Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization

Vaccination has accounted for close to half the total global reduction in infant mortality, and in some regions to the majority of these gains (appendix p 8). As a result of 50 years of vaccination, a child born today has a 40% increase in survival for each year of infancy and childhood. The survival benefits of infant vaccination extend to beyond 50 years of age, a remarkable finding considering the exclusion of smallpox and the exclusion of the anticipated benefits of human papillomavirus (HPV), influenza, SARS-CoV-2, Ebola, mpox and other vaccines affecting adult mortality.

Measles outbreaks are a tracer for vaccine programme performance under the Immunization Agenda 2030 (panel). Historically, the impact of measles vaccination on annual mortality reduction peaked contemporaneously with global scale up of first dose coverage. Vaccine coverage then plateaued (figure 2C), while other non-vaccine factors that reduce infant and child mortality were introduced (figure 2A), although this varies by region (panel; appendix pp 9–10). These non-vaccine factors also contributed to lowering the risk of dying from measles, given infection. Despite the importance of non-vaccine factors, forecasting suggests that measles vaccination will remain the pre-eminent intervention that will maximise lives saved well into the future.

In the 21st century, the increasing effect of other interventions is notable, highlighting the need for sustained investment and implementation efforts, bringing together immunisation and primary health-care services.

New-generation tuberculosis vaccines are in development.

This analysis did not include the putative effects of the BCG or measles vaccine on mortality from causes other than tuberculosis and measles, which some evidence suggests could be substantial. Vaccination against poliomyelitis has had a modest impact on mortality, averting 1% of deaths, but has led to substantial public health gains by reducing poliomyelitis-induced paralysis, accounting for 8% of the 10·8 billion healthy life-years gained. The opportunity to eradicate this long-standing disease, as was done with smallpox, must not be missed. The closer we get to poliomyelitis eradication the greater the challenge to reach it, but so is the commensurate obligation to complete the task.

places vaccination squarely within the remit of primary health care and the Alma Ata Declaration. Vaccine programmes are often the backbone for systems that provide other life-saving health-care delivery. The present authors plan to extend our analyses to examine the effect of sociodemographic factors on the achievable impact of vaccination programmes and examine underlying explanatory differences across and within regions. The analysis presented here is a minimum conservative estimate of vaccine impact. We accounted for external factors that reduce infectious case fatality and diminish the vaccine-attributable impact on mortality. We did not include the downstream benefit of vaccination on non-communicable disease mortality (eg, of diarrhoea on malnutrition), nor broader economic benefit or community development gains that vaccination might facilitate, since the magnitude of causal attribution is more difficult to quantify.

We also did not include possible heterologous effects of vaccines on epitopically non-specific immune training or other potential mechanisms. Such effects might mean that we underestimated the benefits of some vaccines (eg, BCG and measles) or did not sufficiently discount the benefits of others (eg, DTP-containing vaccines). The methods used in this study are well suited for a more thorough assessment of the possible population impacts of potential heterologous effects, but this is beyond the current scope. We cannot claim a complete analysis of the impact of immunisation, since we exclude vaccines such as those against COVID-19, which is arguably yet to achieve equilibrium; influenza, which is subject to local-level variation in seasonality and immunity profiles; and HPV, a vaccination programme which can anticipate a rapid increase in impact in the coming years. We did not include vaccines used for outbreaks such as cholera or Ebola; vaccines targeting disease occurring in adult life; or those used largely in high-income settings such as varicella, herpes zoster, or mumps, and the counterfactual assumed a smallpox free world, meaning that we did not account for the enormous benefit achieved by its eradication. The risk of double counting is a limitation, but we have shown that this has only a small effect on our estimates. We have presented global and regional findings, which delimits the geographical resolution at which conclusions can be drawn. Ongoing work to extend these models in consultation with member states is underway. The calendar-year impact of vaccination over the last 50 years was captured; compared with birth cohort-based or year-of-vaccination approaches, which require longer term projection based on broad assumptions, the calendar-year-based approach does not fully account for any post-2024 lifetime vaccination impacts, especially for diseases that occur later in life, implying a substantial underestimate for diseases such as hepatitis B.

For the above reason, HPV, first licensed in 2006 and introduced more widely in the 2010s, was excluded from the analysis due to incomparability of timeframe.

This imperative is highly dependent on achieving post-COVID-19 pandemic recovery and restoration of the trajectory to Immunization Agenda 2030 targets; achieving and maintaining universally high coverage with measles-containing vaccines (a principle aim of the Big Catch-up initiative; panel); the introductions of the much-anticipated malaria, respiratory syncytial virus, and other potential high impact vaccines; and achieving universal high coverage with an HPV vaccine (a must-win for Gavi, The Vaccine Alliance). HPV vaccine coverage is currently reaching only 21% of adolescent girls globally and is still far from the coverage targets of the WHO Cervical Cancer Elimination strategy, which aims to achieve HPV vaccination for 90% of all adolescent girls by 2030.