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

OBJECTIVE: To 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. METHODS: A 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$1420, cost effective) times Gambian GDP were used. RESULTS: Vaccination with a hexavalent vaccine would avert 24 GBS disease cases (55%) and 768 disability adjusted life years compared to current standard of care (no interventions to prevent GBS disease). At vaccine efficacy of 70%, the programme is cost-effective at a maximum vaccine price per dose of 12 US$ (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. CONCLUSION: The 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.

Economic appraisal of vaccination against Streptoccocus agalactiae in Nile tilapia farms in Brazil.

Infection with Streptococcus agalactiae causes mortality and major economic losses in Nile tilapia (Oreochromis niloticus) farming worldwide. In Brazil, serotype strains Ia, Ib and III have been isolated in streptococcosis outbreaks, but serotype Ib is the most prevalent. Vaccination is considered an effective method to prevent economically-important diseases in aquaculture and has been associated with decreased use of antibiotics and improvements in fish survival. We developed a flexible partial-budget model to undertake an economic appraisal of vaccination against Streptococcus agalactiae in Nile tilapia farmed in net cages in large reservoirs. The model considers the benefits and costs that are likely to be associated with vaccination at the farm-level, in one production cycle. We built three epidemiological scenarios of cumulative mortality attributable to S. agalactiae (5%, 10%, and 20%, per production cycle) in a non-vaccinated farm. For each scenario, we applied a stochastic model to simulate the net return of vaccination, given a combination of values of "vaccine efficacy", "gain in feed conversion ratio", "feed price", "fish market price ", and "cost of vaccine dose". In the 20% cumulative mortality scenario, the net return would break-even (benefits ≥ costs) in at least 97.9% of interactions. Should cumulative mortality be lower than 10%, the profitability of vaccination would be more dependent on better feed conversion ratio. The inputs "feed price" and "cost of vaccine" had minor effects on the output, in all pre-vaccination mortality scenarios. Although our simulations are based on conservative values and consider uncertainty about the modeled parameters, we conclude that vaccination against S. agalactiae is likely to be profitable in Nile tilapia farms, under similar production conditions.

An economic case for a vaccine to prevent group A streptococcus skin infections.

BACKGROUND: Group A streptococcus (GAS) causes an exceptionally diverse range of diseases, raising questions about the optimal product characteristics of a commercially viable vaccine. The objectives of this study were to (1) estimate the current health and economic burdens caused by 24 diseases attributable to GAS each year in Australia and (2) use these estimates to explore the value of a GAS vaccine for different clinical indications, age schedules, and population groups. METHODS: For objective 1, we estimated the population heath and economic burdens by synthesising data from administrative databases, nationally representative surveys, literature reviews, public reimbursement schedules, and expert opinion. For objective 2, we modelled the prospective lifetime burden of GAS for all infants from birth, for children from 5 years of age, and for adults from 65 years of age. A vaccine was assumed to reduce each GAS disease by 70% for a period of 10 years, and the difference in outcomes between vaccinated and non-vaccinated cohorts were used to calculate the cost-effective value of vaccination. RESULTS: The annual health and economic burdens of GAS diseases totalled 23,528 disability-adjusted life years and AU$185.1 million in healthcare costs respectively; approximately half of each measure was due to cellulitis, followed by other skin infections and throat infections. Reducing the incidence of throat infections, skin infections, and cellulitis in non-Indigenous cohorts resulted in 30%, 33%, and 28% of the total vaccine value for an infant schedule (cost-effective vaccine price AU$260 per course); 47%, 26%, and 22% of the value for a child schedule (AU$289); and 2%, 15% and 74% for an adult schedule (AU$489). CONCLUSIONS: A vaccine that prevents GAS cellulitis and other skin infections, in addition to throat infections, would maximise its value and commercial viability, with a cost-effective price in line with other recently-licensed and funded vaccines in Australia.

Cost-effectiveness analysis of maternal immunisation against group B Streptococcus (GBS) disease: A modelling study.

BACKGROUND: There is a considerable global burden of invasive group B streptococcal (GBS) disease. Vaccines are being developed for use in pregnant women to offer protection to neonates. OBJECTIVE: To estimate the potential impact and cost-effectiveness of maternal immunisation against neonatal and maternal invasive GBS disease in the UK. METHODS: We developed a decision-tree model encompassing GBS-related events in infants and mothers, following a birth cohort with a time horizon equivalent to average life expectancy (81 years). We parameterised the model using contemporary data from disease surveillance and outcomes in GBS survivors. Costs were taken from NHS sources and research studies. Maternal immunisation in combination with risk-based intrapartum antibiotic prophylaxis (IAP) was compared to the current standard practice of risk-based IAP alone from an NHS and Personal Social Services (health-provider) perspective. We estimated the cases averted and cost per QALY gained through vaccination. One-way sensitivity analysis, scenario analysis and probabilistic sensitivity analysis were performed. RESULTS: An effective maternal immunisation programme could substantially reduce the burden of GBS disease. The deterministic analysis estimated the threshold cost-effective price for a GBS vaccine to be £54 per dose at £20,000/QALY (£71 per dose at £30,000/QALY). Results were most sensitive to assumptions on disease incidence, sequelae rate and vaccine efficacy. Probabilistic analysis showed 90.66% of iterations fell under the £30,000 threshold at a vaccine price of £55. Inclusion of modest prevention of stillbirths and/or, preterm births, carer health impacts, maternal GBS deaths and 1.5% discounting improved cost-effectiveness compared to the base case. Lowering vaccine strain coverage made the vaccine less cost-effective. A key limitation is that the properties of the final GBS vaccine are unknown. CONCLUSIONS: Maternal GBS immunisation is expected to be cost-effective, even at a relatively high vaccine price.

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

BACKGROUND: In 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. METHODS: Using 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. RESULTS: In 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. CONCLUSIONS: GBS 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.

Prevention of group B streptococcal disease in the first 3 months of life: would routine maternal immunization during pregnancy be cost-effective?

BACKGROUND: A vaccine against group B streptococcus (GBS) that is intended for routine maternal immunization during pregnancy is in clinical development. Addition of vaccination to screening and intrapartum antibiotic prophylaxis (IAP) may further reduce the burden of GBS disease in infancy; its potential cost-effectiveness is unknown, however. METHODS: We evaluated the cost-effectiveness of routine immunization at week 28 of pregnancy with the trivalent GBS (serotypes Ia, Ib and III) vaccine that is in clinical development. The vaccine was assumed to be used in addition to screening and IAP, and reduce the risk of invasive infection in infancy due to covered serotypes. We estimated the effectiveness of immunization in terms of additional cases of GBS disease prevented, deaths averted, life-years saved, and quality-adjusted life-years (QALYs) gained; potential reductions in prematurity and stillbirths were not considered. Costs considered included those of acute care for infants with GBS disease, and chronic care for those with long-term disability. The cost of immunization was assumed to be $100 per person. RESULTS: Assuming 85% coverage, routine maternal immunization against GBS added to screening and IAP would prevent an additional 899 cases of GBS disease and an additional 35 deaths among infants in the US. The total annual cost of immunization would be $362.7 million; estimated cost savings from prevention of GBS disease in infancy would be $43.5 million. The cost-effectiveness of immunization was estimated to be $91,321 per QALY gained. Findings were sensitive to assumptions regarding vaccine efficacy and cost. CONCLUSIONS: Addition of a trivalent GBS maternal vaccine to screening and IAP might further reduce the burden of GBS disease among infants in the US, and may be comparable in cost-effectiveness to other vaccines recently approved for use in children and adolescents.

Cost-effectiveness of a potential group B streptococcal vaccine program for pregnant women in South Africa.

BACKGROUND: In low- and middle-income countries neonatal infections are important causes of infant mortality. Group B streptococcus (GBS) is a major pathogen. A GBS polysaccharide-protein conjugate vaccine, the only option that has the potential to prevent both early- and late-onset GBS disease, has completed Phase II trials. Screening-based intrapartum antibiotic prophylaxis (IAP) for pregnant women, an effective strategy in high-income countries, is often not practical in these settings. Risk factor-based IAP (RFB-IAP) for women with risk factors at delivery has had limited success in preventing neonatal infection. We evaluated the cost and health impacts of maternal GBS vaccination in South Africa. METHODS AND FINDINGS: We developed a decision-analytic model for an annual cohort of pregnant women that simulates the natural history of GBS disease in their infants. We compared four strategies: doing nothing, maternal GBS vaccination, RFB-IAP, and vaccination plus RFB-IAP. Assuming vaccine efficacy varies from 50% to 90% against covered serotypes and 75% of pregnant women are vaccinated, GBS vaccination alone prevents 30-54% of infant GBS cases compared to doing nothing. For vaccine prices between $10 and $30, and mid-range efficacy, its cost ranges from $676 to $2390 per disability-adjusted life-year (DALY) averted ($US 2010), compared to doing nothing. RFB-IAP alone, compared to doing nothing, prevents 10% of infant GBS cases at a cost of $240/DALY. Vaccine plus RFB-IAP prevents 48% of cases at a cost of $664-2128/DALY. CONCLUSIONS: Vaccination would substantially reduce the burden of infant GBS disease in South Africa and would be very cost-effective by WHO guidelines. RFB-IAP is also very cost-effective, but prevents only 10% of cases. Vaccination plus RFB-IAP is more effective and more costly than vaccination alone, and consistently very cost-effective.

Preferences for health outcomes associated with Group A Streptococcal disease and vaccination.

BACKGROUND: A 26-valent Group A Streptococcus (GAS) vaccine candidate has been developed that may provide protection against pharyngitis, invasive disease and rheumatic fever. However, recommendations for the use of a new vaccine must be informed by a range of considerations, including parents' preferences for different relevant health outcomes. Our objectives were to: (1) describe parent preferences for GAS disease and vaccination using willingness-to-pay (WTP) and time trade-off (TTO) methods; and (2) understand how parents' implied WTP for a quality-adjusted life year (QALY) gained might vary depending on the particular health outcome considered (e.g. averted GAS disease vs. vaccine adverse events). METHODS: Telephone interviews were conducted with parents of children diagnosed with GAS pharyngitis at 2 pediatric practice sites in the Boston metropolitan area. WTP and TTO (trading parental longevity for child's health) questions for 2 vaccine and 4 disease-associated health states were asked using a randomly selected opening bid, followed by a 2nd bid and a final open-ended question about the amount willing to pay or trade. Descriptive analyses included medians and interquartile ranges for WTP and TTO estimates. The Wilcoxon signed-rank test was used to assess differences in WTP/QALY values for vaccine adverse events vs. disease states. RESULTS: Of 119 respondents, 100 (84%) and 96 (81%) provided a complete set of responses for WTP and TTO questions, respectively. The median WTP and discounted (at 3% per year) TTO values to avoid each health state were as follows: local reaction, $30, 0.12 days; systemic reaction, $50, 0.22 days; impetigo, $75, 1.25 days; strep throat, $75, 2.5 days; septic arthritis, $1,000, 6.6 days; and toxic shock syndrome, $3,000, 31.0 days. The median WTP/QALY was significantly higher for vaccine adverse events (approximately $60,000/QALY) compared to disease states ($18,000 to $36,000/QALY). CONCLUSIONS: Parents strongly prefer to prevent GAS disease in children compared to vaccine adverse events. However, implied WTP/QALY ratios were higher for the prevention of vaccine adverse events. Regret for errors of commission vs. omission may differ and should be considered by vaccine policymakers.

Development of conformational mimetics of conserved Streptococcus pyogenes minimal epitope as vaccine candidates.

One of the factors responsible for the poor immunogenicity of synthetic peptide antigens is the lack of conformational integrity. Embedding the minimal epitopes in helix-promoting peptide sequences has successfully enhanced the immunogenicity of the epitopes derived from the alpha-helical regions of the M protein of group A streptococci (Streptococcus pyogenes, GAS). However, the introduction of "foreign" peptide sequences is believed to have an unfavourable impact on the antigen specificity. In the current study, we employed a non-peptide approach, using topological carbohydrate templates, to induce helical conformation of the peptide antigens. Utilized together with the advances of the lipid core peptide system and chemoselective ligation, five GAS vaccine candidates incorporating the minimal epitope J14i (ASREAKKQVEKALE) were synthesized with high purity. Circular dichroism studies indicated that the template-assembled peptides formed alpha-helix bundles. This atom-economic strategy also reduces the complexity and cost of vaccine production by simply reducing the peptide epitope size.

The projected health benefits of maternal group B streptococcal vaccination in the era of chemoprophylaxis.

While maternal antibiotic prophylaxis has greatly reduced early-onset group B streptococcal (GBS) disease in the United States, a GBS vaccine currently under development could potentially prevent additional GBS cases and preterm births. A decision analytic model was created to compare preventive strategies using adolescent, maternal (prenatal), or postpartum vaccination with selective chemoprophylactic strategies. The current practice of culture-based chemoprophylaxis was predicted to prevent 55% of early plus late-onset GBS infections. Maternal vaccination strategies were superior to current practice, preventing 68-69% of all GBS infections and 4% of very preterm births (<32 weeks gestation). The most effective adolescent vaccination strategy combined vaccination with culture-based chemoprophylaxis for all women and prevented 66% of all GBS infections. All other strategies were similar in efficacy to current practice or inferior. Maternal GBS vaccination is predicted to prevent more cases of neonatal GBS disease than current practice and would prevent approximately one in 25 very preterm births.