Epidemiology of Invasive Pneumococcal Disease in Southern California: Implications for the Design and Conduct of a Pneumococcal Conjugate Vaccine Efficacy Trial

Zangwill, Kenneth M.; Vadheim, Constance M.; Vannier, Ann M.; Hemenway, Leslie; Greenberg, David; Ward, Joel I.

doi:10.1093/infdis/174.4.752

Cited by 182 publications

(88 citation statements)

References 41 publications

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“…In the United States, pneumococcus causes 50,000 cases of bacteremia and 3,000 cases of meningitis annually (2,3). Faced with one of the most frequent nasopharyngeal colonizers of children, the host immune response can be assumed to play an important role in preventing the progression from colonization to invasive pneumococcal disease.…”

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confidence: 99%

Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection

Malley

Henneke

Morse

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

630

583

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Streptococcus pneumoniae is one of the leading causes of invasive bacterial disease worldwide. Fragments of the cell wall and the cytolytic toxin pneumolysin have been shown to contribute substantially to inflammatory damage, although the interactions between pneumococcal components and host-cell structures have not been elucidated completely. Results of a previous study indicated that cell-wall components of pneumococci are recognized by Toll-like receptor (TLR)2 but suggested that pneumolysin induces inflammatory events independently of this receptor. In this study we tested the hypothesis that pneumolysin interacts with surface proteins of the TLR family other than TLR2. We found that pneumolysin stimulates tumor necrosis factor-␣ and IL-6 release in wild-type macrophages but not in macrophages from mice with a targeted deletion of the cytoplasmic TLR-adapter molecule myeloid differentiation factor 88, suggesting the involvement of the TLRs in pneumolysin recognition. Purified pneumolysin synergistically activated macrophage responses together with preparations of pneumococcal cell walls or staphylococcal peptidoglycan, which are known to activate TLR2. Furthermore, when compared with wild-type macrophages, macrophages from mice that carry a spontaneous mutation in TLR4 (P712H) were hyporesponsive to both pneumolysin alone and the combination of pneumolysin with pneumococcal cell walls. Finally, these TLR4-mutant mice were significantly more susceptible to lethal infection after intranasal colonization with pneumolysin-positive pneumococci than were control mice. We conclude that the interaction of pneumolysin with TLR4 is critically involved in the innate immune response to pneumococcus.

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mentioning

confidence: 99%

Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection

Malley

Henneke

Morse

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

630

583

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“…2,3 By 1999, 38% of laboratory isolates in children who were younger than 2 years were nonsusceptible to penicillin, 4 with higher rates reported in local areas. [5][6][7] In February 2000, heptavalent pneumococcal conjugate vaccine (PCV7) was released to provide immunity to the 7 serotypes responsible for 85% of pediatric invasive pneumococcal disease 8 and 78% of penicillin-nonsusceptible S pneumoniae (PNSP) isolates in children. 9 Prelicensure trials showed a 90% reduction in invasive disease 10 and a 23% reduction in all-cause pneumonia in the first 2 years of life.…”

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confidence: 99%

Post-PCV7 Changes in Colonizing Pneumococcal Serotypes in 16 Massachusetts Communities, 2001 and 2004

et al. 2005

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ABSTRACT. Objective. The introduction of heptavalent conjugate pneumococcal vaccine (PCV7) has raised concerns for replacement with nonvaccine serotypes in both invasive disease and asymptomatic carriage. Analysis of colonizing serotypes among healthy children in the community provides critical data on such changes.Methods. Nasopharyngeal specimens were obtained from children who were younger than 7 years during well-child or sick visits in primary care practices in 16 Massachusetts communities during 2001 and 2004. Susceptibility testing and serotyping were performed on isolated Streptococcus pneumoniae strains. Vaccination history with PCV7 was abstracted from the medical record.Results. Among colonizing pneumococcal isolates, PCV7 serotypes decreased from 36% to 14%, and non-PCV7 serotypes increased from 34% to 55%. Overall carriage did not change (26% to 23%); neither did carriage of potentially cross-reactive serotypes (30% to 31%). The most common non-PCV7 serotypes were serotypes 11, 15, and 29. There was a substantial increase in penicillin nonsusceptibility from 8% to 25% in non-PCV7 serotypes; 35% were highly resistant to penicillin. Penicillin nonsusceptibility increased from 45% to 56% among PCV7 serotypes while remaining stable among PCV7 potentially cross-reactive strains (51% vs 54%).Conclusions. Pneumococcal colonization has changed after the introduction of PCV7, both in serotype distribution and in patterns of antibiotic resistance. The frequency of nonvaccine strains has increased, and the proportion of nonvaccine isolates that are not susceptible to penicillin has tripled. This shift toward increased carriage of nonvaccine serotypes warrants vigilance for changes in the epidemiology of invasive pneumococcal disease. B efore the release of a conjugate vaccine for US children, Streptococcus pneumoniae caused invasive disease in 1 in 500 to 600 children who were younger than 2 years. 1 In addition, rising antibiotic resistance among pneumococcal strains was a major concern among public health officials. 2,3 By 1999, 38% of laboratory isolates in children who were younger than 2 years were nonsusceptible to penicillin, 4 with higher rates reported in local areas. [5][6][7] In February 2000, heptavalent pneumococcal conjugate vaccine (PCV7) was released to provide immunity to the 7 serotypes responsible for 85% of pediatric invasive pneumococcal disease 8 and 78% of penicillin-nonsusceptible S pneumoniae (PNSP) isolates in children. 9 Prelicensure trials showed a 90% reduction in invasive disease 10 and a 23% reduction in all-cause pneumonia in the first 2 years of life. 11 Postlicensure studies have also shown declines in invasive pneumococcal disease from 188 per 100 000 to 59 cases per 100 000 in US children who are younger than 2 years. 4,12 Despite the success of PCV7 in reducing invasive disease, critical questions remain about the changing pneumococcal reservoir. Some trials of immunization with PCV7 have shown a 50% to 65% decrease in carriage of vaccine serotypes [13][14][15] and have rai...

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“…[1][2][3] Resistance among Streptococcus pneumoniae is of particular concern 4,5 because this organism is the leading cause of meningitis 6 and other serious bacterial infections 7 in children, as well as a major cause of more common localized infections such as otitis media. 8 Penicillin-nonsusceptible S pneumoniae (PNSP) have become increasingly common in the United States over the past decade.…”

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confidence: 99%

Antibiotic-Resistant Streptococcus pneumoniae in the Heptavalent Pneumococcal Conjugate Vaccine Era: Predictors of Carriage in a Multicommunity Sample

et al. 2003

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Objective. Despite immunization with heptavalent pneumococcal conjugate vaccine (PCV7), the rising prevalence of antibiotic resistance makes Streptococcus pneumoniae a continuing threat to child health. Data on carriage of resistant organisms by healthy children in communities in which immunization with PCV7 has been implemented will help to define and decrease these risks further. Methods. Children who were <7 years old, resided in a study community, and presented for routine well care or a “sick” visit between March 13 and May 11, 2001, at 31 primary care practices in 16 geographically distinct Massachusetts communities were studied. Consenting parents provided demographic information and data on potential risk factors for carriage of S pneumoniae and of penicillin-nonsusceptible S pneumoniae (PNSP). S pneumoniae isolates from nasopharyngeal specimens were tested for resistance to commonly used antibiotics including penicillin, ceftriaxone, erythromycin, and trimethoprim/sulfamethoxazole. Isolates were serotyped and grouped into PCV7-included serotypes, potentially cross-reactive serotypes (ie, an organism of a serogroup included in the vaccine), or non-PCV7 serotypes. Diagnosis on the day of collection, history of recent antibiotic use, and history of PCV7 immunization were obtained by chart review. Separate bivariate and multivariate analyses were performed to identify correlates of colonization with S pneumoniae and colonization with PNSP, accounting for clustering within communities. Results. S pneumoniae was isolated from the nasopharynx of 190 (26%) of the 742 children studied. Of the 166 tested, 33% were nonsusceptible to penicillin, with 14% showing intermediate susceptibility (minimum inhibitory concentration [MIC] 0.12–1.0) and 19% fully resistant (MIC ≥2). Nonsusceptibility to other antibiotics was common, including ceftriaxone (14%), erythromycin (22%), and trimethoprim/sulfa (31%); 20% of S pneumoniae isolates were not susceptible to ≥3 antibiotics. Thirty-six percent of isolates were of serotypes covered by PCV7; 30% were of PCV7 serogroups and potentially cross-reactive, but not 1 of the 7 included serotypes; and 34% were unrelated to PCV7 serogroups. Nonsusceptibility to penicillin was more common in PCV7-included strains (45%) and potentially cross-reactive strains (51%) than in non-PCV7 serotypes (8%). Risk factors for PNSP colonization included child care attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.3–6.5), current respiratory tract infection (OR: 4.7; 95% CI: 2.5–8.6), and recent antibiotic use (OR: 1.7; 95% CI: 1.0–2.8). PCV7 immunization was associated with decreased carriage of PCV7-included serotypes but not with an overall decrease in S pneumoniae colonization or with a decline in PNSP colonization. Conclusions. In this multicommunity sample, pneumococcal antibiotic resistance was common and was most frequently found in PCV7-included and PCV7 serogroup strains. The long-term impact of PCV7 immunization will be partially determined by the protection that it affords against invasive infection with potentially cross-reactive serotypes, as well as the virulence and future resistance patterns of unrelated serotypes.

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Epidemiology of Invasive Pneumococcal Disease in Southern California: Implications for the Design and Conduct of a Pneumococcal Conjugate Vaccine Efficacy Trial

Cited by 182 publications

References 41 publications

Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection

Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection

Post-PCV7 Changes in Colonizing Pneumococcal Serotypes in 16 Massachusetts Communities, 2001 and 2004

Antibiotic-Resistant Streptococcus pneumoniae in the Heptavalent Pneumococcal Conjugate Vaccine Era: Predictors of Carriage in a Multicommunity Sample

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