Our approach incorporates financial risk protection into the economic evaluation of health interventions and therefore provides information about the efficiency of attainment of both major objectives of a health system: improved health and financial risk protection. One intervention might rank higher on one or both metrics than another, which shows how intervention choice-the selection of a pathway to universal health coverage-might involve weighing up of sometimes competing objectives. This understanding can help policy makers to select interventions to target specific policy goals (ie, improved health or financial risk protection). It is especially relevant for the design and sequencing of universal health coverage to meet the needs of poor populations.

Background Infant rotavirus vaccines have led to substantial reductions in hospital admissions and deaths due to gastroenteritis, but some studies have reported an elevated risk of intussusception, a rare bowel disorder. This analysis aimed to provide evidence on the potential mortality reduction benefits and intussusception risks of current rotavirus vaccination schedules, and to explore whether alternative schedules could have advantages.Methods All 135 low-income and middle-income countries, defined by gross national income per capita of less than US$12 236 in the 2018 fiscal year, were included in the model. Mortality reduction benefits and intussusception risks of rotavirus vaccination were modelled by use of an Excel-based static cohort model with a finely disaggregated age structure. Numbers of rotavirus gastroenteritis deaths and intussusception deaths in each week of age were calculated for all infants born in the year 2015 between birth and age 5•0 years, with and without restrictions on age at administration. Benefit-risk ratios (rotavirus gastroenteritis deaths prevented per excess intussusception death) and other indicators were calculated for two vaccination schedules currently recommended by WHO and 16 alternative schedules. Of these schedules, it was assumed that between one and three doses would be given; the first dose of the rotavirus vaccine would be co-administered with either BCG or diphtheria-tetanus-pertussis (DTP)1; and the second or third dose would be co-administered with either DTP1, DTP2, DTP3, or measles (Meas)1.Findings A three-dose schedule co-administered with DTP (without age restrictions) could prevent about 74 000 (95% uncertainty interval 59 000-100 000) rotavirus gastroenteritis deaths (38% reduction) and could lead to 201 (77-550) excess intussusception deaths (1•4% increase) compared with no vaccination, resulting in a benefit-risk ratio of 369:1 (160:1-895:1). The benefit-risk ratio was most favourable when the relative risk of intussusception was assumed to decline with the national under-5 mortality rate (2386:1) and least favourable with pessimistic assumptions about access to hospital for intussusception treatment (168:1). Schedules that involve giving the first dose with BCG and the second with DTP1 had the fewest excess intussusception deaths and most favourable benefit-risk ratios.Interpretation Rotavirus vaccines have a favourable benefit-risk profile in LMICs. Neonatal schedules have the potential to prevent more rotavirus gastroenteritis deaths and cause fewer excess intussusception deaths than the schedules currently recommended by WHO, but more efficacious rotavirus vaccines would be needed to achieve more substantial mortality reduction benefits.Funding Bill & Melinda Gates Foundation.

Rotavirus vaccines have been introduced into over 95 countries globally and demonstrate substantial impact in reducing diarrheal mortality and diarrheal hospitalizations in young children. The vaccines are also considered by WHO as “very cost effective” interventions for young children, particularly in countries with high diarrheal disease burden. Yet the full potential impact of rotavirus immunization is yet to be realized. Large countries with big birth cohorts and where disease burden is high in Africa and Asia have not yet implemented rotavirus vaccines at all or at scale. Significant advances have been made demonstrating the impact of the vaccines in low- and lower-middle income countries, yet the modest effectiveness of the vaccines in these settings is challenging. Current research highlights these challenges and considers alternative strategies to overcome them, including alternative immunization schedules and host factors that may inform us of new opportunities.

BackgroundPneumonia and pneumococcal disease cause a large disease burden in resource-constrained settings. We pursue an extended cost-effectiveness analysis (ECEA) of two fully publicly financed interventions in Ethiopia: pneumococcal vaccination for newborns and pneumonia treatment for under-five children in Ethiopia.MethodsWe apply ECEA methods and estimate the program impact on: (1) government program costs; (2) pneumonia and pneumococcal deaths averted; (3) household expenses related to pneumonia/pneumococcal disease treatment averted; (4) prevention of household medical impoverishment measured by an imputed money-metric value of financial risk protection; and (5) distributional consequences across the wealth strata of the country population. Available epidemiological and cost data from Ethiopia are applied and the two interventions are assessed separately at various incremental coverage levels.ResultsScaling-up pneumococcal vaccines at around 40% coverage would cost about $11.5 million and avert about 2090 child deaths annually, while a 10% increase of pneumonia treatment to all children under 5 years of age would cost about $13.9 million and avert 2610 deaths annually. Health benefits of the two interventions publicly financed would be concentrated among the bottom income quintile, where 30–40% of all deaths averted would be expected to occur in the poorest quintile. In sum, the two interventions would eliminate a total of $2.4 million of private household expenditures annually, where the richest quintile benefits from around 30% of the total private expenditures averted. The financial risk protection benefits would be largely concentrated among the bottom income quintile. The results are most sensitive to variations in vaccine price, population size, number of deaths due to pneumonia, efficacy of interventions and out-of-pocket copayment share.ConclusionsVaccine and treatment interventions for children, as shown with the illustrative examples of pneumococcal vaccine and pneumonia treatment, can bring large health and financial benefits to households in Ethiopia, most particularly among the poorest socio-economic groups.

Background Previous studies have found rotavirus vaccination to be highly cost-effective in low-income countries. However, updated evidence is now available for several inputs (ie, rotavirus disease mortality rates, rotavirus age distributions, vaccine timeliness, and vaccine efficacy by duration of follow-up), new rotavirus vaccines have entered the market, vaccine prices have decreased, and cost-effectiveness thresholds have been re-examined. We aimed to provide updated cost-effectiveness estimates to inform national decisions about the new introduction and current use of rotavirus vaccines in Gavi countries.Methods We calculated the potential costs and effects of rotavirus vaccination for ten successive birth cohorts in 73 countries previously and currently eligible for Gavi support, compared with no vaccination. We used a deterministic cohort model to calculate numbers of rotavirus gastroenteritis cases, outpatient visits, hospitalisations, and deaths between birth and 5 years, with and without rotavirus vaccination. We calculated treatment costs from the government and societal perspectives. The primary outcome measure was the incremental cost-effectiveness ratio (discounted US$ per disability-adjusted life-year averted). Country-specific model input parameters were based on the scientific literature, published meta-analyses, and international databases. We ran deterministic and probabilistic uncertainty analyses.Findings Over the period 2018-27, rotavirus vaccination has the potential to prevent nearly 600 000 deaths in Gavi countries. Averted outpatient visits and hospitalisations could lead to treatment savings of approximately $484•1 million from the government perspective and $878•0 million from the societal perspective. The discounted dollars per disability-adjusted life-year averted has a very high probability (>90%) of being less than 0•5 times the gross domestic product per capita in 54 countries, and less than 1•0 times gross domestic product per capita in 63 countries.Interpretation Rotavirus vaccination continues to represent good value for money across most Gavi countries despite lower rotavirus mortality estimates and more stringent willingness-to-pay thresholds.Funding Bill & Melinda Gates Foundation.