Cost-effectiveness and benefit-risk of rotavirus vaccination in Afghanistan: a modelling analysis informed by post-licensure surveillance

doi:10.21203/rs.3.rs-4974322/v1

Download PDF

Research Article

Cost-effectiveness and benefit-risk of rotavirus vaccination in Afghanistan: a modelling analysis informed by post-licensure surveillance

https://doi.org/10.21203/rs.3.rs-4974322/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Introduction

Afghanistan added ROTARIX to the routine national immunization programme in 2018. We aimed to estimate the cost-effectiveness and benefit-risk of ROTARIX and compare its continued use with other rotavirus vaccines that could be used in the future.

Methods

We used a static cohort model with a finely disaggregated age structure (weeks of age < 5 years) to assess the use of ROTARIX (1-dose vial) over a seven-year period (2018–2024) in Afghanistan. The primary outcome measure was the discounted cost (2022 US$) per Disability Adjusted Life Year (DALY) averted (from government and societal perspectives) compared to no vaccination. We also calculated the benefit-risk ratio i.e., the number of RVGE deaths prevented per one excess intussusception death. Model inputs were informed by pre- and post-licensure surveillance data, new analyses of household survey data, and updated estimates from the international literature. We ran a separate analysis to compare the potential cost-effectiveness and benefit-risk of ROTARIX (1-dose vial), ROTASIIL (1-dose vial), ROTASIIL (2-dose vial), and ROTAVAC (5-dose vial) over a ten-year period (2025–2034). Each product was compared to no rotavirus vaccination and each other. We ran deterministic and probabilistic uncertainty analyses and interpreted our results over a range of cost-effectiveness thresholds.

Findings

We estimated that routine use of ROTARIX between 2018 and 2024 has prevented 4,600 RVGE deaths (a 41% reduction), 86,400 hospital admissions, and 1.72 million outpatient visits. For every 1,493 RVGE deaths prevented by the vaccine, we estimated one potential excess intussusception death. With a heavily reduced vaccine dose cost (Gavi’s support) the net cost to the Afghanistan government vaccine programme was estimated to be US$ 4.4 million per year. The cost per DALY averted was US$ 125 (0.25 times the national GDP per capita) when using a Gavi-subsidised vaccine cost and including household costs averted by vaccination. This increased to US$ 471 (0.94 times the national GDP per capita) when incorporating the full vaccine price without Gavi's subsidy and excluding household costs averted by vaccination. When assuming continued Gavi support over the period 2025–2034, the dominant product would be ROTARIX. Without Gavi support, ROTASIIL (2-dose vial) dominates.

Conclusion

Our study supports the sustained use of rotavirus vaccination in Afghanistan. The rotavirus vaccine is cost-effective and is health benefits greatly exceed its potential health risks.

Rotavirus vaccine

Cost-utility

Cost-effectiveness

Benefit-risk

Afghanistan

Acute gastroenteritis (AGE) continues to be a leading cause of mortality in children < 5 years old, accounting for over half a million deaths annually and 10% of all fatalities in this age group.[1, 2] Rotavirus gastroenteritis (RVGE) is estimated to be responsible for 24–37% of AGE deaths.[3, 4] Following the World Health Organisation (WHO) recommendation for universal rotavirus (RV) vaccination in 2009, more than 120 countries have incorporated the vaccine into their national immunization programmes.[5, 6] Gavi, the vaccine alliance, has played a pivotal role by offering financial assistance to facilitate the introduction of the RV vaccine in low-income countries.[6] At the global level, RVGE deaths in children aged < 5 years have decreased from around 450,000 in 2008 to around 150,000 in 2019.[3, 7, 8] Recent estimates suggest that RV vaccines prevented 139,000 RVGE deaths in children < 5 years old from 2006–2019.[4] RVGE also imposes an important economic burden; a cost-effectiveness study of 73 Gavi-eligible countries indicated that RV vaccines could avert an estimated US$ 878 million in healthcare costs from the societal perspective over the period 2018–2027.[9]

In January 2018, Afghanistan added ROTARIX (GlaxoSmithKline, Belgium), one of the two pre-qualified rotavirus vaccines available at that time, to the national routine immunization programme, with financial support from Gavi, the vaccine alliance. ROTARIX is an oral vaccine administered to infants in a two-dose schedule at 6 and 10 weeks of age.[10] The decision to introduce the vaccine was informed by a modelling study led by members of the Afghanistan National Immunization Technical Advisory Group (NITAG) and the Ministry of Public Health (MoPH). This study estimated that ROTARIX could prevent 25% of RVGE deaths aged < 5 years at a cost of <$100 per DALY averted.[11]

Following the introduction of ROTARIX, post-licensure surveillance was established at five sites (Indira Gandhi Children Hospital, Herat Regional Hospital, Nangarhar Regional Hospital, Mazar Regional Hospital, and Ataturk Children Hospital) to monitor the effectiveness and safety of ROTARIX. Moderate vaccine effectiveness (VE) (45%; 95% CI: 22, 62) was demonstrated against RVGE hospital admissions aged 6–59 months old, and overall vaccine impact (percent reduction in RVGE admissions aged < 5 years) was 39%.[12] Importantly, no substantial increased risk of intussusception (a rare type of bowel blockage) was observed except a possible increase in risk of intussusception 8–21 days after receiving the first dose.[13, 14]

There are several reasons why the original economic evaluation of rotavirus vaccination in Afghanistan should be updated. First, the collapse of the Afghan government in mid-August 2021 led to a cessation of financial support from international donors who had previously provided crucial assistance to the healthcare system in Afghanistan. While financial aid resumed in October 2021, it remains at a minimum and is focused on the humanitarian response. This situation underscores the critical need to rationalise health investments and re-assess cost-effectiveness. Second, post-licensure surveillance data on the real-world effectiveness of ROTARIX are now available, together with updated estimates of pre-vaccination rotavirus mortality, rotavirus vaccine coverage, and vaccine timeliness. Third, new post-licensure data on vaccine safety provides an opportunity to assess benefit-risk. Finally, four rotavirus vaccines are now available, and an updated analysis provides an opportunity to compare the cost-effectiveness of other available products on the global market.[15] ROTARIX is administered as a two-dose course, while the other three (ROTATEQ [Merck & Co., USA], ROTASIIL [Serum Institute of India Pvt. Ltd. India], and ROTAVAC [Bharat Biotech, India]) require three doses. Each vaccine has different cost characteristics, and some have experienced supply shortages prompting a number of countries to switch to a different product.[16, 17]

This study aims to estimate the cost-effectiveness and benefit-risk ratio for ROTARIX, and to compare its continued use with other rotavirus vaccines.

Study design and model

We used version 1.7.01 of the UNIVAC (Universal Vaccine) decision-support model. UNIVAC is a static cohort model with a finely disaggregated age structure (weeks of age < 5 years) and can be used to assess the impact, cost-effectiveness, and benefit-risk of a range of different vaccines. It features a standardised and user-friendly Excel-based interface with a standard set of input steps and outputs. The model has been widely used by low- and middle-income countries (LMICs) to support decision-making for new vaccine introductions, including RV vaccines.[18]

We ran two types of analysis:

cost-effectiveness and benefit-risk analysis of ROTARIX (1-dose vial) over a seven-year period (2018–2024) compared to no vaccination; and,

cost-effectiveness and benefit-risk analysis of ROTARIX (1-dose vial), ROTASIIL (1-dose vial), ROTASIIL (2-dose vial), and ROTAVAC (5-dose vial) over a ten-year period (2025–2034). ROTATEQ was excluded from the comparison as it is not covered under Gavi’s financial support. Each product was compared to no rotavirus vaccination and each other.

In both analyses, we estimated the numbers of RVGE cases, outpatient visits, admissions, and deaths with and without RV vaccination. We also estimated potential excess intussusception cases and deaths using previously described methods.[19] Vaccine programme costs and healthcare costs were estimated throughout the first five years of life, and disability-adjusted life-years (DALYs) were calculated over the lifetimes of the target birth cohorts. The primary outcome measure was the discounted cost per DALY averted (from government and societal perspectives) compared to no vaccination. The benefit-risk of vaccination was represented by the estimated number of RVGE deaths prevented per one excess intussusception death.

Since 2018, the estimated annual gross domestic product (GDP) per capita in Afghanistan has rarely exceeded US$ 500, so we compared our estimates of the cost per DALY averted to a range of potential cost-effectiveness thresholds (CETs) between US$ 0 and US$ 500.[20, 21] In compliance with WHO vaccine economic evaluation guidelines, we considered both government and societal perspectives, and all future costs and health benefits were presented at a discounted rate of 3% per year, and expressed in 2022 United States Dollars (US$).[22]

Data collection and consensus building

Demographic projections were pre-populated in the model from the United Nations Population (UNPOP-2022), providing population size by age/year, life expectancy at birth by age/year, and < 5 all-cause mortality by year. All other model inputs and their sources are shown in Tables 1 and 2.

Table 1

Input parameters for estimating the burden of rotavirus gastroenteritis (RVGE) in Afghanistan- 2018–2027
Parameter	Mid-point value	Low bound	High bound	Sources
Annual rate per 100,000 < 5 children
RVGE non-severe cases	8224	6990	9458	[24]
RVGE non-severe RVGE visits	4367	3712	5022	[24, 25] *53.1% diarrhoea disease health seeking < 5yrs
RVGE severe cases	1776	1510	2042	[23, 4]
RVGE severe visits	943	802	1085	[23, 25] * 53.1% diarrhoea disease health seeking
RVGE hospital admissions	444	377	511	[26] inflated by DTP 1 coverage in 2022 (73% as proxy of getting healthcare)
RVGE deaths	26	22	30	[27]
Intussusception cases	30	26	35	[4,13,40{Anwari, 2024 #879}] inflated to account for those without access, using 2022 DTP 1 coverage (77%)
Intussusception hospital admissions	23	20	26	[13, 32]
Intussusception deaths	7	6	8	[13, 32]
Relative risk of intussusception
After 1–7 days
Dose 1	1.00	1.00	1.00	[13]
Dose 2	1.00	1.00	1.00
After 8–21 days
Dose 1	1.30	1.11	1.50
Dose 2	1.00	1.00	1.00
Age distribution of non-severe RVGE (%)
< 1 month	1%			[28] (Pakistan RVGE visits age distribution) Burr shape1 (c) = 2.51 Burr shape2 (k) = 1.29 Burr scale (a) = 42.33
< 2 months	2%
< 3 months	8%
< 6 months	28%
< 12 months	73%
< 24 months	95%
< 36 months	98%
< 48 months	99%
< 60 months	100%
Age distribution of severe RVGE (%)				[28] Age distribution fitting: Burr shape1 (c) = 2.59 Burr shape2 (k) = 1 Burr scale (a) = 36.19
< 1 month	0%
< 2 months	5%
< 3 months	8%
< 6 months	28%
< 12 months	73%
< 24 months	95%
< 36 months	98%
< 48 months	99%
< 60 months	100%
Intussusception age distribution**
< 1 month	0%			[13] Age distribution fitting: Burr shape1 (c) = 7.19 Burr shape2 (k) = 0.15 Burr scale (a) = 19.52
< 2 months	1%
< 3 months	2%
< 6 months	22%
< 12 months	75%
< 24 months	85%
< 36 months	90%
< 48 months	95%
< 60 months	100%
DALY calculation
Non-severe RVGE
DALY weight	0.19	0.19	0.26	[29] (proxy: Moderate diarrhoea)
Duration of illness (days)	3	3	7	[30] and EPI assumption
Severe RVGE
DALY weight	0.25	0.25	0.36	[29] (proxy: Severe diarrhoea)
Duration of illness (days)	7	6	8	[30] and EPI assumption
Intussusception
DALY weight	0.32	0.32	0.44	[29] (Abdominopelvic problem, severe)
Duration of illness (days)	7	5	9	[13]
Vaccine effectiveness
dose 1, initial VE	100%	45%*	100%	[12] VE and 95%CI Assume efficacy of 3 doses equal to 2 doses Fitted the observed effectiveness of each dose and time of administration to the post-licensure surveillance data
dose 2, initial VE	100%	45%*	100%
dose 3, initial VE	100%	45%*	100%
Mean duration of VE after each dose (in months)	10	10	10
Parameter 2 (alpha or shape)/standard error	3	3	3
Vaccine coverage
Dose 1
2018	81%	69%	93%	[32], DTP1 as proxy for RV dose1 It was aligned with observed coverage in post-licensure surveillance.
2019	75%	64%	86%
2020	78%	66%	90%
2021	74%	63%	85%
2022	77%	65%	89%
2023–2034	77%	65%	89%
Dose 2
2018	77%	65%	88%	[32] Average DTP 1 and 3, proxy for RV dose 2 It was aligned with observed coverage in post-licensure surveillance.
2019	74%	62%	85%
2020	74%	63%	85%
2021	70%	60%	81%
2022	73%	62%	84%
2023–2034	73%	62%	84%
Dose 3
2018	72%	61%	83%	[32] 2022, DTP3, proxy for RV dose 2 It was aligned with observed coverage in post-licensure surveillance.
2019	72%	61%	83%
2020	70%	60%	81%
2021	66%	56%	76%
2022	69%	59%	79%
2023–2034	69%	59%	79%
Coverage timeliness
Median age at dose 1, in weeks (IQR)	7	6	12	[25, 33]
Median age at dose 2, in weeks (IQR)	20	16	25
Median age at dose 3, in weeks (IQR)	29	19	43
Dose 1
< 1 month	0%	0%	0%	[33] Scale: 12.89 (7.25, 22, 94) Shape: 1.91
< 2 months	53%	45%	61%
< 3 months	63%	54%	72%
< 6 months	71%	60%	82%
< 12 months	75%	64%	86%
< 24 months	77%	65%	89%
< 36 months	77%	65%	89%
< 48 months	77%	65%	89%
< 60 months	77%	65%	89%
Dose 2
< 1 month	1%	1%	1%	[33] Scale: 16.96 (11.72, 24.55) Shape: 2.97
< 2 months	3%	3%	3%
< 3 months	31%	26%	36%
< 6 months	61%	52%	70%
< 12 months	70%	60%	81%
< 24 months	73%	62%	84%
< 36 months	73%	62%	84%
< 48 months	73%	62%	84%
< 60 months	73%	62%	84%
Dose 3
< 1 month	0%	0%	0%	[33] Scale: 28.93 (19.39, 443.15) Shape: 2.75
< 2 months	0%	0%	0%
< 3 months	5%	4%	6%
< 6 months	53%	45%	61%
< 12 months	66%	56%	76%
< 24 months	69%	59%	79%
< 36 months	69%	59%	79%
< 48 months	69%	59%	79%
< 60 months	69%	59%	79%
Vaccine price per dose (US$) with Gavi subsidy
ROTARIX, 1-dose per vial, Liquid	$0.20			[15]
ROTASIIL, 1-dose per vial, liquid	$0.13
ROTASIIL, 2-dose per vial, liquid	$0.13
ROTAVAC, 5-dose per vial, liquid	$0.13
Vaccine price per dose (US$) without Gavi subsidy
ROTARIX, 1-dose per vial, Liquid	$ 2.36
ROTASIIL, 1-dose per vial, liquid	$ 1.05
ROTASIIL, 2-dose per vial, liquid	$ 0.80
ROTAVAC, 5-dose per vial, liquid	$ 1.15
International handling (% of vaccine price)	3.00%	2.55%	4.50%	[36]
International delivery (% of vaccine price)	5.00%	4.00%	7.50%	[36]
Vaccine wastage rate
ROTARIX, 1-dose, Liquid	5%	4%	8%	[35] and expert consensus
ROTASIIL, 1-dose, liquid	5%	4%	8%
ROTASIIL, 2-dose, liquid	9%	8%	14%
ROTAVAC, 5-dose, Liquid	15%	13%	23%
Syringes wastage rate	5%	4%	8%	[35] and expert consensus (the same as vaccine wastage rate)
Health system delivery cost per dose (US$) for 2018 onward	2.18	1.09	4.36	[38]
Additional health system cost per dose in the first year (2025) associated with switching from ROTARIX to ROTAVAC / ROTASIIL (US$)^§	0.80	0.68	0.92	[17, 38] Average of switching cost reported in Palestine and Ghana studies Lower bound: Ghana: US$0.68 per dose Higher bound: Palestine: US$0.92 per dose
^§ We used the mid-range between the switching costs reported by Palestine’s and Ghana’s studies divided by the number of doses to deliver in year 1. We used the low and high values for sensitivity analysis.

Table 2

Input parameters for estimating health service costs in 2022 US$, Afghanistan
Parameter	Mid-point value	Low bound	High bound	Sources
Healthcare costs of RVGE
Government perspective
Non-severe outpatient visit (US$ 2022)	$5.04	$2.52	$10.08	[31]
Severe outpatient visit (US$ 2022)	$5.04	$2.52	$10.08
Severe hospitalization (US$ 2022)	$17.56	$8.78	$35.12
Societal perspective
Non-Severe outpatient visit (US$ 2022)	$15.42	$7.71	$30.84
Severe outpatient visit (US$ 2022)	$15.42	$7.71	$26.46
Severe hospitalization (US$ 2022)	$38.05	$19.03	$76.10
Healthcare costs of intussusception (IS)
Government cost of IS hospitalization (US$ 2022)	$214.75	107.38	$429.50	[41,31]
Societal cost of IS hospitalization (US$ 2022)	$234.38	117.19	$468.76	[41,31]

To build consensus on model input parameters, we conducted consultation sessions with seven national experts between March and June 2024 during data collection and analysis. We engaged national experts in epidemiology, paediatric, immunization, health economics, and health system, representing stakeholders from the national expanded programme on immunization (EPI), WHO, UNICEF, and academia. This evaluation obtained approval from the Research Ethics Committee (ID: 29622, July 2023) of the London School of Hygiene and Tropical Medicine (LSHTM).

RVGE disease burden

All disease input parameters are shown in Table 1. We estimated the incidence of severe RVGE cases in children by multiplying the WHO Eastern Mediterranean region estimate of the rate of severe AGE (5,972 per 100,000 per year, aged < 5 years) by the rotavirus fraction among severe AGE cases (29.74%).[23] The rotavirus fraction was estimated using the mean of three estimates provided by Maternal and Child Epidemiology Estimation (MCEE), WHO/Centres for Disease Control and Prevention (WHO/CDC), and Global Burden of Disease (GBD).[4] The incidence of non-severe RVGE cases was estimated by subtracting the severe RVGE rate from the overall RVGE case rate (10,000 per 100,000 per year, aged < 5 years) estimated in a global systematic review and meta-analysis by Bilcke et al.[24] The rate of RVGE outpatient visits was calculated by multiplying the number of non-severe and severe RVGE cases by the proportion of children with diarrhoea seeking care (53.10%), as estimated from the Afghanistan Multiple Indicator Cluster Survey (MICS) 2022–2023.[25] The rate of RVGE hospital admissions was estimated using pre-vaccination RVGE surveillance in two regions of Afghanistan, Central and Western.[26] To estimate the RVGE mortality rate we used the mean of estimates by MCEE, WHO/CDC and GBD.[27]

The age distribution of severe RVGE (community cases, outpatient visits, admissions, and deaths) was estimated by week of age < 5 years using a parametric (Burr) distribution fitted to data from Afghanistan pre-vaccine surveillance (2013–2015). (Figure S1- panel a).[28] In the absence of national data on the age distribution of non-severe RVGE (community cases and outpatient visits), we used estimates for Pakistan from a study by Hasso-Agopsowicz and colleagues.[28] (Table 1)

For calculating DALYs, we used disability weights from Salomon et al.[29] and for duration of illness, we assumed 7 days for severe RVGE cases and 3 days for non-severe RVGE cases.[30]

RVGE healthcare cost

The cost per RVGE inpatient admission was taken from a systematic review of LMICs by Baral et al. (2020), which estimated the cost per gastroenteritis (GE) admission. The same source was used to estimate the cost per outpatient visit.[31] For the base case analysis, we included direct medical costs in the government perspective and the sum of direct medical, direct non-medical, and indirect costs in the societal perspective. We assumed that the cost per outpatient visit would be the same for severe and non-severe cases. Our analysis did not include costs for treatment given at home or through the informal sector. (Table 2)

Vaccination coverage, timeliness, and effectiveness

Observed RV vaccine coverage from post-licensure surveillance was very similar to the national administrative coverage reported in the WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) for DTP1 and DTP3. Despite disruptions caused by the COVID-19 pandemic and political changes, the official administrative rotavirus vaccination coverage was reported to be stable from 2020 to 2022. We therefore used 2022 WUENIC estimates of DTP1 and DTP3 vaccine coverage as a proxy for RV1 and RV2 (average DTP1 and DTP3) vaccine coverage and assumed this would remain consistent throughout our evaluation period.[32] We included real-world vaccine delays and vaccine timeliness (coverage by week of age) using an analysis of data from a recent nationally representative survey, MICS 2022.[25, 33](Table 1)

We used estimates from a recent test-negative case-control study to approximate VE by time since dose administration using follow-up durations of 8 and 16 months for dose 1, and 7 and 15 months for dose 2.[12] We fitted a parametric gamma curve to each dose, assuming VE would be very high shortly after dose administration and then fall to very low levels after around 18 months of follow-up. (Figure S2) Estimates of VE and waning were very similar for doses 1 and 2, so we assumed the same waning rate for both.

Consistent with our previous analysis, we did not account for the indirect benefits of rotavirus vaccination, such as herd immunity, nor did we apply age restrictions to the vaccination schedule.

Vaccine price and delivery cost

According to Gavi’s eligibility and transition policy version 4 (effective from January 2023) Afghanistan is classified as being in the initial self-financing phase.[34] In our base-case scenario, we applied a co-financing contribution of US$ 0.20 per dose for ROTARIX (2-doses) and US$ 0.13 per dose for ROTAVAC (3-doses) and ROTASIIL (3-doses). In scenario analysis, we ran a separate analysis assuming the government would pay the full price for ROTARIX (US$2.36 per dose for the 1-dose vial presentation), ROTASIIL (US$ 0.80 for the 2-dose vial presentation, and US$ 1.05 for the 1-dose vial presentation) and ROTAVAC ($US 1.15 per dose for the 5-dose vial presentation).[15] We assumed prices would remain unchanged over the evaluation period. (Table 1 )

We applied wastage rates of 5%, 9%, and 15% for 1-dose, 2-dose and 5-dose vaccine presentations, respectively. These values were informed by reviewing the Comprehensive Multi-Year Plan (CMYP) 2021–2025. [[35]& Afghanistan EPI experts] A relatively high wastage rate of 15% for the 5-dose vaccine presentation has been derived from the current high wastage rates of the 1-dose and 2-dose vaccine presentations in the country. To calculate the cost of international handling and delivery, we applied 3% and 5% of the vaccine price, respectively.[35] The per dose cost of a safety bag with a capacity of 100 doses was estimated to be US$ 0.56.[35] No updated national data were available to estimate the health system delivery costs of rotavirus vaccination, so we used estimates for LMICs by Portnoy et, al (US$2.18 per dose in US$2022).[36] (Table 1) Due to limited data on the cost of switching products, we applied the average switching costs, which primarily cover the expenses of training, social mobilization, IEC materials, and stakeholder engagement, as reported by Palestine and Ghana, to the year of switching (2025).[17, 37] We calculated the mid-range cost between Palestine and Ghana and divided it by the number of doses to be delivered in the first year with the 3-dose products. (Table 1 )

Intussusception burden, risk, and costs

Intussusception (IS), invagination of a bowl segment causing blockage, is a rare but fatal medical condition if left untreated.[5, 38] In some (mostly high-income) settings rotavirus vaccination has been associated with a small excess risk of IS.[5] We estimated the potential number of excess IS cases, hospital admissions and deaths to account for the potential excess risk of IS in the 1–7 and 8–21 days following the first and second dose of RV vaccination. The post-licensure self-controlled case series (SCCS) study for ROTARIX in Afghanistan reported a small relative risk (RR = 1.3) in the 8–21 day period following administration of the first dose, so we included this risk in the base analysis.[13]

Our estimates of the background rate of IS cases, hospital admissions, and mortality were obtained from post-licensure surveillance of children aged < 12 months. This was the best available data source given that no IS surveillance existed pre-vaccine, and the RR of vaccination was very minor and restricted to specific age windows post-vaccination. The admission rate < 12 months was rescaled to age < 5 years using estimates from a systematic review of the proportion of < 5 years IS hospital admissions that occurred by age 1 year in the WHO Eastern Mediterranean region.[4, 13, 39] The incidence rate of IS cases was derived by inflating the IS hospital admission rate to account for the percentage of children without access to care, using WUENIC estimates of the coverage of DTP1 in the year 2022 as a proxy for the maximum possible access to healthcare for severe conditions.[13, 32] (Table 1) Estimates of the background rate of IS mortality were based on observed fatality rates among children < 1 year from post-licensure surveillance. These were rescaled to represent children < 5 years and inflated by DTP1 coverage to account for the percentage of children without access to care.[13, 19] The age distribution of all intussusception outcomes was calculated by week of age < 5 years using a parametric (Burr) distribution fitted to post-licensure surveillance data. (2018–2022).[13] (FigureS1- panel b)

Direct healthcare costs associated with intussusception treatment were included in the government perspective. These were estimated using the average cost per bed day in the National Hospitals Cost Analysis report, considering the average number of 5 days required for IS treatment.[40]. From the societal perspective, we also included direct non-medical cost and indirect cost estimates from Baral’s study without accounting for any allowance for the cost of surgery.[31] (Table 2)

Uncertainty analysis

We conducted deterministic scenario analyses to assess the sensitivity of the cost-effectiveness results to changes in different combinations of parameter values. We applied -/+15% to lower and higher bound of base values.[41] We considered the reported switch cost per dose of each country, Palestine and Ghana, to determine the lower and upper bounds of the vaccine delivery cost in the first year of the switch for the sensitivity analysis. We ran a scenario unfavourable to RV vaccination using the upper bound of the vaccine delivery cost per dose, a vaccine price without Gavi’s subsidy, the lower bounds of the disease burden rate, and the lower bounds of the healthcare costs. We also ran scenarios favourable to RV vaccination by assuming “on-time” vaccine administration and using the upper bounds of the disease burden rates and healthcare costs, and lower bound of vaccine delivery cost, and upper bounds of RVGE burden. Lastly, in one of the one-way sensitivity analyses, we assumed no vaccine impact on non-severe RVGE.

We ran a probabilistic sensitivity analysis (PSA) with 1000 Monte Carlo simulation runs. Within each run of the model, all parameters were simultaneously varied within their specified ranges. This was done to generate a 95% uncertainty interval around the central estimates of the cost per DALY averted. It was also done to determine the proportion of probabilistic runs with a cost-effectiveness ratio falling below CETs ranging from US$ 0 to US$ 500.

Role of the funding source

The funder of the study had no involvement in the study design, data collection, data analysis, data interpretation, or report writing. The authors had full access to all the data in the study and had final responsibility for the decision in submit for publication.

We estimated that seven years (2018–2024) of ROTARIX use in Afghanistan prevented 1.72 million RVGE cases, 911,337 outpatient visits, 86,444 RVGE hospital admissions and 4,644 RVGE deaths (a 41% reduction), compared to a scenario with no RV vaccination. We estimated 1,493 RVGE deaths prevented for every one potential excess intussusception death. (Table 3)

Table 3

**Projected impact and cost-effectiveness of rotavirus vaccination in cohort vaccinated over period of 2018–2024 (DALY and costs discounted), government and society perspectives.**
Parameter	No vaccine	ROTARIX
		With Gavi Support	Without Gavi support
Lifetime costs and effects
Non-Severe RVGE cases < 5yrs	3,886,826	2,516,352	2,516,352
Non-RVGE clinic visits < 5yrs	2,063,904	1,336,183	1,336,183
Severe RVGE cases < 5yrs	839,407	493,616	493,616
Severe RVGE clinic visits < 5yrs	445,725	262,110	262,110
Severe RVGE hospital admission < 5yrs	209,843	123,399	123,399
Severe RVGE deaths < 5yrs	11,270	6,626	6,626
Intussusception cases < 5yrs	14,179	14,193	14,193
Intussusception deaths < 5yrs	3,034	3,037	3,037
DALY averted (discounted*)	372,654	250,689	250,689
Vaccine programme costs (discounted*)	$0	$31,110,501	$62,760,329
Government healthcare costs (discounted*)	$16,257,205	$10,947,422	$10,947,422
Societal healthcare costs (discounted*)	$44,795,458	$28,900,879	$28,900,879
Differences (comparator = no vaccine)
Non-Severe RVGE cases < 5yrs	-	1,370,474	1,370,474
Non-RVGE clinic visits < 5yrs	-	727,721	727,721
Severe RVGE cases < 5yrs	-	345,791	345,791
Severe RVGE clinic visits < 5yrs	-	183,615	183,615
Severe RVGE hospital admission < 5yrs	-	86,444	86,444
Severe RVGE deaths < 5yrs	-	4,644	4,644
Intussusception cases < 5yrs	-	15^¥	15^¥
Intussusception deaths < 5yrs	-	-3^¥	-3^¥
Percent reduction in severe RVGE deaths < 5yrs	-	41%	41%
Percent increase in Intussusception deaths < 5yrs	-	-0.10%	-0.10%
DALYs (discounted*)	-	121,965	121,965
Vaccine programme costs (discounted*)	-	$31,110,501	$62,760,329
Government healthcare costs (discounted*)		-$5,309,783	-$5,309,783
Societal healthcare costs (discounted*)	-	-$15,894,579	-$15,894,579
Cost (US$) per DALY averted (comparator = no vaccine)
Governmental perspective
Cost (discounted*)	-	$25,800,718	$57,450,546
DALYs averted (discounted*)	-	121,965	121,965
Cost per DALY averted (discounted*)	-	$212	$472
GDP per capital (2018)	-	$500	$500
Cost per DALY averted (discounted*) - % of GDP/capita	-	42.31	94.21
Societal perspective	-
Cost (discounted*)	-	$15,215,921	$46,865,749
DALYs averted (discounted*)	-	121,965	121,965
Cost per DALY averted (discounted*) - % of GDP/capita	-	$125	$386
GDP per capital (2018)	-	$500	$500
Cost per DALY averted (discounted*) - % of GDP/capita	-	24.95	76.85
*Future costs/effects were discounted at a rate of 3% per year. ¥ Negative values indicate more cases or deaths with vaccination.

With a heavily reduced vaccine dose cost (due to external donor support from Gavi) the estimated vaccine programme cost was US$31.11 million over seven years. Without Gavi support, this increased to US$ 62.76 million. We estimate that the cost of vaccination could be offset by US$ $5.31 million in RVGE treatment costs from the government perspective (or US$ 15.89 million from the societal perspective). (Table 3 )

In the base case analysis, factoring in Gavi's subsidy, the discounted cost per DALY averted was US$212 (0.42 times the national GDP per capita) from the government perspective and US$125 (0.25 times the national GDP per capita) from the societal perspective. However, when incorporating the full vaccine price without Gavi's subsidy, the discounted cost per DALY averted increased to US$472 (0.94 times the national GDP per capita) from the government perspective and US$386 (0.67 times the national GDP per capita) from the societal perspective.

Scenario analysis showed that the cost-effectiveness results were most sensitive to the price per dose (i.e. whether or not Gavi financial support was included), the burden of RVGE disease and the vaccine delivery costs. With a reduced dose price (due to Gavi support), low vaccine delivery costs and high healthcare costs, the discounted cost per DALY averted was US$ 170 from the government's perspective and US$ 71 from a societal perspective. The assumption that the vaccine has no impact on non-severe RVGE is fairly influential. Additional details on various scenarios are provided in supplement tables S2 and figure S3.

ROTARIX had a 95% probability of being cost-effective when using a CET of US$250 (half the national GDP per capita). The full results of the probabilistic sensitivity analysis, including the cost-effectiveness plane and cost-effectiveness acceptability curve, are presented in Fig. 1 and supplement figure S4 (panel a, b).

Over the period 2025–2034, ROTARIX dominated the other three products when Gavi-subsidised prices were used (Table 4, figures S5 and S6). The estimated cost per DALY averted for continued use of ROTARIX was US$259 per DALY averted from a government perspective (and US$ 152 from a societal perspective). (Table 4 ) Without Gavi support, ROTASIIL (2-dose vial) dominates (Table 4, Fig. 2 ) and there is 35% that three-dose vaccines could be cost-effective at a CET of US$ 500 per DALY averted from a government without Gavi’s support. (Figure S6 panel a) With Gavi’s support from societal perspective this probability increases to 95%. (Figure S6 panel b)

Table 4

Economic evaluation of rotavirus vaccine products with and without Gavi subsidy in Afghanistan over the period 2025–2034^§
		With Gavi subsidy				Without Gavi Subsidy
	No vaccine	ROTARIX, 1 dose vial, Liquid	ROTASIIL, 1 dose vial, Liquid	ROTASIIL, 2 dose vial, Liquid	ROTAVAC, 5 dose, liquid	ROTARIX, 1 dose vial, Liquid	ROTASIIL, 1 dose vial, Liquid	ROTASIIL, 2 dose vial, Liquid	ROTAVAC, 5 dose, liquid
Lifetime costs and effects
Non-Severe RVGE cases < 5yrs	5,982,804	3,870,487	3,468,324	3,468,324	3,468,324	3,870,487	3,468,324	3,468,324	3,468,324
Non-RVGE clinic visits < 5yrs	3,176,869	2,055,229	1,841,680	1,841,680	1,841,680	2,055,229	1,841,680	1,841,680	1,841,680
Severe RVGE cases < 5yrs	1,292,059	759,107	661,324	661,324	661,324	759,107	661,324	661,324	661,324
Severe RVGE visits < 5yrs	686,083	403,086	351,163	351,163	351,163	403,086	351,163	351,163	351,163
Severe RVGE hospital admission < 5yrs	323,002	189,769	165,324	165,324	165,324	189,769	165,324	165,324	165,324
Severe RVGE deaths < 5yrs	13,813	8,116	7,070	7,070	7,070	8,116	7,070	7,070	7,070
Intussusception cases < 5yrs	21,824	21,847	21,847	21,847	21,847	21,847	21,847	21,847	21,847
Intussusception deaths < 5yrs	3,719	3,723	3,723	3,723	3,723	3,723	3,723	3,723	3,723
DALY averted (discounted*)	447,553	300,865	273,727	273,727	273,727	300,865	273,727	273,727	273,727
Vaccine programme costs (discounted)	$0	$45,789,790	$66,814,597	$67,002,040	$67,927,617	$92,373,387	$95,746,701	$88,998,319	$103,166,934
Government healthcare costs (discounted*)	$23,992,598	$16,150,212	$14,668,045	$14,668,045	$14,668,045	$16,150,212	$14,668,045	$14,668,045	$14,668,045
Societal healthcare costs (discounted)	$66,109,732	$42,633,813	$38,195,960	$38,195,960	$38,195,960	$42,633,813	$38,195,960	$38,195,960	$38,195,960
Differences (comparator = no vaccine)
Non-Severe RVGE cases < 5yrs	..	2,112,317	2,514,480	2,514,480	2,514,480	2,112,317	2,514,480	2,514,480	2,514,480
Non-RVGE clinic visits < 5yrs	..	1,121,640	1,335,189	1,335,189	1,335,189	1,121,640	1,335,189	1,335,189	1,335,189
Severe RVGE cases < 5yrs	..	532,953	630,736	630,736	630,736	532,953	630,736	630,736	630,736
Severe RVGE visits < 5yrs	..	282,998	334,921	334,921	334,921	282,998	334,921	334,921	334,921
Severe RVGE hospital admission < 5yrs	..	133,233	157,677	157,677	157,677	133,233	157,677	157,677	157,677
Severe RVGE deaths < 5yrs	..	5,698	6,743	6,743	6,743	5,698	6,743	6,743	6,743
Intussusception cases < 5yrs	..	-23^¥	-23^¥	-23^¥	-23^¥	-23^¥	-23^¥	-23^¥	-23^¥
Intussusception deaths < 5yrs	..	-4^¥	-4^¥	-4^¥	-4^¥	-4^¥	-4^¥	-4^¥	-4^¥
Percent reduction in severe RVGE deaths < 5yrs	..	41.25%	48.82%	48.82%	48.82%	41.25%	48.82%	48.82%	48.82%
Percent increase in Intussusception deaths < 5yrs	..	0.10%	0.10%	0.10%	0.10%	0.10%	0.10%	0.10%	0.10%
DALYs (discounted*)	..	146,689	173,826	173,826	173,826	146,689	173,826	173,826	173,826
Vaccine programme costs (discounted*)	..	$45,789,790	$66,814,597	$67,002,040	$67,927,617	$92,373,387	$95,746,701	$88,998,319	$103,166,934
Government healthcare costs (discounted*)	..	$7,842,387	$9,324,553	$9,324,553	$9,324,553	$7,842,387	$9,324,553	$9,324,553	$9,324,553
Societal healthcare costs (discounted*)	..	$23,475,918	$27,903,782	$27,903,782	27,903,782	$23,475,918	$27,903,782	$27,903,782	$27,903,782
Cost (US$) per DALY averted (comparator = no vaccine) (Government perspective)
Governmental perspective
Cost (discounted*)	..	$37,947,404	$57,490,044	$57,677,487	$58,603,063	$84,531,000	$86,422,147	$79,673,765	$93,842,381
DALYs averted (discounted*)	..	$146,689	$173,826	$173,826	$173,826	$146,689	$173,826	$173,826	$173,826
Cost per DALY averted (discounted*)	..	$259	$331	$332	$337	$576	$497	$458	$540
Proportion of the GDP per capita (US$348) (%)		52%	66%	66%	67%	115%	99%	92%	108%
Societal perspective
Cost (discounted*)	..	$22,313,872	$38,900,825	$39,088,268	$40,013,845	$68,897,468	$67,832,929	$61,084,547	75,253,163
DALYs averted (discounted*)	..	146,689	173,826	173,826	173,826	146,689	$173,826	$173,826	$173,826
Cost per DALY averted (discounted*)	..	$152	$224	$225	$230	$470	$390	$351	$433
Proportion of the GDP per capita (US$348) (%)	..	30%	45%	45%	45%	94%	78%	70%	87%
		ROTARIX 1st option	ROTASIIL1 2nd option	ROTASIIL2 3rd option	ROTAVAC 4th option	ROTARIX 2nd option	ROTASIIL1 3rd option	ROTASIIL2 1st option	ROTAVAC 4th option
Cost (US$) per DALY averted (comparator = next least costly non-dominated option)
Government perspective (US$)	..
Costs (discounted*)	..		-$16,586,953	-$16,774,397	-$17,699,973	$4,857,235	-$6,748,382		-$14,168,616
DALY averted (discounted*)	..		-27,138	-27,138	-27,138	-27,138	0		0
Cost per DALY averted (discounted*)	..		$611	$618	$652	-$179
Societal perspective (US$)
Costs (discounted*)	..		-$16,586,953	-$16,774,397	-$17,699,973	$7,812,922	-$6,748,382		-$14,168,616
DALY averted (discounted*)	..		-27,138	-27,138	-27,138	-27,138	0		0
Cost per DALY averted (discounted*)	..		$611	$618	$652	-$288
§Under the assumption of all products (3 doses vs 2 doses) have the same vaccine effectiveness.
*Future costs/effects were discounted at a rate of 3% per year.
¥ negative values indicate more cases or deaths with vaccination.

In scenario analysis, the choice of product (product with the lowest cost per DALY averted) was most sensitive to the dose price, wastage rate, health system delivery cost, and assumptions about whether 3-dose vaccines would have the same or slightly higher impact than the 2-dose vaccine (ROTARIX). (Table 4)

We have updated our previous estimates of cost-effectiveness using real-world post-licensure national data and updated global estimates. Our updated analysis shows that over a seven-year period (2018–2024), ROTARIX had an important public health impact, preventing around 12,000 hospital admissions and 650 deaths each year. Our analysis also estimates a favourable ratio of benefits to risks. We estimated important economic benefits, with ROTARIX averting up to US$5.31 million and US$15.89 million in RVGE treatment costs from government and societal perspectives, respectively. Assuming a heavily discounted dose price due to support from Gavi, we estimated that it cost US$212 and US$125 to prevent each DALY, from a government and societal perspective, respectively. This is less favourable than our previous analysis (US$31 and US$29 respectively), primarily because our previous analysis assumed higher rates of RVGE mortality in the absence of vaccination. Additionally, cost values were adjusted to reflect US dollars as of 2022, a period of significant inflation since 2018. Despite these increases, our current figures are consistent with existing literature; a meta-regression analysis reported a mean incremental cost-effectiveness ratio (ICER) of US$225 per DALY for Gavi-eligible countries.[9]

Afghanistan has faced significant economic hurdles since the Taliban's takeover of the government in August 2021. This economic downturn reduces the population and government's ability to fund health interventions. The country's ranking has declined from 153 in 2022 to 181 in 2023–2024 out of 193 countries, based on composite human development indices. [43] Additionally, the GDP per capita, often used as a basis for interpreting CETs, has seen a 12–62% decline from US$ 562 in 2017 to date. To address the instability in the GDP per capita, we used CETs ranging from $0- US$ 500. Our most favourable analysis suggests a cost-effectiveness ratio of 0.25 times the national GDP per capita, increasing to 0.94 times under assumptions least favourable to vaccination. Pichon-Rivere and colleagues recently recommended a CET of 0.65 time the national GDP per capita in Afghanistan using a method based on current levels of healthcare expenditure.[42] This suggests that RV vaccination is likely to remain cost-effective from a government perspective while it continues to benefit from the favourable assumption of Gavi subsidised prices. This seems likely given the recent political and economic disruption and increased need for donor assistance in Afghanistan. Looking ahead to the period 2025–2034, ROTARIX is projected to remain the dominant product, assuming continued Gavi support.

Affordability is an important consideration. With substantial external financial support from Gavi, the net cost to the Afghan government's vaccine programme was estimated to be US$ 4.44 million annually, accounting for 5.5% of the annual EPI programme budget and around 0.13% of the total national health expenditure. Without Gavi support, the vaccine programme cost would surpass US$ 8.96 million per year.

We estimated a substantial health and economic impact of vaccination. Similar findings have been reported in other low-income countries from both government and societal perspectives.[17, 37, 43–46] We estimated a 41% in RVGE hospitalisations and mortality per birth cohort from 2018–2024, closely replicating the 39% reduction in RVGE hospital admissions observed in the post-licensure evaluation.[47] Historically, rotavirus vaccination has shown a lower performance in LMICs compared to high-income countries. Opportunities to increase impact might involve introducing an additional dose to mitigate the effects of waning vaccine protection. We estimate this has the potential to increase health impact by around 8% (41% for 2-dose vs 49% for 3-dose vaccines).

Our analysis reaffirms the substantial benefits of RV vaccination compared to the potential excess risk of intussusception. We estimated 1,493 RVGE deaths prevented for every one potential excess intussusception death. Recent modelled estimates of benefit-risk for 135 LMICs reported a ratio of 1,503:1.[46] We also ran a scenario with age restrictions applied (first dose < 15 weeks, last dose < 32 weeks). This adjustment reduced the vaccine's impact to 25%, but the benefit-risk ratio subsequently improved (to 2,790:1) because fewer doses were administered during the peak age of intussusception. More favourable benefit-risk ratio was reported in another modelled study when age restrictions were applied 2,385:1.[19]

Our analysis has some limitations. Our estimates of the burden of RVGE, vaccine effectiveness, and intussusception are uncertain. One challenge is the ambiguity surrounding the catchment population size. The last official census in the country was conducted in 1979, leaving a wide range of possible population estimates. To address this, we applied lower and upper bounds and used international estimates for some of the inputs. We also varied the rates in uncertainty analysis. Our estimates of the benefits of rotavirus vaccination may be underestimated because the UNIVAC model does not capture possible herd immunity effects. However, in this study we were able to use real-world data on VE from post-licensure surveillance and using a dynamic model in this context would introduce its own challenges e.g. it would require uncertain input parameters including social contact patterns and the duration of immunity from natural infections. The primary aim of this study is to support vaccine decision-making. While using a dynamic model is unlikely to significantly alter the conclusions, our estimates may be underestimated compared to those from a dynamic model. CEA studies using dynamic models have reported lower costs per DALY gained due to accounting for herd immunity compared to the static model.[48, 49]

Our study underscores the importance of sustaining the use of rotavirus vaccination in Afghanistan. Future research should focus on enhancing vaccine delivery efficiency and addressing barriers to vaccine uptake, thereby increasing the public health impact of rotavirus vaccination.

Conflict of interest: The authors indicate they have no conflict of interest relevant to this article to disclose.

Funding source:

This work was supported, in part, by the Bill & Melinda Gates Foundation [grant number: OPP1147721]. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.

Data availability

This manuscript does not report data generation.

Contributors

PA, AC developed the evaluation concept and methods. PA carried out data collection, expert consultation, data validation, data analysis, produced tables and figures, and wrote the first draft of the manuscript. PA, AC, and FD validate the analysis. All authors have read, provided scientific inputs, contributed to, and approved the final version of the manuscript for submission.

Acknowledgement

This work was supported, in part, by the Bill & Melinda Gates Foundation [grant number OPP1147721]. Support for this project was provided by PATH. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. We thank the national experts who were consulted and validated the model inputs.

Declaration of interests

All authors declare no competing interests.

Sharrow, D., L. Hug, D. You, L. Alkema, R. Black, S. Cousens, et al., Global, regional, and national trends in under-5 mortality between 1990 and 2019 with scenario-based projections until 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation. The Lancet Global Health, 2022. 10(2): p. e195-e206.
Liu, L., S. Oza, D. Hogan, J. Perin, I. Rudan, J.E. Lawn, et al., Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet, 2015. 385(9966): p. 430-40.
Tate, J.E., A.H. Burton, C. Boschi-Pinto, U.D. Parashar, f.t.W.H.O.C.G.R.S. Network, M. Agocs, et al., Global, Regional, and National Estimates of Rotavirus Mortality in Children <5 Years of Age, 2000–2013. Clinical Infectious Diseases, 2016. 62(suppl_2): p. S96-S105.
Clark, A., S. Mahmud, F. Debellut, C. Pecenka, M. Jit, J. Perin, et al., Estimating the global impact of rotavirus vaccines on child mortality. Int J Infect Dis, 2023.
WHO. Rotavirus vaccines: WHO position paper-July 2021. Weekly Epidemiological Record, 2021 [cited 2023 September 29, 2023]; Available from: https://www.who.int/publications/i/item/WHO-WER9628.
International Vaccine Access Center. Rotavirus Vaccine Introduction 2023 12/21/2023]; Available from: https://view-hub.org/vaccine/rota?set=current-vaccine-intro-status&group=vaccine-introduction&category=rv.
Tate, J.E., A.H. Burton, C. Boschi-Pinto, A.D. Steele, J. Duque, and U.D. Parashar, 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis, 2012. 12(2): p. 136-41.
Burnett, E., U.D. Parashar, and J.E. Tate, Real-world effectiveness of rotavirus vaccines, 2006-19: a literature review and meta-analysis. The Lancet Global Health, 2020. 8(9): p. e1195-e1202.
Debellut, F., A. Clark, C. Pecenka, J. Tate, R. Baral, C. Sanderson, et al., Re-evaluating the potential impact and cost-effectiveness of rotavirus vaccination in 73 Gavi countries: a modelling study. The Lancet Global Health. 7(12): p. e1664-e1674.
UNICEF, Afghanistan introduces rotavirus vaccine to protect infants and young children against severe diarrhea. 27 January 2018.
Anwari, P., F. Debellut, C. Pecenka, S.M. Parwiz, A. Clark, D. Groman, et al., Potential impact and cost-effectiveness of rotavirus vaccination in Afghanistan. Vaccine, 2018. 36(51): p. 7769-7774.
Anwari, P., E. Burnett, N. Safi, A. Samsor, H. Safi, T.P. Chavers, et al., Effectiveness and impact of monovalent rotavirus vaccination in Afghanistan: a test-negative case-control analysis. Lancet Glob Health, 2024. 12(9): p. e1517-e1525.
Anwari, P., E. Burnett, T.P. Chavers, A. Samsor, H. Safi, N. Safi, et al., Post-marketing surveillance of intussusception after Rotarix administration in Afghanistan, 2018–2022. Vaccine, 2024. 42(8): p. 2059-2064.
Burnett, E., A. Riaz, P. Anwari, T.W. Myat, T.P. Chavers, N. Talat, et al., Intussusception risk following oral monovalent rotavirus vaccination in 3 Asian countries: A self-control case series evaluation. Vaccine, 2023.
Gavi. Gavi-supported rotavirus vaccines profiles to support country decision making. 2023 [cited 2023 12/21/2023]; Available from: https://www.gavi.org/sites/default/files/programmes-impact/support/Gavi-Rotavirus-vaccines-profiles-ENG-February-2023.pdf.
Mandomando, I., A. Messa, Jr., J.N. Biey, G. Paluku, M. Mumba, and J.M. Mwenda, Lessons Learned and Future Perspectives for Rotavirus Vaccines Switch in the World Health Organization, Regional Office for Africa. Vaccines (Basel), 2023. 11(4).
Debellut, F., S. Jaber, Y. Bouzya, J. Sabbah, M. Barham, F. Abu-Awwad, et al., Introduction of rotavirus vaccination in Palestine: An evaluation of the costs, impact, and cost-effectiveness of ROTARIX and ROTAVAC. PLoS One, 2020. 15(2): p. e0228506.
PAHO, W. About UNIVAC | Provac Toolkit. [cited 2023 December 22, 2023]; Available from: https://www.paho.org/en/provac-toolkit.
Clark, A., J. Tate, U. Parashar, M. Jit, M. Hasso-Agopsowicz, N. Henschke, et al., Mortality reduction benefits and intussusception risks of rotavirus vaccination in 135 low-income and middle-income countries: a modelling analysis of current and alternative schedules. The Lancet Global Health, 2019. 7(11): p. e1541-e1552.
WB. The World Bank, GDP per capita (current US$)- Afghanistan. 2024 [cited 2024 13/1/2024]; Available from: https://data.worldbank.org/indicator/NY.GDP.MKTP.CD?end=2021&locations=AF&start=2003&view=chart.
UNDP, Two Years in Review: Chaning in Afghan Economy, Households and Cross-cutting Sectors (August 2021 to August 2023). December 2023.
WHO. WHO guide for standardization of economic evaluations of immunization programs, Edition II, Licence: CC BY-NC-SA 3.0 IGO. 2019 [cited 2022 December 22, 2023]; Available from: https://apps.who.int/iris/.
Walker, C.L.F., I. Rudan, L. Liu, H. Nair, E. Theodoratou, Z.A. Bhutta, et al., Global burden of childhood pneumonia and diarrhoea. The Lancet, 2013. 381(9875): p. 1405-1416.
Bilcke, J., P. Van Damme, M. Van Ranst, N. Hens, M. Aerts, and P. Beutels, Estimating the Incidence of Symptomatic Rotavirus Infections: A Systematic Review and Meta-Analysis. PLOS ONE, 2009. 4(6): p. e6060.
UNICEF, Afghanistan Multiple Indicator Cluster Survey 2022-23, Survey Findings Report. Kabul, Afghanistan: United Nations Children's Fund (UNICEF). 2023, UNICEF: Kabul, Afghanistan.
Anwari, P., N. Safi, D.C. Payne, M.C. Jennings, S. Rasikh, A.S. Waciqi, et al., Rotavirus is the leading cause of hospitalizations for severe acute gastroenteritis among Afghan children <5 years old. Vaccine, 2018. 36(51): p. 7765-7768.
Clark, A., R. Black, J. Tate, A. Roose, K. Kotloff, D. Lam, et al., Estimating global, regional and national rotavirus deaths in children aged <5 years: Current approaches, new analyses and proposed improvements. PLoS One, 2017. 12(9): p. e0183392.
Hasso-Agopsowicz, M., C.N. Ladva, B. Lopman, C. Sanderson, A.L. Cohen, J.E. Tate, et al., Global Review of the Age Distribution of Rotavirus Disease in Children Aged <5 Years Before the Introduction of Rotavirus Vaccination. Clin Infect Dis, 2019. 69(6): p. 1071-1078.
Salomon, J.A., J.A. Haagsma, A. Davis, C.M. de Noordhout, S. Polinder, A.H. Havelaar, et al., Disability weights for the Global Burden of Disease 2013 study. The Lancet Global Health, 2015. 3(11): p. e712-e723.
CDC. The pink book-Epidemiology and Prevention of Vaccine-Preventable Disease. [cited 2023 11/12/2023]; Available from: https://www.cdc.gov/vaccines/pubs/pinkbook/index.html.
Baral, R., J. Nonvignon, F. Debellut, S.A. Agyemang, A. Clark, and C. Pecenka, Cost of illness for childhood diarrhea in low- and middle-income countries: a systematic review of evidence and modelled estimates. BMC Public Health, 2020. 20(1): p. 619.
WUENIC. WHO/UNICEF Estimates of National Immunisation COverage, 2022 Revision. 2023 [cited 2023 September 8, 2023]; Available from: https://worldhealthorg.shinyapps.io/wuenic-trends-2023/.
Clark, A. and C. Sanderson, Timing of children's vaccinations in 45 low-income and middle-income countries: an analysis of survey data. The Lancet, 2009. 373(9674): p. 1543-1549.
Gavi. Eligiblity and Transition policy, Version 4.0 2023 [cited 2023 12/23/2023]; Available from: https://www.gavi.org/types-support/sustainability/eligibility.
UNICEF. Cost of Vaccinating a Child. 2020 [cited 2023 27 December 2023]; Available from: https://www.unicef.org/supply/handling-fees.
Portnoy, A., K. Vaughan, E. Clarke-Deelder, C. Suharlim, S.C. Resch, L. Brenzel, et al., Producing Standardized Country-Level Immunization Delivery Unit Cost Estimates. PharmacoEconomics, 2020. 38(9): p. 995-1005.
Owusu, R., M. Mvundura, J. Nonvignon, G. Armah, J. Bawa, K.O. Antwi-Agyei, et al., Rotavirus vaccine product switch in Ghana: An assessment of service delivery costs, switching costs, and cost-effectiveness. PLOS Glob Public Health, 2023. 3(8): p. e0001328.
Jiang, J., B. Jiang, U. Parashar, T. Nguyen, J. Bines, and M.M. Patel, Childhood intussusception: a literature review. PLoS One, 2013. 8(7): p. e68482.
Clark, A.D., M. Hasso-Agopsowicz, M.W. Kraus, L.K. Stockdale, C.F.B. Sanderson, U.D. Parashar, et al., Update on the global epidemiology of intussusception: a systematic review of incidence rates, age distributions and case-fatality ratios among children aged <5 years, before the introduction of rotavirus vaccination. International Journal of Epidemiology, 2019. 48(4): p. 1316-1326.
Cost Analysis of Kabul's National Hospitals, H.E.a.F. Directorate, Editor. 2012, Ministry of Public Health: Kabul, Afghanistan.
Davis, R., Teaching Note—Teaching Project Simulation in Excel Using PERT-Beta Distributions. INFORMS Transactions on Education, 2008. 8(3): p. 139-148.
Pichon-Riviere, A., M. Drummond, A. Palacios, S. Garcia-Marti, and F. Augustovski, Determining the efficiency path to universal health coverage: cost-effectiveness thresholds for 174 countries based on growth in life expectancy and health expenditures. Lancet Glob Health, 2023. 11(6): p. e833-e842.
Anderson, J.D.t., C.J. Pecenka, K.H. Bagamian, and R.D. Rheingans, Effects of geographic and economic heterogeneity on the burden of rotavirus diarrhea and the impact and cost-effectiveness of vaccination in Nigeria. PLoS ONE [Electronic Resource]. 15(5): p. e0232941.
Pecenka, C., F. Debellut, N. Bar-Zeev, P. Anwari, J. Nonvignon, M. Shamsuzzaman, et al., Re-evaluating the cost and cost-effectiveness of rotavirus vaccination in Bangladesh, Ghana, and Malawi: A comparison of three rotavirus vaccines. Vaccine, 2018. 36(49): p. 7472-7478.
Rose, J., L. Homa, S.B. Meropol, S.M. Debanne, R. Bielefeld, C. Hoyen, et al., Health impact and cost-effectiveness of a domestically-produced rotavirus vaccine in India: A model based analysis. PloS one, 2017. 12(11): p. e0187446.
Clark, A., J. Tate, U. Parashar, M. Jit, M. Hasso-Agopsowicz, N. Henschke, et al., Mortality reduction benefits and intussusception risks of rotavirus vaccination in 135 low-income and middle-income countries: a modelling analysis of current and alternative schedules. Lancet Glob Health, 2019. 7(11): p. e1541-e1552.
Anwari, P., E. Burnett, N. Safi, A. Samsor, H. Safi, T.P. Chavers, et al., Effectiveness and Impact of Monovalent Rotavirus Vaccination in Afghanistan, a test-negative case-control analysis. Lancet Global Health, 2024 (in press).
Freiesleben de Blasio, B., E. Flem, R. Latipov, A. Kuatbaeva, and I.S. Kristiansen, Dynamic modeling of cost-effectiveness of rotavirus vaccination, Kazakhstan. Emerg Infect Dis, 2014. 20(1): p. 29-37.
Luangasanatip, N., W. Mahikul, K. Poovorawan, B.S. Cooper, Y. Lubell, L.J. White, et al., Cost-effectiveness and budget impact analyses for the prioritisation of the four available rotavirus vaccines in the national immunisation programme in Thailand. Vaccine, 2021. 39(9): p. 1402-1414.

No competing interests reported.

2024825CUASupplementFinal.docx

Download PDF

Editorial decision: Revision requested
29 Aug, 2024
Editor assigned by journal
29 Aug, 2024
Submission checks completed at journal
26 Aug, 2024
First submitted to journal
25 Aug, 2024

You are reading this latest preprint version

Cost-effectiveness and benefit-risk of rotavirus vaccination in Afghanistan: a modelling analysis informed by post-licensure surveillance

Status:

Version 1

Abstract

Introduction

Methods

Findings

Conclusion

Figures

Introduction

Methods

Study design and model

Data collection and consensus building

RVGE disease burden

RVGE healthcare cost

Vaccination coverage, timeliness, and effectiveness

Vaccine price and delivery cost

Intussusception burden, risk, and costs

Uncertainty analysis

Role of the funding source

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1