Predicting the long-term impact of rotavirus vaccination in 112 countries from 2006-2034: a transmission modeling analysis

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 2006-2034 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. ### Competing Interest Statement JMB reports personal fees from WHO outside the submitted work. EWH reports personal fees from Merck & Co for unrelated work. VEP is a member of the WHO Immunization and Vaccine-related Research Advisory Committee (IVIR-AC) and has received reimbursement from Merck and Pfizer for travel expenses to Scientific Input Engagements unrelated to the topic of this manuscript. ### Funding Statement This work was funded by the Vaccine Impact Modeling Consortium and the U.S. NIH/National Institute of Allergy and Infectious Diseases [grant number R01AI112970]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approval to use the data for the present work was provided by the Global Rotavirus Surveillance Network team upon submitting a formal data request. For the present analysis, data were only provided at the country and yearly level and no personally identifiable data were used such that the released data meets federal guidelines for ethical compliance in release of surveillance data, as described in the Public Health Service Act. The original data collection is from public health surveillance and is covered by section 301 of the Public Health Service Act (42 USC 241). As a surveillance activity, the initial data collection is considered not to be research with human subjects based on these guidelines. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All updated model code will be available on GitHub at the time of publication. Model output data files and input coverage estimates are proprietary of the Vaccine Impact ModelingConsortium and will not be publicly available. Validation data is the property of the Global Rotavirus Surveillance Network and will not be publicly available.