COVID-19 impact on infant and adolescent vaccine supplies.

Vaccine production is quadrupling rapidly, creating supply chain challenges.

Estimation of country-level incidence of early-onset invasive Group B Streptococcus disease in infants using Bayesian methods.

Neonatal invasive disease caused by Group B Streptococcus (GBS) is responsible for much acute mortality and long-term morbidity. To guide development of better prevention strategies, including maternal vaccines that protect neonates against GBS, it is necessary to estimate the burden of this condition globally and in different regions. Here, we present a Bayesian model that estimates country-specific invasive GBS (iGBS) disease incidence in children aged 0 to 6 days. The model combines different types of epidemiological data, each of which has its own limitations: GBS colonization prevalence in pregnant women, risk of iGBS disease in children born to GBS-colonized mothers and direct estimates of iGBS disease incidence where available. In our analysis, we present country-specific maternal GBS colonization prevalence after adjustment for GBS detection assay used in epidemiological studies. We then integrate these results with other epidemiological data and estimate country-level incidence of iGBS disease including in countries with no studies that directly estimate incidence. We are able to simultaneously estimate two key epidemiological quantities: the country-specific incidence of early-onset iGBS disease, and the risk of iGBS disease in babies born to GBS-colonized women. Overall, we believe our method will contribute to a more comprehensive quantification of the global burden of this disease, inform cost-effectiveness assessments of potential maternal GBS vaccines and identify key areas where data are necessary.

Immune modulatory capacity of probiotic lactic acid bacteria and applications in vaccine development.

Vaccination is one of the most important prevention tools providing protection against infectious diseases especially in children below the age of five. According to estimates, more than 5 million lives are saved annually by the implementation of six standard vaccines, including diphtheria, hepatitis B, Haemophilus influenza type b, polio, tetanus and yellow fever. Despite these efforts, we are faced with challenges in developing countries where increasing population and increasing disease burden and difficulties in vaccine coverage and delivery cause significant morbidity and mortality. Additionally, the high cost of these vaccines is also one of the causes for inappropriate and inadequate vaccinations in these regions. Thus, developing cost-effective vaccine strategies that could provide a stronger immune response with reduced vaccination schedules and maximum coverage is of critical importance. In last decade, different approaches have been investigated; among which live bacterial vaccines have been the focus of attention. In this regard, probiotic lactic acid bacteria have been extensively studied as safe and effective vaccine candidates. These microorganisms represent the largest group of probiotic bacteria in the intestine and are generally recognised as safe (GRAS) bacteria. They have also attracted attention due to their immunomodulatory actions and their effective role as novel vaccine adjuvants. A significant property of these bacteria is their ability to mimic natural infections, while intrinsically possessing mucosal adjuvant properties. Additionally, as live bacterial vaccines are administered orally or nasally, they have higher acceptance and better safety, but also avoid the risk of contamination due to needles and syringes. In this review, we emphasise the role of probiotic Lactobacillus strains as putative oral vaccine carriers and novel vaccine adjuvants.

Effectiveness and cost-effectiveness of a Clostridium difficile vaccine candidate in a hospital setting.

Toxoid vaccines against Clostridium difficile infections (CDI) appear promising in reducing the risk of developing toxin-mediated symptoms. We sought to evaluate the effectiveness and cost-effectiveness of a vaccine candidate in a hospital setting. We developed an agent-based simulation model of nosocomial CDI in a 300-bed hospital. Targeting high-risk patients for vaccination, we estimated the reduction of symptomatic CDI. Using the net reduction of CDI-associated isolation days, we evaluated the vaccine's cost-effectiveness from a healthcare provider perspective over a 2-year period with an average monthly incidence of 5 cases per 10,000 patient-days pre-vaccination. Assuming a vaccine efficacy in the range 60-90%, vaccinating 40% of high-risk patients pre-admission reduced symptomatic CDI by 16.6% (95% CI: 15.2, 17.9). When the vaccine coverage increased to 80%, the reduction of symptomatic CDI was 34.6% (95% CI: 33.7, 35.9). For a willingness to pay (WTP) of CDN$1000 (corresponding to the average costs of case isolation per day), vaccine was cost-effective for vaccination costs per individual (VCPI) up to CDN$111 in the scenario of 40% vaccine coverage. With the same WTP, vaccine was cost-effective for VCPI up to CDN$121 when the vaccine coverage increased to 80%. A significant portion (~80%) of hospital colonization is caused by environmental transmission of C. difficile, which markedly reduced the effectiveness of vaccine below its assumed efficacy. However, due to the number of CDI-associated isolation days averted, vaccination of high-risk patients can be cost-effective depending on the WTP and the VCPI.

Navigating changes in Clostridioides difficile prevention and treatment.

Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES: Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.

Estimation of the burden of leptospirosis in New Zealand.

BACKGROUND: Human leptospirosis mainly affects people in close occupational contact with domestic livestock and their products in New Zealand. The disease has an unquantified impact on both human health and animal production in the country. This study aimed to estimate the burden of leptospirosis in terms of disability-adjusted life years (DALYs) and cost associated with loss due to absence from work, treatment of disease, animal production loss and cost of vaccination. METHODS: Previously published studies of abattoir workers farmers, and veterinarians, reporting annual risks of influenza-like illness attributable to Leptospira infection, were used to estimate the expected number of cases in a year. The cost of lost animal production was based on results of observational studies in beef cattle, sheep and deer conducted in New Zealand. RESULTS: Expected median annual number of severe and mild cases of human leptospirosis was 2,025 (95% probability interval [95% PI] 1,138-3,422). Median annual DALYs were 0.42 (95% PI: 0.06-2.40) per 100,000 people for the entire population, and 15.82 (95% PI: 2.09-90.80) per 100,000 people working in at-risk occupations (i.e. abattoir workers, farmers and veterinarians). Human infection resulted in a median cost of 4.42 (95% PI: 2.04-8.62) million US dollars (USD) due to absence from work and disease treatment. Median production loss cost in beef cattle, sheep and deer was USD 7.92 (95% PI: 3.75-15.48) million, while median vaccination cost in cattle, (including dairy), sheep and deer was USD 6.15 (95% PI: 5.30-7.03) million. Total annual cost of leptospirosis plus vaccination was USD 18.80 (95% PI: 13.47-27.15) million, equivalent to USD 440,000 (95% PI: 320,000-640,000) per 100,000 people. CONCLUSION: This study provides an estimate of the disease burden and cost of leptospirosis in New Zealand that could support occupational health authorities and livestock industries in assessing interventions for this disease.

Benefit-cost analysis to estimate the payback time and the economic value of two Mycoplasma hyopneumoniae elimination methods in breeding herds.

Mycoplasma hyopneumoniae (Mhyo) is generally accepted to be the most common porcine respiratory pathogen worldwide causing big economical losses in swine production by affecting pig's downstream performance. The objective of this study was to develop a partial budget model to determine the payback period and economic value of two Mhyo elimination protocols. Retrospective data recorded from 2004 to 2017 from 70 breeding herds that implemented herd closure or whole-herd medication protocol targeting Mhyo elimination. Close out data was used to estimate differences in downstream performance between Mhyo-negative and positive flows. Assuming a 5000 sows breed-to-finish operation producing 135,870 weaned pigs and 125,000 finishing pigs/year, the total cost for implementing Mhyo elimination was $112,100 using the herd closure protocol, and $185,700 for the medication protocol. Statistically differences (p < 0.05) in downstream performance were observed for ADG and mortality, but not for feed conversion rate. The parameters that accounts for the greatest benefits were related to the improvement in ADG, savings in antibiotic medication in growing pigs and improvement in feed conversion rate. The benefit of Mhyo elimination was $877,375 per farm per year, or $7.00 per pig marketed. The estimated project value after 1 year was $616,121 for the herd closure considering a probability of success of 83%, and $323,177 for the medication protocol for 58% chance of success. The project value reached the break-even point when the cost per sow was $145.64 for the herd closure and $101.78 for the medication protocol. The payback period was 2 months after the start of marketing Mhyo-negative pigs for the herd closure, and 7 months for the medication protocol adjusted for the probability of success for each protocol. The protocols described here can be easily applied with a good success rate and showing that the benefits obtained are greater than the costs of project failure. Even if the farm stayed negative only a year, the economic benefits downstream are worth the investment. This information may help producers and veterinarians on decision-making process to conduct a Mhyo elimination protocol in their herds.

Biological feasibility and importance of a gonorrhea vaccine for global public health.

There is a growing public health interest in controlling sexually transmitted infections (STIs) through vaccination due to increasing recognition of the global disease burden of STIs and the role of STIs in women's reproductive health, adverse pregnancy outcomes, and the health and well-being of neonates. Neisseria gonorrhoeae has historically challenged vaccine development through the expression of phase and antigenically variable surface molecules and its capacity to cause repeated infections without inducing protective immunity. An estimated 78 million new N. gonorrhoeae infections occur annually and the greatest disease burden is carried by low- and middle-income countries (LMIC). Current control measures are clearly inadequate and threatened by the rapid emergence of antibiotic resistance. The gonococcus now holds the status of "super-bug" as there is currently no single reliable monotherapy for empirical treatment of gonorrhea. The problem of antibiotic resistance has elevated treatment costs and necessitated the establishment of large surveillance programs to track the spread of resistant strains. Here we review the need for a gonorrhea vaccine with respect to global disease burden and related socioeconomic and treatment costs, with an emphasis on the impact of gonorrhea on women and newborns. We also highlight the challenge of estimating the impact of a gonorrhea vaccine due to the need for more data on the burden of gonococcal pelvic inflammatory disease and related sequelae and of gonorrhea-associated adverse pregnancy outcomes and the problem of empirical diagnosis and treatment of STIs in LMIC. There is also a lack of clinical and basic science research in the area of gonococcal/chlamydia coinfection, which occurs in a high percentage of individuals with gonorrhea and should be considered when testing the efficacy of gonorrhea vaccines. Finally, we review recent research that suggests a gonorrhea vaccine is feasible and discuss challenges and research gaps in gonorrhea vaccine development.

Cost-effectiveness of a potential anti-tick vaccine with combined protection against Lyme borreliosis and tick-borne encephalitis in Slovenia.

This study assessed cost-effectiveness of a potential anti-tick vaccine that would protect against both Lyme borreliosis (LB) and tick-borne encephalitis (TBE) in a highly endemic setting of Slovenia. A Markov model was developed to estimate cost-effectiveness of a vaccine with potential combined protection against LB and TBE from the societal perspective. The model expressed time in annual cycles, followed a target population through their lifetime, and applied an annual discounting of 3%. A target population entered the model in a susceptible state, with time dependent probabilities to acquire LB/TBE. Disease manifestations were either resolved within one cycle, or a patient developed LB/TBE sequelae. The vaccination consisted of initial immunization and one revaccination. Estimates of LB/TBE direct and indirect costs, and data on natural course of LB/TBE were obtained from Slovenian databases. Effectiveness of the vaccine with potential combined protection against LB/TBE was derived from studies on existing TBE and LB vaccines, while utility estimates were collected from various literature sources. A vaccine with potential combined protection against LB/TBE was predicted to have an incremental cost of €771,300 per 10,000 vaccinated persons, an incremental utility of 17QALYs and a base-case incremental cost-effectiveness ratio (ICER) of 46,061€/QALY. Vaccine cost, effectiveness and discount rates were identified as the most influential model parameters. A wholesale price for a vaccine shot of €9.13 would lead to cost savings followed by health gains for the vaccination strategy. The base-case ICER was below commonly accepted thresholds of cost-effectiveness, indicating that a combined LB/TBE vaccine might be a cost-effective option in Slovenia. With early Health Technology Assessment becoming increasingly important, this analysis still represents a rare example of cost-effectiveness assessment prior to market authorisation. Although obviously in such a situation some key parameters are unknown, our model sets up a tool to analyse pharmacoeconomic criteria that can help development of a cost-effective health technology, in this case a combined tick-borne diseases vaccine.

Toward economic evaluation of the value of vaccines and other health technologies in addressing AMR.

We discuss the need to make economic evaluations of vaccines antimicrobial resistance (AMR)-sensitive and ways to do so. Such AMR-sensitive evaluations can play a role in value-for-money comparisons of different vaccines within a national immunization program, or in comparisons of vaccine-centric and non-vaccine-centric technologies within an anti-AMR program. In general terms, incremental cost-effectiveness ratios and rates of return and their associated decision rules are unaltered by consideration of AMR-related value. The decision metrics need to have their various health, cost, and socioeconomic terms disaggregated into resistance-related subcategories, which in turn have to be measured carefully before they are reaggregated. The fundamental scientific challenges lie primarily in quantifying the causal impact of health technologies on resistance-related health outcomes, and secondarily in ascertaining the economic value of those outcomes. We emphasize the importance of evaluating vaccines in the context of other potentially complementary and substitutable nonvaccine technologies. Complementarity implies that optimal spending on each set of interventions is positive, and substitutability implies that the ratio of spending will depend on relative value for money. We exemplify this general point through a qualitative discussion of the complementarities and (especially the) substitutability between pneumococcal conjugate vaccines and antimicrobial stewardship and between research and development (R&D) of a gonorrhea vaccine versus R&D of a gonorrhea antibiotic. We propose a roadmap for future work, which includes quantifying the causal effects of vaccination and other health technologies on short-term and long-term resistance-related outcomes, measuring the health-sector costs and broader socioeconomic consequences of resistance-related mortality and morbidity, and evaluating vaccines in the context of nonvaccine complements and substitutes.

Systematic review of the incremental costs of interventions that increase immunization coverage.

Achieving and maintaining high vaccination coverage requires investments, but the costs and effectiveness of interventions to increase coverage remain poorly characterized. We conducted a systematic review of the literature to identify peer-reviewed studies published in English that reported interventions aimed at increasing immunization coverage and the associated costs and effectiveness of the interventions. We found limited information in the literature, with many studies reporting effectiveness estimates, but not providing cost information. Using the available data, we developed a cost function to support future programmatic decisions about investments in interventions to increase immunization coverage for relatively low and high-income countries. The cost function estimates the non-vaccine cost per dose of interventions to increase absolute immunization coverage by one percent, through either campaigns or routine immunization. The cost per dose per percent increase in absolute coverage increased with higher baseline coverage, demonstrating increasing incremental costs required to reach higher coverage levels. Future studies should evaluate the performance of the cost function and add to the database of available evidence to better characterize heterogeneity in costs and generalizability of the cost function.

Cost-effectiveness of a potential vaccine candidate for Haemophilus influenzae serotype 'a'.

The preceding decade has witnessed the emergence of severe community-acquired acute infections caused by Haemophilus influenzae serotype a (Hia), with alarming incidence rates in North America, particularly among indigenous populations. The remarkable success of Hib conjugate vaccine over the past 20 years signify the development of an Hia vaccine candidate as a prevention measure to reduce the incidence of invasive Hia disease. However, quantifications of the long-term epidemiologic and economic impacts of vaccination are needed to inform decision on investment in Hia vaccine development and immunization programs. We sought to evaluate the cost-effectiveness of an Hia vaccine with a similar routine infant immunization schedules currently in practice for Hib in Canada. We developed and parameterized an agent-based simulation model using age-specific incidence rates reported for Nunavut, a Canadian territory with predominantly aboriginal populations. Our results, based on statistical analyses of the incremental cost-effectiveness ratio, show that an Hia conjugate vaccine is highly cost-effective. Sustaining an immunization program with vaccine coverages of 77% for primary series and 93% for booster dose over a 10-year period reduces the incidence of invasive disease by 63.8% on average from 9.97 to 3.61 cases, per 100,000 population. The overall costs of disease management in year 10 are reduced by 53.4% from CDN $1.863 million (95% CI: $1.229-$2.519 M) to CDN $0.868 million (95% CI: $0.627-$1.120 M). The findings suggest an important role for a conjugate vaccine in managing Hia disease as a growing public health threat.

Exploratory study of the dispensing patterns of vaccines by a sample of community pharmacies in Southern Africa.

INTRODUCTION: Vaccination is one of the most cost-effective healthcare interventions. Pharmacies in South Africa provide a vaccination service where childhood immunizations, some travel vaccines and vaccines for specific populations are dispensed and administered, but little has been published on which vaccines are dispensed and at what cost. AREAS COVERED: This retrospective drug utilization study determined the dispensing patterns of vaccines in community pharmacies during 2015 with the focus on the types and cost of vaccines dispensed in ATC group J07. EXPERT COMMENTARY: Of the 140 902 vaccines dispensed to 79 415 patients, viral vaccines (J07B) accounted for most of the prescriptions (82.7% of volume; 62.3% of cost), followed by bacterial vaccines (J07A) (17.1% of volume; 37.5% of cost), and bacterial and viral vaccines combined (0.2% of volume; 0.3% of cost). There was an increase in the dispensing patterns of viral vaccines (J07B) in the period just before the winter months. Half of all vaccines (50.4%) were for the influenza vaccine (J07BB01). This vaccine accounted for only 15.6% of the total cost of vaccines. The most expensive vaccines were pneumococcal polysaccharide conjugate vaccine (13-valent adsorbed, pre-filled syringe) (J07AL01), followed by human papillomavirus bivalent vaccine (J07BM02).

Cost-Benefit Analysis of a Chlamydia trachomatis Vaccine Program in Adolescent Girls in the United States.

BACKGROUND: With >1.4 million cases in the United States reported to the Centers for Disease Control and Prevention in 2012, Chlamydia trachomatis infection is a major public health concern. We examined the impact of a C trachomatis vaccination program using a decision-analysis model to estimate the effects of vaccination on C trachomatis-associated costs and morbidity. METHODS: We developed a Markov model considering a cohort of 2158117 US females aged 9 to 26 years. Morbidity, death, and healthcare-associated costs associated with chlamydial infection of mothers and fetuses/neonates were calculated over a 17-year time frame. We developed 2 major comparison arms, namely, a C trachomatis vaccination program and no C trachomatis vaccination program. Base-case efficacy and coverage were set to those of human papillomavirus in the United States with all variables, including efficacy and coverage, ranged in sensitivity analyses. RESULTS: On the basis of a base-case analysis, a vaccination program would cost an estimated $710 million for a cohort of 2158117 women over a 17-year period, an increase of $41 million over having no vaccination program. A vaccination program would prevent 34000 cases of C trachomatis infection and 5976 cases of pelvic inflammatory disease. CONCLUSIONS: A C trachomatis vaccination program results in increased cost to the healthcare system but averts significant morbidity and death.

A real options approach to biotechnology investment policy-the case of developing a Campylobacter vaccine to poultry.

The aim of the article is to identify and analyse public-private incentives for the development and marketing of new animal vaccines within a real options methodological framework, and to investigate how real options methodology can be utilized to support economic incentives for vaccine development in a cost-effective way. The development of a vaccine against Campylobacter jejuni in poultry is applied as a case study. Employing the real options methodology, the net present value of the vaccine R&D project becomes larger than a purely probabilistic expected present value throughout the different stages of the project - and the net present value becomes larger, when more types of real options are taken into consideration. The insight from the real options analysis reveals opportunities for new policies to promote the development of animal vaccines. One such approach might be to develop schemes combining stage-by-stage optimized subsidies in the individual development stages, with proper account taken of investors'/developers' economic incentives to proceed, sell or cancel the project in the respective stages. Another way of using the real options approach to support the development of desirable animal vaccines could be to issue put options for the vaccine candidate, enabling vaccine developers to hedge against the economic risk from market volatility.

Vaccines for tick-borne diseases and cost-effectiveness of vaccination: a public health challenge to reduce the diseases' burden.

Tick-borne encephalitis (TBE) and Lyme borreliosis (LB) are tick-borne diseases (TBDs), and both present an increasing burden worldwide. Vaccination as public health intervention could be the most effective way to reduce this burden. TBE vaccines are available, but vaccines against LB are still in the phase of development. At the European level, TBE vaccines are likely under-administered to effectively prevent the disease. Cost-effectiveness of vaccination is a helpful tool in the decision making process to include novel vaccines in the national vaccination program or to extend current programs, and its role is only increasing. Cost-effectiveness studies on TBE vaccines have been performed in Slovenia, Sweden, Finland and Estonia so far. Cost-effectiveness studies with the novel vaccines against LB are expected to be performed in the near future.