Vaccines against mpox: MVA-BN and LC16m8.

INTRODUCTION: Global outbreaks involving mpox clade IIb began in mid-2022. Today, clade IIb and clade I outbreaks continue. Reliable mpox vaccines can prevent serious mpox disease and death. AREAS COVERED: Globally, two vaccines hold mpox indications, regardless of mpox viral clade: MVA-BN (Bavarian Nordic) and LC16m8 (KM Biologics). This review summarizes the human and pivotal animal data establishing safety and efficacy for MVA-BN and LC16m8, including real-world evidence gathered during mpox outbreaks from 2022 through 2024. EXPERT OPINION: Some regulatory decisions for MVA-BN and LC16m8 followed pathways based on surrogate outcomes, including lethal-challenge studies in nonhuman primates, among other atypical aspects. Nonetheless, MVA-BN and LC16m8 hold unencumbered registration in multiple countries. Effectiveness of MVA-BN as primary preventive vaccination (PPV) in humans against clade IIb mpox is clear from real-world studies; effectiveness of LC16m8 against clade IIb is likely from surrogate endpoints. Effectiveness of MVA-BN and LC16m8 as PPV against more-lethal clade I is likely, based on animal-challenge studies with multiple orthopoxvirus species and other studies. Both vaccines have solid safety records. MVA-BN's replication incompetence favors adoption, whereas LC16m8 has more pediatric data. Additional real-world evidence, in additional geographic settings and special populations (e.g. pregnancy, immune suppression, atopic dermatitis), is needed.

Situation Mpox outbreaks spread globally in 2022, hospitalizing many people. Many recent mpox cases in Africa occur in children. Two vaccines, known as MVA-BN and LC16m8, can help prevent mpox.MVA-BN MVA-BN protects animals from lethal doses of mpox and similar viruses. During outbreaks, MVA-BN lowered the chance of mpox disease by 62% to 85%. In people already exposed to mpox, MVA-BN reduced disease risk by 20%. MVA-BN may help reduce how serious mpox cases are, even if this vaccine does not block infection fully. MVA-BN cannot grow inside the body, making it very safe, even in children. Side effects include pain, redness, swelling, and itching. Some people feel muscle pain, headache, fatigue, nausea, or chills after vaccination. Several million people have received MVA-BN so far, including thousands of people living with HIV.LC16m8 LC16m8 protects animals from lethal doses of mpox and similar viruses. There are not much data about LC16m8 used during mpox outbreaks. LC16m8 contains a weakened virus. Side effects include fever, fatigue, redness, swollen lymph nodes, and itching. Vaccine virus can spread to other parts of the body. Over 90,000 people have received LC16m8 so far. No significant safety signals were found after these doses, including 50,000 children. People who are immunosuppressed, have certain skin diseases, or are pregnant should not be given LC16m8.Mpox vaccine recommendations Health officials recommend mpox vaccine for people at risk, including children.

Pharmacist assessments and care to improve adult vaccination rates: A report from project IMPACT vaccine confidence.

BACKGROUND: Neglect of vaccination needs among adults results in a needless burden of hospitalization, suffering, and death. America's community pharmacists deliver a substantial portion of adult vaccinations, yet many Americans still have unmet vaccination needs. OBJECTIVES: This study evaluated rates of vaccine contraindications, acceptance, and willingness to be vaccinated among ambulatory adults. PRACTICE DESCRIPTION: This was a prospective, multisite, multistate, observational study conducted in three waves between October 2021 and August 2023. PRACTICE INNOVATION: Pharmacists conducted comprehensive vaccination need assessments. EVALUATION METHODS: The primary outcomes were numbers of vaccination needs per participant and vaccinations administered, scheduled, or declined. RESULTS: Pharmacists identified a mean of 1.8-2.2 unmet vaccination needs per adult assessed, more than in pilot studies. Participants had already received 61%-74% of vaccinations recommended for them hence 26%-39% of needs were unmet at baseline. The leading vaccination needs were COVID-19, influenza, zoster, tetanus-containing, and pneumococcal vaccines. From a baseline mean of 59.1% for these five vaccinations, pharmacists increased the mean percentage vaccinated to 73.2%. When an option for scheduling future vaccination was added to the process, declinations dropped from 46%-18%. CONCLUSION: This study provides insight into adult vaccine acceptance, willingness, and declination behaviors not described elsewhere. Offering options for future vaccination reduced declination rates. Pharmacists resolved substantial proportions of adult vaccination needs. The signal that apportioning adult vaccines needed, but not received on day of assessment, across several months could help resolve unmet vaccination needs warrants additional research, especially with the rising number of vaccines recommended for adults.

Evaluating risk of bias using ROBINS-I tool in nonrandomized studies of adjuvanted influenza vaccine.

Seasonal variation in influenza vaccine effectiveness (VE) makes real-world evidence (RWE) useful in supplementing the clinical-evidence base from randomized clinical trials. Adjuvanted inactivated influenza vaccine (aIIV) VE has been evaluated in multiple nonrandomized RWE studies. A systematic literature review of RWE studies evaluating the absolute or relative VE of aIIV was conducted. Identified studies were assessed by evaluators for risk of bias (RoB) by means of the ROBINS-I (Reduction of Bias In Non-randomized Studies of Interventions) tool to inform evidence-based medicine deliberations. Differences in evaluator assessments were resolved by consensus. The literature review yielded 14 follow-up studies, seven test-negative case-control (TNCC) studies, five traditional case-control studies, and one cluster-randomized clinical trial. Most follow-up studies and three TNCC studies were judged at low RoB. Issues increasing RoB included inadequate control of confounding, selection of controls, and reliance on recall of vaccination. The concerns identified in any of the designs could be mitigated with straightforward revisions to design or implementation. 17 of 27 nonrandomized studies of adjuvanted influenza-vaccine effectiveness, some from each of four study designs, were judged at low risk of material bias. These studies merit credence in assessing aIIV effectiveness relative to other influenza vaccines.

Effect of an Innovative Immunization Practice Model to Improve Population Health: Results of the Project IMPACT Immunizations Scaled Demonstration.

Background: U.S. adult vaccination rates remain low. Community pharmacists have skills and opportunity to improve this shortcoming. This study sought to evaluate an innovative practice model on identification of unmet vaccination needs and their resolution. Methods: This prospective, multi-site, multi-state, observational study was conducted in 22 community pharmacy practices in Iowa and Washington. Adults receiving influenza vaccination, medication therapy review, prescriptions for diabetes or cardiovascular disease, or another clinical encounter with a participating pharmacist from December 2017 through November 2019 were included. Pharmacists reviewed vaccination forecasts generated by clinical decision support technology based on their state immunization information system (IIS) to identify unmet vaccination needs, educate patients, and improve vaccination rates. The primary outcomes were numbers of vaccination forecast reviews, patients educated, unmet vaccination needs identified and resolved, and vaccinations administered. Secondary outcomes included numbers of vaccination declinations; times a forecasted vaccine was not recommended because a contraindication was identified by the pharmacist; and times the patients declined a forecasted vaccine due to self-reported vaccination despite lack of documentation in the state IIS. Descriptive statistics were calculated. Results: Pharmacists reviewed vaccination forecasts for 6,234 patients. The vaccination forecasts predicted there were 11,789 vaccinations needed (1.9 per person). 6,405 of the 11,789 unmet vaccination needs (54.3%) were fulfilled during the study period, including 60% on the same day. Of the forecasted needs, 1,085 (9.2%) were found to be previously administered and 59 (0.5%) contraindicated. The remaining patients received information about their personal vaccination needs and recommendations to be vaccinated. Conclusion: Availability of vaccination histories during patient encounters allowed pharmacists to identify and resolve adult vaccination needs in independent and chain community practice settings.

Pharmacy on the front lines: A century of pandemic response in America.

The history of American pharmacy contributions to pandemic responses can be described for five pandemics: 1918 (influenza A/H1N1 virus), 1957-1958 (H2N2 virus), 1968 (H3N2 virus), 2009 (H1N1pdm09 virus), and 2019-2023 (syndrome coronavirus-2 virus). Using historical surveillance data and published literature, this article provides opportunities to reflect on how the pharmacy profession played a role in preparedness and response.

Global geotemporal distribution of chikungunya disease, 2011-2022.

BACKGROUND: Chikungunya virus is a mosquito-borne alphavirus, transmitted by Aedes mosquitoes. Humans serve as the primary reservoir. Chikungunya infections typically appear with an abrupt onset of fever, rash, and severe joint pain. Some 40% of cases develop chronic rheumatologic complications that can persist months to years. OBJECTIVES: To improve precision of risk characterization by analyzing cases of chikungunya by year and by country and depicting this geotemporal distribution in map form. METHOD: Chikungunya case counts by year were compiled from national or regional health authorities from 2011 to 2022. These data were augmented by published reviews plus the Program for Monitoring Emerging Diseases (ProMED). Country-level distribution was categorized into four groups based on recency and magnitude. Data for India were mapped on a per-state basis. RESULTS: The global map depicts distribution of chikungunya disease from 2011 through 2022. Most cases are reported in tropical and subtropical areas, but notable exceptions include the northern coast of the Mediterranean Sea. Countries of high recency and frequency include India, Brazil, Sudan, and Thailand. Countries with high frequency, but few cases reported in 2019-22 include many Latin American and Caribbean countries. Subnational foci are discussed in general and mapped for India. The range of Aedes mosquitoes is broader than the geography where chikungunya infection is typically diagnosed. CONCLUSIONS: These maps help identify geographical regions where residents or travelers are at greatest risk of chikungunya. Once vaccines are licensed to help prevent chikungunya, maps like these can help guide future vaccine decision-making.

Women in pharmacy: Pearls of wisdom from the 2022 inductees and contemporary leaders.

In 2012, the American Pharmacists Association Foundation (APhAF) recognized 17 women and three organizations for their work as pioneers and leaders among female pharmacists. In 2022, the APhAF selected ten additional leaders among contemporary women in American pharmacy to be honored in the Women in Pharmacy Exhibit and Conference Room on the top floor of the American Pharmacists Association (APhA) headquarters building in Washington, D.C. These ten leaders gathered at a symposium in their honor in October 2022 at APhA headquarters. This paper summarizes the accomplishments of the ten contemporary women and documents their comments at the symposium, where they discussed their perspectives on practice innovation, entrepreneurship, leadership, philanthropy, community service, and mentorship.

Essential services: Quantifying the contributions of America's pharmacists in COVID-19 clinical interventions.

BACKGROUND: As the COVID-19 pandemic spread across the United States, America's pharmacists and their teammates expanded their clinical services to help their communities from every practice setting: community and ambulatory care, inpatient, long-term care, academia, public health, and many others. OBJECTIVES: The objective of the study is to begin to quantify contributions of U.S. pharmacists in providing clinical interventions that mitigate and control the pandemic. These interventions span the gamut of diagnosis, prevention, treatment, and support, intervening patient by patient with vaccines, diagnostic tests, convalescent plasma, monoclonal antibodies, antiviral medications, and supportive therapies. METHODS: Review of published literature, relevant web pages, and queries to national and state professional pharmacy associations and government agencies. RESULTS: From February 2020 through September 2022, pharmacists and their teammates conducted >42 million COVID-19 tests, provided >270 million vaccinations (including 8.1 million COVID-19 vaccinations for long-term care residents) within community pharmacy programs alone, and provided >50 million influenza and other vaccinations per year. Pharmacists plausibly accounted for >50% of COVID-19 vaccinations in the United States. Pharmacists prescribed, dispensed, and administered an uncounted number of antibody products and antiviral medications, including care for 5.4 million inpatients and innumerable outpatients. Using conservative estimates, pandemic interventions by pharmacists and teammates averted >1 million deaths, >8 million hospitalizations, and $450 billion in health care costs. CONCLUSIONS: Pharmacists and their teammates contributed to America's health and recovery during the COVID-19 pandemic by providing >350 million clinical interventions to >150 million people in the form of testing, parenteral antibodies, vaccinations, antiviral therapies, and inpatient care. The number of lives touched and people cared for by pharmacists continues to rise.

Vaccine humanity.

Vaccines to help prevent COVID-19 disease have evoked myriad human emotions. Attitudes of the public toward vaccination can be grouped into hundreds of categories. Pharmacists need to recognize the many elements of what may be termed "vaccine humanity," a complex tangle of human responses. Vaccine humanity applies to all vaccines, not just COVID-19 vaccines. Many of the emotions (pro and con) exhibited toward COVID-19 vaccines were also expressed (pro and con) with Edward Jenner's smallpox vaccine in the 1800s. New disease, new vaccines, same humanity. Human behaviors to seek or decline vaccination typically pivot on several core elements: perceptions of susceptibility to disease, seriousness of the disease, benefits of vaccination, and barriers (e.g., safety concerns, distance, costs, uncertainty). The pharmacist who contributes the time to listen and explain--listen and explain--listen and explain performs a vital clinical service: enabling vaccinations that promote health and prevent disease.

Pharmacy-based interventions to increase vaccine uptake: report of a multidisciplinary stakeholders meeting.

BACKGROUND: Despite the existence of efficacious vaccines, the burden of vaccine-preventable diseases remains high and the potential health benefits of paediatric, adolescent and adult vaccination are not being achieved due to suboptimal vaccine coverage rates. Based on emerging evidence that pharmacy-based vaccine interventions are feasible and effective, the European Interdisciplinary Council for Ageing (EICA) brought together stakeholders from the medical and pharmacy professions, the pharmaceutical industry, patient/ageing organisations and health authorities to consider the potential for pharmacy-based interventions to increase vaccine uptake. We report here the proceedings of this 3-day meeting held in March 2018 in San Servolo island, Venice, Italy, focussing firstly on examples from countries that have introduced pharmacy-based vaccination programmes, and secondly, listing the barriers and solutions proposed by the discussion groups. CONCLUSIONS: A range of barriers to vaccine uptake have been identified, affecting all target groups, and in various countries and healthcare settings. Ease of accessibility is a potentially modifiable determinant in vaccine uptake, and thus, improving the diversity of settings where vaccines can be provided to adults, for example by enabling community pharmacists to vaccinate, may increase the number of available opportunities for vaccination.

Streptococcus pneumoniae outbreaks and implications for transmission and control: a systematic review.

BACKGROUND: Streptococcus pneumoniae is capable of causing multiple infectious syndromes and occasionally causes outbreaks. The objective of this review is to update prior outbreak reviews, identify control measures, and comment on transmission. METHODS: We conducted a review of published S. pneumoniae outbreaks, defined as at least two linked cases of S. pneumoniae. RESULTS: A total of 98 articles (86 respiratory; 8 conjunctivitis; 2 otitis media; 1 surgical site; 1 multiple), detailing 94 unique outbreaks occurring between 1916 to 2017 were identified. Reported serotypes included 1, 2, 3, 4, 5, 7F, 8, 12F, 14, 20, and 23F, and serogroups 6, 9, 15, 19, 22. The median attack rate for pneumococcal outbreaks was 7.0% (Interquartile range: 2.4%, 13%). The median case-fatality ratio was 12.9% (interquartile range: 0%, 29.2%). Age groups most affected by outbreaks were older adults (60.3%) and young adults (34.2%). Outbreaks occurred in crowded settings, such as universities/schools/daycares, military barracks, hospital wards, and long-term care facilities. Of outbreaks that assessed vaccination coverage, low initial vaccination or revaccination coverage was common. Most (73.1%) of reported outbreaks reported non-susceptibility to at least one antibiotic, with non-susceptibility to penicillin (56.0%) and erythromycin (52.6%) being common. Evidence suggests transmission in outbreaks can occur through multiple modes, including carriers, infected individuals, or medical devices. Several cases developed disease shortly after exposure (< 72 h). Respiratory outbreaks used infection prevention (55.6%), prophylactic vaccination (63.5%), and prophylactic antibiotics (50.5%) to prevent future cases. PPSV23 covered all reported outbreak serotypes. PCV13 covered 10 of 16 serotypes. For conjunctival outbreaks, only infection prevention strategies were used. CONCLUSIONS: To prevent the initial occurrence of respiratory outbreaks, vaccination and revaccination is likely the best preventive measure. Once an outbreak occurs, vaccination and infection-prevention strategies should be utilized. Antibiotic prophylaxis may be considered for high-risk exposed individuals, but development of antibiotic resistance during outbreaks has been reported. The short period between initial exposure and development of disease indicates that pneumococcal colonization is not a prerequisite for pneumococcal respiratory infection.

Proportion of adult community-acquired pneumonia cases attributable to Streptococcus pneumoniae among Hajj pilgrims in 2016.

BACKGROUND: The Hajj mass gathering is a risk for pneumococcal disease. This study was performed to evaluate the proportion of adult community-acquired pneumonia (CAP) cases attributable to Streptococcus pneumoniae among Hajj pilgrims in 2016. To add sensitivity to etiological attribution, a urine antigen test was used in addition to culture-based methods. METHODS: Adult subjects hospitalized with X-ray-confirmed CAP were enrolled prospectively from all general hospitals designated to treat Hajj pilgrims in the holy cities of Mecca and Medina. Patients were treated according to local standard of care and administered the BinaxNow S. pneumoniae urine antigen test. RESULTS: From August 23 to September 23, 2016, a total of 266 patients with CAP were enrolled in the study, 70.6% of whom were admitted to hospitals in Mecca; 53% of the cases were admitted after the peak of Hajj. Patients originated from 43 countries. Their mean age was 65.3 years and the male to female ratio was 2:1. Just over 36% of the cases had diabetes, 10% declared that they were smokers, and 45.4% of cases were treated in the intensive care unit (ICU). The overall case-fatality rate was 10.1%, but was higher among those treated in the ICU and in those with invasive disease. The proportion of CAP cases positive for S. pneumoniae, based on culture or urine antigen test, was 18.0% (95% confidence interval 13.9-23.1%). CONCLUSIONS: CAP during Hajj has an important clinical impact. A proportion of CAP cases among Hajj pilgrims were attributable to S. pneumoniae, a pathogen for which vaccines are available. Additional studies to determine the serotypes causing pneumococcal disease could further inform vaccine policy for Hajj pilgrims.

Trends in the Numbers of US Colleges of Pharmacy and Their Graduates, 1900 to 2014.

Objective. To describe the cumulative and contemporary numbers of colleges and schools of pharmacy between 1900 and 2014 based on membership in the American Association of Colleges of Pharmacy or its predecessor, the American Conference of Pharmaceutical Faculties, as well as the mean number of graduates among member schools each year. Methods. A review of published literature for numbers of schools and graduates was conducted and descriptive statistics were calculated. Results. The cumulative number of schools rose from 21 to 152 between those years. The peak contemporary number was 130 in 2014. Including satellite campuses with parallel curricula brings the contemporary total to 172. The smallest number of graduates per member school per year occurred in 1945 and 1946, with peaks in 1951, 1977, and 2013 (∼110 per school per year in the latter two peaks). Conclusions. The number of US pharmacy schools progressively rose between 1900 and 2014, with the fastest rate of growth occurring in 2014. The mean number of graduates per school per year rose or fell with influences such as the Great Depression, World War II, and the GI Bill.

Vaccination of adults with 23-valent pneumococcal polysaccharide vaccine induces robust antibody responses against pneumococcal serotypes associated with serious clinical outcomes.

PNEUMOVAX™ 23, a 23-valent polysaccharide pneumococcal vaccine (PPV23), covers 65% to 91% of the isolates recovered from adult cases of invasive pneumococcal disease. Several studies have demonstrated that pneumococcal serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A are associated with higher case-fatality or meningitis rates than other pneumococcal serotypes. This study (U05-PnPS-403; EudraCT: 2008-003648-12) evaluated the immune response followings administration of PPV23 for 4 of these serotypes (10A, 11A, 15B, and 17F), that are included in PPV23 but not in licensed pneumococcal conjugate vaccines. Serotype-specific IgG geometric mean concentrations (GMCs) and geometric mean fold-rises (GMFRs) for these 4 serotypes were measured by a validated enzyme-linked immunosorbent assay (ELISA) in 104 subjects >50 y of age who were enrolled in a study evaluating the safety and immunogenicity of a single-dose of PPV23. At 1 month post-vaccination, GMCs for serotypes10A, 11A, 15B and 17F were 6.5, 4.3, 14.7, and 5.1 µg/mL, respectively. GMFRs from baseline were 9.0, 4.5, 8.4, and 11.5, respectively. The percentages of subjects achieving >2-fold increases in IgG GMCs between pre-vaccination and 1 month post-vaccination were 90%, 85%, 88% and 89%, respectively. In conclusion, PPV23 induces a robust immune response in adults to pneumococcal serotypes 10A, 11A, 15B, and 17F, which have been associated with elevated case-fatality or meningitis rates.

Treatment of ebola virus disease.

In March 2014, the largest Ebola outbreak in history exploded across West Africa. As of November 14, 2014, the World Health Organization has reported a total of 21,296 Ebola virus disease (EVD) cases, including 13,427 laboratory-confirmed EVD cases reported from the three most affected countries (Guinea, Liberia, and Sierra Leone). As the outbreak of EVD has spread, clinical disease severity and national EVD case-fatality rates have remained high (21.2-60.8%). Prior to 2013, several EVD outbreaks were controlled by using routine public health interventions; however, the widespread nature of the current EVD outbreak as well as cultural practices in the affected countries have challenged even the most active case identification efforts. In addition, although treatment centers provide supportive care, no effective therapeutic agents are available for EVD-endemic countries. The ongoing EVD outbreak has stimulated investigation of several different therapeutic strategies that target specific viral structures and mechanisms of Ebola viruses. Six to eight putative pharmacotherapies or immunologically based treatments have demonstrated promising results in animal studies. In addition, agents composed of small interfering RNAs targeting specific proteins of Ebola viruses, traditional hyperimmune globulin isolated from Ebola animal models, monoclonal antibodies, and morpholino oligomers (small molecules used to block viral gene expression). A number of EVD therapeutic agents are now entering accelerated human trials in EVD-endemic countries. The goal of therapeutic agent development includes postexposure prevention and EVD cure. As knowledge of Ebola virus virology and pathogenesis grows, it is likely that new therapeutic tools will be developed. Deployment of novel Ebola therapies will require unprecedented cooperation as well as investment to ensure that therapeutic tools become available to populations at greatest risk for EVD and its complications. In this article, we review several agents and strategies that are now under active development.

Interwoven support: an historical survey of US federal programs enabling immunization.

The US Government (USG) can date its involvement with immunization to military and civilian efforts in 1777 and 1813 to prevent smallpox. USG involvement began accelerating with federal licensing of vaccine and antibody manufacturers in 1903. In addition to ongoing regulation of manufacturing and product quality, military and civilian arms of the USG have led research efforts into new or improved vaccines. These efforts have included diseases endemic in the United States, as well as medical countermeasures targeted against biological weapons, influenza pandemics, and emerging infectious diseases. Especially since the 1950s, the USG has provided increasing levels of funding to purchase vaccines and conduct vaccination programs. These programs have focused largely on children, although vaccination programs for adults have been expanded somewhat in recent years. Multiple agencies of the USG have convened various panels of accomplished external experts who have generated widely regarded recommendations on vaccine safety and efficacy and optimal immunization practices. USG programs for safety assessment, injury compensation, liability protection, and disease surveillance have been developed to assess needs, evaluate safety questions, ensure vaccine supply, and foster confidence in vaccination efforts. Debates on the extent of government involvement date back to the 1890 s and continue today. Several pivotal expansions of government involvement followed disease outbreaks or manufacturing accidents. This historical survey describes each of the major US federal programs in these categories, including references to applicable law.

Cost-effectiveness of pneumococcal vaccines for adults in the United States.

INTRODUCTION: In 2012, the Advisory Committee on Immunization Practices (ACIP) revised recommendations for adult pneumococcal vaccination to include a sequential regimen of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) for certain high-risk adults with immunocompromising conditions. This study, from a payer perspective, examined: (1) the cost-effectiveness of the new 2012 ACIP vaccine policy recommendation relative to the 1997 ACIP recommendation; (2) the cost-effectiveness of potential future pneumococcal vaccination policies; and (3) key assumptions that influence study results. METHODS: A static cohort model that incorporated costs, health outcomes, and quality-adjusted life-year (QALY) losses associated with invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia (NBPP) was developed to evaluate seven pneumococcal vaccination strategies for a 50-year-old adult cohort over a 50-year period using incremental cost-effectiveness ratios (ICERs). RESULTS: For objective 1, the 2012 ACIP recommendation is the more economically efficient strategy (ICER was $25,841 per QALY gained vs. no vaccination). For objective 2, the most efficient vaccination policy would be to maintain the 2012 recommendation for PPSV23 for healthy and immunocompetent adults with comorbidities, and to modify the recommendation for adults with immunocompromising conditions by replacing PPSV23 with a sequential regimen of PCV13 and PPSV23 at age 65 (ICER was $23,416 per QALY gained vs. no vaccination). For objective 3, cost-effectiveness ratios for alternative pneumococcal vaccine policies were highly influenced by assumptions used for vaccine effectiveness against NBPP and accounting for the herd protection effects of pediatric PCV13 vaccination on adult pneumococcal disease. CONCLUSION: Modifying the 2012 recommendation to include an additional dose of PCV13 at age 65, followed by PPSV23, for adults with immunocompromising conditions appears to be a cost-effective vaccine policy. Given the uncertainty in the available data and the absence of key influential data, comprehensive sensitivity analyses should be conducted by policy-makers when evaluating new adult pneumococcal vaccine strategies.

Differences in serious clinical outcomes of infection caused by specific pneumococcal serotypes among adults.

BACKGROUND: Infections due to Streptococcus pneumoniae serotypes differ in clinical manifestations among adults, varying in propensity for severity, invasiveness, and lethality. To characterize differences in serious outcomes between pneumococcal serotypes, we systematically reviewed the literature. METHODS: After distilling 676 hits to 28 relevant articles, statistically significant differences in individual serotypes associated with serious clinical outcomes were assessed. Serotypes associated with elevated risk of serious clinical outcomes were evaluated in terms of serotypes included in licensed adult pneumococcal vaccines (i.e., 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13)). Repeated findings were considered a measure of robustness. RESULTS: Among adult studies evaluating serious clinical outcomes, the following serotypes were associated with elevated risk: Empyema (serotypes 1, 3, 5, 7F, 8, 19A), necrotizing pneumonia (serotype 3), septic shock (serotypes 3, 19A), meningitis (repeatedly serotypes 10A, 15B, 19F, 23F), reduced quality-adjusted life years (QALYs, serotypes 15B, 3, 10A, 9N, 19F, 11A, 31), and increased case-fatality rates (repeatedly serotypes 3, 6B, 9N, 11A, 16F, 19F, 19A). CONCLUSION: Both vaccine formulations include multiple pneumococcal serotypes associated with increased risk for serious clinical outcomes. Three studies found elevated risk from serotype 6A (unique to PCV13). Fourteen studies found elevated risk from nine serotypes unique to PPSV23 (repeatedly: case-fatality-11A & 9N, meningitis-10A & 15B). Seven studies found elevated risk from serotypes not represented in either vaccine formulation (notably 16F). The pneumococcal serotypes repeatedly associated with elevated risk of serious outcomes in adults are an important consideration for vaccine policy making.