Efficacy Of Pneumococcal Vaccine Research Articles

Evaluation of the epidemiological efficacy of 23-valent pneumococcal polysaccharide vaccine among the elderly in Minhang District of Shanghai

Objective To evaluate the epidemiological efficacy of 23-valent pneumococcal polysaccharide vaccine on the clinical symptoms and the incidence of respiratory tract infections in the elderly over 60 years old in Minhang District, Shanghai. Methods A prospective cohort study was conduct, in which the sample size was 1 200 for both inoculated and uninoculated groups. This study followed the two groups of subjects every quarter for a year. Clinical symptoms and the incidence of respiratory tract infectious diseases as well as the acute onset of chronic respiratory diseases were compared between the subjects of the two groups. Results Compared with the uninoculated group, less people in the inoculated group developed the clinical symptoms of respiratory tract infection (RR=0.894, 95% CI: 0.804-0.994). Immunization with the 23-valent pneumococcal polysaccharide vaccine protected 57.7% of the senior citizens (≥75 years old) from respiratory tract infections(95% CI: 0.207-0.775). Conclusion The 23-valent pneumococcal polysaccharide vaccine can effectively reduce the incidence of respiratory tract infections in the elderly aged 60 years old and over and protects the elderly aged 75 years old and over from respiratory tract infections. Further studies on the immunological efficacy of 23-valent pneumococcal polysaccharide vaccine should be carried out by measuring the antibody titers before and after vaccination. Key words: The elderly; Pneumococcal vaccine; Respiratory tract infection; Cohort study; Efficacy evaluation

South Asia symposium on pneumococcal disease and the promise of vaccines – Meeting report

Despite the licensure of the pneumococcal conjugate vaccine (PCV) in the US and other Western countries for over 14 years, as of September 2014 only 4 South Asian countries were using PCV in their universal immunization program. To generate momentum toward addressing this issue a “South Asia symposium on pneumococcal disease and the promise of vaccines” was organized just prior to the 9th international symposium on pneumococci and pneumococcal diseases held in India recently. Leading scientists, program managers, and decision makers including ministry officials from the region participated in the meeting. The participants discussed available data on pneumococcal disease burden in South Asia, surveillance methods, efficacy and safety of pneumococcal conjugate vaccines (PCV), the status of PCV introduction, programmatic challenges in introducing PCV and available data on the impact of PCV in South Asia and globally. There was a strong consensus that available data on disease burden and the global experience with PCV justified the introduction PCV in all Asian countries in order to accelerate the gains in child survival in the region.

Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers.

BackgroundOne of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model.MethodsTransgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro.ResultsMortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection.ConclusionOur results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population.

Clinical Efficacy of Pneumococcal Conjugate 13-valent Vaccine in Young Children

Objective : Our aim was to study the clinical efficacy of pneumococcal conjugate 13-valent vaccine (PCV13) in children aged less than 3 years. Methods : retrospective comparative study of the incidence of acute respiratory infections (ARI), otitis and pneumonia during the first three years of life in 184 children vaccinated with PKV13 and 186 unvaccinated peers. Results : 91 of 184 children (49.4%) were vaccinated during the 1st year of life, 61 (33.2%) — during the 2nd year, and 32 (17.4%) — during the 3rd year. Number of ARI per 1 child among children vaccinated in the 1st year of life was 5.5 times less than among unvaccinated children (0.42 and 2.31 cases); frequency of otitis during the second year of life was 6.8 times less (7.6% and 52.1%, р < 0,01), and during the third — 34.7 times less (1.1% and 38.2%, р < 0,01). All children vaccinated before the age of 1 were 6.3 times less (1.1% and 6.9%) ill with pneumonias. Additionally it was noted that number of ARI per 1 person among children, vaccinated during the 1st year of life, during the third year of life was lower than among children vaccinated later (0.42; 1.02; 2.03 respectively). There also was a significant in otitis number between children vaccinated during the first and the third years of life (1.1 and 15.6% р < 0,01). Conclusion: to reduce the incidence of ARI, otitis and pneumonia in children, it is necessary to vaccinate children with PCV13 in the age under 1 year. «Catching up» immunization of the second and third years of life is effective, but to a lesser extent.

Streptococcus pneumoniae colonisation in children and adolescents with asthma: impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine

BackgroundThe main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13).MethodsOropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9 %), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction.Results S. pneumoniae was identified in the swabs of 192 subjects (45.4 %): 48.4 % of whom were aged <10 years, 46.9 % aged 10–14 years, and 4.7 % aged ≥15 years (p < 0.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95 % confidence interval [95 % CI] 0.22–0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95 % CI 0.70–1.58) for carriers of any pneumococcal serotype, 1.08 (95 % CI 0.72–1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95 % CI 0.45–1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19 F, 4 and 9 V were the most frequently identified serotypes in vaccinated subjects.ConclusionsThese results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.

Streptococcus pneumoniae oropharyngeal colonization in school-age children and adolescents with type 1 diabetes mellitus: Impact of the heptavalent pneumococcal conjugate vaccine

This study evaluated Streptococcus pneumoniae colonization in children and adolescents with type 1 diabetes mellitus (DM1) to investigate the theoretical risk of invasive pneumococcal disease (IPD) in these patients and the potential protective efficacy of pneumococcal conjugate vaccines (PCVs). An oropharyngeal swab was obtained from 299 patients aged 6–17 y with DM1 who were enrolled during routine clinical visits. DNA from swabs was analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in the swabs of 148 subjects (49.8%). Colonization was strictly age-related and declined significantly in the group aged ≥15 years (odds ratio [OR] 0.28; 95% confidence interval [CI], 0.14–0.57). Carriage was also significantly influenced by sex (lower in females: OR 0.56; 95% CI, 0.35–0.91), ethnicity (less common among non-Caucasians: OR 0.34; 95% CI, 0.13–0.89), parental smoking habit (more frequent among children with at least one smoker between parents: OR 1.76; 95% CI, 0.90–2.07), and the administration of antibiotic therapy in the previous 3 months (less frequent among patients who received antibiotics: OR 0.21; 95% CI, 0.07–0.62). Multivariate analyses of the entire study population showed no association between carriage and PCV7 vaccination status. Serotypes 19F, 9V, and 4 were the most frequently identified serotypes. In conclusion, school-age children and adolescents with DM1 are frequently colonized by S. pneumoniae, and protection against pneumococcal carriage following infant and toddler vaccination was not effective after several years. Together with the need to increase vaccine uptake in all the children aged <2 years, these results suggest that PCV booster doses are needed in DM1 patients to maintain the protection offered by these vaccinations.

First human challenge testing of a pneumococcal vaccine. Double-blind randomized controlled trial.

New vaccines are urgently needed to protect the vulnerable from bacterial pneumonia. Clinical trials of pneumonia vaccines are slow and costly, requiring tens of thousands of patients. Studies of pneumococcal vaccine efficacy against colonization have been proposed as a novel method to down-select between vaccine candidates. Using our safe and reproducible experimental human pneumococcal colonization model, we aimed to determine the effect of 13-valent pneumococcal conjugate vaccine (PCV) on colonization. A total of 100 healthy participants aged 18-50 years were recruited into this double-blind randomized placebo-controlled trial. They were randomly assigned to PCV (n = 49) or hepatitis A (control, n = 50) vaccination and inoculated with 80,000 CFU/100 μl of Streptococcus pneumoniae (6B) per naris. Participants were followed up for 21 days to determine pneumococcal colonization by culture of nasal wash. The PCV group had a significantly reduced rate of 6B colonization (10% [5 of 48]) compared with control subjects (48% [23 of 48]) (risk ratio, 0.22; confidence interval, 0.09-0.52; P < 0.001). Density of colonization was reduced in the PCV group compared with the control group following inoculation. The area under the curve (density vs. day) was significantly reduced in the PCV compared with control group (geometric mean, 259 vs. 11,183; P = 0.017). PCV reduced pneumococcal colonization rate, density, and duration in healthy adults. The experimental human pneumococcal colonization model is a safe, cost-effective, and efficient method to determine the protective efficacy of new vaccines on pneumococcal colonization; PCV provides a gold standard against which to test these novel vaccines. Clinical trial registered with 45340436.

Streptococcus pneumoniae pharyngeal colonization in school-age children and adolescents with cancer

Patients with cancer, particularly those with hematologic malignancies, are at an increased risk of invasive pneumococcal disease (IPD) and they are included in the list of subjects for whom pneumococcal vaccination is recommended. The main aim of this study was to evaluate Streptococcus pneumoniae colonization in school-aged children and adolescents with cancer to determine the potential protective efficacy of 13-valent pneumococcal conjugate vaccine (PCV13). An oropharyngeal swab was obtained from 277 patients (age range 6-17 years) with cancer during routine clinical visits and analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in 52 patients (18.8%), including 47/235 (20.0%) with hematologic malignancies and 5/42 (11.9%) with solid tumors. Colonization declined significantly with an increase in age (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.16-0.71, and OR 0.30, 95% CI 0.11-0.82 in children aged 10-14 and ≥15 years, respectively, as compared to those <10 years). Carriage was more common among patients with leukemia or lymphoma than in children with solid tumors. Co-trimoxazole prophylaxis was significantly associated with reduced pneumococcal carriage (OR 0.41, 95% CI 0.19–0.89). A total of 15/58 (25.9%) and 26/216 (12.0%) children were colonized by PCV13 serotypes among cancer patients previously vaccinated and not vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7), respectively. In conclusion, this study indicates that children and adolescents with cancer are frequently colonized by S. pneumoniae. Because most of the carried serotypes are included in PCV13, this vaccine is presently the best solution to reduce the risk of IPD in these patients.

The Impact of Age on the Efficacy of 13-valent Pneumococcal Conjugate Vaccine in Elderly.

In a post hoc analysis of the Community-Acquired Pneumonia (CAP) immunization Trial in Adults the model-predicted 13-valent pneumococcal conjugate vaccine efficacy for preventing vaccine-type specific CAP and Invasive Pneumococcal Disease declined from 65% to 40% for subjects being 65 and 75 year olds at the time of vaccination, respectively.

Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands.

The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands.Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65–74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted.The ICER for base-case was €8650 per QALY (95% CI 5750–17 100). Vaccination of high-risk individuals aged 65–74 years was cost-saving and extension to medium-risk individuals aged 65–74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100.PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries.

Efficacy of the 7-Valent Pneumococcal Conjugate Vaccine Against Acute Otitis Media Caused by Serotype 6C Pneumococcus.

A new pneumococcal serotype 6C, earlier typed as 6A, was discovered in 2007. We retyped all 6A isolates to evaluate vaccine efficacy against 6C acute otitis media (AOM) in the phase III randomized, double-blind Finnish Otitis Media trial conducted in 1995-1999. Efficacy against 6C AOM was -1 (95% confidence interval: -248 to 71) during the per protocol follow-up period. The updated vaccine efficacy estimate for serotype 6A AOM was 65% (95% confidence interval: 31-82). Seven-valent pneumococcal conjugate vaccine offered excellent cross-protection against 6A AOM, but our data do not support cross-protection against 6C AOM.

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases--a longitudinal study.

IntroductionPatients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects.MethodsThis observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4–8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients.ResultsOf 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p < 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections.ConclusionsPPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections.

Recommended immunizations for older adults: a primer for pharmacists.

To assess the effectiveness and safety of currently recommended vaccines in older adults. PubMed was used to search for relevant articles. Key words searched included: immunosenescence, influenza vaccine efficacy, influenza vaccine safety, Tdap safety and efficacy elderly, Td safety and efficacy elderly, pneumococcal vaccine safety and efficacy elderly, pneumococcal vaccine efficacy, Recombivax safety and efficacy elderly, Zostavax safety and efficacy, influenza vaccine timing, frailty and immunosenescence. Articles were reviewed and selected considering relevance to the subject. Selected articles were written in the English language, conducted mainly in humans, and published from 2008 to 2014, if it was a review article. Articles were then determined to be relevant or irrelevant based on their abstracts. Immunizations are a major means of preventing diseases, and pharmacists are a frontline health professional, with significant interactions with the older population. There are no recent published reviews that compile the efficacy and safety evidence for recommended immunizations in older people. Pharmacists are often asked questions about the efficacy and safety of these immunizations. Overall, efficacy and safety profiles of currently recommended vaccines are positive in the older population. The least-effective vaccine currently recommended is the varicella-zoster vaccine, with a 50% efficacy. The vaccine with the highest rates of adverse events is the tetanus booster, with local pain and swelling at the injection site.

Efficacy of 13-Valent Pneumococcal Conjugate Vaccine in Older Adults

The 13-valent pneumococcal conjugate vaccine (Prevnar 13) was first recommended for use in older adults (age, ≥65; NEJM JW Gen Med Apr 1 2015 and Ann

Assessment of clinical and immunological efficacy and safety of 23-valent pneumococcal vaccine in patients with rheumatoid arthritis

The objective of this trial was to assess clinical efficacy, immunogenicity, and safety of 23valent pneumococcal vaccine (PPV23) in patients with rheumatoid arthritis (RA). Methods . The trial enrolled 95 patients (75 women and 20 men aged 23 to 70 years) including 68 patients with RA and 27 subjects without systemic inflammatory rheumatic diseases (a control group) who had a recent history of ≥ 2 episodes of lower respiratory tract infection. At enrollment, all the patients received antiinflammatory therapy with methotrexate (MT) (n = 48), leflunomide (LEF) (n = 10), or MT + tumor necrosis factorα (TNFα) inhibitors (n = 10). A single 0.5ml dose of PPV23 (Pneumo23, Sanofi Pasteur) was administered subcutaneously under the regular therapy with MT or LEF or 3–4 weeks before TNFα inhibitor administration. During followup (1 and 3 months and 1 year after the vaccination), the patients underwent physical examination and routine clinical and laboratory investigations. Antipneumococcal capsular polysaccharide antibodies were measured in the serum using ELISA assay with commercial VaccZymeTM AntiPCP IgG Enzyme Immunoassay Kit (The Binding Site Group Ltd, Birmingham, UK). Results. Noone case of pneumonia was registered in vaccinated patients during 12month followup. A twofold increase in antipneumococcal antibody level was found 1 year after the vaccination in RA patients and the control group. The vaccine was well tolerated by 63 patients (66%); 25 patients (26%) experienced pain, swelling and hyperemia at the area of vaccine injection and 7 patients (8%) had lowgrade fever. Neither RA exacerbation nor new autoimmune disorders were diagnosed during the followup. Conclusion. The findings suggest that PPV23 showed good clinical efficacy, adequate immunogenicity and good tolerability in RA patients.

Anti-epidemic activities to prevent pneumococcal infections in flooded areas of the Amur region

The aim of this study was to analyze CAP epidemiology and morbidity in the Amur region, to evaluate anti-epidemic measures for prevention of pneumococcal infections in flooded areas and medical and socioeconomic benefits of vaccination of children with risk factors for pneumococcal disease. Material and methods. Common morbidity of pneumonia was analyzed in the Amur region. To evaluate clinical and epidemiological efficacy of pneumococcal vaccination with PCV13 in 2014–2017, 5,000 children aged 2 to 5 yrs with high risk of pneumococcal infection were involved into a special follow-up programme. Clinical, epidemiological, social, hygienic, economic and statistical analyses were used. Results. The total incidence of pneumonia in population of the Amur region reached the peak value (897.3 per 100,000) in 2009; this was associated with influenza pandemic. CAP incidence decreased by 43.8% in 2010–2014. Morbidity of CAP had certain age-related and seasonal differences and was closely related to morbidity of acute respiratory viral infection. Results of microbiological monitoring of CAP pathogens in the Amur region were also discussed. Morbidity of pneumonia and acute respiratory infections decreased in 2014 in 69.4% of children vaccinated with PCV13. Morbidity of CAP reduced by 2,014 cases in 2014 that prevented economic loss of 94 billion RUB. Conclusion. Clinical and economic monitoring of CAP and pneumococcal vaccination with PCV13 in the Amur region have significant medical and socioeconomic efficacy.

Phenotypic and functional analysis of HL-60 cells used in opsonophagocytic-killing assay for Streptococcus pneumoniae.

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1α, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.

Next generation vaccines

Next generation vaccines

109913-valent Pneumococcal Conjugate Vaccine Efficacy is Declining with Old Age: Results from an Exploratory Analysis of the CAPiTA Trial

Old Age: Results from an Exploratory Analysis of the CAPiTA Trial Cornelis H VanWerkhoven, MD; Susanne MHuijts, MD; Marieke Bolkenbaas, MD; Chris Webber, MD, PhD; Beate Schmoele-Thoma, MD; Scott D. Patterson, PhD; William Gruber, MD; Diederick E. Grobbee, MD, PhD; Marc Bonten, MD PhD; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Pfizer Vaccine Clinical Research, Maidenhead, United Kingdom; Pfizer Pharma GmbH, Berlin, Germany; Pfizer Vaccine Clinical Research, Collegeville, PA; Pfizer Vaccine Clinical Research, Pearl River, NY; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands

Prevention of invasive pneumococcal diseases: beyond cultures

Prevention of invasive pneumococcal diseases: beyond cultures