Risk factors for invasive pneumococcal disease in children in the era of conjugate vaccine use.

OBJECTIVE: We conducted a case-control study to evaluate risk factors for invasive pneumococcal disease (IPD) among children who were aged 3 to 59 months in the era of pneumococcal conjugate vaccine (PCV7). METHODS: IPD cases were identified through routine surveillance during 2001-2004. We matched a median of 3 control subjects to each case patient by age and zip code. We calculated odds ratios for potential risk factors for vaccine-type and non-vaccine-type IPD by using multivariable conditional logistic regression. RESULTS: We enrolled 782 case patients (45% vaccine-type IPD) and 2512 matched control subjects. Among children who received any PCV7, children were at increased risk for vaccine-type IPD when they had underlying illnesses, were male, or had no health care coverage. Vaccination with PCV7 did not influence the risk for non-vaccine-type IPD. Presence of underlying illnesses increased the risk for non-vaccine-type IPD, particularly among children who were not exposed to household smoking. Non-vaccine-type case patients were more likely than control subjects to attend group child care, be male, live in low-income households, or have asthma; case patients were less likely than control subjects to live in households with other children. CONCLUSIONS: Vaccination with PCV7 has reduced the risk for vaccine-type IPD that is associated with race and group child care attendance. Because these factors are still associated with non-vaccine-type IPD risk, additional reductions in disparities should be expected with new, higher valency conjugate vaccines.

Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study.

BACKGROUND: When seven-valent pneumococcal conjugate vaccine was introduced in the USA, many children were vaccinated on schedules that differed from those tested in clinical trials. Our aim was to assess the effectiveness of the vaccine against various pneumococcal serotypes, and to measure the effectiveness of the recommended dose schedule and of catch-up and incomplete schedules. METHODS: Invasive disease, defined as isolation of pneumococcus from a sterile site, was identified in children aged 3-59 months through the US Centers for Disease Control and Prevention's Active Bacterial Core surveillance. We tested isolates for serotype and antimicrobial susceptibility. Three controls, matched for age and zip code were selected for each case. We calculated the matched odds ratio for vaccination using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was calculated as one minus the adjusted matched odds ratio times 100%. FINDINGS: We enrolled 782 cases and 2512 controls. Effectiveness of one or more doses against vaccine serotypes was 96% (95% CI 93-98) in healthy children and 81% (57-92) in those with coexisting disorders. It was 76% (63-85) against infections that were not susceptible to penicillin. Vaccination prevented disease caused by all seven vaccine serotypes, and by vaccine-related serotype 6A. Several schedules were more protective than no vaccination; three infant doses with a booster were more protective against vaccine-type disease than were three infant doses alone (p=0.0323). INTERPRETATION: The seven-valent pneumococcal conjugate vaccine prevents invasive disease in both healthy and chronically ill children. The vaccine is effective when used with various non-standard schedules.

Preventability of invasive pneumococcal disease and assessment of current polysaccharide vaccine recommendations for adults: United States, 2001-2003.

UNLABELLED: BACKGROUND. To prevent Streptococcus pneumoniae infection among persons at highest risk for invasive pneumococcal disease (IPD), the pneumococcal polysaccharide vaccine (PPV) is currently recommended for persons >or=65 years old and persons 2-64 years old with certain underlying conditions. Policymakers have considered expanding recommendations for PPV to include persons who are 50-64 years old and additional populations at risk for IPD. Our objectives were to determine the proportion of IPD cases that might have been prevented if all persons with vaccine indications had been vaccinated and to evaluate new indications. METHODS: From 2001 to 2003, we performed a case series study of IPD in adults at 6 sites of the Active Bacterial Core surveillance-Emerging Infections Program Network. A case of IPD was defined as isolation of pneumococcus from a normally sterile site from a resident of 1 of the surveillance areas. RESULTS: Among 1878 case patients, 1558 (83%) had at least 1 current vaccine indication; of these, 968 case patients (62%) were unvaccinated. Adherence to existing vaccine recommendations would have prevented 21% of all cases. The proportions of all cases potentially prevented by each new indication were as follows: lowering the universal age of recommended vaccination to 50 years, 5.0%-7.0%; adding new risk-based indications to include current smoking, 1.5%-2.5%; former smoking, 0.4%-0.7%; black race, 1.0%-1.4%; and asthma, 0.3%-0.4%. CONCLUSIONS: Increasing vaccine coverage rates among persons with a current indication may prevent more cases than expanding existing indications. Of the potential new indications studied, the strategy that may prevent most cases is lowering the recommended age for universal vaccination to 50 years.

Inhibition of pneumococcal adherence to human nasopharyngeal epithelial cells by anti-PsaA antibodies.

The role of pneumococcal (Pnc) surface adhesin A (PsaA) in the adherence of Streptococcus pneumoniae (pneumococcus) to host cells is not well defined. We examined the effect of anti-PsaA antibodies in an inhibition of adherence assay using Detroit 562 nasopharyngeal human epithelial cells. Rabbit polyclonal (Pab) anti-recombinant PsaA (rPsaA) sera, a purified mouse monoclonal antibody (MAb) (MAb 6F62G8E12), and 22 healthy adult sera with known anti-PsaA IgG levels (obtained by enzyme-linked immunosorbent assay) were evaluated for their abilities to inhibit Pnc adherence to confluent monolayers (measured as percent reduction in CFU counts compared to those of uninhibited controls). Pnc adherence was dependent on capsular phenotype (no or low adherence for opaque strains). With an inoculum of 10(4) to 10(5) bacteria/well, the mean +/- standard deviation count in controls was 163 +/- 32 CFU/well for transparent strains. Low adherence was observed for a PsaA-minus mutant even at higher inoculum doses. Mean percent inhibitions of adherence with Pab and MAb were 54 and 50%, respectively. Adult sera showed inhibition in a dose-response fashion with a range of 98 to 8%, depending on the serum anti-PsaA antibody concentration. Absorption of Pab with rPsaA restored Pnc adherence to control levels. Absorption of sera with a PsaA-minus mutant did not result in a significant decrease (P >0.05) of inhibition of adherence activity. Additionally, nearly 100% of Pnc adherence was inhibited by lipidated rPsaA at 2.5 micro g/ml. Our data support the argument that PsaA is an adhesin that mediates Pnc adherence to human nasopharyngeal cells. This functional assay may be useful in evaluating antibodies elicited in response to PsaA vaccination.