The long-term impact and effectiveness of rotavirus vaccination in Malawi: an interrupted time-series and case-control analysis
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Abstract
Background
Rotavirus remains a leading cause of childhood diarrhoeal hospitalisation globally. Malawi introduced the monovalent G1P8 rotavirus vaccine (Rotarix®) in October 2012 and in April 2016 switched from trivalent to bivalent oral poliovirus vaccine (tOPV to bOPV). More than a decade after Rotarix® introduction, evidence on sustained vaccine effectiveness and population-level impact in high-transmission, low-income settings remains limited, and it is uncertain whether programme changes such as the OPV formulation switch have influenced Rotarix® performance over time.
Methods
We estimated the long-term impact and effectiveness of Rotarix® on diarrhoea hospitalisation in Malawi and explored whether OPV type changes Rotarix® effectiveness. We used interrupted time-series and test-negative case-control analyses to assess the impact and effectiveness of Rotarix®, respectively, over seven years post vaccine introduction using data from diarrhoeal surveillance studies in children under five years hospitalised with acute gastroenteritis at Queen Elizabeth Central Hospital, in Blantyre, Malawi, between 1997 and 2019. Stool samples from these children were collected and tested for rotavirus A antigen using enzyme immunoassay (EIA). To assess the effect of concurrent vaccination with OPV, we used a test-negative case-control study to estimate the interaction between the two vaccines.
Findings
The interrupted time-series was based on 7,952 hospitalisations and showed a 23% (95% confidence interval (CI): 10 – 34%) reduction in rotavirus hospitalisations rates among children under five years in the post-vaccine introduction period (January 2013 – December 2019) compared with the pre-vaccine period (July 1997 – December 2012). There was a stronger effect among infants under one year (37%; 95% CI: 25 – 47%). Protection declined with age, with little measurable impact beyond infancy. The test-negative analysis enrolled 1,909 children and Rotarix® effectiveness for two doses was 52% (95% CI: 18 – 71%) overall, 67% (95% CI: 36 – 82%) among infants and 29% (95% CI: −136 – 74%) in those older than one year. Analyses of the tOPV to bOPV switch (n = 1,622) showed no measurable interaction with Rotarix® performance (aOR 1.07; 95% CI: 0.85 – 1.34).
Interpretation
Rotarix® provides moderate protection for Malawian infants, and the transition from tOPV to bOPV did not influence vaccine effectiveness. The lower effectiveness of rotavirus vaccination with increasing child age highlights the need to evaluate alternative vaccination strategies alongside strengthened WASH interventions to sustain vaccine impact in LMICs.
Funding
MRC Discovery Medicine North (DiMeN) Doctoral Training Partnership (UKRI) and National Institute for Health and Care Research (NIHR)
Research in context
Evidence before this study
Multiple reviews have evidenced variable vaccine effectiveness by setting and age. A recent global review and meta-regression of efficacy and effectiveness data by the authors ( https://doi.org/10.1016/j.eclinm.2025.103122 ), updated to October 2024, highlighted lower rotavirus vaccine effectiveness and impact in high-burden, low- and middle-income countries (LMICs) compared with high-income settings. Studies in LMIC’s including those in sub-Saharan Africa (SSA) consistently indicate that protection is strongest in infants, with impact and effectiveness declining in older children. Multiple factors have been implicated for this variability in effectiveness, including interference from co-administration of oral polio vaccines. We also conducted a systematic review of post-licensure rotavirus vaccine impact and effectiveness studies from sub-Saharan Africa (CRD42023436851). We also assessed the principal study designs used and the extent to which they adjusted for concurrent public health and social measures (PHSMs). We searched PubMed, EMBASE, MEDLINE, CINAHL, and Google Scholar for studies of vaccine impact or effectiveness in children under five years and screened reference lists of included studies. Across all eligible studies, none measured or adjusted for concurrent public health or social measures. To date, most SSA evaluations have focused on the early post-introduction period, with limited evidence on longer-term vaccine performance and no epidemiological evaluation of the potential effect of co-administration of oral polio vaccines on rotavirus vaccine effectiveness.
Added value of this study
We provide a long-term evaluation of the monovalent rotavirus vaccine (Rotarix®) in Malawi using a single hospital-based surveillance platform spanning the pre-vaccine and post-vaccine periods. We combine interrupted time-series analyses of population-level impact with test-negative estimates of individual-level effectiveness using consistent age strata. We also examine whether the national switch from trivalent to bivalent oral poliovirus vaccine modified rotavirus vaccine effectiveness, addressing a programme change that has rarely been assessed in rotavirus vaccine evaluations.
Implications of all the available evidence
The available evidence indicates modest rotavirus vaccine benefit in sub-Saharan Africa, with protection concentrated in infancy and little measurable effect in older children. Our findings highlight the need to interpret long-term vaccine impact estimates alongside changes in other PHSMs that influence rotavirus disease burden, including water and sanitation and access to care. The absence of an effect associated with OPV formulation change suggests that modifying OPV valency alone is unlikely to improve rotavirus vaccine performance. Extending protection beyond infancy may require alternative vaccine schedules alongside sustained improvements in broader public health conditions.
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This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/19582622.
Brief summary
This preprint evaluated vaccine impact and effectiveness after introduction from January 2013 to December 2019 using data from children under 5 years hospitalised with acute gastroenteritis at Queen Elizabeth Central Hospital in Blantyre, Malawi.The researchers also tested whether switching from one type of oral polio vaccine (tOPV) to another (bOPV) changed how well the rotavirus vaccine worked. The main findings were: the vaccine gave 67% protection to infants under 1 year, protection dropped to 29% in older children; the polio vaccine switch did not affect rotavirus vaccine performance. There is one major limitation that the preprint only includes children from one urban …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/19582622.
Brief summary
This preprint evaluated vaccine impact and effectiveness after introduction from January 2013 to December 2019 using data from children under 5 years hospitalised with acute gastroenteritis at Queen Elizabeth Central Hospital in Blantyre, Malawi.The researchers also tested whether switching from one type of oral polio vaccine (tOPV) to another (bOPV) changed how well the rotavirus vaccine worked. The main findings were: the vaccine gave 67% protection to infants under 1 year, protection dropped to 29% in older children; the polio vaccine switch did not affect rotavirus vaccine performance. There is one major limitation that the preprint only includes children from one urban hospital, so results may not apply to rural areas.
Strengths of the paper
1. Long follow-up period
The study evaluates rotavirus vaccine performance more than 7 years after introduction, providing evidence on long-term effectiveness. The analysis covers data from July 1997 to December 2019, which allows observation of trends well. This longer window may help capture changes in vaccine protection over time, such as waning immunity or shifts in disease burden to different groups, which shorter follow-up studies could miss.
2. Combining interrupted time-series and test-negative case control study designs
Interrupted time-series used to measure population-level impact and test-negative case-control used to measure individual-level effectiveness allow the findings to compare results across community and individuals. This combination helps assess both direct vaccine protection and broader herd effects. Using two designs together may also provide a way to check whether findings from one approach are consistent with the other, which could strengthen confidence in the conclusions.
3. Adjustment for confounders in the analysis
The authors used generalized linear regression models to adjust for seasonality trends. They also adjusted for changes in healthcare seeking and surveillance intensity by including test-negative diarrhoeal cases as a proxy for background admission trends. This approach helps reduce bias from external factors that are not directly related to vaccination.
Major concerns
1. Gap in the monitoring data (from December 2009 to November 2011).
This missing data may affect the accuracy of the interrupted time series model's estimation of what would have happened without vaccination, especially when it is unknown whether the epidemiology of rotavirus has changed during this gap period. The gap appears between two surveillance periods and is noted but not further assessed in the analysis. Readers might wonder whether rotavirus transmission patterns shifted during those two years.
2. Imprecise estimates for older children
In children aged ≥1 to <5 years, the vaccine effectiveness estimate was 29% with a 95% confidence interval ranging from −136% to 74%, indicating very low precision. This makes it difficult to draw reliable conclusions about protection in this age group. The authors mention this limitation but do not explore whether alternative analytical approaches could improve precision.
Competing interests
The authors declare that they have no competing interests.
Use of Artificial Intelligence (AI)
The authors declare that they did not use generative AI to come up with new ideas for their review.
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