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 impact and cost-effectiveness of rotavirus vaccination in Afghanistan.

INTRODUCTION: Despite progress made in child survival in the past 20 years, 5.9 million children under five years died in 2015, with 9% of these deaths due to diarrhea. Rotavirus is responsible for more than a third of diarrhea deaths. In 2013, rotavirus was estimated to cause 215,000 deaths among children under five years, including 89,000 in Asia. As of April 2017, 92 countries worldwide have introduced rotavirus vaccination in their national immunization program. Afghanistan has applied for Gavi support to introduce rotavirus vaccination nationally. This study estimates the potential impact and cost-effectiveness of a national rotavirus immunization program in Afghanistan. METHODS: This study examined the use of Rotarix® (RV1) administered using a two-dose schedule at 6 and 10 weeks of age. We used the ProVac Initiative's UNIVAC model (version 1.2.09) to evaluate the impact and cost-effectiveness of a rotavirus vaccine program compared with no vaccine over ten birth cohorts from 2017 to 2026 with a 3% annual discount rate. All monetary units are adjusted to 2017 US$. RESULTS: Rotavirus vaccination in Afghanistan has the potential to avert more than one million cases; 660,000 outpatient visits; approximately 50,000 hospital admissions; 650,000 DALYs; and 12,000 deaths, over 10 years. Not accounting for any Gavi subsidy, rotavirus vaccination can avert DALYs at US$82/DALY from the government perspective and US$80/DALY from the societal perspective. With Gavi support, DALYs can be averted at US$29/DALY and US$31/DALY from the societal and government perspective, respectively. The average yearly cost of a rotavirus vaccination program would represent 2.8% of the total immunization budget expected in 2017 and 0.1% of total health expenditure. CONCLUSION: The introduction of rotavirus vaccination would be highly cost-effective in Afghanistan, and even more so with a Gavi subsidy

Impact and cost-effectiveness of rotavirus vaccination in Bangladesh.

INTRODUCTION: Diarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners. METHODS: This analysis used Pan American Health Organization's TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates. RESULTS: Over ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to$142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from$615/DALY to $1514/DALY averted. CONCLUSION: The discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination in Bangladesh

Cost-effectiveness of pharmaceutical strategies to prevent respiratory syncytial virus disease in young children: a decision-support model for use in low-income and middle-income countries

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in young children. A number of mathematical models have been used to assess the cost-effectiveness of RSV prevention strategies, but these have not been designed for ease of use by multidisciplinary teams working in low-income and middle-income countries (LMICs). METHODS: We describe the UNIVAC decision-support model (a proportionate outcomes static cohort model) and its approach to exploring the potential cost-effectiveness of two RSV prevention strategies: a single-dose maternal vaccine and a single-dose long-lasting monoclonal antibody (mAb) for infants. We identified model input parameters for 133 LMICs using evidence from the literature and selected national datasets. We calculated the potential cost-effectiveness of each RSV prevention strategy (compared to nothing and to each other) over the lifetimes of all children born in the year 2025 and compared our results to a separate model published by PATH. We ran sensitivity and scenario analyses to identify the inputs with the largest influence on the cost-effectiveness results. RESULTS: Our illustrative results assuming base case input assumptions for maternal vaccination ($3.50 per dose, 69$3.50 per dose, 77% efficacy, 5 months protection) showed that both interventions were cost-saving compared to status quo in around one-third of 133 LMICs, and had a cost per DALY averted below 0.5 times the national GDP per capita in the remaining LMICs. UNIVAC generated similar results to a separate model published by PATH. Cost-effectiveness results were most sensitive to changes in the price, efficacy and duration of protection of each strategy, and the rate (and cost) of RSV hospital admissions. CONCLUSIONS: Forthcoming RSV interventions (maternal vaccines and infant mAbs) are worth serious consideration in LMICs, but there is a good deal of uncertainty around several influential inputs, including intervention price, efficacy, and duration of protection. The UNIVAC decision-support model provides a framework for country teams to build consensus on data inputs, explore scenarios, and strengthen the local ownership and policy-relevance of results

Pneumococcal conjugate vaccination in The Gambia: health impact, cost effectiveness and budget implications.

INTRODUCTION: Introducing pneumococcal conjugate vaccine (PCV) in many low-income countries has contributed to reductions in global childhood deaths caused by Streptococcus pneumoniae. Many low-income countries, however, will soon reach an economic status leading to transition from Gavi, the Vaccine Alliance vaccine funding support and then face increased expenditure to continue PCV programmes. Evaluating the cost-effectiveness of PCV in low-income countries will inform such country decisions. METHODS: We used empiric data on the costs of vaccine delivery and pneumococcal disease and PCV programme impact on disease among children less than 5 years old in The Gambia. We used the UNIVAC cost-effectiveness modelling tool to compare the impact and cost-effectiveness of pneumococcal conjugate vaccination to no vaccination over 20 birth cohorts starting in 2011. We calculated costs per disability-adjusted-life-year (DALY) averted from government and societal perspectives and undertook scenario and probabilistic sensitivity analysis. RESULTS: We projected that, over 20 years, PCV in The Gambia could avert 117 000 total disease episodes in children less than 5 years old, including outpatient and hospitalised pneumonia, pneumococcal sepsis and meningitis (including sequelae). Vaccination could avert 9000 outpatient pneumonia visits, 88 000 hospitalisations and 3300 deaths due to pneumonia, meningitis and sepsis. Approximately 100 000 DALYs are expected to be averted. Averted visits and hospitalisations represent US$4 million in healthcare costs expected to be saved by the government and US$7.3 million if household costs are included. The cost of the vaccination programme is estimated at US$2 million. In the base scenario, most alternative scenarios and nearly 90% of the probabilistic scenarios, pneumococcal vaccination is cost saving in The Gambia. CONCLUSION: Pneumococcal conjugate vaccination is expected to generate substantial health gains and is likely to be cost saving in The Gambia. Policymakers in similar settings should be confident to maintain their PCV programmes

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

The impact of maternal RSV vaccine to protect infants in Gavi-supported countries: Estimates from two models.

BACKGROUND: Interventions to protect young infants against respiratory syncytial virus (RSV) are in advanced phases of development and are expected to be available in the foreseeable future. Gavi, the Vaccine Alliance, included maternal vaccines and infant monoclonal antibodies for RSV as part of the 2018 vaccine investment strategy (VIS) and decided to support these products subject to licensure, World Health Organization prequalification, Strategic Advisory Group of Experts recommendation, and meeting the financial assumptions used as the basis of the investment case. Impact estimates reported in this manuscript were used to inform the Gavi VIS. METHODS: We compared two independent vaccine impact models to evaluate a potential maternal RSV vaccine's impact on infant health in 73 Gavi-supported countries. Key inputs were harmonized across both models. We analyzed various scenarios to evaluate the effect of uncertain model parameters such as vaccine efficacy, duration of infant protection, and infant disease burden. Estimates of averted cases, severe cases, hospitalizations, deaths, and disability-adjusted life years (DALYs) were calculated over the 2023-2035 horizon. FINDINGS: A maternal RSV vaccine with 60% efficacy offering 5 months of infant protection implemented across 73 low- and middle-income countries could avert 10.1-12.5 million cases, 2.8-4.0 million hospitalizations, 123.7-177.7 thousand deaths, and 8.5-11.9 million DALYs among infants under 6 months of age for the duration of analysis (2023-2035). Maternal RSV vaccination was projected to avert up to 42% of estimated RSV deaths among infants under 6 months in year 2035. Alternative scenario analyses with higher disease burden assumptions showed that a maternal vaccine could avert as many as 325-355 thousand deaths among infants under 6 months. INTERPRETATION: RSV maternal immunization is projected to substantially reduce mortality and morbidity among young infants if introduced across Gavi-supported countries. FUNDING: This work was supported by Bill & Melinda Gates Foundation, Seattle, WA, and Respiratory Syncytial Virus Consortium in Europe. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation or of the Respiratory Syncytial Virus Consortium. LW is supported by Research Foundation-Flanders (1234620 N)

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