Use Of Conjugate Vaccine Research Articles

Recent Progress in the Prevention of Serogroup B Meningococcal Disease.

ABSTRACTThe widespread use of meningococcal polysaccharide conjugate vaccines has highlighted the challenge of providing protection against serogroup B disease. Over a period of 4 decades, vaccine development has focused on subcapsular protein antigens, first with outer membrane vesicle (OMV) vaccines against epidemic outbreaks, and more recently on new multicomponent vaccines designed to offer better cross-protection against the antigenically diverse strains responsible for endemic disease. Because of the low incidence of meningococcal disease, the protective efficacy of these vaccines has not been determined in clinical studies, and their licensure has been based on serological data; however, the serological assays used to predict protective coverage have limitations. As a result, evidence of the effectiveness of these vaccines against different strains and the contribution of specific antigens to protection can only be provided by epidemiological analyses following their implementation in sufficiently large populations. The recent inclusion of the four-component meningococcal serogroup B (4CMenB) vaccine, Bexsero, in the infant immunization program in the UK has provided preliminary evidence that the vaccine is effective. Ongoing surveillance will provide valuable data on its longer-term impact and antigenic coverage. Further development of protein-based vaccines against meningococcal disease is anticipated to improve antigenic coverage and adjust to changes in circulating strains. At the same time, alternative immunization strategies may be explored to improve overall vaccine effectiveness by, for example, protecting the youngest infants or providing herd protection.

Pneumococcal carriage among children after four years of routine 10-valent pneumococcal conjugate vaccine use in Brazil: The emergence of multidrug resistant serotype 6C

BackgroundIn 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced free of charge in Brazil as part of the public immunization program. Here we investigated the carriage prevalence, colonization risk factors, capsular types, and antimicrobial resistance among pneumococcal isolates obtained from children in Brazil four years after routine PCV10 use. MethodsBetween September and December 2014, we conducted a cross-sectional study among children<6years old who attended one public and two private clinics in Niterói, RJ, Brazil to evaluate pneumococcal nasopharyngeal carriage. Antimicrobial susceptibility and capsular types were determined for all isolates. ResultsOf 522 children, 118 (22.6%) were pneumococcal carriers. Being≥2years old, attending childcare center, presenting with any symptoms, having acute or chronic respiratory disease, and residing in a slum were associated with pneumococcal carriage. The most prevalent capsular types were 6C (14.5%), 15B/C (11.5%), 11A/D (9.2%), and 6A (7.6%). PCV10 serotypes represented 2.5%. All isolates were susceptible to levofloxacin, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) comprised 39%, with penicillin and ceftriaxone MICs ranging from 0.12–8.0μg/ml and 0.012–1.0μg/ml, respectively. The 33 (28%) erythromycin-resistant isolates (MICs of 1.5 to >256μg/ml) displayed the cMLSB (72.7%) or M (27.3%) phenotypes, harboring the erm(B) and/or mef(A/E) genes. High non-susceptibility rates (>20%) to clindamycin, erythromycin, penicillin, and tetracycline were largely explained by the prevalence of multidrug resistant (MDR) serotype 6C isolates. ConclusionsEffects of universal childhood PCV10 use on carriage were evident, with the near elimination of PCV10 serotypes. The emergence of MDR serotype 6C isolates, however, is a concern. Ongoing surveillance to monitor serotype 6C increase in invasive diseases is warranted.

Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons - Advisory Committee on Immunization Practices, 2016.

At its June 2016 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of meningococcal conjugate vaccine (serogroups A, C, W, and Y; including MenACWY-D [Menactra, Sanofi Pasteur] or MenACWY-CRM [Menveo, GlaxoSmithKline]) for persons aged ≥2 months with human immunodeficiency virus (HIV) infection. ACIP has previously recommended routine vaccination of persons aged ≥2 months who have certain medical conditions that increase risk for meningococcal disease (1), including persons who have persistent (e.g., genetic) deficiencies in the complement pathway (e.g., C3, properdin, Factor D, Factor H, or C5-C9); persons receiving eculizumab (Soliris, Alexion Pharmaceuticals) for treatment of atypical hemolytic uremic syndrome or paroxysmal nocturnal hemoglobinuria (because the drug binds C5 and inhibits the terminal complement pathway); and persons with functional or anatomic asplenia (including persons with sickle cell disease). Routine vaccination with meningococcal conjugate vaccine is also recommended for all healthy adolescents in the United States (1). This report summarizes the evidence considered by ACIP in recommending vaccination for HIV-infected persons, and provides recommendations and guidance for use of meningococcal conjugate vaccines (serogroups A, C, W, and Y) among HIV-infected persons aged ≥2 months; the majority of meningococcal disease among HIV-infected persons is caused by these four serogroups.

Impact of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Use on Invasive Pneumococcal Disease (IPD) Among Adults With Chronic Conditions, United States

Impact of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Use on Invasive Pneumococcal Disease (IPD) Among Adults With Chronic Conditions, United States

Direct and Indirect Impact of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Use on Invasive Pneumococcal Disease (IPD) Among Children and Adults

Direct and Indirect Impact of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Use on Invasive Pneumococcal Disease (IPD) Among Children and Adults

The importance of surveillance: Group W meningococcal disease outbreak response and control in England.

Invasive meningococcal disease (IMD) is associated with high morbidity and mortality. Recently, use of the quadrivalent MenACWY conjugate vaccines has increased with the emergence of a hypervirulent MenW:cc11 strain in certain parts of the world, especially South America. In England, MenW:cc11 IMD cases increased rapidly after 2009 and was responsible for 24% of all IMD cases in 2014/15 compared to <5% previously, leading to the emergency introduction of a national teenage MenACWY conjugate vaccine programme in August 2015. Unusually, MenW:cc11 cases have been described presenting with severe gastrointestinal symptoms, including abdominal pain and diarrhoea, followed by rapid clinical deterioration and death.

Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis.

ABSTRACTWhile significant protection from pneumococcal disease has been achieved by the use of polysaccharide and polysaccharide-protein conjugate vaccines, capsule-independent protection has been limited by serotype replacement along with disease caused by nonencapsulated Streptococcus pneumoniae (NESp). NESp strains compose approximately 3% to 19% of asymptomatic carriage isolates and harbor multiple antibiotic resistance genes. Surface proteins unique to NESp enhance colonization and virulence despite the lack of a capsule even though the capsule has been thought to be required for pneumococcal pathogenesis. Genes for pneumococcal surface proteins replace the capsular polysaccharide (cps) locus in some NESp isolates, and these proteins aid in pneumococcal colonization and otitis media (OM). NESp strains have been isolated from patients with invasive and noninvasive pneumococcal disease, but noninvasive diseases, specifically, conjunctivitis (85%) and OM (8%), are of higher prevalence. Conjunctival strains are commonly of the so-called classical NESp lineages defined by multilocus sequence types (STs) ST344 and ST448, while sporadic NESp lineages such as ST1106 are more commonly isolated from patients with other diseases. Interestingly, sporadic lineages have significantly higher rates of recombination than classical lineages. Higher rates of recombination can lead to increased acquisition of antibiotic resistance and virulence factors, increasing the risk of disease and hindering treatment. NESp strains are a significant proportion of the pneumococcal population, can cause disease, and may be increasing in prevalence in the population due to effects on the pneumococcal niche caused by pneumococcal vaccines. Current vaccines are ineffective against NESp, and further research is necessary to develop vaccines effective against both encapsulated and nonencapsulated pneumococci.

Pneumococcal Disease Prevention Among Adults: Strategies for the Use of Pneumococcal Vaccines.

Use of the pneumococcal conjugate vaccines among children in the U.S. since 2000 has dramatically reduced pneumococcal disease burden among adults. Significant vaccine-preventable morbidity and mortality from pneumococcal infections still remains, especially among older adults. The U.S. Advisory Committee on Immunization Practices (ACIP) has recently recommended the routine use of both pneumococcal conjugate (PCV13) and polysaccharide vaccines (PPSV23) for adults ≥65 years. These recommendations were based on the remaining burden of illness among adults and the importance of non-bacteremic pneumonia prevention in light of new evidence confirming the efficacy of PCV13 to prevent pneumococcal pneumonia among older adults. This paper reviews the evidence that led ACIP to make recommendations for PCV13 and PPSV23 use among adults, and highlights potential gaps to be addressed by future studies to inform adult vaccination policy. The changing epidemiology of invasive pneumococcal disease and pneumonia should be closely monitored to evaluate the effectiveness and continued utility of the current vaccination strategy, and to identify future directions for pneumococcal disease prevention among older adults.

Persistent occurrence of serogroup Y/sequence type (ST)-23 complex invasive meningococcal disease among patients aged five to 14 years, Italy, 2007 to 2013.

In Italy, the incidence of invasive meningococcal disease (IMD) has remained stable since 2007 (around 0.3 cases/100,000 inhabitants). However, as reported for other European countries, an increase of serogroup Y Neisseria meningitidis has been observed. In this study we report IMD cases from 2007 to 2013 in Italy and investigate the clinical and epidemiological features of cases affected by serogroup Y. Molecular characteristics of serogroup Y strains are also described. During the study period, the proportion of IMD cases due to serogroup Y increased, ranging from 2% in 2007 to 17% in 2013 (odds ratio (OR): 8.8), whereby the five to 14 years age group was mostly affected (p < 0.001). Overall 81 serogroup Y IMD cases were identified, with a median age of 18 years, ranging from three months to 84 years. Of the 81 respective patient samples, 56 were further subject to molecular typing. The sequence type (ST)-23 complex (clonal complex (cc)23) was predominant among serogroup Y meningococci (54/56 samples), and included nine different STs. Presumably, ST-23 was the founding genotype, with all the other STs presenting as single-locus variants. All cc23 isolates analysed harboured mutations in the lpxL1 gene; however, no associations among lpxL1 mutations, ST and age group were identified. Overall, these findings generate scientific evidence for the use of the quadrivalent meningococcal conjugate vaccine in the five to 14 years age group.

Documenting the Results of a Successful Partnership: A New Meningococcal Vaccine for Africa.

The Meningitis Vaccine Project, a partnership between the World Health Organization (WHO) and PATH, an international nonprofit organization, existed from 21 June 2001 to 31 December 2014. The project had a single goal: the development, licensure, and introduction of a group A meningococcal conjugate vaccine in sub-Saharan Africa. It was successful and resulted in the WHO prequalification of 2 products, a PsA-TT 10-µg vaccine for use in mass vaccination campaigns among 1- to 29-year-olds, and a 5-µg vaccine for use in routine immunization programs among children <2 years of age. Since 2010, the 10-µg vaccine has been used to immunize 1- to 29-year-olds in large vaccination campaigns in countries of the sub-Saharan African meningitis belt. WHO has recommended introduction of the 5-µg vaccine into the routine childhood immunization program within 1–5 years following campaign completion. Many lessons have been learned through the development, testing, and introduction of MenAfriVac (PsA-TT), and this collection of articles is an attempt at documenting results and lessons learned. Grouping articles on a single theme is an arbitrary exercise; the editors have chosen to group the purely serologic articles in a separate section. The initial section in general follows the historical procession from an idea that began in 1998 to the assessment of the impact of MenAfriVac introduction. A collection of 4 safety articles bridges sections 1 and 2. The editors have chosen to be inclusive so that readers may have a detailed view of the many steps required to develop and license a new vaccine. In addition to the group of articles that were included, there are previous publications, in particular, those describing the results of clinical trials using PsA-TT. Many of development steps were used as important training opportunities. The article by Dellepiane et al is an excellent description of the regulatory challenges facing companies that wish to license a new vaccine [1]. The use of a fast track for prequalification and WHO's accelerated process for country registration greatly facilitated getting the vaccine properly registered. Diomande's article on pharmacovigilance is particularly important given the all-too-common assertion that pharmacovigilance cannot be done in sub-Saharan Africa [2]. Similarly, the article by Wak et al clearly documents the safety of PsA-TT when given to pregnant women [3]. More than 217 million doses have been given from 2010 through December 2014, and group A Neisseria meningitidis has disappeared wherever the vaccine has been used. The vaccine's impact is well summarized in Diomande's article that amply documents vaccine impact, particularly in Chad and Burkina Faso [4]. Diallo et al describe the antibody persistence in 2- to 29-year-olds, demonstrating that antibodies at 1 and 4 years following immunization with PsA-TT persist significantly better than following polysaccharide vaccination. Four years following a single dose of PsA-TT, most individuals still had protective antibody titers [5]. Tapia et al demonstrated that in 12- to 23-month-old Africans, antibody levels remained significantly above baseline up to 5 years following vaccination, with the majority of children remaining protected [6]. An added benefit of immunizing with PsA-TT is the carrier protein tetanus toxoid (TT) itself. PsA-TT has been shown to generate robust tetanus serologic responses in 1- to 29-year-olds, similar to those expected after a booster dose of TT [7]. Of note, neonatal cases of tetanus have fallen by 25% in countries that completed PsA-TT campaigns in 1- to 29-year-olds. No vaccine-related serious adverse events (SAEs) occurred during the 3 months of follow-up of 4004 healthy Malians vaccinated with a single dose of PsA-TT; in addition, rates of systemic reactions, adverse events, and SAEs were similar to those in the polysaccharide control vaccine group and were considered unrelated to vaccination [8]. This collection of articles offers a unique look into an important public health problem that has been controlled. Nonetheless, the need for continued enhanced meningitis surveillance in Africa remains a high priority because of the threat that 1 or more non-A meningococcal strains in Africa will assume epidemic proportions. PsA-TT's success has generated a new confidence that over time, and with the development and use of affordable polyvalent meningococcal conjugate vaccines, meningococcal disease may well be eliminated from sub-Saharan Africa.

Impact of the Pneumococcal Conjugate Vaccine and Antibiotic Use on Nasopharyngeal Colonization by Antibiotic Nonsusceptible Streptococcus pneumoniae, Alaska, 2000[FIGURE DASH]2010.

We describe the relative impact of the heptavalent pneumococcal conjugate vaccine (PCV7, introduced 2001) and antibiotic use on colonization by antibiotic-resistant pneumococci in urban Alaskan children during 2000-2010. We obtained nasopharyngeal swab specimens from a convenience sample of children aged <5 years at clinics annually during 2000-2004 and 2008-2010. PCV7 status and antibiotic use <90 days before enrollment were determined by interview/medical records review. Pneumococci were characterized by serotype and susceptibility to penicillin (PCN). Isolates with full PCN resistance (PCN-R) or intermediate PCN resistance (PCN-I) were classified as PCN-NS. We recruited 3496 children (median, 452 per year). During 2000-2010, a range of 18-29% per year of children used PCN/amoxicillin (P value for trend = 0.09); the proportion age-appropriately vaccinated with PCV7 increased (0[FIGURE DASH]90%; P < 0.01). Among pneumococcal isolates, the PCV7-serotype proportion decreased (53-<1%; P < 0.01) and non[FIGURE DASH]PCV7-serotype proportion increased (43-95%; P < 0.01). PCN-R pneumococcal colonization prevalence decreased (23-9%; P < 0.01) and PCN-I pneumococcal colonization prevalence increased (13-24%; P < 0.01); overall PCN-NS pneumococcal colonization prevalence was unchanged. PCN-NS among colonizing PCV7-type and non[FIGURE DASH]PCV7-type pneumococci remained unchanged; a mean of 31% per year of PCV7-type and 10% per year of non[FIGURE DASH]PCV7-type isolates were PCN-R, and 10% per year of PCV7 and 20% per year of non[FIGURE DASH]PCV7-type isolates were PCN-I. Overall, PCN-NS pneumococcal colonization remained unchanged during 2000-2010 because increased colonization by predominantly PCN-I non-PCV7 serotypes offset decreased colonization by predominantly PCN-R PCV7 serotypes. Proportion PCN-NS did not increase within colonizing pneumococcal serotype groups (PCV7 vs. non-PCV7) despite stable PCN use in our population.

Epidemiology of Neisseria meningitidis infections: case distribution by age and relevance of carriage.

Notwithstanding different meningococcal serogroups have changed their distribution and their impact in different age classes over time, N. meningitidis' invasive diseases are a major public health issue worldwide, due to the related complications and severe sequelae. Nowadays, the highest rates of invasive disease are registered in children younger than 1 year of age, with a second lesser peak in adolescents and young adults (15-25 years of age). On the contrary, the prevalence of carriage is low in newborns and in school-age children, and increases during adolescence and young-adult age; then it decreases again in older age. N. meningitidis' infection prevalence has greatly decreased in Europe and North America thanks to the use of conjugate vaccines (MenC and MenACWY) as well as the incidence of invasive disease due to serogroup A in sub-saharian Africa after the introduction of MenAfriVac conjugate vaccine. The great success of conjugate vaccines is related not only to the direct protection from disease but also to the impact on carriage; this latter allows an indirect protection of unimmunized subjects. For these reasons, the implementation of immunization with the new generation vaccines in the age classes most impacted by disease and carriage (first year of life, adolescence and young adulthood) could permit to achieve an extraordinary decrease of the incidence of meningococcal disease.

A 13-year survey of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 and PCV13 implementation

BackgroundThis nasopharyngeal (NP) carriage surveillance study was requested by the European Agency for the Evaluation of Medicinal Products as a post-licensing commitment to determine whether the use of the pneumococcal conjugate vaccines (PCVs) including 7 then 13 valents (introduced in 2001 and 2010, respectively) caused a shift in the distribution of Streptococcus pneumoniae serotypes in children with acute otitis media and modified the resistance of this bacterial species to antibiotics. MethodsBetween 2001 and 2014, 121 pediatricians obtained nasopharyngeal swabs from children with acute otitis media aged 6–24 months. The swabs were analyzed by the French National Reference Centre for Pneumococci. Demographics, medical history and physical examination findings were recorded. ResultsOver the 13 years, among the 7991 enrolled patients, the proportion of PCV-vaccinated children (≥1 dose) increased (54.3–99.7%, p<0.001). Overall, pneumococcal carriage was reduced from 71.2% to 56.2% from 2001 to 2014 (p<0.001) and carriage of PCV7 serotypes (STs) from 44.5% to 1.2% (p<0.001). The carriage of 6 additional STs plus 6C increased from 17.2% to 24.3% from 2001 to 2010 (p<0.001) and decreased after PCV13 implementation (21.4–3.5%, p<0.001). The proportion of ST 19A carriage increased from 8.6% to 15.8% from 2001 to 2010 (p<0.001) and decreased to 1.2% in 2014. After PCV13 implementation, the most frequently carried non-PCV13 STs were ST 15B/C, 11A, 15A, and 35B. Penicillin non-susceptible pneumococcal strains decreased from 67.1% in 2001 to 33.1% in 2014 (p<0.001). ConclusionsBy the number of patients enrolled and the duration, this study is the largest performed to date. It allows to demonstrate a strong impact of PCVs and to describe the complex dynamics of pneumococcal carriage during AOM. As pneumococcal carriage decreased during AOM, a reduction in the incidence of pneumococcal AOM could be expected.

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.

Pneumococcal Capsules and Their Types: Past, Present, and Future

Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.

Vaccines for Nontypeable Haemophilus influenzae: the Future Is Now.

Infections due to nontypeable Haemophilus influenzae result in enormous global morbidity in two clinical settings: otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Recurrent otitis media affects up to 20% of children and results in hearing loss, delays in speech and language development and, in developing countries, chronic suppurative otitis media. Infections in people with COPD result in clinic and emergency room visits, hospital admissions, and respiratory failure. An effective vaccine would prevent morbidity, help control health care costs, and reduce antibiotic use, a major contributor to the global crisis in bacterial antibiotic resistance. The widespread use of the pneumococcal conjugate vaccines is causing a relative increase in H. influenzae otitis media. The partial protection against H. influenzae otitis media induced by the pneumococcal H. influenzae protein D conjugate vaccine represents a proof of principle of the feasibility of a vaccine for nontypeable H. influenzae. An ideal vaccine antigen should be conserved among strains, have abundant epitopes on the bacterial surface, be immunogenic, and induce protective immune responses. Several surface proteins of H. influenzae have been identified as potential vaccine candidates and are in various stages of development. With continued research, progress toward a broadly effective vaccine to prevent infections caused by nontypeable H. influenzae is expected over the next several years.

Five winters of pneumococcal serotype replacement in UK carriage following PCV introduction

The seven-valent pneumococcal conjugate vaccine (PCV7) was added to the UK national immunisation programme in September 2006. PCV13 replaced PCV7 in April 2010. As carriage precedes disease cases this study collected carried pneumococci from children each winter from 2006/7 to 2010/11 over PCV introduction. Conventional microbiology and whole genome sequencing were utilised to characterise pneumococcal strains.Overall prevalence of pneumococcal carriage remained stable. Vaccine serotypes (VT) decreased (p<0.0001) with concomitant increases in non-vaccine serotypes (NVT). In winter 2010/11 only one isolate of PCV7 VT was observed (6B). PCV13 unique VTs decreased between winters immediately preceding and following PCV13 introduction (p=0.04). Significant decreases for VTs 6B, 19F, 23F (PCV7) and 6A (PCV13) and increases for NVT 21, 23B, 33F and 35F were detected. The serotype replacement was accompanied by parallel changes in genotype prevalence for associated sequence types with clonal expansion contributing to replacement. By winter 2010/11, serotype coverage of PCV7 and PCV13 was 1% and 11% respectively.VT replacement was observed for PCV7 and PCV13 serotypes. Conjugate vaccine design and use requires continuous monitoring and revision.

596Potential public health impact of 13-valent pneumococcal conjugate vaccine use among US adults 65 years of age or older

596Potential public health impact of 13-valent pneumococcal conjugate vaccine use among US adults 65 years of age or older

Immunization for Streptococcus pneumoniae infections in high-risk children.

Routine use of the pneumococcal conjugate vaccines (PCV7 and PCV13), beginning in 2000, has resulted in a dramatic reduction in the incidence of invasive pneumococcal disease (IPD) attributable to serotypes of Streptococcus pneumoniae contained in the vaccines. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend the expanded use of PCV13 in children 6 through 18 years of age with certain conditions that place them at elevated risk of IPD. This statement provides recommendations for the use of PCV13 in children 6 through 18 years. A single dose of PCV13 should be administered to certain children in this age group who are at elevated risk of IPD. Recommendations for the use of PCV13 in healthy children and for pneumococcal polysaccharide vaccine (PPSV23) remain unchanged.

Nonencapsulated Streptococcus pneumoniae Cause Acute Otitis Media in the Chinchilla That Is Enhanced by Pneumococcal Surface Protein K.

Use of the pneumococcal conjugate vaccine has led to serotype replacement of carriage and acute otitis media (AOM) pneumococcal isolates. Increases in nonencapsulated Streptococcus pneumoniae (NESp) isolates have also occurred, and there are increasing reports of NESp-associated disease. Disease prevalence and virulence factors of NESp isolates have not been studied. A chinchilla model of pneumococcal AOM was utilized, and disease was assessed through bacterial enumeration along with scoring visible signs of pathology. An adhesion-invasion assay using a human epithelial cell line was performed. Nonencapsulated Streptococcus pneumoniae strains containing pneumococcal surface protein K (PspK) were more likely to cause AOM and pathology upon infection. Deletion of PspK from an isolate significantly reduced bacterial loads. Increased epithelial cell adhesion correlated with increased virulence of NESp isolates naturally lacking PspK. Furthermore, expression of PspK by an avirulent NESp resulted in virulence. The presence of PspK increased the disease potential of NESp. Pneumococcal surface protein K is not the only virulence factor of NESp in AOM. Expression of PspK in an avirulent NESp mediated the progression to pneumococcal disease. Genetic exchange between pneumococci may allow dissemination of PspK, increasing the potential of NESp disease. The current study is the first report of a NESp-specific virulence factor.