavirus gastroenteritis is a major contributor to the overall burden of diarrhea disease in Africa. Close to 40% of hospital admissions are as a result of diarrhea in children below the ages of five years are traceable to rotavirus. There is incomplete immunity after infection; however repeated infections tend to be less severe than the severity of the first rotavirus infection. Methods The study estimated the effect of repeated episodes of the number of severe rotavirus diarrhea on the weight of child at study entry, or hospitalization – duration using proportions and regression models. Univariate and bivariate linear and logistic regression models were used in testing for an association of the repeated episodes of the number of severe rotavirus diarrhea and confounding variables on the weight of child at study entry, or hospitalization – duration as outcomes. Results 1098 children were randomly assigned to the Vaccine arm and 1102 children to the Placebo arm. Of the three age groups studied, almost 45% of the children in both arms were in the age group 7 – 9 weeks. A cumulative total of 142 and 151 severe diarrhea episodes were recorded in the Vaccine and Placebo arms respectively. However there were only 30 repeated episodes of gastroenteritis recorded. Of these were 16 cases in the vaccine arm and 14 in the control arm. The occurrence of repeated gastroenteritis was also related to the age at recruitment and was common in the younger age group. Children in the age group 7 – 9 weeks suffered weight loss and hospitalization during the first severe diarrhea episode (Vaccine 66/142 and Placebo 69/151). Fifty-four percent of all children who had diarrhea were hospitalized and 46.0% were outpatients in the Vaccine arm and in the Placebo arm inpatients were 59.7% and outpatients were 40.3%. . The predominant G genotype of rotaviruses identified in diarrhea stools was G2 (Vaccine 46.5% and Placebo 45.0%). Children randomized between 7 – 9 weeks and age group 10 – 12 weeks of age were observed to have greater reduction in weight than the younger age groups (P- Value=0.012 and P-value <0.001 respectively). After adjusting for age group, number of severe diarrhea episode showed a statistical evidence (P-value <0.001) of an association with average weight change in age group 7 – 9 weeks and 10 – 12 weeks in the Vaccine and Placebo arms. The regression coefficient for age group 7 – 9 weeks changed from -0.4 (95% CI=-0.32, 0.24) to -0.08 (95% CI=- 0.31, 0.15) in the Placebo arm. Further indicating that vaccination at an earlier age protects against severe diarrhea. Conclusion The risk of getting severe diarrhea episode is proportional to age, therefore if children are vaccinated at an early age, the lesser the risks of an infection. There was no link between G genotype and occurrence of repeat rotavirus diarrhea episodes. There was progression in hospitalization with increase in the number severe rotavirus diarrhea episodes.