Figure 1 and Table 1, respectively, provide the flow diagram and descriptions of the analytical framework arising from expert discussions about the broader economic impact of vaccines. Additional file 2 describes the relationship of our framework with previous literature in this area.
After review and screening for duplications, 93 unique journal articles from the original reviews were included in the initial study. Of these, 23 were identified as being exempt from or not appropriate for evidence quality review for reasons such as being commentaries rather than analyses. Evidence quality grades for the remaining studies are shown in Table 2; 12 additional studies were identified via expert consultation. Of these 35 studies, we identified 20 that were directly relevant to one or more of the pathways in the framework, the findings of which are summarized below. Details on the studies identified are shown in Additional file 3.
Productivity-related benefits
Productivity gains due to non-utility capabilities (physical, cognitive, and education)
Evidence that immunization improves non-utility capabilities (strength of evidence = moderate experimental/observational)
No experimental studies were reviewed that directly provided evidence of the impact of immunization on the physical development of children via reduced morbidity. A single observational study by Bloom et al. [19], found no impact on physical development of adolescent children in the Philippines from the six recommended childhood vaccines. Moreover, the evidence quality itself was low, limited by small final sample size and results that are potentially inconsistent with other results on cognition from the same study.
One randomised trial of moderate quality by Canning et al. [20], provided direct evidence of the impact of maternal tetanus immunization in Matlab, Bangladesh, on the educational outcomes of children, but found that the effect was confined to only a subset of the study population. Evidence from observational studies was not strong, yet remains suggestive. Four studies point to the same overall conclusion, but all were rated low due to lack of direct causal evidence or inconsistency in the results. Two studies were based in the same study population in Bangladesh as Canning et al. [20]. Driessen et al. [21] found that measles vaccination is positively related to future school enrolment. Barham et al. [22] also found a significant relationship between cognition and exposure to a combined package of maternal and child health interventions, including, but not restricted to, routine childhood immunization. In India, Kumar [23] estimated mixed and potentially inconsistent effects on education from the Expanded Programme on Immunization. Bloom et al. [19] found a significant impact on the cognitive development of adolescent children in the Philippines (subject to the caveat above).
Evidence that immunization produces productivity gains via improvements in non-utility capabilities (strength of evidence = modelling)
By improving human capital in the form of increased physical, cognitive, and educational skills of children, immunization may have an impact on future workforce productivity and hence labour income of households as well as overall economic growth. In one modelling study, Bloom et al. [24] proposed a methodology to model these effects, but no experimental or observational studies were found with long enough follow-up to measure such effects.
Community or health systems externalities
Equity (strength of evidence = moderate experimental/observational, and modelling)
In Bangladesh, Bishai et al. [25] found that the poverty-related gradient in under-five mortality is significantly reduced by measles vaccination, improving health equity directly. As previously cited, Canning et al. [9] found that maternal tetanus immunization in Bangladesh improves the educational outcomes of children in lower-income groups, which could potentially result in lower future income inequality (although none of the reviewed studies investigated income-related outcomes).
Two recent modelling studies also addressed the impact of rotavirus immunization programmes on equity. Rheingans et al. [26] modelled the distribution of potential rotavirus vaccine coverage in 25 Gavi countries by wealth quintile by extrapolating DPT2 coverage in Demographic and Health Surveys and found that, while the greatest potential benefit of rotavirus vaccination in 25 Gavi countries was in the poorest quintiles, existing rates of vaccination coverage are highly skewed towards the richest quintiles. Therefore, programmes that add new vaccines to existing systems without mechanisms to ensure equity in uptake may actually exacerbate rather than reduce existing inequity. Verguet et al. [27] modelled programme impact and consequences of rotavirus vaccination in India across different wealth strata, showing that the health and financial protection benefits of rotavirus would accrue mainly to the poor.
Financial and programmatic synergies and sustainability (strength of evidence = modelling)
No observational or experimental studies were found that provided direct evidence of interaction effects between immunization and other health interventions on economic outcomes. However, two modelling studies have explored the interaction between immunization and other health interventions from a cost-effectiveness perspective, showing mixed results. Jeuland et al. [28] examined combinations of new sanitation technologies and cholera vaccination and found that the incremental impact of cholera vaccination is reduced depending on the extent of a pre-existing improved water supply (although not vice versa). Tan-Torres Edejer et al. [29] examined measles immunization in South East Asia and Africa, both singly and as part of a package of nine potential interventions for child health, and found that combinations of interventions offer additive or near-additive gains (suggesting few interactions).
Several observational studies [30–32] used contingent valuation or willingness to pay methods to document substantial positive household demand for various vaccines, including HIV, dengue, and oral cholera, suggesting that households would experience private benefits from their introduction. However, these studies are limited because the vaccines examined were hypothetical only. In some cases, it is not clear that ex ante valuations of vaccines that did not yet exist would match ex post valuations in a future context. Further, while they provide evidence that significant private economic benefits exist to households, it is not possible to distinguish among the various pathways that may contribute to those benefits.
Household financial protection (strength of evidence = modelling)
Two mechanisms have been proposed by which immunization may reduce household financial vulnerability: firstly, through overall changes in labour earnings or savings behaviour, and secondly by reducing the risk from specific health shocks. None of the reviewed studies provided direct empirical evidence for either of these pathways. However, Verguet et al. [27] has proposed a method of ‘extended cost-effectiveness analysis’ that explicitly measures the value of the financial benefits of vaccination that accrue from risk mitigation, and applied it to a model of rotavirus vaccination in India and Ethiopia.
Broader economic indicators
Changes to household behaviour (strength of evidence = conjecture)
If labour income rises, all else equal, we expect that households will be able to increase consumption, savings, and investment in human capital (such as education). Even in the absence of evidence for longer-term increases in labour income due to improved human capital, we would expect changes in immediate household consumption, savings, and investment because of increased disposable income as a result of reduced health expenditure and lost wages. However, no experimental, observational, or modelling studies were found that directly examine the effect of immunization on changes to household consumption, saving, or investment behaviour.
As the risk of childhood mortality and morbidity decreases and survival rates increase, households may also be expected to produce fewer children and invest more in their health [33]. However, no experimental, observational, or modelling studies were found that directly examine the impact of immunization on fertility decisions, and their consequent impact on households.
Public sector budget impact (strength of evidence = modelling)
One modelling study [34] considered the impact of the fiscal space created by the benefits of immunization by projecting lifetime net tax changes as a result of vaccination using an accounting model. However, no study provided direct primary evidence that immunization would yield such an impact.
Short-term macroeconomic impact (via mitigation of shocks) (strength of evidence = modelling)
No empirical studies were found that estimated the effects of vaccination in mitigating the short-term macroeconomic consequences of an infectious disease outbreak. However, several modelling studies have examined the impact of vaccination (alongside other policy responses) in the context of an influenza pandemic. Using a computable general equilibrium model, Smith et al. [35] estimated the impact of vaccination during an influenza pandemic in the United Kingdom, using either a pre-pandemic or a matched vaccine. They found that both strategies can substantially reduce the potential macroeconomic impact of a pandemic regardless of disease severity. Similarly, Keogh-Brown e al. [36] used a multi-sector single country computable general equilibrium model to evaluate the impact of antiviral, vaccination, and combined strategies in the United Kingdom, France, Belgium, and the Netherlands. They found that both vaccine-only and combined strategies would be cost-saving in either a mild or severe pandemic.
Long-term macro-economic impact (via changes in population health, labour force and productivity) (strength of evidence = none, but weak observational from non-vaccine fields)
We found no studies of any kind directly examining the impact that vaccination may have on long-term macro-economic indicators such as national income, growth, or foreign direct investment. However, outside the field of vaccination, there were several studies examining the relationship between improved health in general and such indicators. In a longitudinal cross-country study, Alsan et al. [37] found a positive association between population health (in terms of life expectancy) and foreign direct investment. In addition, four modelling or case studies [24, 38–40] discuss or illustrate how population or labour force changes may affect national income and growth. In other work, Soares [41] proposed a model in which changes in child mortality and life expectancy stimulate drops in fertility and rises in educational attainment, hence driving economic growth.