The cost-effectiveness of typhoid Vi vaccination programs: calculations for four urban sites in four Asian countries

The burden of typhoid fever remains high in impoverished settings, and increasing antibiotic resistance is making treatment costly. One strategy for reducing the typhoid morbidity and mortality is vaccination with the Vi polysaccharide vaccine. We use a wealth of new economic and epidemiological data to evaluate the cost-effectiveness of Vi vaccination against typhoid in sites in four Asian cities: Kolkata (India), Karachi (Pakistan), North Jakarta (Indonesia), and Hue (Vietnam). We report results from both a societal as well as a public sector financial perspective. Baseline disease burden estimates in the four areas are: 750 cases per year in two Kolkata neighborhoods (pop 185,000); 84 cases per year in the city of Hue (pop 280,000); 298 cases per year in two sub-districts in North Jakarta (pop 161,000), and 538 cases per year in three squatter settlements in Karachi (pop 102,000). We estimate that a vaccination program targeting all children (2-14.9) would prevent 456, 158, and 258 typhoid cases (and 4.6, 1.6, and 2.6 deaths), and avert 126, 44, and 72 disability-adjusted life years (DALYs) over 3 years in Kolkata, North Jakarta and Karachi, respectively. The net social costs would be US$160 and US$549, per DALY averted in Kolkata and North Jakarta, respectively. These programs, along with a similar program in Karachi, would be considered "very cost-effective" (e.g. costs per DALY averted less than per capita gross national income (GNI)) under a wide range of assumptions. Community-based vaccination programs that also target adults in Kolkata and Jakarta are less cost-effective because incidence is lower in adults than children, but are also likely to be "very cost-effective". A program targeting school-aged children in Hue, Vietnam would prevent 21 cases, avert 6 DALYs, and not be cost-effective (US$3779 per DALY averted) because of the low typhoid incidence there.     

Comparison of model predictions of typhoid conjugate vaccine public health impact and cost-effectiveness

Models are useful to inform policy decisions on typhoid conjugate vaccine (TCV) deployment in endemic settings. However, methodological choices can influence model-predicted outcomes. To provide robust estimates for the potential public health impact of TCVs that account for structural model differences, we compared four dynamic and one static mathematical model of typhoid transmission and vaccine impact. All models were fitted to a common dataset of age-specific typhoid fever cases in Kolkata, India. We evaluated three TCV strategies: no vaccination, routine vaccination at 9 months of age, and routine vaccination at 9 months with a one-time catch-up campaign (ages 9 months to 15 years). The primary outcome was the predicted percent reduction in symptomatic typhoid cases over 10 years after vaccine introduction. For three models with economic analyses (Models A-C), we also compared the incremental cost-effectiveness ratios (ICERs), calculated as the incremental cost (US$) per disability-adjusted life-year (DALY) averted. Routine vaccination was predicted to reduce symptomatic cases by 10–46 % over a 10-year time horizon under an optimistic scenario (95 % initial vaccine efficacy and 19-year mean duration of protection), and by 2–16 % under a pessimistic scenario (82 % initial efficacy and 6-year mean protection). Adding a catch-up campaign predicted a reduction in incidence of 36–90 % and 6–35 % in the optimistic and pessimistic scenarios, respectively. Vaccine impact was predicted to decrease as the relative contribution of chronic carriers to transmission increased. Models A-C all predicted routine vaccination with or without a catch-up campaign to be cost-effective compared to no vaccination, with ICERs varying from $95–789 per DALY averted; two models predicted the ICER of routine vaccination alone to be greater than with the addition of catch-up campaign. Despite differences in model-predicted vaccine impact and cost-effectiveness, routine vaccination plus a catch-up campaign is likely to be impactful and cost-effective in high incidence settings such as Kolkata.     

Considerations around the introduction of a cholera vaccine in Bangladesh

Cholera is an endemic and epidemic disease in Bangladesh. On 3 March 2013, a meeting on cholera and cholera vaccination in Bangladesh was convened by the Foundation Mérieux jointly with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B). The purpose of the meeting was to discuss the investment case for cholera vaccination as a complimentary control and prevention strategy. The performance of a new low cost oral cholera vaccine, Shanchol™, used in recent trials in Bangladesh, was also reviewed in the context of a potential large-scale public-sector vaccination program. Findings showed the oral vaccine to be highly cost-effective when targeting ages 1–14y, and cost-effective when targeting ages 1+y, in high-burden/high-risk districts. Other vaccination strategies targeting urban slums and rural areas without improved water were found to be cost-effective. Regardless of cost-effectiveness (value), the budget impact (affordability) will be an important determinant of which target population and vaccination strategy is selected. Most importantly, adequate vaccine supply for the proposed vaccination programs must be addressed in the context of global efforts to establish a cholera vaccine stockpile and supply other control and prevention efforts.     

Age-Based Programs for Vaccination against HPV

Background:  The risk of infection with human papillomavirus (HPV) increases with age. Answering the question of which age groups are appropriate to target for catch-up vaccination with the newly licensed quadrivalent HPV vaccine (types 6/11/16/18) will be important for developing vaccine policy recommendations.
Objectives:  To assess the value of varying female HPV vaccination strategies by specific age groups of a catch-up program in the United States.
Methods:  The authors used previously published mathematical population dynamic model and cost-utility analysis to evaluate the public health impact and cost-effectiveness of alternative quadrivalent HPV (6/11/16/18) vaccination strategies. The model simulates heterosexual transmission of HPV infection and occurrence of cervical intraepithelial neoplasia (CIN), cervical cancer, and external genital warts in an age-structured population stratified by sex and sexual activity groups. The cost-utility analysis estimates the cost of vaccination, screening, diagnosis, and treatment of HPV diseases, and quality-adjusted survival.
Results:  Compared with the current screening practices, vaccinating girls and women ages 12 to 24 years was the most effective strategy, reducing the number of HPV6/11/16/18-related genital warts, CIN grades 2 and 3, and cervical cancer cases among women in the next 25 years by 3,049,285, 1,399,935, and 30,021; respectively. The incremental cost-effectiveness ratio of this strategy when compared with vaccinating girls and women ages 12 to 19 years was $10,986 per quality-adjusted life-year gained.
Conclusion:  Relative to other commonly accepted health-care programs, vaccinating girls and women ages 12 to 24 years appears cost-effective.     

Cost-effectiveness of oral cholera vaccine in a stable refugee population at risk for epidemic cholera and in a population with endemic cholera.

Recent large epidemics of cholera with high incidence and associated mortality among refugees have raised the question of whether oral cholera vaccines should be considered as an additional preventive measure in high-risk populations. The potential impact of oral cholera vaccines on populations prone to seasonal endemic cholera has also been questioned. This article reviews the potential cost-effectiveness of B-subunit, killed whole-cell (BS-WC) oral cholera vaccine in a stable refugee population and in a population with endemic cholera. In the population at risk for endemic cholera, mass vaccination with BS-WC vaccine is the least cost-effective intervention compared with the provision of safe drinking-water and sanitation or with treatment of the disease. In a refugee population at risk for epidemic disease, the cost-effectiveness of vaccination is similar to that of providing safe drinking-water and sanitation alone, though less cost-effective than treatment alone or treatment combined with the provision of water and sanitation. The implications of these data for public health decision-makers and programme managers are discussed. There is a need for better information on the feasibility and costs of administering oral cholera vaccine in refugee populations and populations with endemic cholera.     

Cost-effectiveness of HPV vaccination compared with Pap smear screening on a national scale: a literature review

Recommendations for worldwide use of human papillomavirus (HPV) vaccine are increasing. This study conducted a systematic review of articles related to cost-effectiveness analysis of wide-range HPV vaccination programs compared with Pap smear screening published before August 2007. Eight articles were identified using predefined inclusion and exclusion criteria. After excluding two outliers, the range of incremental cost-effectiveness ratios (ICERs) from six articles is between $16,600 and $27,231 per quality-adjusted life year (QALY) gained. The World Health Organization's guideline that compares incremental cost-effectiveness ratios (ICERs) with per capita Gross Domestic Product (GDP) was used to determine whether nation-wide application of HPV vaccine would be cost-effective. The HPV vaccination program is cost-effective in only 46 countries where per capita GDP is high. Further cost-effectiveness studies in developing and third-world countries are needed for making policy decisions.     

Cost-effectiveness analysis of a gender-neutral human papillomavirus vaccination program in the Netherlands

BackgroundVaccinating girls against human papillomavirus (HPV) infection is a highly effective and cost-effective intervention to provide protection against HPV-induced cancers. Since vaccination coverage rates among girls is modest in the Netherlands, additional strategies should be implemented to improve the protection against HPV-related cancer. Here we assessed the benefits and cost-effectiveness of gender-neutral vaccination.MethodsWe designed a static Markov model with a lifelong time horizon to simulate a cohort of 100,000 12-year-old Dutch boys. The model compares health and economic effects of HPV vaccination taking the current female vaccination coverage into consideration. HPV prevalence in boys was corrected for the predicted herd effects of the female programme in 2017. We extracted transition probabilities from peer-reviewed literature and previously constructed models. The robustness of the model was tested with multiple sensitivity analyses.ResultsVaccinating 30% of 100,000 12-year-old boys prevents 18, 13 and 25 cases of anal, penile, and oropharyngeal cancers in men, respectively. A total of 205 quality-adjusted life-years (QALYs) are saved by preventing cancer-related morbidity and mortality. Assuming a vaccine price of €50 per dose, the incremental cost-effectiveness ratio (ICER) is €17,907 per QALY. In addition, due to vaccine-induced herd effects, we estimated that 110 cases of cancer in females would be additionally prevented and 246 QALYs would be gained in the female cohort, bringing the total to 166 cancers prevented and 451 QALYs gained. Taking these additional benefits of boys’ vaccination into account, the overall ICER was estimated at €7310 per QALY gained. The model outcomes are most sensitive to variation in vaccine price, herd immunity from females and vaccine efficacy.ConclusionsVaccination of boys, additional to girls, will prevent a relevant number of cancers in both boys and girls. Based on the current Dutch situation vaccination of HPV in boys is likely cost-effective.GSK Study identifier: HO-18-19169. A graphical abstract and supplementary data to this article can be found online at https://doi.org/10.1016/j.vaccine.2020.05.031.     

Cost-effectiveness analysis of pneumococcal conjugate vaccination in England and Wales

AIM: To establish whether universal vaccination of infants with the pneumococcal conjugate vaccine is likely to be cost-effective from the perspective of the health care provider (NHS). METHOD: Two hypothetical cohorts--one vaccinated and one unvaccinated--were followed over their lifetime, and the expected net costs and benefits (measured in terms of life-years and quality adjusted life years (QALY) gained) were compared in the two cohorts. The impact of indirect effects of the vaccine, such as herd immunity and serotype replacement, were investigated and their relative importance was assessed by performing univariate sensitivity analysis and multivariate Monte Carlo simulations. RESULTS: Under base-case assumptions (no herd immunity and no serotype replacement) the programme is not expected to be cost-effective from the NHS perspective at the current price of the vaccine (assumed 30 pounds per dose, three-dose programme). A reduction of the cost of the vaccine to half of its current level could bring the cost per QALY gained within normally acceptable ranges. If the burden of disease is significantly underestimated by current surveillance systems, then the cost per QALY gained approaches acceptable levels at the current vaccine price. Herd immunity may substantially reduce the burden of pneumococcal disease, particularly of pneumonia among the elderly, leading to a significant improvement in the cost per life year and QALY gained. Serotype replacement would partly offset these benefits, although only with a complete substitution of vaccine types with non-vaccine types and a low level of herd immunity, would pneumococcal vaccination programme would not be cost-effective. CONCLUSIONS: Conclusions on the cost-effectiveness of pneumococcal conjugate vaccine are sensitive to assumptions regarding the current burden of pneumococcal disease and the future impact that vaccination will have in the unvaccinated and on the future serotype distribution. This study quantifies, for the first time, how these indirect effects may change the cost-effectiveness of pneumococcal vaccination.     

Optimizing immunization schedules in endemic cholera regions: cost-effectiveness assessment of vaccination strategies for cholera control in Bangladesh

This study is to examine the cost-effectiveness of deployment strategies of oral cholera vaccines (OCVs) in controlling cholera in Bangladesh. We developed a dynamic compartment model to simulate costs and health outcomes for 12 years for four OCVs deployment scenarios: (1) vaccination of children aged one and above with two doses of OCVs, (2) vaccination of population aged 5 and above with a single dose of OCVs, (3) vaccination of children aged 1–4 with two doses of OCVs; and (4) combined strategy of (2) and (3). We obtained all parameters from the literature and performed a cost-effectiveness analysis from both health systems and societal perspectives, in comparison with the base scenario of no vaccination. The incremental cost-effectiveness ratios (ICERs) for the four strategies from the societal perspective were $2,236, $2,250, $1,109, and $2,112 per DALY averted, respectively, with herd immunity being considered. Without herd immunity, the ICERs increased substantially for all four scenarios except for the scenario that vaccinates children aged 1–4 only. The major determinants of ICERs were the case fatality rate and the incidence of cholera, as well as the efficacy of OCVs. The projection period and frequency of administering OCVs would also affect the cost-effectiveness of OCVs. With the cut-off of 1.5 times gross domestic product per capita, the four OCVs deployment strategies are cost-effective. The combined strategy is more efficient than the strategy of vaccinating the population aged one and above with two doses of OCVs and could be considered in the resource-limited settings.     

中国婴幼儿普遍接种轮状病毒疫苗的成本效果分析

目的 对中国现阶段是否应将婴幼儿接种轮状病毒疫苗纳入免疫规划进行经济学评价,并探讨其成本效果。方法 通过构建决策树Markov模型,模拟2012年中国出生的新生儿分别在不接种轮状病毒疫苗及接种Rotarix疫苗或Rotateq疫苗3种方案下的成本和健康结局,基于各方案间的增量成本效果比(ICER)与中国2012年人均国内生产总值(GDP)的比较确定最优方案。结果 与不接种方案相比,Rotarix疫苗和Rotateq疫苗接种方案可分别减少发生238万和253万例轮状病毒腹泻,避免12.6万和13.3万个伤残调整寿命年的损失,ICER分别为3 760元和7 578元,均小于我国2012年人均GDP(38 420元);Rotateq疫苗相对于Rotarix疫苗,ICER为81 068元,介于1与3倍人均GDP之间。结论 在中国婴幼儿中开展轮状病毒疫苗普遍接种具有高的成本效果,应考虑将其纳入计划免疫;考虑到疫苗免疫费用、大规模组织实施的难度等因素,在现阶段更适宜推广接种Rotarix疫苗。