Cost-effectiveness analysis of quadrivalent and nonavalent human papillomavirus vaccines in Ethiopia

BackgroundIn Ethiopia, cervical cancer is the second most common cancer among women of the reproductive age group. Since 2018, the quadrivalent human papillomavirus (4vHPV) vaccine targeting four HPV types (6/11/16/18) has been introduced in the national immunization program in Ethiopia. Currently, however, a nonavalent HPV (9vHPV) vaccine which provides broader protection against nine HPV types (?6/11/16/18/31/33/45/52/58) is available for global use. Our study, therefore, aims to estimate the cost-effectiveness of 9vHPV vaccine compared to the current HPV vaccination program in Ethiopia.MethodA static Markov cohort model was used to simulate the progression of HPV infection to cervical cancer for a cohort of 12-years-old girls (N = 100,000) in Ethiopia. The model ran up to the age of 100 years, with a cycle length of 1 year. One-way and probabilistic sensitivity analyses were used to explore the robustness of the model and uncertainties around the parameters included in the model. Cost-effectiveness thresholds of one and three times gross domestic product (GDP) per quality-adjusted life-year (QALY) gained were considered.ResultsAt a price of US$ 6.9, the incremental cost-effectiveness ratio (ICER) per QALY gained for the 9vHPV vaccine was US$ 454 compared to the 4vHPV vaccine, which is less than one times GDP per capita of Ethiopia. The ICER was most sensitive to the change in the discount rate of QALYs. Compared to 4vHPV vaccine, for 9vHPV vaccine to remain very cost-effective and cost-effective, its price per dose should not exceed US$ 8.4 and US$ 15, respectively, at a threshold of one and three times GDP per capita.ConclusionCompared to the 4vHPV vaccine, the 9vHPV vaccine is a cost-effective option in Ethiopia, given that its price per dose does not exceed US$15.     

Public health impact and cost-effectiveness of a nine-valent gender-neutral HPV vaccination program in France

ObjectivesIn France, 9-valent HPV vaccination is recommended routinely for 11–14-years-old girls and as catch-up for 15–19-years-old girls. Recently, recommendation for gender-neutral vaccination (GNV) has been approved. The objectives of the study were to assess the public health impact and cost-effectiveness of a 9-valent GNV compared with girls-only vaccination program (GOV).MethodsA published HPV disease transmission dynamic model accounting for herd protection effects with a 100-year time horizon was adapted and calibrated to French data. Epidemiological and economic outcomes included disease cases averted and quality-adjusted life years (QALY). Costs and incremental cost-effectiveness ratio (ICER) were measured in 2018 Euros (€). A coverage rate of 26.2% among girls and boys was assumed for the GNV program based on the current female coverage rate in France. The base case included genital warts, cervical, vulvar, vaginal, and anal cancers. Scenario analyses included all HPV-related diseases and considered higher vaccination coverage rate (60%). Deterministic sensitivity analyses on key inputs were performed.ResultsOver 100 years, GNV resulted in an additional reduction of 9,519 and 3,037 cervical cancer cases and deaths; 6,901 and 1,166 additional anal cancer cases and deaths; and a reduction of additional 1,284,077 genital warts compared with current GOV and an ICER of 24,763€/QALY. When including all HPV-related diseases, the ICER was 15,184€/QALY. At a higher coverage rate (60%), GNV would prevent 17,430 and 4,334 additional anogenital cancer cases and deaths and over two million genital warts compared with GOV with an ICER of 40,401€/QALY. Results were sensitive to a higher discount rate (6% versus 4%) and a shorter duration of protection (20 years versus lifetime).ConclusionsIn France, GNV has a significant impact in terms of public health benefits and may be considered cost-effective compared with GOV at low and high coverage rates.     

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5 years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1 × gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective.     

Targeted hepatitis E vaccination for women of childbearing age is cost-effective in China

BackgroundHepatitis E virus (HEV) infection is hyper-endemic in China, it is characterized with a high morbidity of fulminant hepatitis and mortality in pregnant women. The first hepatitis E vaccine, HEV 239, was licensed in China in 2011 which provides an effective preventive measure.ObjectiveTo evaluate the cost-effectiveness of vaccination with HEV 239 in women of childbearing age in China and whether HEV antibody screening should be considered before vaccination.MethodsA decision tree-Markov model was constructed to simulate HEV infection in a closed female cohort with an average first-marriage age of 25 years and evaluate health and economic outcomes of two potential vaccination strategies, direct vaccination and combined screening and vaccination, from a societal perspective. An incremental cost-effectiveness ratio (ICER, additional costs per disability-adjusted life-year (DALY) averted) was calculated for each vaccination strategy versus no vaccination and between two vaccination strategies. Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of the model findings.ResultsICERs of direct vaccination and combined screening and vaccination versus no vaccination were $4040 and $3114 per DALY averted, respectively, much lower than 1-time Chinese per-capita GDP ($8127). Direct vaccination would need additional $45,455 for each DALY averted compared with combined screening and vaccination, far more than the 3-time per-capita GDP. Probabilistic sensitivity analyses confirmed our findings that two vaccination strategies would be cost-effective if the willingness-to-pay reached the 1-time per-capita GDP, and that combined screening and vaccination would be more cost-effective than direct vaccination strategy.ConclusionVaccinating women of childbearing age with HEV 239 would cost less than the 1-time per-capita GDP for each DALY averted in China, and the vaccination with a prior screening would be the optimal option.     

Cost-effectiveness of quadrivalent versus trivalent influenza vaccine for elderly population in China

BackgroundInfluenza-associated excess death occurred most in the elderly. We aimed to assess the cost-effectiveness of quadrivalent influenza vaccine (QIV) versus trivalent influenza vaccine (TIV) for prevention of influenza infection among elderly population in China.MethodsA decision-analytic model was developed to compare 1-year clinical and economic outcomes of three influenza vaccination options (no vaccination, TIV, and QIV) in a hypothetical cohort of Chinese elderly aged 69 years. Outcome measures included cost, influenza infection rate, influenza-related mortality rate, quality-adjusted life-years (QALY) loss, and incremental cost-effectiveness ratio (ICER) from societal perspective. Sensitivity analyses were performed to examine the uncertainty of model inputs.ResultsBase-case results showed no vaccination was dominated (more costly at higher QALY loss) by TIV and QIV. QIV was more costly (USD56.29 versus USD54.28) with lower influenza infection rate (0.608 versus 0.623), mortality rate (0.00199 versus 0.00204), and QALY loss (0.01213 versus 0.01243) than TIV. QIV was cost-effective compared to TIV with ICER of 6,700 USD/QALY below the willingness-to-pay threshold (29,580 USD/QALY). One-way sensitivity analysis found the cost-effectiveness of QIV was subject to the relative risk of vaccine effectiveness of QIV versus TIV, and TIV would be cost-effective if the relative risk was below 1.05. In 10,000 Monte Carlo simulations, the probabilities of QIV, TIV, and no vaccination to be cost-effective were 86.3%, 13.7%, and 0%, respectively.ConclusionQIV appears to be a cost-effective option compared to TIV and no influenza vaccination for elderly population in China.     

Economic evaluation of the introduction of rotavirus vaccine in Hong Kong

BackgroundRotavirus is a common cause of severe gastroenteritis in young children in Hong Kong (HK) with a high economic burden. This study aimed to evaluate the cost-effectiveness of introducing rotavirus vaccination into the HK Government’s Childhood Immunisation Programme (CIP) and to include the potential protective effect of the vaccine against seizures.MethodsA decision-support model was customised to estimate the potential impact, cost-effectiveness and benefit-risk of rotavirus vaccination in children below 5 years over the period 2020–2029 in HK. Two doses of Rotarix® and three doses of RotaTeq® were each compared to no vaccination. Rotavirus treatment costs were calculated from a governmental health sector perspective (i.e., costs of public sector treatment) and an overall health sector perspective (both governmental and patient, i.e., costs of public sector treatment, private sector treatment, transport and diapers). We ran probabilistic and deterministic uncertainty analyses.ResultsIntroduction of rotavirus vaccination in HK could prevent 49,000 (95% uncertainty interval: ~44,000–54,000) hospitalisations of rotavirus gastroenteritis and seizures and result in ~50 (95% uncertainty interval: ~25–85) intussusception hospitalisations, over the period 2020–2029 (a benefit-risk ratio of ~1000:1), compared to a scenario with no public or private sector vaccine use. The discounted vaccination cost would be US$51–57 million over the period 2020–2029 based on per-course prices of US$72 (Rotarix®) or US$78 (RotaTeq®), but this would be offset by discounted treatment cost savings of US$70 million (government) and US$127 million (governmental and patient health sector). There was a greater than 94% probability that the vaccine could be cost-saving irrespective of the vaccine product or perspective considered. All deterministic ‘what-if’ scenarios were cost-saving from an overall health sector perspective (governmental and patient).ConclusionsRotavirus vaccination is likely to be cost-saving and have a favourable benefit-risk profile in HK. Based on the assumptions made, our analysis supports its introduction into CIP.     

Cost effectiveness of trivalent and quadrivalent influenza vaccines in 50- to 64-year-old adults in Korea

BackgroundInfluenza causes severe complications in at-risk populations, resulting in significant morbidity and mortality. Vaccination is the most effective measure to prevent infection and complications caused by seasonal influenza. However, no study has analyzed the cost-effectiveness of influenza vaccines in 50- to 64-year-olds in South Korea.ObjectiveWe examined the application of the National Immunization Program (NIP) in 50- to 64-year-olds and compared the cost-effectiveness of quadrivalent influenza vaccine (QIV) with that of trivalent influenza vaccine (TIV) in South Korea.MethodsOne-year static model was assumed by constructing separate decision trees for age subgroups: 50–54, 55–59, and 60–64. Each subgroup was divided into at-risk and not-at-risk groups. Using circulation data from previous studies and Korea Centers for Disease Control and Prevention, we estimated the probabilities of influenza infection, outpatient treatment, hospitalization, and deaths. Medical cost was estimated from 2015 to 2017 National Health Insurance Sharing Service claim data, while productivity losses from work absenteeism or death were estimated from labor and economic surveys of Korean government. Disutility was estimated based on previous studies.ResultsCompared with non-vaccination, incremental cost-effectiveness ratios (ICERs) for the 50–54, 55–59, and 60–64 age groups for TIV were US$2010.90, US$2004.58, and US$1865.55, respectively, while for QIV were US$2187.17, US$2190.89, and US$2074.52, respectively. Compared with TIV, ICERs for QIV were US$4445.66, US$4578.06, and US$4751.93, respectively. All the aforementioned ICER values were lower than the 2017 Korean GDP per capita of US$29,742.839.ConclusionImplementing the NIP in the 50- to 64-year-old age group was found to be cost effective. Since both TIV and QIV were cost effective, we recommend QIV as the preferred option, based on its greater protection against Influenza B.     

Effect of provider recommendation style on the length of adolescent vaccine discussions

ObjectiveTo determine whether providers’ vaccine recommendation style affects length of the adolescent vaccine discussions.MethodsWe analyzed vaccine discussions using audio-recordings of clinical encounters where adolescents were eligible for HPV vaccines ± meningococcal vaccines. We measured length of vaccine discussions, the provider’s use of an “indicated” (vaccination due at visit) or “elective” (vaccination is optional) recommendation style, and vaccine receipt. Parent and child demographics, parental vaccination intentions, and parental satisfaction with vaccine discussion were collected from pre- and post-visit surveys. We used linear and logit regressions with random effects to estimate recommendation style’s association with discussion length and with vaccine receipt, respectively.ResultsWe analyzed 106 vaccine discussions (82 HPV; 24 meningococcal) across 82 clinical encounters and 43 providers. Vaccine discussions were longer when providers presented vaccination as elective versus indicated (140 vs. 74 s; p-value < 0.001). Controlling for vaccine type, parental vaccination intent, and patient characteristics, an elective style was associated with 41 seconds longer vaccine discussion (p-value < 0.05). Providers used the indicated style more frequently with the meningococcal vaccine than with the HPV vaccine (96% vs. 72%; p-value < 0.05). Parents’ odds of vaccinating were 9.3 times higher following an indicated versus an elective presentation (p-value < 0.05). Vaccine discussion length and presentation style were not associated with parental satisfaction.ConclusionsOur results suggest that using an indicated recommendation improves vaccine discussions’ efficiency and effectiveness, but this style is used more often with meningococcal than HPV vaccines. Increasing providers’ use of indicated styles for HPV vaccines has the potential to increase vaccination rates and save time during medical visits.     

Human papillomavirus vaccine coverage in Rwanda: A population-level analysis by birth cohort

BackgroundIn 2011, Rwanda became the first African nation to implement a national human papillomavirus (HPV) vaccination program, conceived to protect girls aged <15 years (i.e. born ≥1997). After an initial school-grade-targeted catch-up campaign, there was a transition to routine vaccination of 12 year-olds only. We aimed to produce population-level vaccine coverage estimates.MethodsThe Rwandan Expanded Program on Immunization (EPI) collected data on number of eligible girls and HPV vaccines delivered, stratified by calendar year (2011–2018), girl’s age, district and vaccination round. HPV vaccine coverage was estimated by birth cohort (reconstituted using calendar year and age), as a proportion of (1) eligible target, and (2) the 2012 Rwandan census population.Results1,156,863 girls received first dose of HPV vaccine between 2011 and 2018, corresponding to 98% of the eligible target. Median vaccination age was 15 years (interquartile range [IQR] 13–16) in 2011–2013 (school grade-targeted catch-up), 13 years (IQR 12–14) in 2014 (transition) and 12 years in 2015–2018 (routine). Population-level coverage versus the census increased from 10 to 40% for girls born in 1993–1995 (median vaccination age = 17 years) to 50–65% for 1996–2000 birth cohorts (14 years), and 80–90% for 2001–2006 birth cohorts (12 years). Coverage trends were similar across provinces and in the capital, Kigali. Second and third round coverage suggested most vaccinated girls completed their recommended dosing regimen (which reduced from 3 to 2 doses in 2015).ConclusionsBirth cohorts provide a clear picture of population-level HPV vaccine coverage after a pragmatic catch-up campaign, particularly in Rwanda where eligible school grades included wide age ranges. Whilst the catch-up campaign resulted in some coverage gaps in out-of-school teenagers, coverage remains high in cohorts routinely targeted as 12 year-olds.     

Systematic literature review of neutralizing antibody immune responses to non-vaccine targeted high-risk HPV types induced by the bivalent and the quadrivalent vaccines

IntroductionStudies on the cross-protective effect of HPV bivalent and quadrivalent vaccines demonstrated inconsistent findings against additional HPV types covered by the nonavalent vaccine. The objective of this study was to conduct a systematic literature review to assess the consistency and durability of the cross-protective neutralizing antibody immune responses of the currently licensed bivalent and quadrivalent vaccines to non-vaccine HPV types targeted by the nonavalent vaccine (HPV 6, 11, 31, 33, 45, 52, and 58).MethodsPubMed and EMBASE databases were searched from 2008 to 2019 to identify studies reporting antibody/immune response after vaccination with either the bivalent, quadrivalent, or nonavalent vaccine. Key outcomes were seroconversion, seropositivity or geometric mean titers against HPV types 6, 11, 31, 33, 45, 52, and 58.ResultsEighteen publications met inclusion criteria, reporting on 14 interventional and five observational studies. Across all studies, immune responses to non-vaccine high-risk HPV types after bivalent vaccination were higher than baseline or quadrivalent vaccine. Nonavalent vaccine elicited near total seroconversion to HPV types 31, 33, 45, 52, and 58, with seropositivity remaining near 100% up to 24 months post-dose 1. In contrast, bivalent and quadrivalent vaccination resulted in lower seroconversion levels for non-vaccine types, which waned over time.ConclusionsThe cross-protection antibody/immune response among participants having received all three doses of bivalent or quadrivalent vaccine is not comparable to the specific response elicited by HPV vaccine types. Even in cases where a statistically significant cross-reactive immunological response is reported, long-term data on the duration of the response beyond two years are very limited. Further, the lack of a standard for assays limits comparability of results between studies.     

Identification of subgroups in the Danish population for targeted human papillomavirus vaccination efforts

BackgroundIn the Danish childhood vaccination program, the human papillomavirus (HPV) vaccination coverage is lower than for other vaccines. To tailor a targeted HPV vaccination effort, we aimed to identify girls in Denmark with lower first dose HPV vaccination coverage than girls in general.MethodsA population-based retrospective cohort study was performed of girls born in 2001–2004, residing in Denmark in September 2019 (N = 128,351). Data from the Danish Vaccination Register was linked to sociodemographic data from the Danish Civil Registration System and Statistics Denmark. Cox's proportional hazard regression models were used to compare vaccination uptake rates between subgroups of girls.ResultsHPV vaccination coverage at 14 years of age varied widely by municipality (53.4–80.6%). Girls living with neither of their parents had a lower chance of being vaccinated compared to girls living with both their parents (HR 0.43; 95% CI 0.41–0.46), likewise for girls attending special need education compared with girls attending public schools (HR 0.50; 95% CI 0.42–0.59). The vaccination uptake among immigrants was lower compared to Danish-born girls (HR 0.51; 95% CI 0.49–0.54), especially among immigrant girls whose parents had not passed any Danish exams. Finally, girls who were DTaP-IPV revaccinated had a 50% greater chance of being HPV vaccinated compared to girls who were not (HR 1.61; 95% CI 1.58–1.64).ConclusionTo increase the HPV vaccination uptake, we recommend vaccination efforts targeting girls living without any of their parents, girls attending special need education, immigrants, and girls who are not DTaP-IPV revaccinated. When targeting immigrants, the effort should focus on disseminating sufficient and understandable information about the Danish childhood vaccination program to the parents.     

Cost-effectiveness of sub-national geographically targeted vaccination programs: A systematic review

Immunization is an essential component of national health plans. However, the growing number of new vaccine introductions, vaccination campaigns and increasing administrative costs create logistic and financial challenges, especially in resource-limited settings. Sub-national geographic targeting of vaccination programs is a potential strategy for governments to reduce the impact of infectious disease outbreaks while optimizing resource allocation and reducing costs, promoting sustainability of critically important national immunization plans. We conducted a systematic review of peer-reviewed literature to identify studies that investigated the cost-effectiveness of geographically targeted sub-national vaccination programs, either through routine immunization or supplementary immunization activities. A total of 16 studies were included in our review, covering nine diseases of interest: cholera, dengue, enterotoxigenic Escherichia coli (ETEC), hepatitis A, Japanese encephalitis, measles, rotavirus, Shigella and typhoid fever. All studies modelled cost-effectiveness of geographically targeted vaccination. Despite the variation in study design, disease focus and country context, studies generally found that in countries where a heterogenous burden of disease exists, sub-national geographic targeting of vaccination programs in areas of high disease burden was more cost-effective than a non-targeted strategy. Sensitivity analysis revealed that cost-effectiveness was most sensitive to variations in vaccine price, vaccine efficacy, mortality rate, administrative and operational costs, discount rate, and treatment costs. This systematic review identified several key characteristics related to geographic targeting of vaccination, including the vaccination strategy used, variations in modelling parameters and their impact on cost-effectiveness. Additional research and guidance is needed to support the appropriateness and feasibility of geographically targeted vaccination and to determine what country context would make this a viable complement to routine immunization programs.     

Efficacy of quadrivalent human papillomavirus vaccine against persistent infection and genital disease in Chinese women: A randomized,placebo-controlled trial with 78-month follow-up

BackgroundA quadrivalent human papillomavirus vaccine (qHPV; HPV6/11/16/18) has demonstrated efficacy and effectiveness worldwide. We report qHPV vaccine efficacy for up to 6.5 years after first administration among Chinese women 20–45 years of age.MethodsIn this randomized, double-blind, placebo-controlled, multicenter, Phase 3 study (NCT00834106), women were randomized 1:1 to receive 3 doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). Endo-ecto-cervical and external genital swabs were collected for HPV testing and gynecologic examinations, and cervical cytology testing were performed at Day 1 and Months 7, 12, 18, 24, 30, 42, 54, 66, and 78. Any abnormality in cytology testing would trigger colposcopy examination and cervical biopsy, if necessary. Efficacy against genital disease, persistent infection, and the composite endpoint was assessed. Primary efficacy analyses were conducted in the per-protocol efficacy (PPE) population.ResultsOf 3006 participants randomized, 2759 (91.8%) and 2374 (79%) completed the Month 30 and Month 78 visits, respectively. At Month 78, efficacy among women aged 20–45 years was 100% (95% CI: 32.3, 100; 0 vs 7 cases) and 100% (95% CI: 70.9, 100; 0 vs 14 cases) against HPV16/18-related cervical intraepithelial neoplasia Grade 2 or 3, adenocarcinoma in situ, and cervical cancer (CIN 2+) and HPV6/11/16/18-related CIN 1+, respectively, in the PPE population. The efficacy against cervical 6-month and 12-month persistent infection was 91.6% (95% CI: 66.0, 99.0) and 97.5% (95% CI: 85.1, 99.9) at Month 30 and Month 78, respectively, in the PPE population. The vaccine also reduced the rate of cervical cytology abnormalities associated with HPV6/11/16/18, with an efficacy of 94.0% (95% CI: 81.5, 98.8). The vaccine was generally well tolerated (reported separately).ConclusionThe qHPV vaccine is efficacious against endpoints of persistent infection and genital precancerous lesions in Chinese women aged 20–45 years.     

Reduction of HPV16/18 prevalence in young women after eight years of three- and two-dose vaccination schemes

BackgroundRecommendations for human papillomavirus vaccination have relied on immunogenicity studies and efficacy results derived from adult women. Insufficient information exists regarding HPV effectiveness in vaccinated girls as they become sexually active, regardless of dose scheme. We aimed to compare the prevalence of high-risk HPV between unvaccinated and vaccinated young women eight years after immunization.MethodsAfter eight years, we recontacted women who received two-dose of bivalent or three-dose—either bivalent or quadrivalent—, HPV vaccine when aged 9–10 years-old as part of a clinical trial. Additionally, we recruited a contemporaneous unvaccinated woman group for comparison. Only those sexually active were included. High-risk HPV DNA was determined in urine samples and compared across groups.ResultsThe prevalence of HPV16/18 types was 6.8% (95 %CI 3.2–14.1%) in the unvaccinated (n = 6/88), 1.1% (95 %CI 0.2–5.8%) in the three-dose (n = 1/93), and 0.0% (95 %CI 0.0–7.0%) in the two-dose group (n = 0/51).ConclusionHPV vaccination, with two-dose of bivalent or three-dose schemes—either with the bivalent or quadrivalent vaccine—, was associated with a lower prevalence of HPV16/18 types eight years after primary immunization.     

Cost-effectiveness of routine catch-up hepatitis a vaccination in the United States: Dynamic transmission modeling study

BackgroundDespite routine vaccination of children against hepatitis A (HepA), a large segment of the United States population remains unvaccinated, imposing a risk of hepatitis A virus (HAV) to adolescents and adults. In July of 2020, the Advisory Committee on Immunization Practices recommended that all children and adolescents aged 2–18 years who have not previously received a HepA vaccine be vaccinated. We evaluated the public health impact and cost-effectiveness of this HepA catch-up vaccination strategy.MethodsWe used a dynamic transmission model to compare adding a HepA catch-up vaccination of persons age 2–18 years to a routine vaccination of children 12–23 months of age with routine vaccination only in the United States. The model included various health compartments: maternal antibodies, susceptible, exposed, asymptomatic infectious, symptomatic infectious (outpatient, hospitalized, liver transplant, post- liver transplant, death), recovered, and vaccinated with and without immunity. Using a 3% annual discount rate, we estimated the incremental cost per quality-adjusted life year (QALY) gained from a societal perspective over a 100-year time horizon. All costs were converted into 2020 US dollars.FindingsCompared with the routine vaccination policy at 12–23 months of age over 100 years, the catch-up program for unvaccinated children and adolescents aged 2–18 years, prevented 70,072 additional symptomatic infections, 51,391 outpatient visits, 16,575 hospitalizations, and 413 deaths. The catch-up vaccination strategy was cost-saving when compared with the routine vaccination strategy. In scenario analysis allowing administering a second dose to partially vaccinated children, the cost-effectiveness of was not favorable at a higher vaccination coverage ($196,701/QALY at 5% and $476,241/QALY at 50%).InterpretationHepA catch-up vaccination in the United States is expected to reduce HepA morbidity and mortality and save cost. The catch-up program would be optimized when focusing on unvaccinated children and adolescents and maximizing their first dose coverage.     

Assessment of thyroiditis risk associated with HPV vaccination among girls aged 9–18 years: A time-varying cohort study

BackgroundPrevious studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain.MethodsIn this retrospective cohort study, girls in BIFAP aged 9–18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included. Hazard Ratios (HRs; 95% CI) of thyroiditis were calculated within exposed periods (up to 2 years of vaccination) and post-exposed periods (from 2 years after vaccination onwards) compared with non-exposed periods, overall, by dose and by type of vaccine, adjusted for potential confounders collected at different times. In a post-hoc analysis, we moved back the thyroiditis date (30 days) as a theoretical delay in diagnosis.ResultsOut of the 388,411 girls included in the cohort, 153,924 were vaccinated against HPV and 480 thyroiditis (253 autoimmune) cases were identified (334 non-exposed; 103 exposed; 43 post-exposed). Adjusted HR was 1.18 [95% CI: 0.79–1.76] for exposed (1.25 [0.77–2.04] for bi- and 1.15 [0.76–1.76] for quadri-valent vaccines) and 1.26 [0.74–2.14] for post-exposed periods. HR was 1.50 [0.87–2.59] for the 1^st dose, 1.13 [0.66–1.91] for the 2^nd and 1.11 [0.71–1.72] for the 3^rd one. When the diagnosis date was moved back, the risk was 1.14 [0.76–1.70] for exposed period, being 1.80 [0.86–3.76] and 1.40 [0.74–2.66] after 1^st dose of bi- and quadri-valent, respectively.ConclusionsWe did not observe an increased risk of thyroiditis following HPV vaccination (whether bi- or quadri-valent). Even though the point estimate was higher after 1^st HPV vaccination dose than after subsequent doses, a dose–effect was not confirmed. Results remained similar after applying a lag time.     

Cost-effectiveness of maternal immunization against neonatal invasive Group B Streptococcus in the Netherlands

BackgroundNeonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates.ObjectiveExplore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands.MethodsWe assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017.ResultsUnder base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands.ConclusionsA maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.     

Modeling the health and economic implications of adopting a 1-dose 9-valent human papillomavirus vaccination regimen in a high-income country setting: An analysis in the United Kingdom

Although no human papillomavirus (HPV) vaccine is indicated for single-dose administration, some observational evidence suggests that a 1-dose regimen might reduce HPV infection risk to that achieved with 2 doses. This study estimated the potential health and economic outcomes associated with switching from a 2-dose HPV vaccination program for girls and boys aged 13–14 years to an off-label 9-valent (9vHPV), 1-dose regimen, accounting for the uncertainty of the effectiveness and durability of a single dose. A dynamic HPV transmission infection and disease model was adapted to the United Kingdom and included a probabilistic sensitivity analysis using estimated distributions for duration of protection of 1-dose and degree of protection of 1 relative to 2 doses. One-way sensitivity analyses of key inputs were performed. Outcomes included additional cancer and disease cases and the difference in net monetary benefit (NMB). The 1-dose program was predicted to result in 81,738 additional HPV-related cancer cases in males and females over 100 years compared to the 2-dose program, ranging from 36,673 to 134,347 additional cases (2.5% and 97.5% quantiles, respectively), and had a 7.8% probability of being cost-effective at the £20,000/quality-adjusted life years willingness-to-pay (WTP) threshold. In one-way sensitivity analyses, the number of additional cancer cases was sensitive to the median of the duration of protection distribution and coverage rates. The differences in NMBs were sensitive to the median of the duration of protection distribution, dose price and discount rate, but not coverage variations. Across sensitivity analyses, the probability of 1 dose being cost-effective vs 2 doses was < 50% at the standard WTP threshold. Adoption of a 1-dose 9vHPV vaccination program resulted in more vaccine-preventable HPV-related cancer and disease cases in males and females, introduced substantial uncertainty in health and economic outcomes, and had a low probability of being cost-effective compared to the 2-dose program.     

Post-vaccination HPV seroprevalence among female sexual health clinic attenders in England

BackgroundThe National HPV Immunisation Programme was introduced in England in September 2008 using the HPV16/18 bivalent vaccine. We conducted serological surveillance to explore vaccination coverage levels. We also conducted a case-control study to investigate a hypothesised cross-protective effect of the HPV16/18 vaccine against genital warts.MethodsResidual serum specimens from 16 to 20 year-old women attending six specialist sexual health services (SSHS) between 2011 and 2015 in England were tested for antibodies against HPV16 and HPV18 using a virus-like particle (VLP)-based multiplex serology assay. Patients were classified as having vaccine-induced seropositivity if they were seropositive for both HPV types and either had high antibody levels for at least one HPV type, or moderately high levels for both HPV types.Differences in vaccine-induced seropositivity by patient characteristics were investigated using logistic regression. Vaccine-induced seropositivity was then compared for patients with genital warts (cases) and matched patients without (controls).ResultsOf 3,973 serum specimens collected, 3,870 (97.4%) had a valid result. The proportion of women with vaccine-induced seropositivity decreased with age (from 78.1% in 16-year-olds to 52.6% in 20-year-olds). Vaccine-induced seropositivity was lower among women born outside the UK, from more deprived areas and with a history of chlamydia diagnosis. A difference in uptake by ethnic group was also seen but this was largely confounded by differences in deprivation and country of birth. Among 537 cases and 1,515 controls, there was little evidence of a protective effect of the bivalent HPV vaccine against genital warts (adjusted odds ratio 0.93; 95% CI: 0.74–1.18).DiscussionVaccine-induced seropositivity in this high-risk population was in line with vaccination coverage in the general population although was lower in some at-risk sub-groups. This study does not provide evidence to support a cross-protective effect of the HPV16/18 vaccine against genital warts.     

Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9–45 years: A randomized,double-blind,placebo-controlled phase 1 clinical trial

BackgroundWe evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine.MethodsIn this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9–45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies.ResultsA total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMT_{HPV 16} = 10816 [95 % CI: 7824–14953]), GMT_{HPV 18} = 3966 [95 % CI: 2693–5841]) and high dose group (GMT _{HPV 16} = 14482 [95 % CI: 10848–19333], GMT _{HPV 18} = 3428 [95 % CI: 2533–4639]).ConclusionThe pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9–45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.