Estimating the Health Impact of Vaccination Against 10 Pathogens in 98 Low and Middle Income Countries from 2000 to 2030

Background: The last two decades have seen substantial expansion of childhood vaccination programmes in low and middle income countries (LMICs). Here we quantify the health impact of these programmes by estimating the deaths and disability-adjusted life years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. Methods: Independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B (HepB), Haemophilus influenzae type b (Hib), human papillomavirus (HPV), Japanese encephalitis (JE), measles, Neisseria meningitidis serogroup A (MenA), Streptococcus pneumoniae, rotavirus, rubella, yellow fever. Using standardized demographic data and vaccine coverage estimates for routine and supplementary immunization activities, the impact of vaccination programmes on deaths and DALYs was determined by comparing model estimates from the no vaccination counterfactual scenario with those from a default coverage scenario. We present results in two forms: deaths/DALYs averted in a particular calendar year, and in a particular annual birth cohort. Findings: We estimate that vaccination will have averted 69 (2⋅5-97⋅5% quantile range 52-88) million deaths between 2000 and 2030 across the 98 countries and ten pathogens considered, 35 (29-45) million of these between 2000-2018. From 2000-2018, this represents a 44% (36-57%) reduction in deaths due to the ten pathogens relative to the no vaccination counterfactual. Most (96% (93-97%)) of this impact is in under-five age mortality, notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 122 (96-147) million deaths will be averted by vaccination, of which 58 (39-75) and 38 (26-52) million are due to measles and Hepatitis B vaccination, respectively. We estimate that recent increases in vaccine coverage and introductions of additional vaccines will result in a 72% (61-79%) reduction in lifetime mortality caused by these 10 pathogens in the 2018 birth cohort. Interpretation: Increases in vaccine coverage and the introduction of new vaccines into LMICs over the last two decades have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. Funding Statement: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill & Melinda Gates Foundation (BMGF). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMCfunded institutions represented in this paper: Imperial College London, London School of Hygiene & Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Metiers). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: Professor Hallett, Professor Grassly, Dr Cucunuba, Professor Jit, Dr Xiang Li, Dr Mukandavire, Ms Woodruff, Professor Ferguson, Dr Garske); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). In addition, the following funding declarations are noted: Dr Eilertson and Dr Ferrari report grants from BMGF, outside the submitted work. Mr Gamkrelidze, Dr Razavi and Mr Razavi-Shearer report grants from John C Martin Foundation during the conduct of the study; and grants from AbbVie, Gilead, Intercept, Pan American Health Organization, and Association of State and Territorial Health Officials outside the submitted work; all three authors are employees of the Center for Disease Analysis Foundation which had no role in study design, data collection and analysis, interpretation of data, or preparation of the manuscript. Dr Gaythorpe reports personal fees from Wellcome Genome Campus advanced courses and scientific conferences, and grants from MRC during the conduct of the study. Dr Hallett reports grants and personal fees from WHO, Pharos, Avenhir Health, outside the submitted work. Dr Nayagam reports Consultancy work for WHO and Pharos Global Health Advisors, and acknowledges support from NIHR Imperial Biomedical Research Centre (BRC). Dr Trotter reports personal fees from GSK, outside the submitted work. Professor Hallett, Dr Nayagam, Dr Garske, Dr Gaythorpe, Dr Hinsley, Dr Jean, and Professor Ferguson acknowledge joint Centre funding from the UK Medical Research Council and Department for International Development (MR/R015600/1). Development of LSHTM's models for HPV, measles, PCV, Hib and rotavirus was funded by WHO, Gavi and BMGF under several grants, past and current. BMGF supported the development and maintenance of the Lives Saved Tool. Dr Resch and Mr Sy acknowledge other funding from BMGF not related to this work and with no influence on the manuscript or the decision to submit it for publication. Declaration of Interests: This publication is authored by members of the Vaccine Impact Modelling Consortium (VIMC, www.vaccineimpact.org). VIMC is jointly funded by Gavi, the Vaccine Alliance, and by the Bill & Melinda Gates Foundation. The views expressed are those of the authors and not necessarily those of the Consortium or its funders. The funders were given the opportunity to review this paper prior to publication, but the final decision on the content of the publication was taken by the authors. Consortium members received funding from Gavi and BMGF via VIMC during the course of the study (see funding statement above). In addition, the following potential conflicts of interest were disclosed: Dr Eilertson and Dr Ferrari report grants from Bill and Melinda Gates Foundation, outside the submitted work. Dr Gamkrelidze, Dr Razavi and Dr Razavi-Shearer report grants from John C Martin Foundation during the conduct of the study; and grants from AbbVie, Gilead, Intercept, Pan American Health Organization, and Association of State and Territorial Health Officials outside the submitted work. Dr Gaythorpe reports personal fees from Wellcome Genome Campus advanced courses and scientific conferences, and grants from MRC during the conduct of the study. Dr Hallett reports grants and personal fees from WHO, Pharos, Avenhir Health, outside the submitted work. Dr Nayagam reports Consultancy work for WHO and Pharos Global Health Advisors. Dr Trotter reports personal fees from GSK, outside the submitted work. Professor Ferguson reports grants from UK Medical Research Council during the conduct of the study, and grants from NIH NIGMS, UK National Institute of Health Research, Janssen Pharmaceuticals, outside the submitted work. Dr Garske reports grants from Janssen Pharmaceuticals, outside the submitted work. Ethical Approval Statement: Not required.