Explore the vast range of titles available.

Despite 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. Children 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. 2320 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]). Following 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.

Investment in vaccine product development should be guided by up-to-date and transparent global burden of disease estimates, which are also fundamental to policy recommendation and vaccine introduction decisions. For low- and middle-income countries (LMICs), vaccine prioritization is primarily driven by the number of deaths caused by different pathogens. Enteric diseases are known to be a major cause of death in LMICs. The two main modelling groups providing mortality estimates for enteric diseases are the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle and the Maternal Child Epidemiology Estimation (MCEE) group, led by Johns Hopkins Bloomberg School of Public Health. Whilst previous global diarrhoea mortality estimates for under five-year-olds from these two groups were closely aligned, more recent estimates for 2016 have diverged, particularly with respect to numbers of deaths attributable to different enteric pathogens. This has impacted prioritization and investment decisions for vaccines in the development pipeline. The mission of the Product Development for Vaccines Advisory Committee (PDVAC) at the World Health Organisation (WHO) is to accelerate product development of vaccines and technologies that are urgently needed and ensure they are appropriately targeted for use in LMICs. At their 2018 meeting, PDVAC recommended the formation of an independent working group of subject matter experts to explore the reasons for the difference between the IHME and MCEE estimates, and to assess the respective strengths and limitations of the estimation approaches adopted, including a review of the data on which the estimates are based. Here, we report on the proceedings and recommendations from a consultation with the working group of experts, the IHME and MCEE modelling groups, and other key stakeholders. We briefly review the methodological approaches of both groups and provide a series of proposals for investigating the drivers for the differences in enteric disease burden estimates.

•Rotavirus vaccination is expected to reduce rotavirus mortality by 49% globally.•These benefits are present for countries at all income levels.•Most impact is due to direct benefits, but indirect effects also enhance impact.•To sustain this benefit, a complete vaccine series is needed. Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006 to 2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two- dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1 % (95 % UI: 46.6–54.3 %) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69–97 % of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57 % as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.

We review the basic classification of rotaviruses, as well as the mechanisms of rotavirus evolution and their significance. We then provide an overview of laboratory methods that have been used to characterize rotaviruses since their discovery in the 1970s, and the role that these methods have played in our understanding of the molecular epidemiology of rotaviruses. The global distribution of rotavirus genotypes, as well as, how these patterns vary over space and time, are described. Finally, we outline how our understanding of the transmission dynamics of rotavirus helps to explain the observed epidemiological trends.