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Potential impact and cost-effectiveness of future ETEC and Shigella vaccines in 79 low- and lower middle-income countries.

ABSTRACT: While diarrhea mortality in children has declined over the last two decades, there has been a slower decline in diarrheal episodes. Repeated diarrheal episodes are associated with childhood stunting, which leads to increased mortality risk from infectious diseases. Vaccine candidates are under development for enterotoxigenic Escherichia coli [ETEC] and Shigella, important enteric pathogens in children in low income countries. These future vaccines could significantly reduce diarrheal burden, prevent ETEC- and Shigella-induced stunting, and stunting-associated mortality. We developed a cost-effectiveness model for two putative standalone ETEC and Shigella vaccine candidates to evaluate vaccine impact on mortality, morbidity, stunting, and stunting-associated deaths from other infectious diseases. We modeled impact over the first ten years after vaccine introduction in children under five years old living in 79 low and low-middle income countries. ETEC and Shigella diarrhea would cause an estimated 239,300 [95% UL: 179,700-309,800] and 340,300 [256,500-440,800] child deaths, respectively, from years 2025 to 2034. Most of these deaths would occur in AFRO countries. ETEC and Shigella moderate-to-severe diarrheal episodes would result in over 13.7 [8.4-19.0] and 21.4 [13.1-29.8] million stunted children, respectively. Introducing ETEC or Shigella vaccine each with 60% efficacy could prevent 92,000 [61,000-129,000] ETEC and 126,600 [84,000-179,000] Shigella direct deaths and 21,400 [11,300-34,800] ETEC- and 34,200 [18,000-56,000] Shigella-induced stunting deaths. ETEC ICERs ranged from $2172/DALY [1457-4369] in AFRO to $19,172/DALY [12,665-39,503] in EURO. Shigella ICERs ranged from $952/DALY [632-2001] in EMRO to $640,316/DALY [434,311-1,297,192] in EURO. Limitations of this analysis include uncertainty of vaccine efficacy, duration of protection, and vaccine price. Inclusion of other infectious disease mortality due to stunting provides a more accurate assessment of total ETEC and Shigella disease burden and increased the projected impact and cost-effectiveness of vaccination. Introducing vaccines only in high burden countries and regions could substantially reduce cost without substantially reducing impact.

SUBMITTER: Anderson JD

PROVIDER: S-EPMC6668229 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Potential impact and cost-effectiveness of future ETEC and Shigella vaccines in 79 low- and lower middle-income countries.

Anderson John D JD Bagamian Karoun H KH Muhib Farzana F Baral Ranju R Laytner Lindsey A LA Amaya Mirna M Wierzba Thomas T Rheingans Richard R

Vaccine: X 20190418

While diarrhea mortality in children has declined over the last two decades, there has been a slower decline in diarrheal episodes. Repeated diarrheal episodes are associated with childhood stunting, which leads to increased mortality risk from infectious diseases. Vaccine candidates are under development for enterotoxigenic Escherichia coli [ETEC] and Shigella, important enteric pathogens in children in low income countries. These future vaccines could significantly reduce diarrhe ...[more]

PMID: 31384741

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Project description:BackgroundTuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies.Methods and findingsWe developed a system of epidemiological and economic models, calibrated to demographic, epidemiological, and health service data in 105 LMICs. For each country, we assessed the likely future course of TB-related outcomes under several vaccine introduction scenarios, compared to a "no-new-vaccine" counterfactual. Vaccine scenarios considered 2 vaccine product profiles (1 targeted at infants, 1 at adolescents/adults), both assumed to prevent progression to active TB. Key economic inputs were derived from the Global Health Cost Consortium, World Health Organization (WHO) patient cost surveys, and the published literature. We estimated the incremental impact of vaccine introduction for a range of health and economic outcomes. In the base-case, we assumed a vaccine price of $4.60 and used a 1× per-capita gross domestic product (GDP) cost-effectiveness threshold (both varied in sensitivity analyses). Vaccine introduction was estimated to require substantial near-term resources, offset by future cost-savings from averted TB burden. From a health system perspective, adolescent/adult vaccination was cost-effective in 64 of 105 LMICs. From a societal perspective (including productivity gains and averted patient costs), adolescent/adult vaccination was projected to be cost-effective in 73 of 105 LMICs and cost-saving in 58 of 105 LMICs, including 96% of countries with higher TB burden. When considering the monetized value of health gains, we estimated that introduction of an adolescent/adult vaccine could produce $283 to 474 billion in economic benefits by 2050. Limited data availability required assumptions and extrapolations that may omit important country-level heterogeneity in epidemiology and costs.ConclusionsTB vaccination would be highly impactful and cost-effective in most LMICs. Further efforts are needed for future development, adoption, and implementation of novel TB vaccines.

Project description:IntroductionA majority of low-income (LIC) and lower-middle-income countries (LMIC) were unable to achieve at least 10% population coverage during initial vaccine rollouts, despite the rapid development of the coronavirus disease 2019 (COVID-19) vaccines. Nearly three years into this pandemic, evaluating the impact of inequities in vaccine access, uptake, and availability is long overdue. We hypothesized that a delay in receiving COVID-19 vaccines was associated with an increased toll on cumulative cases and mortality. Furthermore, this relationship was modified by the size of a country's economy.MethodsWe performed an ecological study assessing these relationships, in which a country's economic standing was assessed by world bank income classification, gross domestic product based on the purchasing power parity (GDP PPP) per capita category, and crude GDP PPP.ResultsCountries with the smallest economies reported first vaccination much later than larger economies on all three rankings, as much as 100 days longer. Among low-income countries, a one-day increase until the first vaccination was associated with a 1.92% (95% CI: 0.100, 3.87) increase in cumulative cases when compared to high-income countries (p = 0.0395) when adjusting for population size, median age, and testing data availability. Similarly, among the lowest GDP PPP countries a one-day increase until the first vaccination was associated with a 2.73% (95% CI: 0.100, 5.44) increase in cumulative cases when compared to the highest GDP PPP countries (p = 0.0415). When modeling cumulative mortality, effects in the same direction and magnitude were observed, albeit statistically non-significant.ConclusionEconomic standing modified the effects of delayed access to COVID-19 vaccination on cumulative cases and mortality, in which LMICs tended to fare worse in outcomes than high-income countries despite the eventual rollout of vaccines. These findings highlight the importance of prioritizing equitable and timely access to COVID-19 vaccines across all countries, irrespective of economic size. Future studies should examine the impacts that vaccine inequities had on local transmission dynamics.

Project description:ImportanceMany randomized clinical trials (RCTs) led by high-income countries (HICs) now enroll patients from lower middle-income countries (LMICs) and upper middle-income countries (UMICs). Although enrolling diverse populations promotes research collaborations, there are issues regarding which countries participate in RCTs and how this participation may contribute to global research.ObjectiveTo describe which UMICs and LMICs participate in RCTs led by HICs.Design, setting, and participantsA cross-sectional study of all oncology RCTs published globally during January 1, 2014, to December 31, 2017, was conducted. The study cohort was restricted to RCTs led by HICs that enrolled participants from LMICs and UMICs. Study analyses were conducted in November 1, 2021, to May 31, 2022.Main outcomes and measuresA bibliometric approach (Web of Science 2007-2017) was used to explore whether RCT participation was proportional to other measures of cancer research activity. Participation in RCTs (ie, percentage of RCTs in the cohort in which each LMIC and UMIC participated) was compared with country-level cancer research bibliometric output (ie, percentage of total cancer research bibliometric output from the same group of countries that came from a specific LMIC and UMIC).ResultsAmong the 636 HIC-led RCTs, 186 trials (29%) enrolled patients in LMICs (n = 84 trials involving 11 LMICs) and/or UMICs (n = 181 trials involving 26 UMICs). The most common participating LMICs were India (42 [50%]), Ukraine (39 [46%]), Philippines (23 [27%]), and Egypt (12 [14%]). The most common participating UMICs were Russia (115 [64%]), Brazil (94 [52%]), Romania (62 [34%]), China (56 [31%]), Mexico (56 [31%]), and South Africa (54 [30%]). Several LMICs are overrepresented in the cohort of RCTs based on proportional cancer research bibliometric output: Ukraine (46% of RCTs but 2% of cancer research bibliometric output), Philippines (27% RCTs, 1% output), and Georgia (8% RCTs, 0.2% output). Overrepresented UMICs include Russia (64% RCTs, 2% output), Romania (34% RCTs, 2% output), Mexico (31% RCTs, 2% output), and South Africa (30% RCTs, 1% output).Conclusions and relevanceIn this cross-sectional study, a substantial proportion of RCTs led by HICs enrolled patients in LMICs and UMICs. The LMICs and UMICs that participated in these trials did not match overall cancer bibliometric output as a surrogate for research ecosystem maturity. Reasons for this apparent discordance and how these data may inform future capacity-strengthening activities require further study.

Project description:Diarrheal disease burden has become more heterogenous in low- and lower middle-income countries as access to clean water, sanitation and health care has increased in wealthier urban populations. Enterotoxigenic Escherichia coli (ETEC) and Shigella are among the top five causes of diarrheal mortality in children living in sub-Saharan Africa. Here, we explored how accounting for subnational and economic heterogeneity in ETEC and Shigella disease burden affects projected vaccine impact and cost-effectiveness of standalone ETEC and Shigella vaccines during the first decade after introduction in four sub-Saharan African countries. We developed dynamic models for provincial areas and socioeconomic subpopulations of children in the Democratic Republic of Congo (DRC), Kenya, Zambia, and Zimbabwe. We estimated deaths and morbidity due to ETEC and Shigella diarrhea plus additional deaths from other infectious diseases attributable to ETEC- and Shigella-induced stunting. We analyzed cost-effectiveness using Incremental Cost-Effectiveness Ratios (ICERs) with Disability-Adjusted Life Years (DALYs) and Moderate-and-Severe Diarrheal episodes (MSD) averted as denominators. Other infectious disease deaths due to induced stunting accounted for 9-28% and 9-32% of the total provincial level ETEC and Shigella disease burden, respectively, across these four countries from years 2025 to 2034. Our results indicated that the lowest and most cost-effective provincial DALYs averted ICERs were below $600 and $500/DALY averted for ETEC and Shigella vaccination, respectively in Zimbabwe. ICERs were the highest in Zambia and Kenya, where all provincial ICERs where above $2000/DALY. The highest national and provincial MSD averted ICERs were in DRC, while the lowest were in Kenya and Zimbabwe. Vaccinations were most cost-effective in averting DALYs in lower wealth subpopulations living in the highest burden provincial areas. Our approach focused on subnational heterogeneity in ETEC and Shigella burden and vaccination access found that impact and cost-effectiveness were more favorable if vaccinations reach the most vulnerable children in underserved provinces.

Project description:BackgroundDiabetes is one of the world's most prevalent and serious non-communicable diseases (NCDs). It is a leading cause of death, disability and financial loss; moreover, it is identified as a major threat to global development. The chronic nature of diabetes and its related complications make it a costly disease. Estimating the total cost of an illness is a useful aid to national and international health policy decision making. The aim of this systematic review is to summarise the impact of the cost-of-illness of type 2 diabetes mellitus in low and lower-middle income countries, and to identify methodological gaps in measuring the cost-of-illness of type 2 diabetes mellitus.MethodsThis systematic review considers studies that reported the cost-of-illness of type 2 diabetes in subjects aged 18 years and above in low and lower-middle income countries. The search engines MEDLINE, EMBASE, CINAHL, PSYCINFO and COCHRANE were used form date of their inception to September 2018. Two authors independently identified the eligible studies. Costs reported in the included studies were converted to US dollars in relation to the dates mentioned in the studies.ResultsThe systematic search identified eight eligible studies conducted in low and lower-middle income countries. There was a considerable variation in the costs and method used in these studies. The annual average cost (both direct and indirect) per person for treating type 2 diabetes mellitus ranged from USD29.91 to USD237.38, direct costs ranged from USD106.53 to USD293.79, and indirect costs ranged from USD1.92 to USD73.4 per person per year. Hospitalization cost was the major contributor of direct costs followed by drug costs.ConclusionType 2 diabetes mellitus imposes a considerable economic burden which most directly affects the patients in low and lower-middle income countries. There is enormous scope for adding research-based evidence that is methodologically sound to gain a more accurate estimation of cost and to facilitate comparison between studies.

Dataset Information

Potential impact and cost-effectiveness of future ETEC and Shigella vaccines in 79 low- and lower middle-income countries.

Publications

Potential impact and cost-effectiveness of future ETEC and <i>Shigella</i> vaccines in 79 low- and lower middle-income countries.

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