Direct and possible indirect effects of vaccination on rotavirus hospitalisations among children in Malawi four years after programmatic introduction

Abstract

IntroductionDespite increased use of vaccine in routine immunisation, rotavirus remains a major cause of acute gastroenteritis (AGE) in low-income countries. We describe rotavirus prevalence and hospitalisation in Malawi pre and four years post vaccine introduction; provide updated vaccine effectiveness (VE) estimates; and assess rotavirus vaccine indirect effects.MethodsChildren under five years of age presenting to a referral hospital in Blantyre with AGE were recruited. Stool samples were tested for rotavirus using Enzyme Immunoassay. The change in rotavirus prevalence was evaluated using Poisson regression. Time series analysis was used to further investigate trends in prevalence over time. VE against rotavirus diarrhoea of any severity was estimated using logistic regression. Indirect effects were estimated by evaluating rotavirus prevalence in unvaccinated children over time, and by comparing observed reductions in incidence of rotavirus hospitalisation to those expected based on vaccine coverage and trial efficacy estimates.Results2320 children were included. Prevalence of rotavirus in hospitalised infants (<12 months) with AGE decreased from 69/139(49.64%) prior to vaccine introduction to 197/607(32.45%) post-vaccine introduction (adjusted RR 0.67[95% CI 0.55, 0.82]). Prevalence in children aged 12–23 months demonstrated a less substantial decline: 15/37(40.54%) pre- and 122/352(34.66%) post-vaccine introduction (adjusted RR 0.85, 95% CI 0.57, 1.28). Adjusted VE was 61.89%(95% CI 28.04–79.82), but lower in children aged 12–23 months (31.69% [95% CI −139.03 to 80.48]). In hospitalised infants with rotavirus disease, the observed overall effect of the vaccine was 9% greater than expected according to vaccine coverage and efficacy estimates. Rotavirus prevalence among unvaccinated infants declined post-vaccine introduction (RR 0.70[95% CI 0.55–0.80]).ConclusionsFollowing rotavirus vaccine introduction in Malawi, prevalence of rotavirus in hospitalised children with AGE has declined significantly, with some evidence of an indirect effect in infants. Despite this, rotavirus remains an important cause of severe diarrhoea in Malawian children, particularly in the second year of life.

Evaluating strategies to improve rotavirus vaccine impact during the second year of life in Malawi

“…The greatest reduction in incidence was predicted to occur among infants 4-11 months of age, with more modest reductions in incidence predicted among 0-to 3-and 12-to 23-month-olds in all models; a slight increase in cases among 12-to 23-month-olds was predicted when we assumed waning of vaccineinduced immunity ( Table 2). The range of model predictions was generally consistent with the observed number of cases (Table 2), and with the 33% decline in rotavirus positivity previously reported (30). However, none of our models captured the observed increase in RVGE cases among 12-23month-olds in the first year following vaccine introduction (Fig.…”

“…However, no indirect protection was observed during a cluster randomized trial of rotavirus vaccine in Bangladesh (45). In Malawi, some evidence of indirect protection was observed among infants <1 year of age, as noted previously (30), but the number of cases among children 1 year of age and older actually increased relative to the pre-vaccination period, particularly during the first year following vaccine introduction. This may be due in part to variation in reporting effort, as we also observed an increase in the number of rotavirus-negative acute gastroenteritis cases.…”

“…We estimated the observed vaccine effectiveness (VE obs ) and corresponding 95% confidence interval (CI) as one minus the odds ratio of receiving two doses of rotavirus vaccine among rotavirus-positive acute gastroenteritis cases versus rotavirus-negative diarrheal controls using logistic regression, adjusting for age and year and month of presentation, as in previous analyses (30,35).…”

Childhood vaccines and antibiotic use in low- and middle-income countries

“…Finally, our focus on the direct effects of the vaccines, which we were able to estimate through a casecontrol study, may lead to underestimation of the population-level impact of vaccination programmes. Indirect effects of PCV10/13 and rotavirus vaccines have also been reported in LMICs in which these vaccines have been implemented in routine paediatric immunization programmes [34][35][36][37] . Several further considerations inform the interpretation of the effects of PCV10/13 on antibiotic consumption.…”

Etiology of Diarrhea Among Hospitalized Children in Blantyre, Malawi, Following Rotavirus Vaccine Introduction: A Case-Control Study

“…Monovalent rotavirus vaccine is administered according to the World Health Organization–recommended schedule of 6 and 10 weeks of age. Vaccine coverage increased rapidly following introduction and has exceeded 90% among age-eligible children since 2014 [1, 6].…”