Of the 4338 children who were age eligible to receive rotavirus vaccine (ie, born between 1 March 2014 and 31 December 2017), 3643 met the inclusion criteria for this analysis (Figure 1). Of the eligible children, 99% had verified vaccination status; there was no difference in the percentage of children with and without verified vaccination status by age group or rotavirus positivity. We included 903 rotavirus-positive cases and 2685 rotavirus-negative controls in this analysis.

Characteristics of the children included in the cohort are shown in Table 1. Among children >6 months old included in the analysis, the median age for cases and controls was 12 months. The percentage of cases enrolled by year was 1% in 2014, 27% in 2015, 39% in 2016, and 33% in 2017; the percentage of controls admitted by year was 1% in 2014, 18% in 2015, 39% in 2016, and 41% in 2017 (P < .01). Rotavirus-positive children had more severe diarrhea than rotavirus-negative children; 61% of cases vs 46% of controls had a modified Vesikari score ≥11 (P < .01). However, the mortality rate was similar in both groups, with 0% and 1% cases and controls, respectively, who died during the hospitalization (P = .37). Among cases, 31% were stunted for their age; 37% of controls were stunted (P < .01).

In terms of socioeconomic factors, a higher proportion of cases had electricity (71% rotavirus positive; 64% rotavirus negative; P < .01) and a refrigerator (59% rotavirus positive; 53% rotavirus negative; P < .01) in their household compared to controls. Both groups of children were similar in terms of mother’s age, maternal education, the number of people living in the home, owning a car in the household, and at least 1 member of the household owning a mobile phone.

Rotavirus vaccination coverage was very high and adherent to the recommended ages of administration for both doses (Figure 2). By 1 year of age, 96% of enrolled children had received the first dose of rotavirus vaccine and 94% had received the second dose. The majority of children received the first and second doses within 1 month of the recommended ages of 6 and 10 weeks, respectively. There was no difference in full series vaccination coverage between cases and controls; 94% had completed the rotavirus vaccine series prior to their hospitalization.

Among children 6–11 months of age, VE against hospitalization or treatment in A&E due to rotavirus diarrhea of any severity was 61% (95% CI, 21%–81%) with 2 doses, adjusted for age in months, season of birth, year of admission, and if the child’s household had electricity (Table 2). The adjusted VE against hospitalization or treatment in A&E due to severe rotavirus diarrhea was 68% (95% CI, 13%–88%) in this age group. Stratified by nutritional status, the adjusted VE was 45% (95% CI, –148% to 88%) among stunted infants and 71% (95% CI, 29%–88%) among infants with a normal height for age.

Among children ≥12 months of age, VE against hospitalization or treatment in A&E due to rotavirus diarrhea of any severity was –48% (95% CI, –148% to 11%) with 2 doses, adjusted for age in months, season of birth, year of admission, and if the child’s household had electricity. The adjusted VE against hospitalization or treatment in A&E due to severe rotavirus diarrhea was –38% (95% CI, –164% to 28%) in this age group. Stratified by nutritional status, the adjusted VE was –67% (95% CI, –313% to 32%) among stunted children ≥12 months old and –35% (95% CI, –178% to 35%) among children ≥12 months old with a normal height for age.

VE with any dose was comparable to 2-dose VE in all analyses.

In this evaluation of real-world monovalent oral rotavirus vaccine performance in Zimbabwe, we found VE against severe rotavirus disease among infants to be 68%, with high adherence to the recommended ages of vaccination. This estimate is slightly higher than rotavirus VE findings from neighboring countries using a similar protocol and other countries with high child mortality [7, 9–11]. In both age groups, the VE against hospitalizations due to severe rotavirus diarrhea disease was higher than VE against hospitalizations for rotavirus diarrhea of any severity. This is consistent with previously published findings [7]. There were very few partially vaccinated children in this population; therefore, the VE point estimates for 2 doses and any number of doses were very similar in all analyses. However, the estimated 2-dose rotavirus vaccination coverage in this study population is comparable to administrative estimates of national rotavirus vaccination coverage in Zimbabwe [5]. The VE point estimates for stunted and nonstunted children suggest malnutrition may play a role in vaccine performance, but our sample size was inadequate to detect statistically significant differences.

The infant VE estimate corroborates previous findings showing significant reductions in rotavirus hospitalizations in Zimbabwe; however, the much lower and nonsignificant VE among older children is not in agreement with observed reductions in rotavirus hospitalizations among children 12–23 months old of 21%–33% and among children 24–59 months old of 5%–22% [6]. However, because the VE estimates for children ≥12 months old lack precision, they are difficult to interpret. Previous studies have found that immunity from rotavirus vaccination may wane in the second year of life [7] and, given the differences between the VE point estimate and CIs between infants and children ≥12 months old, our findings suggest this may be a factor in Zimbabwe. A recent study found that naturally acquired immunity to rotavirus may somewhat reduce the calculated rotavirus VE in populations with high incidence of disease, especially in older age groups [14]. In this population, we do not know how many children may have naturally acquired immunity; however, because of the high vaccination coverage and small number of unvaccinated children ≥12 months old (n = 86 rotavirus negative; n = 19 rotavirus positive), our estimated VE is susceptible to even minor changes in the distribution of unvaccinated children. While our findings suggest rotavirus vaccine may be less effective in preventing hospitalizations after the first year of life in Zimbabwe, we are unable to draw conclusions about the exact magnitude of, or reasons for, any difference between the 2 age groups.

Nutritional status and interference by maternal antibodies have been proposed as factors contributing to lower rotavirus VE in high-child-mortality settings compared with low-child-mortality countries [7, 15]. In developing our adjusted model, we found season of birth, a proxy for maternal antibodies against rotavirus at birth, to be an important confounder of rotavirus VE in this population. In models stratified by nutritional status, rotavirus vaccine provided no protection against hospitalization for malnourished infants compared to nonmalnourished infants. Evaluations of VE in Botswana and Malawi have also shown that rotavirus vaccination did not protect against hospitalizations in undernourished children and stunted children, respectively [11, 16]. Further research is needed to determine the magnitude of the impact of nutrition and rotavirus maternal antibodies in Zimbabwe.

This analysis has limitations. Both sites in this analysis are located in Harare, an urban setting, and primarily serve children living in Harare. Our findings may not be representative of rural or diverse socioeconomic settings in Zimbabwe. Second, vaccinated children without vaccination cards were excluded and may be different in other ways when compared to children with documentation of vaccination. However, the number of children excluded due to lack of verified vaccination history was very small and did not differ by rotavirus testing status. Finally, this evaluation was not powered to detect a difference in VE between the stunted and nonstunted groups and we are limited in interpreting these findings.

The results from this analysis in Zimbabwe show that monovalent rotavirus vaccine is effective in preventing hospitalizations due to severe rotavirus diarrhea among infants. While our VE is slightly higher than other estimates from neighboring countries, the findings of this analysis are consistent with a large ecological reduction in all-cause and rotavirus hospitalizations that have been previously reported [6]. This evaluation provides additional evidence for countries considering rotavirus vaccine introduction that live, oral rotavirus vaccines are effective in settings of high child mortality.