Impact of conjugate vaccine on transmission of antimicrobial-resistant Streptococcus pneumoniae among Alaskan children.

BACKGROUND: The impact of heptavalent pneumococcal conjugate vaccine (PCV7) on transmission of antimicrobial-resistant Streptococcus pneumoniae is an important concern for countries considering PCV7 introduction. METHODS: Every winter from 2000 to 2004, as PCV7 was routinely introduced, we obtained nasopharyngeal swabs for pneumococcal culture, serotyping, and susceptibility testing from 150 children aged 3-59 months at each of 3 Anchorage, Alaska clinics. We assessed risk factors for pneumococcal carriage, including vaccination status and antimicrobial use. RESULTS: Between 2000 and 2004, 2250 nasopharyngeal swabs from 2061 infants and children were collected. The proportion of children receiving > or = 1 PCV7 vaccination increased from 0 to 89%, whereas overall pneumococcal carriage remained stable (38% versus 41%, respectively). Among S. pneumoniae carriers, we observed declines in carriage of PCV7 serotypes (from 54% to 10%, P < 0.01) and trimethoprim-sulfamethoxazole nonsusceptible strains (44% to 16%, P < 0.01), but not in PCN-nonsusceptible strains (36% versus 37%). Among PCN-nonsusceptible types, the proportion of serotype 19A strains increased from 10% to 32% (P = 0.0002). Recent beta-lactam use was stable throughout the period (29% overall), whereas trimethoprim-sulfamethoxazole use declined from 6% to 2% (P = 0.02). CONCLUSIONS: PCV7 vaccination in the first 5 years did not affect overall pneumococcal carriage, but was associated with a shift in serotype distribution from PCV7 types to non-PCV7 types. With persistent pressure of some antimicrobials, reductions in carriage of antimicrobial nonsusceptible PCV7 types may be offset by increases in carriage of nonsusceptible non-PCV7 types.

Immunogenicity and reactogenicity to Haemophilus influenzae type B (Hib) conjugate vaccine among rural Alaska adults.

BACKGROUND: Despite routine vaccination and declining disease rates, Haemophilus influenzae type b (Hib) invasive disease still occurs in rural Alaska. Colonization studies indicate persistent transmission of Hib among village residents, including adults. As part of a project to eliminate Hib carriage in three rural villages, we evaluated a cohort of Alaska adults for antibody response and reactogenicity to a single dose of Hib conjugate vaccine (HbOC). METHODS: 75 previously unvaccinated, randomly-selected adults in one village received a single dose of HbOC vaccine and completed a side-effects diary. Sera and oropharyngeal specimens were collected at baseline, two months and one year. RESULTS: No participants were colonized with Hib or reported serious side-effects. At baseline, 97% of adults had IgG anti-PRP concentrations > or = 0.15 microg/mL, 69% > or = 1 microg/mL, and 28% > or = 5 microg/mL. Two months post-vaccination, 100% of participants had concentrations > or = 0.15 microg/mL, 93% > or = 1 microg/mL, and 86% > or = 5 microg/mL. After 1 year, 98% had IgG anti-PRP concentrations > or = 0.15 microg/mL, 86% > or = 1 microg/mL, and 67% > or = 5 microg/mL. GMCs were 1.9, 33.3 and 8.4 microg/mL at baseline, 2 months and 1 year post-vaccine, respectively (p < 0.01). Serum bactericidal activity increased from a baseline geometric mean titer of 2,205 to 8,349 two months post vaccination and declined to 1102 after one year. CONCLUSIONS: HbOC vaccine was immunogenic and well-tolerated among Alaskan adults. Nearly 90% of the adults developed an antibody level associated with protection against Hib colonization which persisted for 1 year in 67% of participants.

Evaluation of a volunteer sample in nasopharyngeal colonization surveys for Streptococcus pneumoniae in rural Alaska.

OBJECTIVE: To compare characteristics of persons in rural northern communities who participated in a study on antimicrobial use and drug-resistant Streptococcus pneumoniae (SP) to those who did not participate. STUDY DESIGN: The original study (1998--2000) was a community-based, controlled intervention trial designed to determine the penicillin susceptibility of nasopharyngeal SP isolates in relation to community-wide use of antibiotics. The study continued after 2000, in a subset of the original communities, to prospectively evaluate the impact of the heptavalent pneumococcal conjugate vaccine on the carriage of SP. The results presented here are an analysis of the first five years of data. METHODS: We conducted annual surveys (1998--2002) for nasopharyngeal colonization of SP using a volunteer sample of residents in rural communities. Medical chart reviews for health clinic visitation and antibiotic use were completed for all village residents. RESULTS: Participants were younger (22.8 vs. 28.4 years), had more health clinic utilization (3.3 vs. 2.4 visits) and received more antibiotics (1.0 vs. 0.6 courses) than non-participants. Differences between participants and non-participants were similar across all years of the study. CONCLUSIONS: Our study provides further empirical evidence that selection bias should be considered when designing studies. However, a volunteer sample provided internal consistency for comparison of our main study outcomes across time.

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska.

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.