Gail L. Rodgers

Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: Potential implications for pneumococcal conjugate vaccines

Acute otitis media (AOM) is the most common infection following pneumococcal colonization of the upper respiratory tract. Streptococcus pneumoniae causes 30-60% of AOM cases worldwide. However, not all pneumococcal serotypes cause disease and an association exists with nasopharyngeal colonization by certain serotypes and their propensity to cause AOM. This review examines the global serotype distribution relationship between pneumococcal serotypes and AOM in children aged <18 years and demonstrates that the most common pneumococcal serotypes causing AOM globally are 3, 6A, 6B, 9V, 14, 19A, 19F, and 23F.

The future of pneumococcal disease prevention

Pneumococcal disease (PD) is the leading cause of vaccine preventable deaths in children <5 years of age worldwide, with most of the deaths occurring in the developing world. Prevention of PD in children has been achieved by vaccination with pneumococcal conjugate vaccine (PCV), the basis for which is induction of a protective antibody response against the bacterial polysaccharide capsule. Conjugation of the polysaccharide capsule to a protein carrier enables the generation of an immunologic response to the vaccine in young children, leading to protection against infection. The heptavalent PCV, which contains 7 of the 93 known pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) was the first PCV available, licensed in the US in 2000 and subsequently in many countries worldwide, including Latin American and Caribbean countries. Since its introduction, PCV7 has been documented effective for reducing invasive PD mortality and burden, as well as that of pneumonia and otitis media. Additionally, PD caused by the vaccine serotypes has decreased in the unimmunized population due to herd immunity induced by PCV7. Despite this success, significant disease burden still exists globally due to serotypes not included in PCV7. Currently there are 2 new PCVs that have been approved for use in children, a 10-valent vaccine (includes PCV7 serotypes plus serotypes 1, 5 and 7F) and a 13-valent vaccine (includes PCV7 serotypes plus serotypes 1, 3, 5, 6A, 7F and 19A). The selection of new serotypes to be included was based on importance of these serotypes as causes of PD. An additional 15-valent vaccine (includes PCV 7 serotypes plus serotypes 1, 3, 5, 6A, 7F, 19A, 22F and 33F) is undergoing clinical trial testing. In view of the 93 serotypes that are currently known, it seems clear that vaccines with greater coverage, likely based on proteins common to all serotypes, will be needed in the future. Technical and regulatory challenges to the development and approval of newer PCVs include a need for licensing criteria of common protein vaccines, establishment of correlates of protection for disease manifestations other than invasive disease, comparative efficacy data, and clinical trial testing of concomitant immunization of higher valency PCVs with other vaccines.

Population-based surveillance for invasive pneumococcal disease and pneumonia in infants and young children in Bogotá, Colombia.

BACKGROUND Streptococcus pneumoniae is the leading cause of vaccine-preventable death in children <5 years of age globally. We determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest X-ray-confirmed pneumonia (CXR+Pn), S. pneumoniae serotype distribution, and antimicrobial susceptibility in children in Goiânia, Brazil. METHODS Prospective, population-based surveillance was conducted from May 2007 to May 2009 in children 28 days to <36 months of age presenting to all 33 pediatric healthcare services (outpatient departments, emergency rooms, hospitals) in Goiânia. Eligibility criteria were temperature ≥39.0 °C in the previous 24h and/or clinical suspicion of pneumonia or IPD. RESULTS 14,509 subjects were enrolled. Median age was 14.0 months. S. pneumoniae was detected in 64 samples from 62 subjects: 58 (90.6%) blood; 4 (6.3%) cerebrospinal fluid; and 2 (3.1%) pleural fluid. Incidence rate of IPD (culture- and polymerase chain reaction-positive) for all children aged 28 days to <36 months was 57.5/100,000; overall incidence for culture-positive only was 54.9/100,000. Age stratification of culture-positive-only subjects found the highest rates were, 114.6/100,000 and 69.8/100,000, respectively, for the 6 months to <12 months and 12 months to <24 months age groups. The overall incidence of invasive pneumonia and pneumococcal meningitis was 37.2/100,000 and 5.3/100,000, respectively. The most common IPD serotypes were 14 (45.0%), 6B (13.3%), 18C (6.7%), and 23F (5.0%). Eight isolates (13.3%) were penicillin nonsusceptible. The cumulative percentages of serotypes included in 7-valent, 10-valent, and 13-valent pneumococcal conjugate vaccines were 78.3%, 80.0%, and 88.3%, respectively. The overall incidence of clinical pneumonia and CXR+Pn was, 9598/100,000 and 3428/100,000, respectively. CXR+Pn rates for hospitalized and non-hospitalized subjects were 1751/100,000 and 1677/100,000, respectively. CONCLUSIONS The burden of IPD and pneumonia is considerable in children in a large Brazilian city, and is seen in hospitalized as well as ambulatory subjects. Vaccination with pneumococcal conjugate vaccines has the potential to decrease this burden.

Immune response to 13-valent pneumococcal conjugate vaccine with a reduced dosing schedule

BACKGROUND The 7-valent pneumococcal conjugate vaccine (PCV7) has demonstrated effectiveness against pneumococcal illnesses when administered as 3 infant doses plus a toddler dose (3+1 schedule) or as an abbreviated schedule of 2 infant doses plus a toddler dose (2+1 schedule). The 13-valent pneumococcal conjugate vaccine (PCV13) is approved and World Health Organization-prequalified for administration in a 2+1 schedule when used as part of routine immunization programs. OBJECTIVE To summarize immunologic responses elicited by PCV13 administered in a 2+1 schedule and following 2 doses in a 3+1 schedule. METHODS Studies were double-blind, randomized, active-controlled, multicenter studies except the Mexico study (open-label, single-arm). In 2+1 studies, PCV13 was administered at 2, 4, and 12 (UK) or 3, 5, and 11 (Italy) months. In 3+1 studies (Spain and Mexico), assessment was made postdose 2 of the primary series (2, 4, and 6 months). The primary immunogenicity endpoint was the proportion of participants achieving serotype-specific antipolysaccharide immunoglobulin (Ig)G concentrations ≥ 0.35μg/mL (i.e., responders) 1 month postdose 2. Pneumococcal IgG geometric mean concentrations (GMCs), opsonophagocytic activity (OPA), and concomitant vaccine responses were assessed. RESULTS PCV13 and PCV7 elicited comparable immune responses for the 7 common serotypes after 2 infant doses. The proportion of PCV13 responders postdose 2 was >85% for most of the 7 common and 6 additional serotypes, except common serotypes 6B (27.9-81.4%) and 23F (55.8-77.5%) and additional serotypes 3 (73.8-96.9%) and 6A (79.2-94.4%). Serotypes 6B and 23F elicited lower IgG GMCs postdose 2 compared with other serotypes; all serotypes demonstrated boosting posttoddler dose. All serotypes demonstrated functional activity; >95% of participants achieved OPA levels ≥ 1:8 postdose 2. Concomitant vaccine responses were similar between PCV13 and PCV7 groups. CONCLUSION Immune responses elicited by PCV13 following 2 infant doses support transition from PCV7 to PCV13 in countries using a 2+1 schedule.

Prospective epidemiologic surveillance of invasive pneumococcal disease and pneumonia in children in San José, Costa Rica

BACKGROUND Streptococcus pneumoniae (SP) is the leading cause of vaccine-preventable death in children <5 years of age, globally. This surveillance determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest radiograph-confirmed pneumonia (CXR+Pn); and SP serotype distribution and antimicrobial susceptibility in children in San José, Costa Rica. METHODS This was a 2-year prospective, population-based surveillance conducted in 2007-2009 in children aged 28 days to 36 months presenting to participating healthcare centers. Eligibility criteria for study inclusion were as follows: temperature ≥ 39.0°C within 24h and/or clinical suspicion of IPD or pneumonia. RESULTS 8801 subjects were enrolled. Median age: 14.5 months. A total of 25 children had invasive pneumococcal disease with S. pneumoniae isolated from nonduplicative cultures (22) or detected solely by PCR and a clinical picture consistent with IPD (3). Sources of positive cultures (some children had >1 positive culture) were: blood (20), pleural fluid (4), and cerebrospinal fluid (3). Of the 3 cases detected solely by PCR, 2 were from cerebrospinal fluid and 1 from pleural fluid. The overall IPD incidence rates for culture-positive only cases for children aged 28 days to <3 years was 33.7/100,000 per year for years 1 and 2 combined. Age stratification of culture-positive only subjects showed a peak during year 1 (106.8/100,000) in children 28 days to <6 months of age group, and in year 2 (45.5/100,000) in children 12 months to <24 months of age group. Most common serotypes were 14 (28.6%), followed by 3, 4, 6A, 19A, and 22F (9.5% each). Of 22 nonduplicative IPD isolates, 42.9% were penicillin- and trimethoprim/sulfamethoxazole nonsusceptible isolates. Consideration of PCR-positive cases increases the incidence of IPD for children aged 28 days to <3 years to 46.0/100,000. Overall incidence of clinical pneumonia and CXR+Pn was 1968/100,000 and 551/100,000, respectively. CONCLUSIONS There is a considerable burden of IPD and pneumonia in children in San José. These epidemiologic data serve as a baseline to evaluate the effectiveness of the incorporation of new conjugate pneumococcal vaccines into the National Immunization Program in Costa Rican children.

Surveillance of the impact of pneumococcal conjugate vaccines in developing countries

Infection due to Streptococcus pneumoniae is a leading cause of morbidity and mortality in young children, especially in developing countries. With the support of Gavi, the Vaccine Alliance, the majority of these countries have introduced pneumococcal conjugate vaccines (PCV) into their national immunization programs and early data demonstrate a high degree of effectiveness, translating to enormous public health benefit through both direct and indirect (herd) effects. Future vaccination strategy may be focused on maintaining herd effects rather than individual protection. Evaluation of vaccine-type carriage, particularly in pneumonia cases, may be an easy, feasible way of measuring continued vaccine impact.

Seasonality of respiratory viruses causing hospitalizations for acute respiratory infections in children in Nha Trang, Vietnam.

Abstract Background Acute respiratory infections (ARIs) are the most common causes of death in children under 5 years of age. While the etiology of most pneumonia and ARI episodes is undiagnosed, a broad range of ARI-causing viruses circulate widely in South East Asia. However, the patterns and drivers of the seasonal transmission dynamics are largely unknown. Here we identify the seasonal patterns of multiple circulating viruses associated with hospitalizations for ARIs in Nha Trang, Vietnam. Methods Hospital based enhanced surveillance of childhood ARI is ongoing at Khanh Hoa General Hospital in Nha Trang. RT-PCR was performed to detect 13 respiratory viruses in nasopharyngeal samples from enrolled patients. Seasonal patterns of childhood ARI hospital admissions of various viruses were assessed, as well as their association with rainfall, temperature, and dew point. Results Respiratory syncytial virus peaks in the late summer months, and influenza A in April to June. We find significant associations between detection of human parainfluenza 3 and human rhinovirus with the months mean dew point. Using a cross-wavelet transform we find a significant out-of-phase relationship between human parainfluenza 3 and temperature and dew point. Conclusions Our results are important for understanding the temporal risk associated with circulating pathogens in Southern Central Vietnam. Specifically, our results can inform timing of routing seasonal influenza vaccination and for when observed respiratory illness is likely viral, leading to judicious use of antibiotics in the region.

Comment on serotypes and susceptibility of Streptococcus pneumoniae strains isolated from children in Mexico

) and the investigational 10-valent vaccine (containing serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F conjugated to protein D, diphtheria and tetanus carrier proteins) for meningeal, non-meningeal invasive infections and nasopharyngeal carriage are shown in table I of the article by Villasenor-Sierra and colleagues.