High Risk For Pneumococcal Disease Research Articles

Expert panel opinion on adult pneumococcal vaccination in the post-COVID era (NAP- EXPO Recommendations-2024).

Pneumococcal diseases pose a significant public health concern in India, with substantial morbidity and mortality, with the elderly and those with coexisting medical conditions being most at risk. Pneumococcus was also seen to be one of the main reasons for co-infection, pneumonia and complications in COVID. Current guidelines recommend vaccination for specific adult populations, but there is a lack of uniformity and guidance on risk stratification, prioritisation and optimal timing. Nation Against Pneumococcal Infections - Expert Panel Opinion (NAP-EXPO) is a panel convened to review and update recommendations for adult pneumococcal vaccination in India. The panel of 23 experts from various medical specialties engaged in discussions and evidence-based reviews, discussed appropriate age for vaccination, risk stratification for COPD and asthma patients, vaccination strategies for post-COVID patients, smokers and diabetics, as well as methods to improve vaccine awareness and uptake. The NAP-EXPO recommends the following for adults: All healthy individuals 60 years of age and above should receive the pneumococcal vaccine; all COPD patients, regardless of severity, high-risk asthma patients, post-COVID cases with lung fibrosis or significant lung damage, should be vaccinated with the pneumococcal vaccine; all current smokers and passive smokers should be educated and offered the pneumococcal vaccine, regardless of their age or health condition; all diabetic individuals should receive the pneumococcal vaccine, irrespective of their diabetes control. Strategies to improve vaccine awareness and uptake should involve general practitioners (GPs), primary health physicians (PHPs) and physicians treating patients at high risk of pneumococcal disease. Advocacy campaigns should involve media, including social media platforms. These recommendations aim to enhance pneumococcal vaccination coverage among high-risk populations in India in order to ensure a reduction in the burden of pneumococcal diseases, in the post-COVID era. There is a need to create more evidence and data to support the recommendations that the vaccine will be useful to a wider range of populations, as suggested in our consensus.

Influenza and Pneumococcal Vaccination Among Male Veterans and Nonveterans, 2016-2018.

The Advisory Committee on Immunization Practices recommends persons aged ≥6 months receive an influenza vaccination annually, and certain adults aged ≥19 years receive the 23-valent pneumococcal polysaccharide vaccine alone or in series with the 13-valent pneumococcal conjugate vaccine, depending on age, chronic conditions, and smoking status. This study examines the prevalence of influenza and pneumococcal vaccination relative to Healthy People 2020 goals to understand how vaccination receipt differs by veteran status and sociodemographic subgroups. We analyzed pooled data from the 2016-2018 National Health Interview Survey (N = 35 094) in 2021 to estimate the prevalence of influenza and pneumococcal vaccination for men aged 25-64 years and for men aged ≥65 years by veteran status and selected sociodemographic subgroups. We used 2-tailed t tests with an α = .05 to identify significant differences. Among men, 44.7% of veterans and 33.5% of nonveterans aged 25-64 years and 71.0% of veterans and 64.9% of nonveterans aged ≥65 years received an influenza vaccine in the past year. Among men aged 25-64 years at high risk for pneumococcal disease, 35.9% of veterans and 20.8% of nonveterans had ever received ≥1 dose of any pneumococcal vaccination. Disparities in the prevalence of vaccination within examined sociodemographic characteristics were often smaller in magnitude among veterans than among nonveterans for both vaccinations. Vaccination rates were below Healthy People 2020 targets for both groups, except influenza vaccination among veterans aged ≥65 years. Understanding differences in vaccine uptake may inform efforts to improve vaccination rates by identifying subgroups who are at high risk of disease and have low vaccination rates.

Predictors of pneumococcal vaccination among Australian adults at high risk of pneumococcal disease

BackgroundAlthough nearly all Australian children are vaccinated against pneumococcal disease, pneumococcal vaccine uptake is low among high-risk adults. This study aimed to identify perceived barriers to pneumococcal vaccination among high-risk adults. MethodsThis paper reports combined data on pneumococcal vaccination collected from three different online, cross-sectional surveys that were administered in Australia between August 2019 and September 2020. Using Poisson regression, we identified characteristics and beliefs associated with self-reported pneumococcal vaccination among adults aged 65 and over or with chronic health conditions. ResultsThe weighted estimate for pneumococcal vaccine coverage was 24% for high-risk adults under 65 and 53% for adults aged 65 and over. Nearly half of those under 65 reported they had never heard of the pneumococcal vaccine, while 26% of those aged 65 and over had never heard of the vaccine. Among those under 65, pneumococcal vaccination was associated with high perceived disease susceptibility (PR = 1.97, 95% CI: 1.23, 3.18), not having heard of the pneumococcal vaccine (PR = 0.44, 95% CI: 0.28–0.69), awareness that their chronic health condition puts them at increased risk of pneumonia (PR = 2.44, 95% CI: 1.51–3.98), and having a doctor recommend the vaccine (PR = 3.02, 95% CI: 2.05–4.44). Among adults aged 65 and over, self-reported pneumococcal vaccination was associated with influenza vaccination in the previous 12 months (PR = 4.28, 95% CI: 2.85–6.44) and awareness that they are eligible for free pneumococcal vaccination (PR = 5.02, 95% CI: 2.34–10.77). ConclusionAwareness of pneumococcal vaccines was low among adults at high risk of pneumococcal disease, which appears to be contributing to low vaccine uptake. A doctor’s recommendation was associated with increased uptake of pneumococcal vaccine, so interventions should be developed to promote pneumococcal vaccine uptake in GP practices.

A phase 3, multicenter, single-arm, open-label study to assess the safety, tolerability, and immunogenicity of a single dose of 13-valent pneumococcal conjugate vaccine in Japanese participants aged 6–64 years who are considered to be at increased risk of pneumococcal disease and who are naive to pneumococcal vaccines

BackgroundThis open-label, single-arm, phase 3 study evaluated safety and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) in pneumococcal vaccine-naive Japanese individuals aged 6–64 years at increased risk of pneumococcal disease (PD). MethodsParticipants received 1 PCV13 dose. Reactogenicity events were recorded for 7 days (individuals aged 6- to 17-year-old) or 14 days (individuals aged 18 to 64 years old) postvaccination. Adverse events (AEs) were collected for 1 month postvaccination. Opsonophagocytic activity (OPA) and anticapsular immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured for vaccine serotypes before and 1 month postvaccination. Post hoc analyses compared immunogenicity in participants categorized as at-risk (immunocompetent but having chronic medical conditions associated with increased PD risk) or high-risk (immunocompromised due to diseases/conditions and/or medications). Results206 participants aged 6- to 17-year-old (n = 53) and 18 to 64 years old (n = 153) completed the study. Reactogenicity events were generally mild to moderate in severity. AEs were reported in 16% (33/206) of participants; 1.0% (2/206) were severe. Six AEs were vaccine-related; most were associated with local reactions. No serious AEs occurred. Circulating antibody levels for all 13 serotypes increased postvaccination. OPA geometric mean fold rises (GMFRs) from prevaccination to 1 month postvaccination were 5.5–61.7; lower limits of the 2-sided, 95% CI were > 1 for all serotypes. IgG GMFRs were consistent with OPA analyses. In post hoc analyses, 55.8% (115/206) and 44.2% (91/206) of participants were categorized as at risk and at high risk of PD, respectively; OPA GMFRs from prevaccination to 1 month postvaccination were 3.9–635.1, with lower limits of the 2-sided 95% CIs > 1 for all 13 serotypes across these risk groups; IgG GMFRs were consistent with OPA analyses. ConclusionsPCV13 was well tolerated and immunogenic in Japanese individuals aged 6–64 years considered at increased risk of PD. Results were broadly comparable with past PCV13 studies in other Japanese and non-Japanese populations.Registration number: NCT03571607; JapicCTI-184024.

Pneumococcal vaccination coverage in France by general practitioners in adults with a high risk of pneumococcal disease

ABSTRACT Streptococcus pneumoniae, the main cause of community-acquired pneumonia (CAP), also leads to exacerbations, hospitalizations, and mortality in chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF). The risk of CAP is increased in patients with diabetes mellitus (DM), and the risk of invasive pneumococcal disease is increased in HIV-infected patients. Pneumococcal vaccination is recommended for these patients in France. The objective was a large survey of pneumococcal vaccination coverage (PVC) by general practitioners (GPs) in these patients in France. Diagnosis and treatment forms were extracted from the database of 2000 GPs. The GPs and population panels were representative of the metropolitan populations. The primary endpoint was the comparison of PVC in the adult patients diagnosed with COPD, CHF, DM, or HIV infection during the study (April 2013–April 2017) and the control (March 2012–March 2013) periods. Of the 17,865 and 4,690 patients identified, 756 (4%) and 267 (6%) were vaccinated, respectively. During the study period, the PVC was significantly higher (35/282, 12%) in HIV-infected patients and lower in patients with DM (95/5994, 2%) than in other patients. Even though French pneumococcal vaccine recommendations in adults were updated in 2013, the PVC did not increase according to the years of the study period and slightly increased according to time after diagnosis. S. pneumoniae is responsible only for some CAP and meningitis, and incomplete protection by vaccine, hesitancy from practitioners and patients, and the moving schedule of vaccination could explain the results. New tools and/or strategies must be implemented to increase PVC in France. Abbreviations: CAP: community-acquired pneumonia; COPD: chronic obstructive pulmonary diseases; CHF: congestive heart failure; DM: diabetes mellitus; IPD: invasive pneumococcal disease; HIV: human immunodeficiency virus; PVC: pneumococcal vaccination coverage; PCV7: 7-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; GPs: general practitioners; CLM: Cegedim Logiciels Médicaux; MLM: monLogicielMedical; ICD-10: International Classification of Diseases; CNIL: Commission nationale de l’informatique et des libertés; HPV: human papillomavirus; HBV: hepatitis B virus

Immunogenicity and Immune Memory after a Pneumococcal Polysaccharide Vaccine Booster in a High-Risk Population Primed with 10-Valent or 13-Valent Pneumococcal Conjugate Vaccine: A Randomized Controlled Trial in Papua New Guinean Children

We investigated the immunogenicity, seroprotection rates and persistence of immune memory in young children at high risk of pneumococcal disease in Papua New Guinea (PNG). Children were primed with 10-valent (PCV10) or 13-valent pneumococcal conjugate vaccines (PCV13) at 1, 2 and 3 months of age and randomized at 9 months to receive PPV (PCV10/PPV-vaccinated, n = 51; PCV13/PPV-vaccinated, n = 52) or no PPV (PCV10/PPV-naive, n = 57; PCV13/PPV-naive, n = 48). All children received a micro-dose of PPV at 23 months of age to study the capacity to respond to a pneumococcal challenge. PPV vaccination resulted in significantly increased IgG responses (1.4 to 10.5-fold change) at 10 months of age for all PPV-serotypes tested. Both PPV-vaccinated and PPV-naive children responded to the 23-month challenge and post-challenge seroprotection rates (IgG ≥ 0.35 μg/mL) were similar in the two groups (80–100% for 12 of 14 tested vaccine serotypes). These findings show that PPV is immunogenic in 9-month-old children at high risk of pneumococcal infections and does not affect the capacity to produce protective immune responses. Priming with currently available PCVs followed by a PPV booster in later infancy could offer improved protection to young children at high risk of severe pneumococcal infections caused by a broad range of serotypes.

1434. Cost-Effectiveness of Sequencial Vaccination With the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Followed by the 23 Valent Polysaccharide Vaccine (PPV23) in The Netherlands

Background Streptococcus pneumoniae causes significant morbidity and mortality among adults, especially among the elderly and those with underlying medical conditions. To reduce the disease burden the Health Council of the Netherlands recently recommended that people aged 60 and over should be offered vaccination against pneumococcal infections with the vaccine 23 valent polysaccharide vaccine (PPV23). This study aimed to evaluate the cost-effectiveness vaccinating people aged 60 with PPV23 compared with sequential vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by vaccination with PPV23.MethodsA previously published microsimulation model was used to compare the cost-effectiveness of PPV23 vaccination vs. sequential PCV13-PPV23 vaccination by age and risk group. PPV23 effectiveness was based on published literature, PCV13 effectiveness was based on CAPiTA; all other model parameters were based on published data. Outcomes and costs were evaluated assuming use of PPV23 alone, and alternatively, use of PCV13 → PPV23 among all adults aged 60 years and those at with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) aged 60 years.ResultsVaccinating individuals aged 60 years with PCV13 followed by vaccination with PPV23 would prevent 215 cases of IPD, 360 cases of hospitalized pneumonia, and 2,200 cases of outpatient pneumonia cases per vaccinated cohort compared with vaccination with PPV23 alone. At list price (€68.56 for PCV13 and €19.99 for PPV23) the ICER of vaccinating all adults of 60 years of age resulted in an ICER of €5,000/QALY. Adding a single dose of PCV13 for those with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) was shown to be cost saving compared with vaccination with PPV23 alone. Sensitivity analysis showed that a proportional decrease in list price decreased the ICER disproportionally in favor of adding a single dose of PCV13.ConclusionExpanding the recommendation of only PPV23 to PCV13→PPV23 among Dutch adults aged 60 years and older is a cost-effective use of healthcare resources. In particular adding a single dose of PCV13 for those with moderate or high risk of pneumococcal disease was shown to be cost-saving.Disclosures M. Rozenbaum, Pfizer: Employee and Shareholder, Salary.

Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea

BackgroundChildren in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections.MethodsThis report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG’s accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population.ResultsThis open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge.ConclusionLaboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal carriage, antibody production and function, and immune memory. The final data will inform policy on pneumococcal vaccine schedules in countries with children at high risk of pneumococcal disease by providing direct comparison of an accelerated schedule of 10vPCV and 13vPCV and the potential advantages of PPV following PCV immunization.Trial registrationClinicalTrials.gov CTN NCT01619462, retrospectively registered on May 28, 2012

Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination

Trial designIn an earlier trial, Papua New Guinean (PNG) children at high risk of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7), followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV23) at 9 months of age. We here studied in a non-randomized follow-up trial the persistence of pneumococcal immunity in these children at 3–5 years of age (n = 132), and in 121 community controls of a similar age with no prior pneumococcal vaccination.MethodsCirculating IgG antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific memory B-cells were enumerated at 10 months and 3–5 years of age for a subgroup of study children.ResultsSerotype-specific IgG antibody titers before and after challenge were similar for children who received PCV7/PPV23, PPV23 only, or no pneumococcal vaccines. Before challenge, at least 89% and 59% of children in all groups had serotype-specific titers ≥ 0.35μg/ml and ≥ 1.0 μg/ml, respectively. Post-challenge antibody titers were higher or similar to pre-challenge titers for most children independent of pneumococcal vaccination history. The rise in antibody titers was significantly lower when pre-challenge titers were higher. Overall the relative number of serotype-specific memory B-cells remained the same or increased between 10 months and 3–5 years of age, and there were no differences in serotype-specific memory B-cell numbers at 3–5 years of age between the three groups.ConclusionsImmunity induced by PCV7 and/or PPV23 immunization in infancy does not exceed that of naturally acquired immunity in 3-5-year-old children living in a highly endemic area. Also, there was no evidence that PPV23 immunization in the first year of life following PCV7 priming induces longer-term hypo-responsiveness.Trial registrationClinicaltrials.gov NCT01414504 and NCT00219401.

Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects

ABSTRACTPneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD.Methods: Approximately 100 subjects from the Russian Federation who were either 2 to 49 y of age with increased risk for PD or ≥50 years of age were enrolled into the study (NCT01734239) to receive a single dose of PPV23 administered intramuscularly. Each subject was followed for local and systemic adverse events (AEs) for 5 and 14 days, respectively. Serious AEs were collected for 28 d postvaccination. Blood samples were collected immediately prior to vaccination and 28 d postvaccination for the measurement of IgG to serotypes 1, 6B, 14, 19F, and 23F.Results: High proportion of subjects had ≥2 -fold increase in IgG following receipt of PPV23. Rates were 92.0%, 83.0%, 89.0%, 81%, 84% for serotypes 1, 6B, 14, 19F, and 23F, respectively. Similar rates of responders and increases in the magnitude of immune responses were observed in both age groups (2–49, ≥50 ). PPV23 was generally safe and well tolerated. Injection site and systemic AEs were reported by 14.7% and 18.6% of study subjects, respectively.Conclusions: PPV23 is generally safe, well tolerated, and highly immunogenic when given as a single dose to Russian individuals 50 y of age and older, as well as Russian individuals 2 to 49 y of age who are at high risk for PD.

A Virtual Clinic Improves Pneumococcal Vaccination for Asplenic Veterans at High Risk for Pneumococcal Disease.

We developed a “virtual clinic” to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients.

Intervals Between PCV13 and PPSV23 Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP).

Two pneumococcal vaccines are currently licensed for use in the United States: the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer Inc.]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). The Advisory Committee on Immunization Practices (ACIP) currently recommends that a dose of PCV13 be followed by a dose of PPSV23 in all adults aged ≥65 years who have not previously received pneumococcal vaccine and in persons aged ≥2 years who are at high risk for pneumococcal disease because of underlying medical conditions (Table) (1-4). The recommended intervals between PCV13 and PPSV23 given in series differ by age and risk group and the order in which the two vaccines are given (1-4).

Pneumococcal polysaccharide vaccination for adults: new perspectives for Europe

Vaccination is the only public-health measure likely to reduce the burden of pneumococcal diseases. In 2010, a group of European experts reviewed evidence on the burden of pneumococcal disease and the immunogenicity, clinical effectiveness and cost–effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). They also considered issues affecting the future use of PPV23 and pneumococcal conjugate vaccines in the elderly and adults at high risk of pneumococcal disease. PPV23 covers 80–90% of the serotypes responsible for invasive pneumococcal disease in Europe. Primary vaccination and revaccination with PPV23 are well tolerated, induce robust, long-lasting immune responses in elderly adults and are cost effective. Ensuring protection against pneumococcal disease requires monitoring of the changing epidemiology of pneumococcal serotypes causing invasive pneumococcal disease and improving vaccine coverage. In the future, it will be critically important for pneumococcal vaccination recommendations for elderly adults to be based on comparative evaluations of PPV23 and newer pneumococcal conjugate vaccines with regard to their long-term immunogenicity, clinical effectiveness and cost–effectiveness.

Impact of conjugate pneumococcal vaccines on the changing epidemiology of pneumococcal infections

Streptococcus pneumoniae-related infections have a major global impact on healthcare, especially in the developing world, and are considered the number one vaccine-preventable cause of death in children. There are more than 90 pneumococcal serotypes and 46 serogroups. The first capsular polysaccharide pneumococcal vaccine was licensed in the USA in 1977 for individuals older than 2 years of age at high risk for pneumococcal disease. Two decades later, the first 7-valent pneumococcal polysaccharide–protein conjugate vaccine completed the required clinical trials and was introduced as part of the national immunization program of various countries. New-generation vaccines that include emerging serotypes, while maintaining protection against the 7-valent pneumococcal serotypes, have recently been approved. With the addition of these serotypes, the majority of potential pneumococcal serotypes causing invasive disease in most parts of the world could be covered.

Initial and subsequent response to pneumococcal polysaccharide and protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal pneumonia.

Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) for adults at high risk for pneumococcal disease. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), and immunologic "priming" with PCV followed by "boosting" with PPV in adults who had recovered from pneumococcal pneumonia. Subjects received PPV followed by PCV 6 months later, or vice versa. The levels of IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline and at 4-8 weeks and 6 months after each vaccination. PPV and PCV stimulated similar IgG levels and OPK at 4-8 weeks after vaccination. Six months after receipt of PPV, the antibody levels declined to baseline but remained modestly elevated after receipt of PCV. PCV administered 6 months after PPV stimulated modest increases in IgG level that failed to reach the peaks observed after receipt of PPV. In contrast, PPV administered 6 months after PCV caused dramatic increases in the levels of IgG and OPK for all polysaccharides at 4-8 weeks, consistent with a booster effect. Six months after receipt of the second vaccination, however, levels of IgG and OPK fell precipitously in all patients, approaching baseline levels. In these high-risk subjects who have recovered after treatment for pneumonia, the effect of PPV is short-lived; PCV stimulates a more prolonged response. The use of PPV as a booster following PCV causes early increases in antibody levels, but the level of IgG declines rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults.

Safety and effectiveness against respiratory tract infections for pneumococcal conjugate vaccine co-administered with routine vaccine combinations

Streptococcus pneumoniae is a major cause of bacterial pneumonia and other respiratory tract infections (RTI) in children. The heptavalent conjugated pneumococcal vaccine (PCV7) is offering a promising strategy against pneumococcal disease in children younger than 2 years. In this prospective epidemiological study in Germany, children between 2 and 6 months of age received in a 3:1 ratio a routine childhood vaccine combination with or without PCV7 according to a four-dose schedule. Five thousand nine hundred and eighty-four children were evaluable 1 year after the booster dose. Due to German guidelines children with underlying medical conditions were preferentially included into the PCV7 group and hence 66% of the children in the PCV7 group had at least one medical risk factor and 40% were preterm born compared to 18% and 6% in the control group. Overall PCV7 reduced respiratory tract infections by 10.5% (95% CI: 2.9–17.3%) and clinically diagnosed pneumonia by 6.3% (95% CI: −15.9 to 23.7%) in this unbalanced situation. In a propensity score matched pair analysis controlling for risk factors, effectiveness of PCV7 against pneumonia was 24.8% (95% CI: 0.9–43.1%). In children with at least one medical risk factor vaccine effectiveness against pneumonia was 38.4% (95% CI: 10.7–55.9%) compared to 10.9% (95% CI: −20.2 to 33.9%) without a risk factor. In preterm and term born children, PCV7 was well tolerated when simultaneously administered with widely used hexavalent routine vaccine combinations. The results demonstrate that PCV7 is safe and effective against RTI in preterm children and in children with comorbidities stressing the benefit of pneumococcal conjugate vaccine in these children at high risk for pneumococcal disease.

Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects

In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease. Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating (1) children at high risk, (2) all children when considering only benefits for vaccinated individuals and (3) all children when also considering herd immunity benefits. Costs in the model included vaccination, management of meningitis, bacteraemia, pneumonia and acute otitis media, insurance payments to parents and the costs of care for long-term disabilities. The model estimated that the cost-effectiveness of vaccination would be 38,222 euros per life year gained in children at high risk and 100,636 euros per life year gained in all children when not considering herd immunity. When considering herd immunity effects, the model estimated that offering vaccination for all children would reduce adult deaths by 3,027 per year, and vaccination would be broadly cost neutral. The findings are sensitive to the effect of conjugate vaccine on the rates of pneumonia and invasive disease in the elderly. If the herd immunity effect of conjugate vaccination in Germany is similar to that observed elsewhere, offering vaccine to all children will be more attractive than the current policy of restricting vaccination to children at high risk of pneumococcal disease.

An Emergency Department–based Vaccination Program: Overcoming the Barriers for Adults at High Risk for Vaccine‐preventable Diseases

More than 10% of the population visit emergency departments (ED) every year. Many of these patients are not up-to-date on routine vaccinations that could prevent future illnesses. The ED could significantly impact these vaccination trends. This study was a feasibility study to determine whether patients would be amenable to an ED-based program that provided appropriate immunizations when they were at high risk for these diseases. In addition, the authors sought to identify barriers that predict high-risk patients who did not receive immunizations before ED presentation and to identify barriers that predict those high-risk unvaccinated patients who are unwilling to receive vaccinations when offered in the ED. This study was a prospective cross-sectional study of all patients arriving in the ED at one inner-city trauma center between 10 am and 10 pm over the course of a three-week intervention period. The subjects completed a survey that included information about their risk of influenza (flu) and pneumococcal disease, their immunization history, and their perceptions of their need for immunization. Demographic information collected included insurance status, age, gender, and primary language. All high-risk patients who were not current with their immunizations were offered vaccination. The primary outcome was improvement in vaccination coverage based on an ED surveillance and treatment system for vaccinations. The secondary outcomes were barriers to successful vaccination before ED presentation and barriers to acceptance of vaccination in the ED. Results were compared using chi-square test and confidence interval analysis. Characteristics of barriers to immunization were determined using a logistic regression model. A p-value < 0.05 was considered significant. A total of 674 subjects were entered into the study. Vaccination of subjects at high risk for flu increased significantly from 16% before to 83% after ED evaluation and treatment, and vaccination of subjects at high risk for pneumococcal disease increased significantly from 18% before to 84% after ED evaluation and treatment. Significant barriers to vaccination before ED presentation were lack of insurance (odds ratio [OR] = 0.31 for flu, 0.22 for pneumococcal disease), age younger than 50 years (OR = 0.18 for flu, 0.24 for pneumococcal disease), and no perceived need for vaccination (OR = 0.07 for flu). The sole significant barrier to vaccine administration in the ED was perceived need for vaccination (OR = 0.32 for flu). An ED-based vaccination program is both feasible and successful. Other than a shortage of vaccine, the only ED barrier to vaccination (perceived need) might be overcome with patient education.

Asthma as a Risk Factor for Invasive Pneumococcal Disease

The risk of invasive pneumococcal disease among persons with asthma is unknown. We conducted a nested case-control study to examine the association between asthma and invasive pneumococcal disease. The study population included persons 2 to 49 years of age who were enrolled in Tennessee's Medicaid program (TennCare) for more than one year during the study period (1995 through 2002) and who resided in counties participating in a prospective laboratory-based program of surveillance for invasive pneumococcal disease. For each subject with invasive pneumococcal disease, 10 age-matched controls without invasive pneumococcal disease were randomly selected from the same population. TennCare files were queried to identify the presence of coexisting conditions that confer a high risk of pneumococcal disease. For the purpose of our study, asthma was defined by documentation of one or more inpatient or emergency-department diagnoses of asthma, two outpatient diagnoses, or the use of asthma-related medications. High-risk asthma was defined as asthma requiring admission to a hospital or a visit to an emergency department, the use of rescue therapy or long-term use of oral corticosteroids, or the dispensing of three or more prescriptions for beta-agonists within the year before enrollment in the study. A total of 635 persons with invasive pneumococcal disease and 6350 controls were identified, of whom 114 (18.0 percent) and 516 (8.1 percent), respectively, had asthma. Persons with asthma had an increased risk of invasive pneumococcal disease (adjusted odds ratio, 2.4; 95 percent confidence interval, 1.9 to 3.1) as compared with controls. Among those without coexisting conditions, the annual incidence of invasive pneumococcal disease was 4.2 episodes per 10,000 persons with high-risk asthma and 2.3 episodes per 10,000 persons with low-risk asthma, as compared with 1.2 episodes per 10,000 persons without asthma. Asthma is an independent risk factor for invasive pneumococcal disease. The risk among persons with asthma was at least double that among controls.

Immunogenicity of the seven valent pneumococcal conjugate vaccine in patients with ataxia-telangiectasia.

Immune responses to a 7-valent pneumococcal conjugate vaccine were determined in 10 patients with ataxia-telangiectasia who are at high risk for pneumococcal disease because of immunodeficiency. Pneumococcal antibody titers for 7 serotypes measured increased 2.0- to 7.5-fold after immunization.