Human papillomavirus (HPV) vaccination program in Sri Lanka: Ongoing costs and operational context of a routinized program.

Existing evidence on the cost of human papillomavirus (HPV) vaccination programs has focused on pilot and demonstration projects or initial introductions, which resulted in a perceived high cost. We aimed to study the ongoing cost and operational context of an established HPV vaccination program in Sri Lanka. We conducted a retrospective operational research and microcosting study focusing on 2019. We collected data from 30 divisional health units, 10 districts, and the central level. We then evaluated financial and economic costs, reported by level of the health system, program activity, cost types, and per dose delivered. In 2019, Sri Lanka delivered a total of 314,815 doses of HPV vaccine. In our study sample, 95 % of the HPV vaccination sessions took place at schools, with peaks of delivery in February-March and September-October. The weighted mean financial cost per dose delivered was $0.27 (95 % confidence interval [CI]: $0.15-$0.39) and the economic cost per dose was $3.88 (95 % CI: $2.67-$5.10), excluding the cost of vaccines and supplies. Most of the cost was borne by the divisional health unit level. Service delivery and social mobilization were major contributors to overall costs at the divisional health unit level, and vaccine collection or distribution and storage were the most costly activities at the district and central levels. Cost drivers included the opportunity cost of health worker and non-health worker time at the divisional health unit level and capital costs for vehicles and equipment, along with fuel, maintenance, and energy, at the district and central levels. This study provides new evidence on the cost and cost drivers of a routinized HPV vaccination program. Results can be used for financial planning purposes in Sri Lanka and may inform other countries as they consider use of HPV vaccines.

Typhoid fever.

Typhoid fever is an invasive bacterial disease associated with bloodstream infection that causes a high burden of disease in Africa and Asia. Typhoid primarily affects individuals ranging from infants through to young adults. The causative organism, Salmonella enterica subsp. enterica serovar Typhi is transmitted via the faecal-oral route, crossing the intestinal epithelium and disseminating to systemic and intracellular sites, causing an undifferentiated febrile illness. Blood culture remains the practical reference standard for diagnosis of typhoid fever, where culture testing is available, but novel diagnostic modalities are an important priority under investigation. Since 2017, remarkable progress has been made in defining the global burden of both typhoid fever and antimicrobial resistance; in understanding disease pathogenesis and immunological protection through the use of controlled human infection; and in advancing effective vaccination programmes through strategic multipartner collaboration and targeted clinical trials in multiple high-incidence priority settings. This Primer thus offers a timely update of progress and perspective on future priorities for the global scientific community.

Cost and operational context for national human papillomavirus (HPV) vaccine delivery in six low- and middle-income countries.

INTRODUCTION: There are concerns from immunization program planners about high delivery costs for human papillomavirus (HPV) vaccine. Most prior research evaluated costs of HPV vaccine delivery during demonstration projects or at introduction, showing relatively high costs, which may not reflect the costs beyond the pilot or introduction years. This study sought to understand the operational context and estimate delivery costs for HPV vaccine in six national programs, beyond their introduction years. METHODS: Operational research and microcosting methods were used to retrospectively collect primary data on HPV vaccination program activities in Ethiopia, Guyana, Rwanda, Senegal, Sri Lanka, and Uganda. Data were collected from the national level and a sample of subnational administrative offices and health facilities. Operational data collected were tabulated as percentages and frequencies. Financial costs (monetary outlays) and economic costs (financial plus opportunity costs) were estimated, as was the cost per HPV vaccine dose delivered. Costing was done from the health system perspective and reported in 2019 United States dollars (US$). RESULTS: Across the study countries, between 53 % and 99 % of HPV vaccination sessions were conducted in schools. Differences were observed in intensity and frequency with which program activities were conducted and resources used. Mean annual economic costs at health facilities in each country ranged from $1,207 to $3,190, while at the national level these ranged from $7,657 to $304,278. Mean annual HPV vaccine doses delivered per health facility in each country ranged from 162 to 761. Mean financial costs per dose per study country ranged from $0.27 to $3.32, while the economic cost per dose ranged from $3.09 to $17.20. CONCLUSION: HPV vaccine delivery costs were lower than at introduction in some study countries. There were differences in the activities carried out for HPV vaccine delivery and the number of doses delivered, impacting the cost estimates.

Estimating the global impact of rotavirus vaccines on child mortality.

OBJECTIVES: We estimated the global impact of rotavirus vaccines on deaths among children under five years old by year. METHODS: We used a proportionate outcomes model with a finely disaggregated age structure to estimate rotavirus deaths prevented by vaccination over the period 2006-2019 in 186 countries. We ran deterministic and probabilistic uncertainty analyses and compared our estimates to surveillance-based estimates in 20 countries. RESULTS: We estimate that rotavirus vaccines prevented 139,000 under-five rotavirus deaths (95% uncertainty interval 98,000-201,000) in the period 2006-2019. In 2019 alone, rotavirus vaccines prevented 15% (95% uncertainty interval 11-21%) of under-five rotavirus deaths (0.5% of child mortality). Assuming global use of rotavirus vaccines and coverage equivalent to other co-administered vaccines could prevent 37% of under-five rotavirus deaths (1.2% of child mortality). Our estimates were sensitive to the choice of rotavirus mortality burden data and several vaccine impact modeling assumptions. The World Health Organization's recommendation to remove age restrictions in 2012 could have prevented up to 17,000 rotavirus deaths in the period 2013-2019. Our modeled estimates of rotavirus vaccine impact were broadly consistent with estimates from post-vaccination surveillance sites. CONCLUSION: Rotavirus vaccines have made a valuable contribution to global public health. Enhanced rotavirus mortality prevention strategies are needed in countries with high mortality in under-5-year-old children.

Rotavirus vaccine product switch in Ghana: An assessment of service delivery costs, switching costs, and cost-effectiveness.

Ghana introduced rotavirus vaccine (ROTARIX 1-dose presentation) into the routine national immunization program in 2012 and switched to a different product (ROTAVAC 5-dose presentation) in 2020. ROTAVAC has a lower price per dose (US$0.85 versus US$2.15 for ROTARIX) and smaller cold chain footprint but requires more doses per regimen (three versus two). This study estimates the supply chain and service delivery costs associated with each product, the costs involved in switching products, and compares the cost-effectiveness of both products over the next ten years. We estimated the supply chain and service delivery costs associated with ROTARIX and ROTAVAC (evaluating both the 5-dose and 10-dose presentations) using primary data collected from health facilities in six of the 14 regions in the country. We estimated the costs of switching from ROTARIX to ROTAVAC using information collected from key informant interviews and financial records provided by the government. All costs were reported in 2020 US$. We used the UNIVAC decision-support model to evaluate the cost-effectiveness (US$ per disability-adjusted life-year (DALY) averted from government and societal perspectives) of ROTARIX and ROTAVAC (5-dose or 10-dose presentations) compared to no vaccination, and to each other, over a ten-year period (2020 to 2029). We ran probabilistic sensitivity analyses and other threshold analyses. The supply chain and service delivery economic cost per dose was $2.40 for ROTARIX, $1.81 for ROTAVAC 5-dose, and $1.76 for ROTAVAC 10-dose. The financial and economic cost of switching from ROTARIX to ROTAVAC 5-dose was $453,070 and $883,626, respectively. Compared to no vaccination, the cost per DALY averted was $360 for ROTARIX, $298 for ROTAVAC 5-dose, and $273 for ROTAVAC 10-dose. ROTAVAC 10-dose was the most cost-effective option and would be cost-effective at willingness-to-pay thresholds exceeding 0.12 times the national GDP per capita ($2,206 in the year 2020). The switch from ROTARIX to ROTAVAC 5-dose in 2020 was cost-saving. Rotavirus vaccination is highly cost-effective in Ghana. A switch from ROTAVAC 5-dose to ROTAVAC 10-dose would be cost-saving and should be considered.

Impact and Cost-Effectiveness of Alternative Human Papillomavirus Vaccines for Preadolescent Girls in Mozambique: A Modelling Study.

Mozambique has one of the highest rates of cervical cancer in the world. Human papillomavirus (HPV) vaccination was introduced in 2021. This study evaluated the health and economic impact of the current HPV vaccine (GARDASIL® hereafter referred to as GARDASIL-4) and two other vaccines (CECOLIN® and CERVARIX®) that could be used in the future. A static cohort model was used to estimate the costs and benefits of vaccinating girls in Mozambique over the period 2022-2031. The primary outcome measure was the incremental cost per disability-adjusted life-year averted from a government perspective. We conducted deterministic and probabilistic sensitivity analyses. Without cross-protection, all three vaccines averted approximately 54% cervical cancer cases and deaths. With cross-protection, CERVARIX averted 70% of cases and deaths. Without Gavi support, the discounted vaccine program costs ranged from 60 million to 81 million USD. Vaccine program costs were approximately 37 million USD for all vaccines with Gavi support. Without cross-protection, CECOLIN was dominant, being cost-effective with or without Gavi support. With cross-protection and Gavi support, CERVARIX was dominant and cost-saving. With cross-protection and no Gavi support, CECOLIN had the most favorable cost-effectiveness ratio. Conclusions: At a willingness-to-pay (WTP) threshold set at 35% of Gross Domestic Product (GDP) per capita, HPV vaccination is cost-effective in Mozambique. The optimal vaccine choice depends on cross-protection assumptions.

Cost-effectiveness analysis of typhoid conjugate vaccines in an outbreak setting: a modeling study.

BACKGROUND: Several prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant Salmonella Typhi. The World Health Organization recommends the use of typhoid conjugate vaccines (TCVs) in outbreak settings; however, current data are limited on how and when TCVs might be introduced in response to outbreaks. METHODOLOGY: We developed a stochastic model of typhoid transmission fitted to data from Queen Elizabeth Central Hospital in Blantyre, Malawi from January 1996 to February 2015. We used the model to evaluate the cost-effectiveness of vaccination strategies over a 10-year time horizon in three scenarios: (1) when an outbreak is likely to occur; (2) when an outbreak is unlikely to occur within the next ten years; and (3) when an outbreak has already occurred and is unlikely to occur again. We considered three vaccination strategies compared to the status quo of no vaccination: (a) preventative routine vaccination at 9 months of age; (b) preventative routine vaccination plus a catch-up campaign to 15 years of age; and (c) reactive vaccination with a catch-up campaign to age 15 (for Scenario 1). We also explored variations in outbreak definitions, delays in implementation of reactive vaccination, and the timing of preventive vaccination relative to the outbreak. RESULTS: Assuming an outbreak occurs within 10 years, we estimated that the various vaccination strategies would prevent a median of 15-60% of disability-adjusted life-years (DALYs). Reactive vaccination was the preferred strategy for WTP values of $0-300 per DALY averted. For WTP values > $300, introduction of preventative routine TCV immunization with a catch-up campaign was the preferred strategy. Routine vaccination with a catch-up campaign was cost-effective for WTP values above $890 per DALY averted if no outbreak occurs and > $140 per DALY averted if implemented after the outbreak has already occurred. CONCLUSIONS: Countries for which the spread of antimicrobial resistance is likely to lead to outbreaks of typhoid fever should consider TCV introduction. Reactive vaccination can be a cost-effective strategy, but only if delays in vaccine deployment are minimal; otherwise, introduction of preventive routine immunization with a catch-up campaign is the preferred strategy.

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

BACKGROUND: Typhoid 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. METHODS: In 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. RESULTS: From July 2019-March 2020, of 109 cases, 63 (58%) were <15 years old, 44 (40%) were inpatients. Mean hospitalization length was 7.7 days (SD 4.1). For inpatients, mean total household and provider costs were $93.85 (95%CI: 68.87-118.84) and $296.52 (95%CI: 225.79-367.25), respectively. For outpatients, these costs were $19.05 (95%CI: 4.38-33.71) and $39.65 (95%CI: 33.93-45.39), respectively. Household costs were due mainly to direct non-medical and indirect costs, medical care was free. Catastrophic illness cost, defined as cost >40% of non-food monthly household expenditure, occurred in 48 (44%) households. CONCLUSIONS: Typhoid 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.

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% chance to be cost-effective at a US$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.

Cost-effectiveness of rotavirus vaccination in Mozambique.

INTRODUCTION: Rotavirus is one of the most common cause of severe gastroenteritis in children, with the largest mortality burden in low- and middle-income countries. To prevent rotavirus gastroenteritis, Mozambique introduced ROTARIX® vaccine in 2015, however, its cost-effectiveness has never been established in the country. In 2018, additional vaccines became available globally. This study estimates the cost-effectiveness of the recently introduced ROTARIX in Mozambique and compares the cost-effectiveness of ROTARIX®, ROTAVAC®, and ROTASIIL® to inform future use. METHODS: We used a decision-support model to calculate the potential cost-effectiveness of vaccination with ROTARIX compared to no vaccination over a five-year period (2016-2020) and to compare the cost-effectiveness of ROTARIX, ROTAVAC, and ROTASIIL to no vaccination and to each other over a ten-year period (2021-2030). The primary outcome was the incremental cost per disability-adjusted life-year (DALY) averted from a government perspective. We assessed uncertainty through sensitivity analyses. RESULTS: From 2016 to 2020, we estimate the vaccine program with ROTARIX cost US$12.3 million, prevented 4,628 deaths, and averted US$3.1 million in healthcare costs. The cost per DALY averted was US$70. From 2021 to 2030, we estimate all three vaccines could prevent 9,000 deaths and avert US$7.8 million in healthcare costs. With Global Alliance for Vaccines and Immunization (Gavi) support, ROTARIX would have the lowest vaccine program cost (US$31 million) and 98 % probability of being cost-effective at a willingness-to-pay threshold of 0.5x GDP per capita. Without Gavi support, ROTASIIL would have the lowest vaccine program cost (US$75.8 million) and 30 % probability of being cost-effective at the same threshold. CONCLUSION: ROTARIX vaccination had a substantial public health impact in Mozambique between 2016 and 2020. ROTARIX is currently estimated to be the most cost-effective product, but the choice of vaccine should be re-evaluated as more evidence emerges on the price, incremental delivery cost, wastage, and impact associated with each of the different rotavirus vaccines.

Potential impact and cost-effectiveness of injectable next-generation rotavirus vaccines in 137 LMICs: a modelling study.

While current live, oral rotavirus vaccines (LORVs) are reducing severe diarrhea everywhere, their effectiveness is lower in high burden settings. Alternative approaches are in advanced stages of clinical development, including injectable next-generation rotavirus vaccine (iNGRV) candidates, which have the potential to better protect children, be combined with existing routine immunizations and be more affordable than current LORVs. In an effort to better understand the real public health value of iNGRVs and to help inform decisions by international agencies, funders, and vaccine manufacturers, we conducted an impact and cost-effectiveness analysis examining 20 rotavirus vaccine use cases. We evaluated several currently licensed LORVs, one neonatal oral NGRV (oNGRV), one iNGRV, and one iNGRV-DTP (iNGRV comprising part of a DTP-containing combination) over a ten-year timeframe in 137 low- and middle-income countries. The most promising use case identified was a high efficacy iNGRV-DTP, predicted to have the lowest vaccine program cost (US$1.4 billion), the highest vaccine benefit (750,000 rotavirus deaths averted, 13 million rotavirus hospital admissions averted, US$ 2.7 billion health-care cost averted), and most favorable cost-effectiveness (cost-saving). iNGRV-DTP vaccine remained the most affordable, safe, and cost-effective option even when it was assumed to have equivalent efficacy to the current LORVs. This study shows that while the development of iNGRVs with superior efficacy to currently licensed LORVs would be ideal, iNGRVs with similar efficacy to LORVs would offer substantial public health value. It also highlights the economic value of accelerating the development of DTP-based combination vaccines that include iNGRV to provide rotavirus protection.

Does Anybody Want an Injectable Rotavirus Vaccine, and Why? Understanding the Public Health Value Proposition of Next-Generation Rotavirus Vaccines.

Routine infant immunization with live, oral rotavirus vaccines (LORVs) has had a major impact on severe gastroenteritis disease. Nevertheless, in high morbidity and mortality settings rotavirus remains an important cause of disease, partly attributable to the sub-optimal clinical efficacy of LORVs in those settings. Regardless of the precise immunological mechanism(s) underlying the diminished efficacy, the introduction of injectable next-generation rotavirus vaccines (iNGRV), currently in clinical development, could offer a potent remedy. In addition to the potential for greater clinical efficacy, precisely how iNGRVs are delivered (multiple doses to young infants; alongside LORVs or as a booster; co-formulated with Diphtheria-Tetanus-Pertussis (DTP)-containing vaccines), their pricing, and their storage and cold chain characteristics could each have major implications on the resultant health outcomes, on cost-effectiveness as well as on product preferences by national stakeholders and healthcare providers. To better understand these implications, we critically assessed whether there is a compelling public health value proposition for iNGRVs based on potential (but still hypothetical) vaccine profiles. Our results suggest that the answer is highly dependent on the specific use cases and potential attributes of such novel vaccines. Notably, co-formulation of iNGRVs with similar or greater efficacy than LORVs with a DTP-containing vaccine, such as DTP-Hib-HepB, scored especially high on potential impact, cost-effectiveness, and strength of preference by national stakeholders and health care providers in lower and middle income countries.

Projecting the cost of introducing typhoid conjugate vaccine (TCV) in the national immunization program in Malawi using a standardized costing framework.

BACKGROUND: There is a substantial typhoid burden in sub-Saharan Africa, and TCV has been introduced in two African countries to date. Decision-makers in Malawi decided to introduce TCV and applied for financial support from Gavi, the Vaccine Alliance in 2020. The current plan is to introduce TCV as part of the national immunization program in late 2022. The introduction will include a nationwide campaign targeting all children aged 9 months to 15 years. Following the campaign, TCV will be provided through routine immunization at 9 months. This study aims to estimate the cost of TCV introduction and recurrent delivery as part of the national immunization program. METHODS: This costing analysis is conducted from the government's perspective and focuses on projecting the incremental cost of TCV introduction and delivery for Malawi's existing immunization program before vaccine introduction. The study uses a costing tool developed by Levin & Morgan through a partnership between the International Vaccine Institute and the World Health Organization and leverages primary and secondary data collected through key informant interviews with representatives of the Malawi Expanded Programme on Immunization team at various levels. RESULTS: The total financial and economic costs of TCV introduction over three years in Malawi are projected to be US$8.5 million and US$29.8 million, respectively. More than two-thirds of the total cost is made up of recurrent costs. Major cost drivers include the procurement of vaccines and injection supplies and service delivery costs. Without vaccine cost, we estimate the cost per child immunized to be substantially lower than US$1. DISCUSSION: Findings from this analysis may be used to assess the economic implications of introducing TCV in Malawi. Major cost drivers highlighted by the analysis may also inform decision-makers in the region as they assess the value and feasibility of TCV introduction in their national immunization program.

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).

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.

Economic evaluation of rotavirus vaccination in children of Bhutan.

BACKGROUND: Diarrhoea remains one of the top ten causes of under-five child morbidity in Bhutan, and rotavirus is a significant cause of child diarrhoeal hospitalisations. This study sought to determine the health outcomes, cost-effectiveness, and budget and human resource implications of introducing rotavirus vaccines in the routine immunisation program to inform Bhutan's decision-making process. METHODS: We used UNIVAC model (version 1.3.41) to evaluate the cost-effectiveness of a rotavirus vaccination programme compared with no vaccination from a government perspective. We also projected the impact of rotavirus vaccination on human resources and budget. Acost-effectiveness threshold was determined to be 0.5 times the gross domestic product (GDP) per capita (equivalent to the United States dollar ($) 1,537) per Disability-Adjusted Life-Year (DALY) averted.One-way deterministic and probabilistic sensitivity analyses, and threshold analyses were performed to capture parameter uncertainties. RESULTS: In Bhutan, a rotavirus vaccination programme over 10 years (2020 to 2029) can avert between 104 and 115 DALYs, at an incremental cost ranging from $322,000 to $1,332,000. The incremental cost-effectiveness ratio (ICER) across four vaccination programmes compared to no vaccination scenario were $9,267, $11,606, $3,201, and $2,803 per DALY averted for ROTARIX, RotaTeq, ROTAVAC, and ROTASIIL, respectively. The net five-year budget impact of introducing a rotavirus vaccination programme ranged from $0.20 to $0.81 million. The rotavirus vaccination programme has a potential to reduce the workload of health care workers such as paediatricians, nurses, dieticians, and pharmacists; however, the programme would require an additional 1.93-2.88 full-time equivalent of health assistants. CONCLUSION: At the current cost-effectiveness threshold, routine rotavirus vaccination in Bhutan is unlikely to be cost-effective with any of the currently available vaccines. However, routine vaccination with ROTASIIL was under the cost-effectiveness threshold of one times the GDP per capita ($3,074). ROTASIIL and ROTAVAC would provide the best value for money in Bhutan.

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.

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.

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% of the country's total immunization budget for 2018 or 0.13% of total health expenditures. CONCLUSION: In Afghanistan, HPV vaccine introduction targeting a single cohort is potentially cost-effective (0.7 times the GDP per capita of $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.