Sharon Gray

Surveillance for invasive pneumococcal disease during 2000-2005 in a population of children who received 7-valent pneumococcal conjugate vaccine

Objectives: To assess the incidence of invasive pneumococcal disease (IPD) in all children younger than 5 years of age in the Northern California Kaiser Permanente (NCKP) health care system during a 5-year surveillance period (2000–2005) after the introduction in April 2000 of routine use of 7-valent pneumococcal conjugate vaccine (PCV7). Methods: This was a laboratory-based surveillance study of all children younger than 5 years of age in the NCKP health care system from April 2000 to March 2005. The comparison group was all children younger than 5 years of age in the NCKP health care system from April 1996 to March 2000. Data obtained from clinical databases included microbiologic identification and susceptibility testing; serotyping of isolates; immunization records; and IPD diagnoses for inpatients and outpatients. IPD was defined as a positive culture of Streptococcus pneumoniae from a normally sterile body site. Results: For all serotypes, the mean annual incidence of IPD during the postlicensure surveillance period was 15.3 cases/100,000 person-years (105 p-y) compared with 62.5 cases/105 p-y in the prelicensure years of 1996–2000. The average incidence of IPD caused by vaccine serotypes was reduced from 50.1 cases/105 p-y during the prelicensure years to 4.9 cases/105 p-y during the postlicensure period. The average incidences of IPD caused by cross-reactive and by nonvaccine serotypes were 5.8 and 5.3 cases/105 p-y, respectively, during the prelicensure years and 2.5 and 6.2 cases/105 p-y, respectively, during the postlicensure period. Of the 131 IPD cases observed during the postlicensure surveillance period, bacteremia (50.4%) and pneumonia (31.3%) were the most common diagnoses. During the 5-year postlicensure surveillance period, only 3 subjects who were identified to be fully vaccinated for age with PCV7 (3 doses by 7 months of age or 4 doses by 18 months of age) developed vaccine-serotype IPD. Conclusion: The incidence of IPD has significantly decreased in a large population of children after the introduction of PCV7. Vaccine-type IPD was rare in patients who received full 4-dose immunization with PCV7. There is no clear evidence of a significant increase in nonvaccine-serotype IPD. Introduction of a 4-dose infant schedule of PCV7 into this population has resulted in a marked and sustained reduction of IPD in children.

Distribution of 13-Valent Pneumococcal Conjugate Vaccine Streptococcus pneumoniae Serotypes in US Adults Aged ≥50 Years With Community-Acquired Pneumonia

BACKGROUND Streptococcus pneumoniae causes a substantial proportion of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) in the United States. Limited data are available regarding the pneumococcal serotypes causing CAP and HCAP. METHODS Adults aged ≥ 50 years presenting to participating US hospitals with radiographically confirmed pneumonia between February 2010 and September 2011 were screened for inclusion. S. pneumoniae was identified using microbiological cultures, BinaxNOW® S. pneumoniae assay, or urine antigen detection (UAD) assay capable of detecting 13-valent pneumococcal conjugate vaccine (PCV13)-associated serotypes. RESULTS Among 710 subjects enrolled, the median age was 65.4 years; 54.2% of subjects were male, 22.4% of radiographically confirmed pneumonia cases were considered HCAP, and 96.6% of subjects were hospitalized. S. pneumoniae was detected in 98 subjects (13.8%) by any test, and PCV13-associated serotype(s) were identified by UAD in 78 (11.0%). Serotype 19A was most prevalent, followed by 7F/A, 3, and 5. Serotypes associated with 7-valent pneumococcal conjugate vaccine (PCV7) accounted for 25% of UAD-positive isolates. CONCLUSIONS Pneumococcal serotypes causing noninvasive pneumonia in adults may differ significantly from those causing invasive disease, with PCV7-associated serotypes overrepresented. Serotype 5, rarely seen in contemporary surveillance of invasive disease in the United States, substantially contributed to the observed cases of S. pneumoniae-positive CAP or HCAP.

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.

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.

A Retrospective Study of the Clinical Burden of Hospitalized All-Cause and Pneumococcal Pneumonia in Canada

Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec) were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004–2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children <5 years and in adults >70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P < 0.001). Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%). Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec). Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high.

Longitudinal DRG-based survey of all-cause and pneumococcal pneumonia and meningitis for inpatients in France (2005–2010)

OBJECTIVE This population-based retrospective study quantified the burden of all-cause and pneumococcal pneumonia and meningitis in the Rhône-Alpes region of France from 2005 to 2010, when the 7-valent pneumococcal conjugate vaccine uptake increased from 50 to>90% in children. PATIENTS AND METHODS Hospital admission data was obtained from the French Diagnosis Related Groups program database (French acronym PMSI). Patients were residents of the Rhône-Alpes region hospitalized for the diseases of interest during 2005-2010. Hospitalization and in-hospital mortality rates were calculated by age, sex, and year on the basis of the Rhône-Alpes region population. Hospitalization and in-hospital mortality rates were compared using Chi(2) tests with statistical significance adjusted for multiple comparisons. RESULTS The highest hospitalization rates by age group were: all-cause pneumonia, oldest group (>65 years); all-cause and pneumococcal meningitis, youngest group (0-4 years), and pneumococcal pneumonia, youngest and oldest groups. Hospitalization rates significantly decreased for all-cause pneumonia (5-19 years: -12.71%) and all-cause meningitis (20-49 years: -29.22%). Pneumococcal disease rates did not significantly change in any age group. Mortality rates from all-cause pneumonia and meningitis were highest in the oldest age groups. CONCLUSIONS The burden of all-cause and pneumococcal pneumonia and meningitis remains substantial. Significant changes (decreases) between 2005 and 2010 in hospitalization rates were limited and varied among age groups, most likely because this study began 2 years after PCV7 was first introduced in France for children at broadly-defined high risk. Further research is needed on the relationship between serotype epidemiology and clinical patterns of disease.

Clinical burden of pneumonia, meningitis and septicemia in Norway 2 years after 7-valent pneumococcal conjugate vaccine introduction

Aims: This population-based, retrospective study quantified the rates of all-cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008 to 2009 and determined the proportions of cases caused by pneumococcal vaccine serotypes. Methods: Data on patients with all-cause and pneumococcal pneumonia, meningitis and septicemia were obtained from the Norwegian Patient Registry, which collects hospitalization data from all Norwegian public hospitals based on International Classification of Diseases codes. Norwegian Patient Registry case records linked to the Norwegian Surveillance System for Communicable Diseases provided serotype data for invasive pneumococcal disease in patients with microbiological cultures. Results: In 2008 and 2009, hospitalization rates were relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per 1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for International Classification of Diseases-10 diagnosed pneumococcal pneumonia (from 13.66 to 10.52 per 100,000), although these cases may be under-reported because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal disease rates were highest in younger children and older adults, peaking at ⩾60 years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes included in the 7-valent pneumococcal conjugate vaccine decreased substantially during the study period, with corresponding serotype replacement by non-7-valent pneumococcal conjugate vaccine serotypes. Conclusions: From 2008 to 2009, International Classification of Diseases-10 diagnosed pneumococcal pneumonia, meningitis and septicemia decreased in most age groups but remained greatest among subjects aged 0–1 and ⩾60 years.

Prospective, population-based surveillance of the burden of Streptococcus pneumoniae in community-acquired pneumonia in older adults, Chrzanów County, Poland, 2010 to 2012.

INTRODUCTION Community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae is a substantial cause of morbidity and mortality among older adults. This study estimated incidences of CAP, chest x-ray-confirmed CAP (CXR+CAP), S pneumonia- positive CAP, S pneumonia-positive CXR+CAP, and S. pneumoniae serotype distribution among 46,000 at-risk adults aged ≥ 50 years residing in Chrzanów County, Poland. MATERIAL AND METHODS From January 2010 to January 2012, all facilities providing ambulatory and inpatient care enrolled all consenting resident patients with suspicion of CAP. Chest x-rays, urine, blood, and sputum samples were analyzed. Annualized incidence rates were determined. Presence of S pneumonia-positive CAP and/or S. pneumoniae serotype distribution was determined using the urine antigen detection assay (capable of detecting the serotypes in the 13-valent pneumococcal conjugate vaccine [PCV13]), BinaxNOW®, and/or microbiology cultures. RESULTS Among 5055 enrolled patients, 1195 (23.7%) were diagnosed with CAP and 1166 (23.4%) had CXR+CAP. S. pneumoniae was detected in 144 (12.1%) and 131 (11.2%) patients from the CAP and CXR+CAP cohorts, respectively. Annualized incidence rates of CAP, CXR+CAP, S pneumonia-positive CAP, and S. pneumonia-positive CXR+CAP were 12.8, 12.5, 1.6, and 1.4 per 1000 residents, respectively. Among CXR+CAP patients, 39.7% were aged 50 to 64 years and 60.3% were aged ≥ 65 years. Incidence rates generally increased with age. The most common serotypes in S. pneumoniae-positive CXR+CAP patients were 3 (n = 15), 23F (n = 10), 18C (n = 9), and 9V (n = 6). CONCLUSIONS CAP due to PCV13 serotypes is a source of morbidity among adults >50 years and may be reduced by greater access to pneumococcal vaccines.

Distribution of 13-Valent pneumococcal conjugate vaccine serotype streptococcus pneumoniae in adults 50 Years and Older presenting with community-acquired pneumonia in Israel

ABSTRACT Background: Community acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide, and is a leading cause of hospitalization in previously healthy individuals without predisposing risk factors or comorbidities. In this study we determined PCV13 serotype distribution in adults aged ≥50 years with radiographically confirmed CAP in Israel. Methods: Subjects aged ≥50 years were enrolled from one of three hospitals (Emek Medical Center, Meir Medical Center and Sheba Medical Center) from March 2014 to July 2015. Information was collected on subject demographics, comorbidities, risk factors, and pneumococcal vaccine immunization status. Subjects presented with suspected CAP supported by radiographic evidence, and provided a urine sample and informed consent. Subjects without radiographic confirmation of CAP or who received PPSV23 within 30 days of study enrollment were excluded from the final analysis. Serotype distribution was performed using the urinary antigen detection (UAD) assay and/or microbiological culture. Results: Overall, 498 subjects with radiographically confirmed CAP were enrolled in the study. Eighty subjects (16.1%) were positive for any S. pneumoniae serotype by ≥1 assay, and 38 (7.6%) were positive for PCV13 serotypes via the UAD. The overall 30-day mortality rate was 1.2%, though S. pneumoniae was not isolated from any case leading to death. Conclusion: Despite six years of high pneumococcal immunization coverage in children in Israel, we have shown that 7.6% of CAP cases among adults in Israel remain related to PCV13 serotypes; and that the burden of PCV13 may be as high as 47% of observed pneumococcal CAP.

Clinical burden of multi-cause and pneumococcal pneumonia, meningitis, and septicemia in Hungary. Results of a retrospective study (2006–2011)

INTRODUCTION Assessment of the impact of pneumococcal conjugate vaccines on the burden of pneumonia, meningitis, and septicemia in Hungary is limited. AIM The aim of this retrospective study was to quantify rates of hospitalized multi-cause and pneumococcal pneumonia, meningitis, and septicemia in all age groups in Hungary between 2006 and 2011. METHOD Aggregate data were obtained from the Hungarian National Healthcare Fund using pre-specified ICD-10 codes. Comparisons included average rates pre-vaccine (2006-2007) versus post-vaccine (2010-2011) using a χ2 test. RESULTS Hospitalization rates among children aged 0-4 years significantly declined for multi-cause pneumonia and meningitis, but increased for septicemia. There were significant increases in multi-cause pneumonia and septicemia in other age groups. In-hospital mortality rates increased with age. Limited use of pneumococcal-specific codes led to inconclusive findings for pneumococcal diseases. CONCLUSIONS Declines in multi-cause pneumonia and meningitis in children aged 0-4 years suggest direct effects of pneumococcal conjugate vaccination on hospitalization rates.