Monitoring the impact of rotavirus vaccines on a global scale
Authors: Elizabeth T Rogawski McQuade, James A Platts-Mills
Journal: The Lancet Global Health (2019)

The introduction of rotavirus vaccines into national immunisation programmes has changed the landscape of acute gastroenteritis among children younger than 5 years of age, and continued surveillance is crucial for monitoring progress and prioritising further interventions. The Global Rotavirus Surveillance Network (GRSN) was established in 2008 to provide global hospital-based surveillance for rotavirus gastroenteritis.1Agócs MM Serhan F Yen C et al.WHO global rotavirus surveillance network: a strategic review of the first 5 years, 2008–2012.MMWR Morb Mortal Wkly Rep. 2014; 63: 634-637PubMed Google Scholar Importantly, the network was initiated prior to vaccine introduction in the majority of included countries, which created the opportunity to measure vaccine impact. In this issue of The Lancet Global Health, Negar Aliabadi and colleagues2Aliabadi N Antoni S Mwenda JM et al.Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008–16: findings from the Global Rotavirus Surveillance Network.Lancet Global Health. 2019; 7: e893-e903Summary Full Text Full Text PDF PubMed Scopus (81) Google Scholar report the first analysis of rotavirus vaccine impact from the GRSN, from 2008 to 2016. The primary analysis includes more than 300 000 cases of acute gastroenteritis requiring hospital admission from 198 sites in 69 countries, highlighting the success of the massive coordination effort that was necessary to build the network over the past decade. Participating countries came from all WHO regions, but excluded high-income countries in Europe, the Americas, and Australia. Therefore, the results are broadly generalisable to low-income and middle-income countries. The primary analysis found a 39·6% (95% CI 35·4–43·8) relative reduction in the proportion of acute gastroenteritis hospital admissions due to rotavirus in the post-vaccine introduction period. As an inevitable consequence of including sites from diverse low-resource settings—many with relatively little research infrastructure—the granularity of the data is poor: individual-level vaccine coverage is not reliably available, sites fall in and out of surveillance over the years, and no population denominators are available to calculate incidence estimates. However, these constraints are balanced by the sheer magnitude of data, which allowed for more precise impact estimates than have previously been available. Most previously published vaccine impact data3Burnett E Jonesteller CL Tate JE Yen C Parashar UD Global impact of rotavirus vaccination on childhood hospitalizations and mortality from diarrhea.J Infect Dis. 2017; (published online April 18.)DOI:10.1093/infdis/jix186Crossref Scopus (158) Google Scholar have come from sites with substantial research infrastructure and resources—and probably higher vaccine coverage. Thus, Aliabadi and colleagues' estimates from more representative hospitals, reflecting variable vaccine coverage, have the highest public health relevance and robustly support the continued introduction of rotavirus vaccines. There are several important limitations to note. First, the use of the rotavirus-positive proportion as a proxy for rotavirus incidence assumes that there were no secular changes in acute gastroenteritis hospital admissions due to other causes. However, all-cause diarrhoea incidence decreased over the considered time period due to improvements in access to water and sanitation, oral rehydration, and adequate nutrition in addition to vaccine introduction.4GBD 2016 Diarrhoeal Disease CollaboratorsEstimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Infect Dis. 2018; 18: 1211-1228Summary Full Text Full Text PDF PubMed Scopus (605) Google Scholar If other causes of acute gastroenteritis also decreased over the post-vaccine introduction period, the reduction in the rotavirus-positive proportion would underestimate the true reduction in rotavirus incidence. Second, inclusion of the year of vaccine introduction in the pre-vaccine period is conservative because it will necessarily include children who have been vaccinated; inclusion of the first year after vaccine introduction in the post-vaccine period before peak coverage was reached is similarly conservative. Third, because the year of vaccine introduction varied by country, the comparison included more post-vaccine site-years from countries that introduced vaccination earlier and more pre-vaccine site-years from those that introduced vaccination later. If, for example, countries that introduced vaccination earlier had a lower baseline rotavirus incidence, this would result in inflated estimates of impact. Inclusion of a sensitivity analysis that required sites to contribute at least 1 year to both pre-vaccine and post-vaccine periods only partially mitigates this potential bias. Finally, these data could not assess an impact on diarrhoea or rotavirus-specific mortality; however, the observed shift towards an older age distribution would be expected to be associated with a lower case-fatality rate. Despite the impressive reductions seen, the residual burden of rotavirus disease was high. Indeed, testing for other causes from the African Region showed rotavirus to be the leading cause of acute gastroenteritis, even in children who were eligible to be vaccinated.5Operario DJ Platts-Mills JA Nadan S et al.Etiology of severe acute watery diarrhea in children in the Global Rotavirus Surveillance Network using quantitative polymerase chain reaction.J Infect Dis. 2017; 216: 220-227Crossref PubMed Scopus (74) Google Scholar The high residual burden of rotavirus disease suggests that additional strategies, including introduction of a birth dose6Bines JE At Thobari J Satria CD et al.Human neonatal rotavirus vaccine (RV3-BB) to target rotavirus from birth.N Engl J Med. 2018; 378: 719-730Crossref PubMed Scopus (81) Google Scholar or a booster dose7Zaman K Fleming JA Victor JC et al.Noninterference of rotavirus vaccine with measles-rubella vaccine at 9 months of age and improvements in antirotavirus immunity: a randomized trial.J Infect Dis. 2016; 213: 1686-1693Crossref PubMed Scopus (39) Google Scholar and the development of parenteral vaccines,8Groome MJ Koen A Fix A et al.Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial.Lancet Infect Dis. 2017; 17: 843-853Summary Full Text Full Text PDF PubMed Scopus (84) Google Scholar might be important. Several extensions of these analyses could be helpful to provide further context. First, estimates among sites with at least 60% vaccination coverage were not substantially higher than overall estimates, suggesting a different coverage threshold might be more relevant in low-income and middle-income countries. Further investigation of the relationship between coverage and impact would better inform coverage targets. Second, in the USA, the rotavirus season was delayed and shortened after vaccine introduction.9Tate JE Panozzo CA Payne DC et al.Decline and change in seasonality of US rotavirus activity after the introduction of rotavirus vaccine.Pediatrics. 2009; 124: 465-471Crossref PubMed Scopus (195) Google Scholar Understanding whether this phenomenon is consistent across diverse geographies and climates is needed. Finally, it will be important to further characterise the shift in the age distribution as the cohort of vaccinated children ages. Looking forwards, this global infrastructure could also allow for surveillance of other enteric pathogens. Vaccines are currently under development for several pathogens including Shigella, enterotoxigenic Escherichia coli, norovirus, and Campylobacter. Global surveillance will be important for establishing the potential value of these vaccines, identifying target populations for vaccine studies, and monitoring the effectiveness and impact of vaccine introduction. The ongoing adaptation of the GRSN into a Global Pediatric Diarrhea Surveillance network10WHOWHO global invasive bacterial vaccine-preventable disease and rotavirus surveillance bulletin.https://mailchi.mp/9379015a2472/who-ib-vpd-and-rotavirus-surveillance-bulletin-june-1737585Date: January, 2019Date accessed: May 16, 2019Google Scholar can help to advance these objectives. We declare no competing interests. ETRM was supported by the US National Institutes of Health (K01AI130326). Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008–16: findings from the Global Rotavirus Surveillance NetworkA significant and sustained reduction in the proportion of hospital admissions for acute gastroenteritis due to rotavirus was seen among children younger than 5 years in GRSN sites following rotavirus vaccine introduction. These findings highlight the need to incorporate rotavirus vaccines into immunisation programmes in countries that have not yet introduced them and underline the importance of high-quality surveillance. Full-Text PDF Open Access