Cost-eff ectiveness of female human papillomavirus vaccination in 179 countries: a PRIME modelling study

Background Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specifi c eff ects on health and economic costs. We aimed to develop and validate a simple generic model of such eff ects that could be used and understood in a range of settings with little external support. Methods We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-eff ectiveness and health eff ects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine effi cacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-eff ectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed diff erences between countries in terms of cost-eff ectiveness and health eff ects. Findings In validation, PRIME reproduced cost-eff ectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690 000 cases of cervical cancer and 420 000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost eff ective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200 000 cases of cervical cancer and 100 000 deaths in some of the highest-burden countries. Interpretation Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions

Model Comparisons of the Effectiveness and Cost-Effectiveness of Vaccination: A Systematic Review of the Literature.

OBJECTIVES: To describe all published articles that have conducted comparisons of model-based effectiveness and cost-effectiveness results in the field of vaccination. Specific objectives were to 1) describe the methodologies used and 2) identify the strengths and limitations of the studies. METHODS: We systematically searched MEDLINE and Embase databases for studies that compared predictions of effectiveness and cost-effectiveness of vaccination of two or more mathematical models. We categorized studies into two groups on the basis of their data source for comparison (previously published results or new simulation results) and performed a qualitative synthesis of study conclusions. RESULTS: We identified 115 eligible articles (only 5% generated new simulations from the reviewed models) examining the effectiveness and cost-effectiveness of vaccination against 14 pathogens (69% of studies examined human papillomavirus, influenza, and/or pneumococcal vaccines). The goal of most of studies was to summarize evidence for vaccination policy decisions, and cost-effectiveness was the most frequent outcome examined. Only 33%, 25%, and 3% of studies followed a systematic approach to identify eligible studies, assessed the quality of studies, and performed a quantitative synthesis of results, respectively. A greater proportion of model comparisons using published studies followed a systematic approach to identify eligible studies and to assess their quality, whereas more studies using new simulations performed quantitative synthesis of results and identified drivers of model conclusions. Most comparative modeling studies concluded that vaccination was cost-effective. CONCLUSIONS: Given the variability in methods used to conduct/report comparative modeling studies, guidelines are required to enhance their quality and transparency and to provide better tools for decision making

Comparison of two dose and three dose human papillomavirus vaccine schedules: cost effectiveness analysis based on transmission model.

OBJECTIVE: To investigate the incremental cost effectiveness of two dose human papillomavirus vaccination and of additionally giving a third dose. DESIGN: Cost effectiveness study based on a transmission dynamic model of human papillomavirus vaccination. Two dose schedules for bivalent or quadrivalent human papillomavirus vaccines were assumed to provide 10, 20, or 30 years' vaccine type protection and cross protection or lifelong vaccine type protection without cross protection. Three dose schedules were assumed to give lifelong vaccine type and cross protection. SETTING: United Kingdom. POPULATION: Males and females aged 12-74 years. INTERVENTIONS: No, two, or three doses of human papillomavirus vaccine given routinely to 12 year old girls, with an initial catch-up campaign to 18 years. MAIN OUTCOME MEASURE: Costs (from the healthcare provider's perspective), health related utilities, and incremental cost effectiveness ratios. RESULTS: Giving at least two doses of vaccine seems to be highly cost effective across the entire range of scenarios considered at the quadrivalent vaccine list price of £86.50 (€109.23; $136.00) per dose. If two doses give only 10 years' protection but adding a third dose extends this to lifetime protection, then the third dose also seems to be cost effective at £86.50 per dose (median incremental cost effectiveness ratio £17,000, interquartile range £11,700-£25,800). If two doses protect for more than 20 years, then the third dose will have to be priced substantially lower (median threshold price £31, interquartile range £28-£35) to be cost effective. Results are similar for a bivalent vaccine priced at £80.50 per dose and when the same scenarios are explored by parameterising a Canadian model (HPV-ADVISE) with economic data from the United Kingdom. CONCLUSIONS: Two dose human papillomavirus vaccine schedules are likely to be the most cost effective option provided protection lasts for at least 20 years. As the precise duration of two dose schedules may not be known for decades, cohorts given two doses should be closely monitored

Human papillomavirus vaccine effectiveness by number of doses: Systematic review of data from national immunization programs.

BACKGROUND: Human papillomavirus (HPV) vaccines were first licensed as a three-dose series; a two-dose series is now recommended in some age groups and there is interest in possible one-dose vaccination. METHODS: We conducted a systematic literature review of HPV vaccine effectiveness by number of doses, including assessment of biases and impact of varying buffer periods (time between vaccination and outcome counting). RESULTS: Of 3787 articles identified, 26 full articles were assessed and 14 included in our review. All studies were conducted within the context of recommended three-dose schedules of bivalent (3) or quadrivalent HPV vaccine (11). Two evaluated effectiveness for prevention of HPV prevalence, six anogenital warts, and six abnormal cervical cytology or histology. Many studies found differences between three-, two- and one-dose vaccine recipients, indicating possible differences in HPV exposure prior to vaccination or in risk behavior. Adjusted or stratified analyses were conducted to control for potential confounding. All studies found significant vaccine effectiveness with three doses, 11 with two doses at various intervals, and six with one dose. Most studies showed a relationship (not always statistically significant) between effectiveness and number of doses, with greater decreases in HPV-related outcomes with three, followed by two and one dose(s). Few studies conducted formal comparisons of three vs fewer doses. Three of four studies that examined buffer periods found higher effectiveness and a smaller difference by number of doses with longer periods. CONCLUSION: Most post-licensure studies report highest effectiveness with three doses; some found no statistically significant difference between two and three doses. Additionally, almost half found some effectiveness with one dose. Several biases impact estimates, with most biasing two- and one-dose results away from showing effectiveness. Future effectiveness studies, examining persons vaccinated prior to sexual activity and using methods to reduce potential sources of bias, can help inform vaccination policy

Incomplete Wood-Ljungdahl pathway facilitates one-carbon metabolism in organohalide-respiring Dehalococcoides mccartyi.

The acetyl-CoA "Wood-Ljungdahl" pathway couples the folate-mediated one-carbon (C1) metabolism to either CO2 reduction or acetate oxidation via acetyl-CoA. This pathway is distributed in diverse anaerobes and is used for both energy conservation and assimilation of C1 compounds. Genome annotations for all sequenced strains of Dehalococcoides mccartyi, an important bacterium involved in the bioremediation of chlorinated solvents, reveal homologous genes encoding an incomplete Wood-Ljungdahl pathway. Because this pathway lacks key enzymes for both C1 metabolism and CO2 reduction, its cellular functions remain elusive. Here we used D. mccartyi strain 195 as a model organism to investigate the metabolic function of this pathway and its impacts on the growth of strain 195. Surprisingly, this pathway cleaves acetyl-CoA to donate a methyl group for production of methyl-tetrahydrofolate (CH3-THF) for methionine biosynthesis, representing an unconventional strategy for generating CH3-THF in organisms without methylene-tetrahydrofolate reductase. Carbon monoxide (CO) was found to accumulate as an obligate by-product from the acetyl-CoA cleavage because of the lack of a CO dehydrogenase in strain 195. CO accumulation inhibits the sustainable growth and dechlorination of strain 195 maintained in pure cultures, but can be prevented by CO-metabolizing anaerobes that coexist with D. mccartyi, resulting in an unusual syntrophic association. We also found that this pathway incorporates exogenous formate to support serine biosynthesis. This study of the incomplete Wood-Ljungdahl pathway in D. mccartyi indicates a unique bacterial C1 metabolism that is critical for D. mccartyi growth and interactions in dechlorinating communities and may play a role in other anaerobic communities

Economic analyses to support decisions about HPV vaccination in low- and middle-income countries: a consensus report and guide for analysts.

Low- and middle-income countries need to consider economic issues such as cost-effectiveness, affordability and sustainability before introducing a program for human papillomavirus (HPV) vaccination. However, many such countries lack the technical capacity and data to conduct their own analyses. Analysts informing policy decisions should address the following questions: 1) Is an economic analysis needed? 2) Should analyses address costs, epidemiological outcomes, or both? 3) If costs are considered, what sort of analysis is needed? 4) If outcomes are considered, what sort of model should be used? 5) How complex should the analysis be? 6) How should uncertainty be captured? 7) How should model results be communicated? Selecting the appropriate analysis is essential to ensure that all the important features of the decision problem are correctly represented, but that the analyses are not more complex than necessary. This report describes the consensus of an expert group convened by the World Health Organization, prioritizing key issues to be addressed when considering economic analyses to support HPV vaccine introduction in these countries

From cervical cancer elimination to eradication of vaccine-type human papillomavirus: Feasibility, public health strategies and cost-effectiveness.

The Director-General of the World Health Organization has called for global action towards elimination of cervical cancer as a public health problem. Cervical cancer is caused by human papillomavirus (HPV), an infectious agent with no non-human reservoir. One way to achieve this is through very high levels of vaccine coverage that could enable global eradication of vaccine-type HPV. Using the case study of India, we show that HPV eradication can meet all the Dahlem and Strüngmann criteria for feasibility of eradication. It can be achieved with 90% gender-neutral HPV vaccine coverage together with 95% coverage in high-risk groups such as female sex workers. Such a strategy would likely be cost-effective compared to no vaccination. Although it would be more costly in the short-term than achieving cervical cancer elimination alone, it would save costs in the long-term by removing or at least sharply reducing the need for preventive measures

Salt marsh die-off and recovery reveal disparity between the recovery of ecosystem structure and service provision

a b s t r a c t Coastal ecosystems, such as sand dunes, salt marshes, and mangroves, stabilize shorelines and protect coastal populations. In New England, salt marshes have experienced widespread cordgrass (Spartina alterniflora) die-off and habitat loss, and it is unknown how this has affected their ability to provide coastal protection. We quantified wave attenuation and shoreline stability on healthy, die-off and recovered marsh creek banks. We found that coastal protection has been severely compromised by salt marsh die-off, and that to date, S. alterniflora recovery, while superficially impressive, has not returned this ecosystem service to the levels of intact marshes. Climate driven sea-level rise and predicted increases in the frequency and severity of storms over the next century will likely further increase the vulnerability of coastal populations. Therefore, recovery of coastal protection is essential for maintaining the ecological and economic wellbeing of coastal communities. Our results suggest that quantification of the recovery of ecosystem services should be employed in order to successfully measure recovery in degraded ecosystems

Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: a transmission-dynamic modelling study.

BACKGROUND: Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada. METHODS: We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost. FINDINGS: Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between$7900-24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated. INTERPRETATION: Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls