Cost of illness for childhood diarrhea in low- and middle-income countries: a systematic review of evidence and modelled estimates.

BACKGROUND: Numerous studies have reported the economic burden of childhood diarrhea in low- and middle-income countries (LMICs). Yet, empirical data on the cost of diarrheal illness is sparse, particularly in LMICs. In this study we review the existing literature on the cost of childhood diarrhea in LMICs and generate comparable estimates of cost of diarrhea across 137 LMICs. METHODS: The systematic literature review included all articles reporting cost estimates of diarrhea illness and treatment from LMICs published between January 2006 and July 2018. To generate country-specific costs, we used service delivery unit costs from the World Health Organization's Choosing Interventions that are Cost-Effective (WHO-CHOICE database). Non-medical costs were calculated using the ratio between direct medical and direct non-medical costs, derived from the literature review. Indirect costs (lost wages to caregivers) were calculated by multiplying the average GDP per capita per day by the average number of days lost to illness identified from the literature. All cost estimates are reported in 2015 USD. We also generated estimates using the IHME's service delivery unit costs to explore input sensitivity on modelled cost estimates. RESULTS: We identified 25 articles with 64 data points on either direct or indirect cost of diarrhoeal illness in children aged < 5 years in 20 LMICs. Of the 64 data points, 17 were on the cost of outpatient care, 28 were on the cost of inpatient care, and 19 were unspecified. The average cost of illness was US$36.56 (median$15.73; range $4.30 -$145.47) per outpatient episode and $159.90 (median$85.85; range $41.01 -$538.33) per inpatient episode. Direct medical costs accounted for 79% (83% for inpatient and 74% for outpatient) of the total direct costs. Our modelled estimates, across all 137 countries, averaged (weighted) $52.16 (median$47.56; range $8.81 -$201.91) per outpatient episode and $216.36 (median$177.20; range $23.77 -$1225.36) per inpatient episode. In the 12 countries with primary data, there was reasonable agreement between our modelled estimates and the reported data (Pearson's correlation coefficient = .75). CONCLUSION: Our modelled estimates generally correspond to estimates observed in the literature, with a few exceptions. These estimates can serve as useful inputs for planning and prioritizing appropriate health interventions for childhood diarrheal diseases in LMICs in the absence of empirical data

Potential health impact and cost-effectiveness of bivalent human papillomavirus (HPV) vaccination in Afghanistan.

INTRODUCTION: Human papillomavirus (HPV) vaccination has not been introduced in many countries in South-Central Asia, including Afghanistan, despite the sub-region having the highest incidence rate of cervical cancer in Asia. This study estimates the potential health impact and cost-effectiveness of HPV vaccination in Afghanistan to inform national decision-making. METHOD: An Excel-based static cohort model was used to estimate the lifetime costs and health outcomes of vaccinating a single cohort of 9-year-old girls in the year 2018 with the bivalent HPV vaccine, compared to no vaccination. We also explored a scenario with a catch-up campaign for girls aged 10-14 years. Input parameters were based on local sources, published literature, or assumptions when no data was available. The primary outcome measure was the discounted cost per disability-adjusted life-year (DALY) averted, evaluated from both government and societal perspectives. RESULTS: Vaccinating a single cohort of 9-year-old girls against HPV in Afghanistan could avert 1718 cervical cancer cases, 125 hospitalizations, and 1612 deaths over the lifetime of the cohort. The incremental cost-effectiveness ratio was US$426 per DALY averted from the government perspective and US$400 per DALY averted from the societal perspective. The estimated annual cost of the HPV vaccination program (US$3,343,311) represents approximately 3.53$586) from both the government and societal perspective with additional health benefits generated by a catch-up campaign, depending on the government's willingness to pay for the projected health outcomes

Introduction of rotavirus vaccination in Palestine: An evaluation of the costs, impact, and cost-effectiveness of ROTARIX and ROTAVAC.

INTRODUCTION: The Palestinian Ministry of Health (MOH) started a routine rotavirus immunization program with ROTARIX in May 2016, with support for vaccine procurement and introduction provided through a global development organization. In 2018, financial responsibility for rotavirus vaccine procurement was transferred to the Palestinian government, which elected to shift to ROTAVAC vaccine because of its lower price per dose. This study aims to assess the cost, impact, and cost-effectiveness of rotavirus vaccination, specifically evaluating the economic implications of the change in vaccine product, accounting for the different characteristics of each rotavirus vaccine used. METHODS: We conducted primary and secondary data collection to assess the introduction, procurement, supply chain, and service delivery costs related to each vaccine. We used the UNIVAC model to project costs and benefits of rotavirus vaccination over a 10-year period comparing the use of ROTARIX versus no vaccination; ROTAVAC versus no vaccination; and ROTAVAC versus ROTARIX. We undertook scenario and probabilistic analyses to capture uncertainty in some of the study parameters. We used a 3% discount rate, and all costs are in 2018 US$. RESULTS: The cost to deliver one dose was lower for ROTAVAC than ROTARIX (US$2.36 versus $2.70), but the total cost per course, excluding vaccine cost, favored ROTARIX ($7.09 versus $5.39). Both vaccines had high probability of being cost-effective interventions in Palestine compared to no vaccine. Because of lower vaccination program costs for ROTAVAC, however, switching from ROTARIX to ROTAVAC was cost-saving. CONCLUSION: National decision-makers should consider systematically assessing multiple criteria beyond vaccine price when comparing the health and economic value of several products in order to fully account for all characteristics including product presentation, number of doses per course, cold chain volume, cost of delivery, and wastage

Evaluating the potential economic and health impact of rotavirus vaccination in 63 middle-income countries not eligible for Gavi funding: a modelling study.

BACKGROUND: Middle-income countries (MICs) that are not eligible for funding from Gavi, the Vaccine Alliance, have been slow to adopt rotavirus vaccines. Few studies have evaluated the cost-effectiveness and benefit-risk of rotavirus vaccination in these settings. We aimed to assess the potential economic and health impact of rotavirus vaccination in 63 MICs not eligible for funding from Gavi. METHODS: In this modelling study, we estimated the cost-effectiveness and benefit-risk of rotavirus vaccination in 63 MICs not eligible to Gavi funding. We used an Excel-based proportionate outcomes model with a finely disaggregated age structure to estimate the number of rotavirus gastroenteritis cases, clinic visits, hospitalisations, and deaths averted by vaccination in children younger than 5 years over a 10-year period. We calculated cost-effectiveness ratios (costs per disability-adjusted life-years averted compared with no vaccination) and benefit-risk ratios (number of hospitalisations due to rotavirus gastroenteritis averted per excess hospitalisations due to intussusception). We evaluated three alternative vaccines available globally (Rotarix, Rotavac, and Rotasiil) and used information from vaccine manufacturers regarding anticipated vaccine prices. We ran deterministic and probabilistic uncertainty analyses. FINDINGS: Over the period 2020-29, rotavirus vaccines could avert 77 million (95% uncertainty interval [UI] 51-103) cases of rotavirus gastroenteritis and 21 million (12-36) clinic visits, 3 million (1·4-5·6) hospitalisations, and 37 900 (25 900-55 900) deaths due to rotavirus gastroenteritis in 63 MICs not eligible for Gavi support. From a government perspective, rotavirus vaccination would be cost-effective in 48 (77%) of 62 MICs considered. The benefit-risk ratio for hospitalisations prevented versus those potentially caused by vaccination exceeded 250:1 in all countries. INTERPRETATION: In most MICs not eligible for Gavi funding, rotavirus vaccination has high probability to be cost-effective with a favourable benefit-risk profile. Policy makers should consider this new evidence when making or revisiting decisions on the use of rotavirus vaccines in their respective countries. FUNDING: Bill & Melinda Gates Foundation

Impact and cost-effectiveness of rotavirus vaccination in Niger: a modelling study evaluating alternative rotavirus vaccines.

OBJECTIVES: To evaluate the cost-effectiveness of alternative rotavirus vaccines in Niger, using UNIVAC, a proportionate outcomes model. SETTING: The study leverages global, regional and local data to inform cost-effectiveness modelling. Local data were collected as part of a clinical trial taking place in the Madarounfa district, Maradi region, Niger. PARTICIPANTS: The study models impact of infants vaccination on rotavirus gastroenteritis in children under 5 years of age. INTERVENTIONS: We compared the use of ROTARIX (GlaxoSmithKline, Belgium), ROTAVAC (Bharat Biotech, India) and ROTASIIL (Serum Institute, India) to no vaccination and to each other over a 10-year period starting in 2021. RESULTS: We estimated that ROTARIX, ROTAVAC and ROTASIIL would each prevent 13 million cases and 20 000 deaths of children under 5 years over a 10-year period in Niger. Compared with no vaccination, the cost to avert a disability-adjusted life-year was US$146 with ROTARIX, US$107 with ROTASIIL and US$76 with ROTAVAC from the government perspective. ROTAVAC dominated ROTARIX and ROTASIIL (eg, provided similar or higher benefits at a lower cost) and had 90$100 willingness-to-pay threshold. CONCLUSIONS: This study can inform decision-making around rotavirus vaccination policy in Niger, demonstrating that ROTAVAC is likely the most cost-effective option. Alternative products (ROTASIIL and ROTARIX) may also be considered by decision-makers if they are priced more competitively, or if their cold chain requirements could bring additional economic benefits

Re-evaluating the potential impact and cost-effectiveness of rotavirus vaccination in 73 Gavi countries: a modelling study.

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

Direct and indirect costs of acute diarrhea in children under five years of age in Indonesia: Health facilities and community survey

Background: Diarrhea remains a major cause of child morbidity and mortality in low- and middle-income countries. Reliable data on the economic burden of diarrhea is required to support the selection of appropriate health intervention programs. This study aimed to estimate the costs of acute diarrhea in children under five years of age in Indonesia, a large middle-income country with a substantial diarrheal burden. Methods: Direct medical cost data were extracted retrospectively for 1050 children under five years of age with acute diarrhea receiving inpatient care across 45 health facilities in seven Indonesian provinces during 2017–2020. Direct medical costs for children treated in outpatient settings were estimated by collecting unit costs associated with standard diarrhea case management in children. A structured interview of 240 caregivers of inpatients was also conducted retrospectively to estimate direct non-medical costs as well as indirect costs from caregiver income loss. Results: The weighted average direct medical cost for treatment of acute diarrhea as an inpatient and outpatient across health facility types was US$99.8 (SD±$56.8)(35% room costs, 29% professional fees, 26% medication costs, 10% diagnostic costs) and US$7.6 (SD±$4.3) (34% diagnostic costs, 28% medication costs, 27% professional fees, 10% registration fees), respectively. The average direct non-medical household cost for an acute diarrheal admission was US$4.90 and the indirect cost was US$9.90. Conclusion: There is a significant economic burden associated with acute diarrhea in children in Indonesia. This study, based on a wide variety of health care settings and geographical regions, provides data to inform the economic evaluation of rotavirus vaccines and other diarrheal prevention programs. Funding: This work was supported by a research grant from the Murdoch Children's Research Institute (MCRI) and PATH; and the Indonesian Technical Advisory Group on Immunization (ITAGI)

Projected impact, cost-effectiveness, and budget implications of rotavirus vaccination in Mongolia.

INTRODUCTION: Rotavirus disease in Mongolia is estimated to cause more than 50 deaths yearly and many more cases and hospitalizations. Mongolia must self-finance new vaccines and does not automatically access Gavi prices for vaccines. Given the country's limited resources for health, it is critical to assess potential new vaccine programs. This evaluation estimates the impact, cost-effectiveness, and budget implications associated with a nationwide rotavirus vaccine introduction targeting infants as part of the national immunization program in Mongolia, in order to inform decision-making around introduction. METHODS: The analysis examines the use of the two-dose vaccine ROTARIX®, and three-dose vaccines ROTAVAC® and RotaTeq® compared to no vaccination from the government and the societal perspective. We use a modelling approach informed by local data and published literature to analyze the impact and cost-effectiveness of rotavirus vaccination over a ten-year time period starting in 2019, using a 3% discount rate. Our main outcome measure is the incremental cost-effectiveness ratio (ICER) expressed as US dollar per DALY averted. We assessed uncertainty around a series of parameters through univariate sensitivity analysis. RESULTS: Rotavirus vaccination in Mongolia could avert more than 95,000 rotavirus cases and 271 deaths, over 10?years. Averted visits and hospitalizations represent US$2.4?million in health care costs saved by the government. The vaccination program cost ranges from$6 to $11?million depending on vaccine choice. From the governmental perspective, ICER ranged from$412 to $1050 and from$77 to $715 when considering the societal perspective. Sensitivity analysis highlights vaccine price as the main driver of uncertainty. CONCLUSION: Introduction of rotavirus vaccination is likely to be highly cost-effective in Mongolia, with ICERs estimated at only a fraction of Mongolia's per capita GDP. From an economic standpoint, ROTAVAC® is the least costly and most cost-effective product choice

Estimating the economic burden of typhoid in children and adults in Blantyre, Malawi: A costing cohort study.

BackgroundTyphoid causes preventable death and disease. The World Health Organization recommends Typhoid Conjugate Vaccine for endemic countries, but introduction decisions depend on cost-effectiveness. We estimated household and healthcare economic burdens of typhoid in Blantyre, Malawi.MethodsIn a prospective cohort of culture-confirmed typhoid cases at two primary- and a referral-level health facility, we collected direct medical, non-medical costs (2020 U.S. dollars) to healthcare provider, plus indirect costs to households.ResultsFrom July 2019-March 2020, of 109 cases, 63 (58%) were 40% of non-food monthly household expenditure, occurred in 48 (44%) households.ConclusionsTyphoid can be economically catastrophic for families, despite accessible free medical care. Typhoid is costly for government healthcare provision. These data make an economic case for TCV introduction in Malawi and the region and will be used to derive vaccine cost-effectiveness

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study.

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5?years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1?×?gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective