Laboratory methods for determining pneumonia etiology in children

Laboratory diagnostics are a core component of any pneumonia etiology study. Recent advances in diagnostic technology have introduced newer methods that have greatly improved the ability to identify respiratory pathogens. However, determining the microbial etiology of pneumonia remains a challenge, especially in children. This is largely because of the inconsistent use of assays between studies, difficulties in specimen collection, and problems in interpreting the presence of pathogens as being causally related to the pneumonia event. The laboratory testing strategy for the Pneumonia Etiology Research for Child Health (PERCH) study aims to incorporate a broad range of diagnostic testing that will be standardized across the 7 participating sites. We describe the current status of laboratory diagnostics for pneumonia and the PERCH approach for specimen testing. Pneumonia diagnostics are evolving, and it is also a priority of PERCH to collect and archive specimens for future testing by promising diagnostic methods that are currently under development.     

Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine

Context  A conjugate vaccine targeting 7 pneumococcal serotypes was licensed for young children in 2000. In contrast to the 23-valent polysaccharide vaccine used in adults, the 7-valent conjugate vaccine affects pneumococcal carriage and transmission. Early after its introduction, incidence of invasive pneumococcal disease declined among older adults, a group at high risk for pneumococcal disease. Objective  To determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease, disease characteristics, or the spectrum of patients acquiring these illnesses have changed over the 4 years since pneumococcal conjugate vaccine licensure. Design, Setting, and Population  Population-based surveillance of invasive pneumococcal disease in 8 US geographic areas (total population, 18 813 000), 1998-2003. Main Outcome Measures  Incidence of invasive pneumococcal disease by pneumococcal serotype and other characteristics; frequency among case patients of comorbid conditions and other factors influencing mortality. Results  Incidence of invasive pneumococcal disease among adults aged 50 years or older declined 28% (95% confidence interval [CI], –31% to –24%), from 40.8 cases/100 000 in 1998-1999 to 29.4 in 2002-2003. Among those aged 65 years or older, the 2002-2003 rate (41.7 cases/100 000) was lower than the Healthy People 2010 goal (42 cases/100 000). Among adults aged 50 years or older, incidence of disease caused by the 7 conjugate vaccine serotypes declined 55% (95% CI, –58% to –51%) from 22.4 to 10.2 cases/100 000. In contrast, disease caused by any of the 16 serotypes only in polysaccharide vaccine did not change, and disease caused by serotypes not in either vaccine increased somewhat, from 6.0 to 6.8 cases/100 000 (13%; 95% CI, 1% to 27%). Between 1998-1999 and 2002-2003, the proportion of case-patients with human immunodeficiency virus infection increased from 1.7% (47/2737) to 5.6% (124/2231) (P<.001), and those with any comorbid condition that is an indication for pneumococcal polysaccharide vaccination increased from 62.3% (1842/2955) to 72.0% (1721/2390) (P<.001). Conclusions  Our findings indicate that use of conjugate vaccine in children has substantially benefited older adults. However, persons with certain comorbid conditions may benefit less than healthier persons from the indirect effects of the new vaccine.      

Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections

Context  Historically, incidence of pneumococcal disease in the United States has been higher among blacks than among whites. Following recommendation of a new 7-valent pneumococcal conjugate vaccine for children in October 2000, the incidence of invasive pneumococcal disease has declined dramatically, but the impact of vaccination on racial disparities in incidence of pneumococcal disease is unknown. Objective  To assess the effect of conjugate vaccine introduction on rates of pneumococcal disease among whites and blacks in the United States. Design, Setting, and Patients  Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based surveillance system in 7 states. Patients were 15 923 persons with invasive pneumococcal disease occurring between January 1, 1998, and December 31, 2002. Main Outcome Measures  Age- and race-specific pneumococcal disease incidence rates (cases per 100 000 persons), rate ratios, and rate differences. Results  Between 1998 and 2002, annual incidence rates for invasive pneumococcal disease decreased from 19.0 to 12.1 cases per 100 000 among whites and from 54.9 to 26.5 among blacks. Due to these declines, 14 730 fewer cases occurred among whites and 8780 fewer cases occurred among blacks in the United States in 2002, compared with 2 prevaccine years, 1998 and 1999. Before vaccine introduction, incidence among blacks was 2.9 times higher than among whites (95% confidence interval [CI], 2.7-3.0); in 2002, the black-white rate ratio had been reduced to 2.2 (95% CI, 2.0-2.4). Incidence among black children younger than 2 years went from being 3.3 times higher (95% CI, 3.0-3.7) than among white children in the prevaccine period to 1.6 times higher (95% CI, 1.1-2.2) in 2002. By 2002, 74% of white children and 68% of black children aged 19 to 35 months in the 7 states had received at least 1 dose of pneumococcal conjugate vaccine; 43% of white and 39% of black children received 3 or more doses. Conclusion  Although blacks remain at higher risk of invasive pneumococcal disease, introduction of childhood pneumococcal vaccination has reduced the racial disparity in incidence of pneumococcal disease.      

Emergence of Streptococcus pneumoniae with very-high-level resistance to penicillin

Penicillin resistance threatens the treatment of pneumococcal infections. We used sentinel hospital surveillance (1978 to 2001) and population-based surveillance (1995 to 2001) in seven states in the Active Bacterial Core surveillance of the Emerging Infections Program Network to document the emergence in the United States of invasive pneumococcal isolates with very-high-level penicillin resistance (MIC > or = 8 microg/ml). Very-high-level penicillin resistance was first detected in 1995 in multiple pneumococcal serotypes in three regions of the United States. The prevalence increased from 0.56% (14 of 2,507) of isolates in 1995 to 0.87% in 2001 (P = 0.03), with peaks in 1996 and 2000 associated with epidemics in Georgia and Maryland. For a majority of the strains the MICs of amoxicillin (91%), cefuroxime (100%), and cefotaxime (68%), were > or =8 microg/ml and all were resistant to at least one other drug class. Pneumonia (50%) and bacteremia (36%) were the most common clinical presentations. Factors associated with very highly resistant infections included residence in Tennessee, age of <5 or > or =65 years, and resistance to at least three drug classes. Hospitalization and case fatality rates were not higher than those of other pneumococcal infection patients; length of hospital stay was longer, controlling for age. Among the strains from 2000 and 2001, 39% were related to Tennessee(23F)-4 and 35% were related to England(14-)9. After the introduction of the pneumococcal conjugate vaccine, the incidence of highly penicillin resistant infections decreased by 50% among children <5 years of age. The emergence, clonality, and association of very-high-level penicillin resistance with multiple drug resistance requires further monitoring and highlights the need for novel agents active against the pneumococcus.