Projecting the long-term economic benefits of reducing Shigella-attributable linear growth faltering with a potential vaccine: a modelling study

Background: Linear growth is an important outcome of child development with implications for economic productivity. Enteric infections, particularly Shigella, have been linked to linear growth faltering (LGF). However, benefits from potential reductions in LGF are rarely included in economic analyses of enteric infections. We aimed to quantify the economic benefits of vaccination related to reduced Shigella-attributable disease and associated LGF compared with the net costs of a vaccine programme. Methods: In this benefit–cost analysis, we modelled productivity benefits in 102 low-income and middle-income countries that had recent stunting estimates available, at least one Shigella-attributable death annually, and available economic data, particularly on gross national income and growth rate projections. We modelled benefits strictly related to linear growth improvements and no other benefits associated with reducing diarrhoeal burden. The effect size in each country was calculated as shifts in height-for-age Z score (HAZ), representing population average changes for preventing Shigella-attributable less-severe diarrhoea and moderate-to-severe diarrhoea separately for children younger than 5 years. Benefits data were calculated per country and combined with estimated net costs of the vaccine programme in the form of benefit–cost ratios (BCRs); BCRs above parity, or $1 in benefits per$1 in costs (with a 10% margin representing borderline results: 1·10:1), were considered cost-beneficial. Countries were aggregated for analysis by WHO region, World Bank income category, and eligibility for support from Gavi, the Vaccine Alliance. Findings: In the base-case scenario, all regions exhibited cost-beneficial results, with the South-East Asia region and Gavi-eligible countries exhibiting the highest BCRs (21·67 for the South-East Asia region and 14·45 for Gavi-eligible countries), and the Eastern Mediterranean region yielding the lowest BCRs (2·90). All regions exhibited cost-beneficial results from vaccination, except in more conservative scenarios (eg, those assuming early retirement ages and higher discount rates). Our findings were sensitive to assumed returns for increased height, assumptions about vaccine efficacy against linear growth detriments, the anticipated shift in HAZ, and discount rate. Incorporating the productivity benefits of LGF reduction into existing cost-effectiveness estimates resulted in longer-term cost-savings in nearly all regions. Interpretation: LGF is a secondary outcome of Shigella infection and reduction in LGF is not often quantified as a health or economic benefit of vaccination. However, even under conservative assumptions, a Shigella vaccine only moderately effective against LGF could pay for itself from productivity gains alone in some regions. We recommend that LGF be considered in future models assessing the economic and health impacts of interventions preventing enteric infections. Further research is needed on vaccine efficacy against LGF to inform such models. Funding: Bill & Melinda Gates Foundation, Wellcome Trust.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Potential impact and cost-effectiveness of Shigella vaccination in 102 low-income and middle-income countries in children aged 5 years or younger: a modelling study

Background: Vaccine impact and cost-effectiveness models have mostly focused on acute burden. Shigella-attributable moderate-to-severe diarrhoea has been shown to be associated with childhood linear growth faltering. Evidence also links less severe diarrhoea to linear growth faltering. As Shigella vaccines are in late stages of clinical development, we aimed to estimate the potential impact and cost-effectiveness of vaccination against Shigella burden that includes stunting and the acute burden attributable to less severe diarrhoea and moderate-to-severe diarrhoea. Methods: We used a simulation model to estimate Shigella burden and potential vaccination in children aged 5 years or younger from 102 low-income to middle-income countries from 2025 to 2044. Our model included stunting associated with Shigella-related moderate-to-severe diarrhoea and less severe diarrhoea and we explored vaccination impact on health and economic outcomes. Findings: We estimate 109 million (95% uncertainty interval [UI] 39−204) Shigella-attributable stunting cases and 1·4 million (0·8–2·1) deaths in unvaccinated children over 20 years. We project that Shigella vaccination could avert 43 million (13−92) stunting cases and 590 000 (297 000–983 000) deaths over 20 years. The overall mean incremental cost-effectiveness ratio (ICER) was US$849 (95$790 [IQR 635–1005]) per disability-adjusted life-year averted. Vaccination was most cost-effective in the WHO African region and in low-income countries. Including the burden of Shigella-related less severe diarrhoea improved mean ICERs by 47−48% for these groups and substantially improved ICERs for other regions. Interpretation: Our model suggests that Shigella vaccination would be a cost-effective intervention, with a substantial impact in specific countries and regions. Other regions could potentially benefit upon the inclusion of the burden of Shigella-related stunting and less severe diarrhoea in the analysis. Funding: Bill & Melinda Gates Foundation and Wellcome Trust.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Understanding a migratory species in a changing world: climatic effects and demographic declines in the western monarch revealed by four decades of intensive monitoring

Migratory animals pose unique challenges for conservation biologists, and we have much to learn about how migratory species respond to drivers of global change. Research has cast doubt on the stability of the eastern monarch butterfly (Danaus plexippus) population in North America, but the western monarchs have not been as intensively examined. Using a Bayesian hierarchical model, sightings of western monarchs over approximately 40 years were investigated using summer flight records from ten sites along an elevational transect in Northern California. Multiple weather variables were examined, including local and regional temperature and precipitation. Population trends from the ten focal sites and a subset of western overwintering sites were compared to summer and overwintering data from the eastern migration. Records showed western overwintering grounds and western breeding grounds had negative trends over time, with declines concentrated early in the breeding season, which were potentially more severe than in the eastern population. Temporal variation in the western monarch also appears to be largely independent of (uncorrelated with) the dynamics in the east. For our focal sites, warmer temperatures had positive effects during winter and spring, and precipitation had a positive effect during spring. These climatic associations add to our understanding of biotic-abiotic interactions in a migratory butterfly, but shifting climatic conditions do not explain the overall, long-term, negative population trajectory observed in our data