Trial Of Pneumococcal Conjugate Vaccine Research Articles

Otitis media at 6-monthly assessments of Australian First Nations children between ages 12–36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines

ObjectivesIn remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. MethodsIn two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28–38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12–36 months, by booster dose. ResultsFrom March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference −3% [95% Confidence Interval −11, 5]). At each age prevalence of bilateral OM was 52%–78%, and tympanic membrane perforation was 10%–18%. ConclusionDespite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Randomised Controlled Trial of Pneumococcal Conjugate Vaccine Shows Protection Against Experimental Pneumococcal Carriage in First Human Infection Study in Africa

Randomised Controlled Trial of Pneumococcal Conjugate Vaccine Shows Protection Against Experimental Pneumococcal Carriage in First Human Infection Study in Africa

An affordable pneumococcal conjugate vaccine after 20 years

An affordable pneumococcal conjugate vaccine after 20 years

Pneumococcal Conjugate Vaccine Protection against Coronavirus-Associated Pneumonia Hospitalization in Children Living with and without HIV.

In December 2019 a new coronavirus (CoV) emerged as a human pathogen, SARS-CoV-2. There are few data on human coronavirus infections among individuals living with HIV. In this study we probed the role of pneumococcal coinfections with seasonal CoVs among children living with and without HIV hospitalized for pneumonia. We also described the prevalence and clinical manifestations of these infections. A total of 39,836 children who participated in a randomized, double-blind, placebo-controlled clinical trial on the efficacy of a 9-valent pneumococcal conjugate vaccine (PCV9) were followed for lower respiratory tract infection hospitalizations until 2 years of age. Nasopharyngeal aspirates were collected at the time of hospitalization and were screened by PCR for four seasonal CoVs. The frequency of CoV-associated pneumonia was higher in children living with HIV (19.9%) than in those without HIV (7.6%, P < 0.001). Serial CoV infections were detected in children living with HIV. The case fatality risk among children with CoV-associated pneumonia was higher in those living with HIV (30.4%) than without HIV (2.9%, P = 0.001). C-reactive protein and procalcitonin levels were elevated in 36.8% (≥40 mg/liter) and 64.7% (≥0.5 ng/ml), respectively, of the fatal cases living with HIV. Among children without HIV, there was a 64.0% (95% CI: 22.9% to 83.2%) lower incidence of CoV-associated pneumonia hospitalizations among PCV9 recipients compared to placebo recipients. These data suggest that Streptococcus pneumoniae infections might have a role in the development of pneumonia associated with endemic CoVs, that PCV may prevent pediatric CoV-associated hospitalization, and that children living with HIV with CoV infections develop more severe outcomes.IMPORTANCE SARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of PCV to examine its impact on human CoV infections before the pandemic. We found that both children living with and without HIV randomized to receive PCV had evidence of less hospitalization due to seasonal CoV, suggesting that pneumococcal coinfection may play a role in severe hospitalized CoV infections.

1714. Influenza C Virus in U.S. Children with Acute Respiratory Infection 2016-2019

BackgroundInfluenza C virus (ICV) is associated with acute respiratory infection (ARI); however, the burden of ICV is not well-described. We sought to determine the burden and characteristics of ICV in a prospective, population-based cohort.MethodsThe study was conducted within the New Vaccine Surveillance Network (NVSN), a CDC-led, seven-site network that performs population-based surveillance for ARI in children < 5 years. Nasal/throat swabs were collected from emergency department (ED) or inpatient children with ARI, or healthy controls in clinic, between 12/05/2016-10/31/2019 and tested by real-time RT-PCR for ICV and other respiratory viruses. Preliminary data were extracted and demographic/clinical features of ICV+ cases analyzed. We sequenced the hemagglutinin-esterase (HE) gene from ICV+ Pittsburgh samples.ResultsAmong 19,321 children with ARI or healthy controls enrolled and tested for ICV from 2016-2019, 115/17,668 (0.7%) ARI cases and 8/1653 (0.5%) healthy controls tested positive for ICV. The median age of ICV+ ARI subjects was 19 months (IQR 10,46) and 81(70%) were ≤36 months. 42.6% (49) were white, 33.9% (39) black, and 16.5% (19) Hispanic, with the remainder Asian or unknown; 56.5% (62) attended daycare. Among ICV+ ARI cases, 67.8% (78) had fever, 94.8% (109) cough, and 60.8% (70) wheezing. 45.2% (52) ICV+ cases occurred in 2016-17, 6.5% (8) in 2017-2018, and 47.8% (55) in 2018-19 (Table). 40% (46) of ICV+ cases were seen in the ED, while the remainder were inpatients. Median length of stay was 2d (IQR,1-3) with 15 admitted to ICU. 67.8% (78/115) ARI cases had 1 or 2 co-detected pathogens, with rhinovirus (26), respiratory syncytial virus (26), and adenovirus (14) most frequently co-detected. ARI symptoms including fever, myalgias, chills, and wheezing did not differ significantly between coinfected subjects and those who were only ICV+. HE sequences were in the two currently circulating Kanagawa and Sao Paulo lineages.ICV+ Cases by Site and Year ConclusionICV was an uncommon cause of ARI symptoms leading to healthcare encounters in young children. The prevalence varied year-to-year and between different geographic regions. Most children infected with ICV were ≤3 years old and had co-detected pathogens. ICV was similarly rarely detected in healthy controls.Disclosures Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member)

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

Hospital surveillance predicts community pneumococcal antibiotic resistance in Vietnam.

In Vietnam, Streptococcus pneumoniae is a leading cause of disease, including meningitis. Antibiotics are available without physician prescription at community pharmacies and rates of antibiotic non-susceptibility are high. Appropriate treatment and antibiotic stewardship need to be informed by surveillance data. To report community-based pneumococcal antibiotic susceptibility testing data from children enrolled in a pneumococcal conjugate vaccine trial in Ho Chi Minh City [the Vietnam Pneumococcal Project (ViPP)] and compare these with published hospital-based data from the nationwide Survey of Antibiotic Resistance (SOAR) to determine whether hospital surveillance data provide an informative estimate of circulating pneumococcal resistance. Pneumococcal isolates from 234 nasopharyngeal swabs collected from ViPP participants at 12 months of age underwent antibiotic susceptibility testing using CLSI methods and the data were compared with SOAR data. Antibiotic susceptibility testing identified penicillin-non-susceptible pneumococci in 93.6% of pneumococcus-positive ViPP swabs (oral, non-meningitis breakpoints). Non-susceptibility to erythromycin, trimethoprim/sulfamethoxazole, clindamycin and tetracycline also exceeded 79%. MDR, defined as non-susceptibility to three or more classes of antibiotic, was common (94.4% of swabs). Low or no resistance was detected for ceftriaxone (non-meningitis breakpoints), ofloxacin and vancomycin. Antibiotic non-susceptibility rates in ViPP and SOAR were similar for several antibiotics tested. A very high proportion of pneumococci carried in the community are MDR. Despite wide disparities in population demographics between ViPP and SOAR, the non-susceptibility rates for several antibiotics were comparable. Thus, with some qualification, hospital antibiotic susceptibility testing data in Vietnam can inform circulating pneumococcal antibiotic non-susceptibility in young children, the group at highest risk of pneumococcal disease, to guide antibiotic prescribing and support surveillance strategies.

Phase 1 trial of a 20-valent pneumococcal conjugate vaccine in healthy adults

IntroductionStreptococcus pneumoniae is a leading cause of bacteremia, bacterial pneumonia, and meningitis, and is associated with substantial morbidity and mortality, particularly in those under 2 years of age and those over 65 years of age. While significant progress against S. pneumoniae-related disease has been made as a result of the introduction of pneumococcal conjugate vaccines (PCV7, PCV10 and PCV13), there remains value in further expanding pneumococcal vaccine serotype coverage. Here we present the first report of a 20-valent pneumococcal conjugate vaccine (PCV20) containing capsular polysaccharide conjugates present in PCV13 as well as 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) which are important contributors to pneumococcal disease. MethodsThis Phase I first-in-human study was a randomized, controlled, observer-blinded study with a two-arm parallel design to assess the safety, tolerability, and immunogenicity of PCV20 in adults. A total of 66 healthy adults 18–49 years of age with no history of pneumococcal vaccination were enrolled and randomized to receive a single dose of PCV20 or a licensed tetanus, diphtheria, acellular pertussis combination vaccine (Tdap) control. Local injection site reactions, select systemic symptoms, laboratory studies, and adverse events were assessed. Opsonophagocytic activity (OPA) titers and IgG concentrations were measured in sera collected prior to, and approximately one month (28–35 days) after vaccination. ResultsVaccination with PCV20 elicited substantial IgG and functional bactericidal immune responses as demonstrated by increases in IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) to the 20 vaccine serotypes. The overall safety profile of PCV20 was similar to Tdap, and generally consistent with that observed after PCV13 administration. ConclusionsVaccination with PCV20 was well tolerated and induced substantial functional (OPA) and IgG responses to all vaccine serotypes. There were no safety issues identified in this Phase 1 study, and the data supported further evaluation of PCV20.

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

Herd immunity alters the conditions for performing dose schedule comparisons: an individual-based model of pneumococcal carriage

BackgroundThere is great interest in the use of reduced dosing schedules for pneumococcal conjugate vaccines, a strategy premised on maintaining an acceptable level of protection against disease and carriage of the organism. We asked about the practicality of measuring differential effectiveness against carriage in a population with and without widespread use of the vaccine for infants.MethodsWe adapted an existing transmission-dynamic, individual-based stochastic model fitted to the prevaccine epidemiology of pneumococcal carriage in the United States, and compared the observed vaccine-type carriage prevalence in different arms of a simulated trial with one, two, or three infant doses plus a 12-month booster. Using these simulations, we calculated vaccine efficacy that would be estimated at different times post-enrollment in the trial and calculated required sample sizes to see a difference in carriage prevalence.ResultsIn a pneumococcal conjugate vaccine (PCV)-naïve population, the difference in vaccine-type (VT) pneumococcal carriage prevalence between trial arms was less than 7% and varied with sampling time. In a population already receiving routine PCV administration, VT pneumococcal prevalence is nearly indistinguishable between trial arms. Relative efficacy of different dosing schedules was strongly dependent on the time between enrollment and sampling, with maximal prevalence differences reached 1–3 years post-enrollment. Moreover, vaccine efficacy estimates were typically slightly higher in trials in communities already receiving vaccination. Despite this, much larger sample sizes—by more than an order of magnitude—are required for a vaccine trial conducted in a population receiving routine PCV administration as compared to in a PCV-naïve population.ConclusionsThese findings highlight some underappreciated aspects of clinical trials of pneumococcal conjugate vaccines with efficacy endpoints, such as the context- and time-dependence of efficacy estimates. They support the wisdom of conducting comparative dose schedule trials of conjugate vaccine effects on carriage in vaccine-naïve populations.

Large-scale otoscopic and audiometric population assessment: A pilot study

ObjectiveLarge-scale otoscopic and audiometric assessment of populations is difficult due to logistic impracticalities, particularly in low- and middle-income countries (LMIC). We report a novel assessment methodology based on training local field workers, advances in audiometric testing equipment and cloud-based technology. MethodsProspective observational study in Bohol, Philippines. A U.S. otolaryngologist/audiologist team trained 5 local nurses on all procedures in a didactic and hands-on process. An operating otoscope (Welch-AllynR) was used to clear cerumen and view the tympanic membrane, images of which were recorded using a video otoscope (JedMedR). Subjects underwent tympanometry and distortion product otoacoustic emission (DPOAE) (Path SentieroR), and underwent screening audiometry using noise cancelling headphones and a handheld Android device (HearScreenR). Sound-booth audiometry was reserved for failed subjects. Data were uploaded to a REDCap database. Teenage children previously enrolled in a 2000–2004 Phase 3 pneumococcal conjugate vaccine trial, were the subjects of the trainees. ResultsDuring 4 days of training, 47 Filipino children (M/F = 28/19; mean/median age = 14.6/14.6 years) were the subjects of the trainee nurses. After the training, all nurses could perform all procedures independently. Otoscopic findings by ears included: normal (N = 77), otitis media with effusion (N = 2), myringosclerosis (N = 5), healed perforation (N = 6), perforation (N = 2) and retraction pocket/cholesteatoma (N = 2). Abnormal audiometric findings included: tympanogram (N = 4), DPOAE (N = 4) and screening audiometry (N = 0). ConclusionTraining of local nurses has been shown to be robust and this methodology overcomes challenges of distant large-scale population otologic/audiometric assessment.

Safety and Immunogenicity of Pneumococcal Conjugate Vaccines in a High-risk Population: A Randomized Controlled Trial of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccine in Papua New Guinean Infants.

BackgroundThere are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population.MethodsPCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age.ResultsOne month after the third dose of PCV10 or PCV13, ˃80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85–96) of children vaccinated with PCV10 and 81% (95% CI 72–88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events.ConclusionsInfant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed.Clinical Trials RegistrationNCT01619462.

Register-Based Ecologic Evaluation of Safety Signals Related to Pneumococcal Conjugate Vaccine in Children.

Background:In clinical trials of Pneumococcal Conjugate Vaccines (PCV), some adverse events have been reported more frequently in the PCV vaccinated. Ten-valent PCV (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010.Objective:We conducted an ecologic register-based study to investigate further the reported adverse events after PCV.Methods:This study included data obtained from the Finnish nationwide, population-based registers. First diagnoses of febrile seizures, breath-holding, urticarial rash, asthma and Kawasaki’s disease were included as outcomes obtained from the hospital discharge register. Data from Finnish Population Register during 2000-2014 for children age from 3 months to 10 years were used to estimate annual incidence rates. Incidence rate ratios of the outcomes were calculated between the target cohort of children eligible for PCV10 during 2010-2014 and a reference cohort before the NVP introduction (2004-2008).Results:No increases in the incidence of the adverse events after PCV10 introduction were found except for urticarial rash (incidence rate 2.48 vs. 1.60/1000 pyrs; incidence rate ratio, 1.54;95% CI 1.42-1.67). This increase was seen also in the unvaccinated older age groups in the post-vaccination era. The higher incidence of urticarial rash after the PCV10 introduction was due to the inclusion of diagnoses made in general medicine specialty in the discharge register because of a concomitant administrative change.Conclusion:The results do not support public health concerns related to the previously reported adverse events. Concomitant changes in health care administration and coding introduced bias, which was controlled after further evaluation of the data. We consider this register-based approach with real-world data feasible in the signal validation process after any signal detection.

A public health evaluation of 13-valent pneumococcal conjugate vaccine impact on adult disease outcomes from a randomized clinical trial in the Netherlands

BackgroundWe conducted a post-hoc analysis of a double blind, randomized, placebo-controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged 65 years or older to assess public health impact. MethodsFor all outcomes, we included all randomized subjects, using a modified intention-to-treat (mITT) approach to determine vaccine efficacy (VE), vaccine preventable disease incidence (VPDI) defined as control minus vaccinated group incidence, and numbers needed to vaccinate (NNV) (based on a five-year duration of protection). ResultsResults are reported for, in order, clinical, adjudicated (clinical plus radiologic infiltrate determined by committee), pneumococcal, and vaccine-type pneumococcal (VT-Sp) community-acquired pneumonia; invasive pneumococcal disease (IPD) and VT-IPD. VEs (95% CI) for all hospital episodes were 8.1% (−0.6%, 16.1%), 6.7% (−4.1%, 16.3%), 22.2% (2.0%, 38.3%), 37.5% (14.3%, 54.5%), 49.3% (23.2%, 66.5%), and 75.8% (47.6%, 88.8%). VPDIs per 100,000 person-years of observation (PYOs) were 72, 37, 25, 25, 20, and 15 with NNVs of 277, 535, 816, 798, 1016, and 1342. For clinical CAP, PCV13 was associated with a reduction of 909 (−115, 2013) hospital days per 100,000 PYOs translating to a reduction over 5 years of one hospital day for every 22 people vaccinated. When comparing at-risk persons (defined by self-report of diabetes, chronic lung disease, or other underlying conditions) to not at-risk persons, VEs were similar or lower, but because baseline incidences were higher the VPDIs were approximately 2–10 times higher and NNVs 50–90% lower. ConclusionA public health analysis of pneumonia and IPD outcomes in a randomized controlled trial found substantial burden reduction following adult PCV13 immunization implemented in a setting with an ongoing infant PCV7-PCV10 program. VPDIs were higher among at-risk adults. FundingThe original study and the current analysis were funded by Pfizer.

A longitudinal study of natural antibody development to pneumococcal surface protein A families 1 and 2 in Papua New Guinean Highland children: a cohort study

BackgroundPneumococcal surface protein A (PspA), a conserved virulence factor essential for Streptococcus pneumoniae attachment to upper respiratory tract (URT) epithelia, is a potential vaccine candidate for preventing colonisation.MethodsThis cohort study was conducted in the Asaro Valley in the Eastern Highlands Province of Papua New Guinea, of which Goroka town is the provincial capital. The children included in the analysis were participants in a neonatal pneumococcal conjugate vaccine trial (ClinicalTrials.gov NCT00219401) that was conducted between 2005 and 2009. We investigated the development of anti-PspA antibodies in the first 18 months of life relative to URT pneumococcal carriage in Papua New Guinean infants who experience one of the earliest and highest colonisation rates in the world. Blood samples and nasopharyngeal swabs were collected from a cohort of 88 children at ages 3, 9, and 18 months to quantify immunoglobulin G (IgG) levels to PspA families 1 and 2 using an enzyme-linked immunosorbent assay and to determine URT carriage.ResultsSeventy-three per cent (64/88) of infants carried S. pneumoniae at age 3 months; 85 % (75/88) at 9 months, and 83 % (73/88) at 18 months. PspA-IgG levels declined between ages 3 and 9 months (p < 0.001), then increased between 9 and 18 months (p < 0.001). At age 3 months, pneumococcal carriers showed lower PspA1-IgG levels (geometric mean concentration [GMC] 602 arbitrary units [AU]/ml, 95 % confidence interval [CI] 497–728) than non-carriers (GMC 1058 AU/ml [95 % CI 732–1530]; p = 0.008), while at 9 months, PspA1- and PspA2-IgG levels were significantly higher in carriers (PspA1: 186 AU/ml, 95 % CI 136–256; PspA2: 284 AU/ml, 95 % CI 192–421) than in non-carriers (PspA1 87 AU/ml, 95 % CI 45–169; PspA2 74 AU/ml, 95 % CI 34–159) (PspA1: p = 0.037, PspA2: p = 0.003).ConclusionOur findings confirm that PspA is immunogenic and indicate that natural anti-PspA immune responses are acquired through exposure and develop with age. PspA may be a useful candidate in an infant pneumococcal vaccine to prevent early URT colonisation.

WU and KI polyomavirus infections in Filipino children with lower respiratory tract disease

BackgroundWU and KI are human polyomaviruses initially detected in the respiratory tract, whose clinical significance remains uncertain. ObjectivesTo determine the epidemiology, viral load and clinical characteristics of WU and KI polyomaviruses. Study designWe tested respiratory specimens collected during a randomized, placebo-controlled pneumococcal conjugate vaccine trial and related epidemiological study in the Philippines. We analyzed 1077 nasal washes from patients aged 6 weeks to 5 years who developed lower respiratory tract illness using quantitative real-time PCR for WU and KI. We collected data regarding presenting symptoms, signs, radiographic findings, laboratory data and coinfection. ResultsThe prevalence and co-infection rates for WU were 5.3% and 74% respectively and 4.2% and 84% respectively for KI. Higher KI viral loads were observed in patients with severe or very severe pneumonia, those presenting with chest indrawing, hypoxia without wheeze, convulsions, and with KI monoinfection compared with co-infection. There was no significant association between viral load and clinical presentation for WU. ConclusionsThese findings suggest a potential pathogenic role for KI, and that there is an association between KI viral load and illness severity.

Changing Epidemiology of Pneumococcal Disease in the Era of Conjugate Vaccines

Pneumococcal disease is a major cause of illness and death in the young, the elderly, and those with certain medical conditions. Pneumococcal conjugate vaccines are changing both the epidemiology of pneumococcal disease and disease burden. Conjugate vaccines were first licensed in 2000 for use in young children; second generation conjugates covering more serotypes became available in 2009 and are now part of the routine infant immunization programs of most countries around the world. When part of a routine program, conjugate vaccines not only prevent disease in the targeted age group but also in unvaccinated children and adults because of reduced pneumococcal transmission. Measurement of these direct and indirect benefits of immunization programs has illustrated how young children serve as the primary reservoir of pneumococci in the community. Clinical trials of pneumococcal conjugate vaccines have proven to be an effective method for eliciting the proportion of disease syndromes like pneumonia that is caused by pneumococci or pneumococcal and viral co-infections. While these highly successful vaccines are introduced into more places, surveillance programs are monitoring for signs of any increase in disease caused by serotypes the vaccines are not designed to prevent.

Is the timing of recommended childhood vaccines evidence based?

Vaccines undergo extensive testing and review before licensing to evaluate their immunogenicity, safety, and effectiveness in preventing disease.1 For example, prelicensing trials of pneumococcal conjugate and rotavirus vaccines are among...

Epidemiological Markers for Interactions Among Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Upper Respiratory Tract Carriage.

Cocolonization by Streptococcus pneumoniae and Haemophilus influenzae among children has been noted in numerous studies, as has an inverse relationship involving colonization with these species and Staphylococcus aureus. Interactions among these pathogens could mediate unanticipated outcomes of clinical interventions, including changes in H. influenzae and S. aureus disease incidence following pneumococcal vaccine introduction. However, it remains unclear whether cocolonization patterns represent true interspecies interactions or whether they result from confounding factors. We investigated polymicrobial carriage using longitudinal data from 369 Bedouin children and 400 Jewish children in Israel who were enrolled in a 7-valent pneumococcal conjugate vaccine (PCV7) trial. Children were swabbed 10 times between 2 and 30 months of age. The pathogens followed distinct age and seasonal distributions, but polymicrobial carriage associations persisted after controlling for these and other confounding factors. Receipt of PCV7 resulted in pneumococcal serotype replacement but did not influence total carriage of S. pneumoniae, H. influenzae, or S. aureus. The fact that S. pneumoniae, H. influenzae, and S. aureus polymicrobial carriage patterns do not result from confounding by age and season supports the idea of active interspecies interactions. However, pneumococcal serotype replacement may prevent changes in H. influenzae and S. aureus carriage among PCV7 recipients.

Maternal immunization with pneumococcal 9-valent conjugate vaccine and early infant otitis media

A randomized trial of an investigational 9-valent pneumococcal conjugate vaccine (PCV-9) or placebo given to pregnant women during the last trimester to prevent early infant otitis media (OM) was conducted. All infants received Prevnar® at 2, 4, 6, and 12 months. Clinic and adverse event records were reviewed to identify OM. Variables significantly related to acute OM by age 6 months (p<0.05) were: vaccine group (9 valent or placebo), sibling history of tympanostomy tubes, upper respiratory infection, and number of clinic visits by 6 months. Infant OM rates were similar between 6 and 12 months (58% and 56%). Results suggested that immunizing pregnant women with PCV-9 increased infants’ risk of acute OM in the first 6 months of life, and this correlated with decreased infant antibody responses to their infant Streptococcus pneumoniae vaccine serotypes, but did not influence antibody responses to 3 other serotypes two of which were in maternal vaccine (types 1 and 5) and one was a control (type 7F). Explanations for these results include dampening of infant antibody production by high levels of passively acquired maternal pneumococcal antibodies and/or altered B lymphocyte immune responses in infants exposed to these specific polysaccharide antigens in utero.