Cost-effectiveness of a potential group B streptococcal vaccine for pregnant women in the United States

BackgroundIn the U.S., intrapartum antibiotic prophylaxis (IAP) for pregnant women colonized with group B streptococcus (GBS) has reduced GBS disease in the first week of life (early-onset/EOGBS). Nonetheless, GBS remains a leading cause of neonatal sepsis, including 1000 late-onset (LOGBS) cases annually. A maternal vaccine under development could prevent EOGBS and LOGBS.MethodsUsing a decision-analytic model, we compared the public health impact, costs, and cost-effectiveness of five strategies to prevent GBS disease in infants: (1) no prevention; (2) currently recommended screening/IAP; (3) maternal GBS immunization; (4) maternal immunization with IAP when indicated for unimmunized women; (5) maternal immunization plus screening/IAP for all women. We modeled a pentavalent vaccine covering serotypes 1a, 1b, II, III, and V, which cause almost all GBS disease.ResultsIn the base case, screening/IAP alone prevents 46% of EOGBS compared to no prevention, at a cost of $70,275 per quality-adjusted life-year (QALY) from a healthcare and $51,249/QALY from a societal perspective (2013 US$). At coverage rates typical of maternal vaccines in the U.S., a pentavalent vaccine alone would not prevent as much disease as screening/IAP until its efficacy approached 90%, but would cost less per QALY. At vaccine efficacy of ≥70%, maternal immunization together with IAP for unimmunized women would prevent more disease than screening/IAP, at a similar cost/QALY.ConclusionsGBS maternal immunization, with IAP as indicated for unvaccinated women, could be an attractive alternative to screening/IAP if a pentavalent vaccine is sufficiently effective. Coverage, typically low for maternal vaccines, is key to the vaccine’s public health impact.     

High rates of colonization and antimicrobial resistance of group B streptococcus highlight the need for vaccination even after implementation of guidelines for intrapartum antibiotic prophylaxis

IntroductionIt is estimated that about 11–35% of pregnant women are colonized with Group B streptococcus. Intrapartum antibiotic prophylaxis (IAP) is the primary intervention to decrease the risk of infecting babies born to GBS colonized mothers.MethodsA total of 5,996 pregnant women, who received the Taiwanese universal GBS screening program from 2012 to 2020, were included in this study that investigated GBS colonization, antimicrobial resistance rates and their neonatal incidence of invasive GBS infection.ResultsThe average GBS colonization rate was 18.5%. Older age groups had higher colonization rates than younger age groups. Compared to Taiwanese, immigrant women from Indonesia had a greater positive rate. GBS isolated from Vietnamese women had significant greater resistance to clindamycin relative to Taiwanese women. Rates of resistance to erythromycin increase from 35.5% to 45.5% over the 9 years of measurements. The incidence of invasive GBS disease was about 0.6/1,000 (4/6,204) live births during the study.ConclusionsAlthough relatively low incidence of invasive GBS diseases was observed after implementation of IAP, the colonization of GBS remains high and antimicrobial resistance of GBS is increasing. An effective GBS vaccine holds promise to be a solution for these issues.     

The potential cost-effectiveness of adding a human papillomavirus vaccine to the cervical cancer screening programme in South Africa

This study was designed to answer the question of whether a cervical cancer prevention programme that incorporates a human papillomavirus (HPV) vaccine is potentially more cost-effective than the current strategy of screening alone in South Africa. We developed a static Markov state transition model to describe the screening and management of cervical cancer within the South African context. The incremental cost-effectiveness ratio of adding HPV vaccination to the screening programme ranged from US $1078 to 1460 per quality-adjusted life year (QALY) gained and US$3320–4495 per life year saved, mainly depending on whether the study was viewed from a health service or a societal perspective. Using discounted costs and benefits, the threshold analysis indicated that a vaccine price reduction of 60% or more would make the vaccine plus screening strategy more cost-effective than the screening only approach. To address the issue of affordability and cost-effectiveness, the pharmaceutical companies need to make a commitment to price reductions.     

Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa

Background

RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective.

Potential cost-effectiveness of a maternal Group B streptococcal vaccine in The Gambia

ObjectiveTo estimate neonatal health benefits and healthcare provider costs of a theoretical Group B streptococcal (GBS) hexavalent maternal vaccination programme in The Gambia, a low-income setting in West Africa.MethodsA static decision analytic cost-effectiveness model was developed from the healthcare provider perspective. Demographic data and acute care costs were available from studies in The Gambia undertaken in 2012–2015. Further model parameters were taken from United Nations and World Health Organisation sources, supplemented by data from a global systematic review of GBS and literature searches. As vaccine efficacy is not known, we simulated vaccine efficacy estimates of 50–90%. Costs are reported in US dollars. Cost-effectiveness thresholds of one (US$473, very cost effective) and three (US$1420, cost effective) times Gambian GDP were used.ResultsVaccination with a hexavalent vaccine would avert 24 GBS disease cases (55%) and 768 disability adjusted life years compared to current standard of care (no interventions to prevent GBS disease). At vaccine efficacy of 70%, the programme is cost-effective at a maximum vaccine price per dose of 12 US$ (2016 US$), and very cost-effective at a maximum of $3/dose. The total costs of vaccination at $12 is $1,056,962 for one annual cohort of Gambian pregnant women. One-way sensitivity analysis showed that GBS incidence was the most influential parameter on the cost effectiveness ratio.ConclusionThe introduction of a hexavalent vaccine would considerably reduce the current burden of GBS disease in The Gambia but to be cost-effective, the vaccine price per dose would need to be $12/dose or less.     

新生儿早发型GBS败血症1例并文献复习

目的介绍新生儿早发型B族溶血链球菌（GBS）败血症的临床表现、治疗及预防方法。方法报道1例血培养及脑脊液培养均为阳性的早发型GBS败血症患儿的,临床表现、实验室检查及治疗经过,并进行文献复习。结果该病例为一例以化脓性脑膜炎为主要表现的早发型GBS败血症,先后经积极1周青霉素及4周万古霉素抗感染治疗,治愈出院,随访预后良好。结论GBS是新生儿早发型败血症重要的致病菌,青霉素是治疗的首选药物,必要时也可使用万古霉素抗感染治疗,建议对孕妇开展产前GBS筛查并进行预防性治疗,尤其应对高危新生儿进行监测以减少早发型GBS败血症的发生和远期严重后遗症。免疫预防和疫苗预防有望成为更有效的预防策略。     

Potential coverage of a multivalent M protein-based group A streptococcal vaccine

Background

The greatest burden of group A streptococcal (GAS) disease worldwide is due to acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Safe, effective and affordable vaccines designed to prevent GAS infections that trigger ARF could reduce the overall global morbidity and mortality from RHD. The current study evaluated the potential coverage of a new 30-valent M protein-based vaccine using GAS isolates from school children in Bamako, Mali, a population at high risk for the development of RHD.

Methods

The bactericidal activity of rabbit antisera against the 30-valent vaccine was assessed using a collection of GAS isolates recovered during a study of the epidemiology of pharyngitis in Bamako.

Results

Single isolates representing 42 of 67 emm-types, accounting for 85% of the GAS infections during the study, were evaluated. All (14/14) of the vaccine emm-types in the collection were opsonized (bactericidal killing >50%) and 26/28 non-vaccine types were opsonized. Bactericidal activity was observed against 60% of the total emm-types recovered in Bamako, which accounted for 81% of all infections.

Conclusions

Multivalent vaccines comprised of N-terminal M peptides elicit bactericidal antibodies against a broad range of GAS serotypes, indicating that their efficacy may extend beyond the emm-types included in the vaccine.     

The potential impact of RV144-like vaccines in rural South Africa: a study using the STDSIM microsimulation model

Background

The only successful HIV vaccine trial to date is the RV144 trial of the ALVAC/AIDSVAX vaccine in Thailand, which showed an overall incidence reduction of 31%. Most cases were prevented in the first year, suggesting a rapidly waning efficacy. Here, we predict the population level impact and cost-effectiveness of practical implementation of such a vaccine in a setting of a generalised epidemic with high HIV prevalence and incidence.

Methods

We used STDSIM, an established individual-based microsimulation model, tailored to a rural South African area with a well-functioning HIV treatment and care programme. We estimated the impact of a single round of mass vaccination for everybody aged 15-49, as well as 5-year and 2-year re-vaccination strategies for young adults (aged 15-29). We calculated proportion of new infections prevented, cost-effectiveness indicators, and budget impact estimates of combined ART and vaccination programmes.

Results

A single round of mass vaccination with a RV144-like vaccine will have a limited impact, preventing only 9% or 5% of new infections after 10 years at 60% and 30% coverage levels, respectively. Revaccination strategies are highly cost-effective if vaccine prices can be kept below 150 US$/vaccine for 2-year revaccination strategies, and below 200 US$/vaccine for 5-year revaccination strategies. Net cost-savings through reduced need for HIV treatment and care occur when vaccine prices are kept below 75 US$/vaccine. These results are sensitive to alternative assumptions on the underlying sexual network, background prevention interventions, and individual's propensity and consistency to participate in the vaccination campaign.

Discussion

A modestly effective vaccine can be a cost-effective intervention in highly endemic settings. To predict the impact of vaccination strategies in other endemic situations, sufficient knowledge of the underlying sexual network, prevention and treatment interventions, and individual propensity and consistency to participate, is key. These issues are all best addressed in an individual-based microsimulation model.     

A randomized,observer-blind Phase Ib study to identify formulations and vaccine schedules of a trivalent Group B Streptococcus vaccine for use in non-pregnant and pregnant women

BackgroundGroup B streptococcus (GBS) is a leading cause of sepsis and meningitis in early infancy. Substantial data demonstrate that women with higher levels of circulating antibody against the capsular polysaccharide (CPS) deliver infants at reduced risk of GBS infection, which serves as the basis for vaccine design. This study evaluates two different dosages, two injection schedules and three formulations of an investigational trivalent (serotypes Ia, Ib and III) CRM₁₉₇-glycoconjugate GBS vaccine in healthy, non-pregnant women.Methods678 healthy non-pregnant women received one or two injections of one of two dosages (5/5/5 μg or 20/20/20 μg) of the investigational vaccine, formulated with or without aluminum hydroxide (Enrolment Group 1), or with full or half dosages of MF59^® (Enrolment Group 2); or a placebo (Enrolment Groups 1 and 2). Geometric mean serotype-specific antibody concentrations (GMCs) at Days 61 (Enrolment Group 1) and 361 (both Groups) were analyzed to select a formulation suitable for pregnant or non-pregnant women, respectively. Solicited adverse reactions were recorded up to Day 7 and adverse events (AEs) were recorded throughout the study.ResultsRates of reported AEs were similar across all groups. Higher rates of local reactogenicity were seen in adjuvanted vaccine groups compared with non-adjuvanted vaccine (or placebo) groups. All vaccine groups elicited higher GMCs than placebo; differences between treatments were not statistically significant, indicating no additional potential benefit of higher antigen content, addition of adjuvant, or a second dose.ConclusionsAll GBS vaccine formulations induced a persistent antibody response and showed similar immunogenicity profiles (NCT01150123).     

新生儿B族链球菌败血症15例的临床分析

目的 探讨新生儿B族链球菌(GBS)败血症的临床特点.方法 选择2012年1月至2015年12月在广东省佛山市南海区人民医院接受治疗的血培养阳性的GBS败血症新生儿15例,分析其临床特点.结果 15例GBS败血症患儿中早发型GBS败血症患儿10例,晚发型GBS败血症患儿5例,早发型GBS败血症患儿以呼吸系统症状为主,出生24h内发病,晚发型GBS败血症患儿以高热为首发症状,均合并化脓性脑膜炎.GBS败血症患儿的白细胞水平较低,降钙素原反应灵敏,C反应蛋白反应相对滞后.GBS菌株对青霉素和万古霉素高度敏感,敏感性均为100%,其次为头孢呋辛(93.33%).结论 新生儿GBS败血症起病凶险,可造成永久神经系统损伤,医院开展产前GBS筛查对减少新生儿GBS感染有较大的意义,对于存在白细胞下降、PCT异常,且存在呼吸系统症状的新生儿,应尽早给予治疗.     

Cost-effectiveness of a tetravalent human papillomavirus vaccine in Germany

Aim  Clinical trials have demonstrated the efficacy of the tetravalent human papillomavirus (HPV) vaccination in the prevention of cervical cancer and genital warts associated with HPV types 6, 11, 16 and 18. We used an empirically calibrated Markov cohort model of the natural history of HPV to assess the cost-effectiveness of the vaccine administered to 12-year-old girls alongside existing cervical screening programmes in Germany. Subjects and methods  The model estimated cervical cancer (CC), cervical intraepithelial neoplasia (CIN) and genital wart lifetime risks and total lifetime health care costs, life years gained and quality-adjusted life years (QALY) gained. The analysis was conducted from the perspective of the German health care payer. Results  In the base case (considering a lifetime duration of protection and 100% efficacy) it was estimated that 2,835 cervical cancer cases and 679 deaths could be prevented among a cohort of 400,000, at an incremental cost per QALY gained of 10,530 €. A total of 120 girls needed to be vaccinated to prevent 1 case of CC. Cost-effectiveness is sensitive to a duration of protection of less than 20 years and to the discount rate for costs and benefits. Conclusion  A policy of vaccinating adolescent girls has been recommended by the German Standing Committee on Vaccinations. This study has demonstrated that such a policy is cost-effective based on thresholds of cost-effectiveness that apply in Germany.     

Lessons learnt from enrolment and follow up of pregnant women and their infants in clinical trials in South Africa,a low-middle income country

IntroductionInfectious causes are a significant contributor to morbidity and mortality in neonates and young infants. Immunization of pregnant women to protect the mother and/or her infant is gaining momentum due to the benefits of this strategy demonstrated in numerous implemented strategies (Maternal and Neonatal Tetanus Elimination Initiative) and clinical trials.Reluctance by regulators, participants and healthcare providers to include pregnant women in clinical trials is considerable, but reducing. Infectious disease burden, and therefore need for interventions to reduce morbidity and mortality in mothers and infants, is highest in low-middle income countries (LMIC), however, reliable background data on adverse pregnancy outcomes and lack of experience in clinical trials and community opinions on immunization during pregnancy are not well documented.MethodsWe used our experiences in conducting two clinical studies in pregnant women in South Africa to illustrate the challenges experienced and lessons learnt which may benefit others working in the maternal immunization field.ResultsAccurate gestational age assessment, which is essential for clinical trials, is challenging in LMIC due to limited access to early ultrasound examinations, and unreliable assessment by history (last menstrual period date) and physical examination (symphyseal-fundal height).Concomitant administration of recommended vaccines has previously been avoided in clinical trials; however, this limitation could impact the potentially beneficial interventions that participants can access during antenatal care.Women in LMIC have a higher burden of concomitant illnesses (e.g. HIV infection, malaria and anaemia) and adverse pregnancy outcomes (e.g. stillbirth) than pregnant women in higher income countries. Availability of local data is essential for safety monitoring committees to identify vaccine-related adverse event triggers.ConclusionImmunization of pregnant women to reduce disease burden in them and their infants is promising, and women in high-risk settings should be included in trials (Clinical trial registry number: ‘Study A’: NCT01193920, ‘Study B’: NCT01888471).     

The potential impact of a moderately effective HIV vaccine with rapidly waning protection in South Africa and Thailand

Background

Although published data from the recent ALVAC/AIDSVAX trial in Thailand (RV144) indicated the HIV vaccine provided very modest protection overall (31.2%), new analysis of trial data has suggested higher efficacy levels earlier in the follow-up period. CDC and UNAIDS organized several modeling research teams to explore the implications of the trial results and potential utility of this vaccine.

Methods

We explored the impact of a vaccine with moderate but rapidly waning protection (78%, 1.43 years) using an exponential decay function fit to trial data. We varied program coverage levels (20-80%), vaccine efficacy (30-90%), timing (single or multi-year programs), targeting (general or populations at higher risk), and background levels of all other prevention programs (constant or scaled-up). We simulated these various vaccination scenarios in two representative countries using demographic projections generated with Spectrum modeling software. We assumed the vaccine becomes available in 2020 and target coverage is achieved by 2025.

Results

A general vaccination strategy in South Africa covering 60% of the population, for example, would prevent 3.0 million infections between 2020 and 2030—36% of expected infections—and would be very effective, requiring only 39 vaccinations/infection averted. The same strategy in Thailand would prevent 81,000 infections—35% of expected infections—but would require 1725 vaccinations/infection averted. Targeting only populations at higher risk of exposure in Thailand would reduce total vaccinations given by more than ten-fold and would still prevent 52,000 infections—23% of expected infections—while requiring only 220 vaccinations/infection averted. Outcomes were sensitive to program coverage, vaccine efficacy and background levels of all other prevention programs.

Conclusions

A vaccine with rapidly waning protection could have a substantial impact on the epidemic in South Africa and Thailand. Due to the short duration of effect, large numbers of vaccinations would be needed to maintain high population coverage levels. Further research into the immunological effects of booster vaccinations is warranted.     

Acceptability of a hypothetical group B strep vaccine among pregnant and recently delivered women

Objective

Group B Streptococcus (GBS) causes significant infant morbidity and mortality. Promising GBS vaccines are currently in clinical trials. Because GBS vaccines would be the first to specifically target pregnant women, we sought to assess acceptability of a hypothetical GBS vaccine.

Study design

We performed an internet survey among currently pregnant or recently delivered women receiving care at one of 9 Ob/Gyn practices in Colorado. Vaccine acceptability was assessed using questions based on constructs from the Health Belief Model. Multivariable analyses assessed the characteristics associated with GBS vaccine acceptability during the current/recent pregnancy.

Results

The response rate was 50% (n = 231). While 78% agreed that a GBS vaccine would be a good way to protect newborns, 90% and 83% agreed, respectively, that they worried generally about the safety and effectiveness of new vaccines. Moreover, 39% believed it is generally dangerous for pregnant women to get vaccines. Seventy nine percent ‘definitely’ or ‘probably’ would have gotten a GBS vaccine in their most recent pregnancy if available. The most influential factors associated with this outcome were a strong belief in the vaccine's benefits (adjusted odds ratio [AOR] 6.37, 95% confidence interval [CI] 2.01–20.16), and low perceived barriers to vaccination (AOR 0.11, 95% CI (0.03–0.37)).

Conclusion

A GBS vaccine may be acceptable to pregnant women but would benefit from strong provider support and education about the risks and consequences of GBS infection and the benefits to vaccination.     

Cost-effectiveness of a 3-dose pneumococcal conjugate vaccine program in the province of Quebec,Canada

In the province of Quebec, Canada, the pneumococcal 7-valent conjugate vaccine (PCV-7) was licensed in 2001 and a publicly funded program was implemented in 2004, recommending 3 doses for healthy children. An economic analysis was performed both from a health care and societal perspective. Outcomes possibly prevented by PCV-7 and observed in 2006–2007 were compared to expected frequencies based on rates measured before PCV-7 use. Annual program costs were close to $21 M for the health system and $23 M for society. Approximately 20 000 infections were prevented annually and estimated economic benefits were $5 M for the health system and $23 M for society, using a 3% per annum discounting rate. The incremental cost-effectiveness ratio was $18 000 per QALY gained for the health system and the program was close to the break-even threshold in a societal perspective.     

Low fecal rotavirus vaccine virus shedding is significantly associated with non-secretor histo-blood group antigen phenotype among infants in northern Pretoria,South Africa

Histo-blood group antigens are recognized by rotaviruses in a P- genotype dependent manner and their frequency in a population can influence fecal virus shedding. This study investigated the rate of fecal shedding of Rotarix vaccine and its association with HBGA phenotype distribution in South Africa. Stool and saliva specimens were collected from 150 infants attending immunization on the day of both first and second doses and 7 days later. Virus shedding was detected by real-time qPCR while HBGA phenotypes in saliva were determined by enzyme linked immunosorbent assay. Vaccine virus shedding was higher (23.6%) after the first dose than the second dose (4.7%). About 77% of virus-shedding infants were secretors (OR = 129; 95% CI, 6.088 – 2733), compared with none of non-virus shedding infants. Non-secretor status was significantly associated with low vaccine virus shedding while the likelihood of shedding was significantly higher in secretors.     

Cost-effectiveness analysis of human resources policy interventions to address the shortage of nurses in rural South Africa

Recent policy recommendations have called for increased research efforts to inform the design of cost-effective interventions to address the shortage of health workers in rural areas. This paper takes forward the recent use of Discrete Choice Experiments to assess the effects of potential incentives to attract nurses to rural areas. The analysis relies on data collected in South Africa between August and November 2008. Effectiveness measures derived from Discrete Choice Experiments are combined in a Markov model to derive the long-term effects of policies, and costs are evaluated with secondary data. Measures involving the selection of more nursing students who are more likely to accept positions in rural areas are shown to be the most cost-effective interventions. If such policies could not be implemented, the next best options are to offer preferential access to specialist training to nurses willing to work in rural areas.     

一种新型B群链球菌显色培养基在孕妇产前B群链球菌检测中的应用效果研究

目的通过与CDC推荐THB+BAP及质谱鉴定(MS)相结合的参考方法比对,评估一种新型B群链球菌显色肉汤(GBSB)在孕妇产前B群链球菌(GBS)检测中的应用效果。方法接种不同浓度的GBS标准株测定GBSB检测限,并用87株GBS临床分离株进行验证;接种干扰菌测定GBSB的杂菌抑制性。以THB+BAP+MS为对比方法,分别对702例临床孕妇拭子样本(378例阴道分泌物和324例肛周分泌物)同步进行了2种方法对比检测,分析二者检测结果差异。结果标准菌株ATCC12386测定GBSB的检测限为100 cfu/ml,在该检出限条件下共验证87株GBS临床株,其中85株GBSB检测为阳性,10株常见杂菌即使0.5麦氏单位也不干扰。以对比方法为参比,702例临床孕妇拭子样本GBSB检测的灵敏度、特异度、阳性预测值、阴性预测值均达到了93%~100%,Kappa分析二者的一致性较好。结论GBSB是一种更简单、方便、高效、低耗的GBS检测方法,具有较好临床推广应用价值。     

北京市1992—2013年乙肝疫苗免疫规划对急性乙肝成本效果分析

目的 评价北京市1992—2013年急性乙肝报告发病率指标与乙肝疫苗免疫规划总成本之间的成本效果关系。 方法 以乙肝疫苗免疫规划总成本为成本指标,对急性乙肝发病率进行成本效果分析,主要包括成本分析、增量成本效果比以及边际效果分析。 结果 1992—2013年间北京市乙肝疫苗接种的总成本增加,人力成本占比上升;随着乙肝疫苗免疫规划总成本的增长,急性乙肝发病率先增长后下降,由1992年的3.58/10万人下降到2013年的1.34/10万人;多期间增量成本效果比方面,1999—2005年这一期间的增量成本效果比较好。 结论 乙肝疫苗成本变化符合实际发展规律;急性乙肝发病率的变化可能与流动人口中乙肝病毒携带者数量增加、传染病报告规定变化、乙肝诊断标准变化以及机构投入优化有关;急性乙肝的发病率随成本投入的增加而下降,但是最优组合尚未出现,可进行乙肝疫苗免疫规划的跟踪评估并结合实际调整防控策略。