Pneumococcal conjugate vaccination and nasopharyngeal acquisition of pneumococcal serotype 19A strains.
BACKGROUND
The rapid increase in multiresistant serotype 19A as a cause of invasive and respiratory pneumococcal disease has been associated in time with the widespread implementation of 7-valent pneumococcal conjugate vaccination (PCV-7) in several countries. Because spontaneous fluctuations in time and antibiotic selective pressure may have induced this serotype 19A increase, controlled studies are needed to assess the role of PCV-7.


OBJECTIVE
To examine the association of PCV-7 vaccination and nasopharyngeal acquisition of serotype 19A pneumococci, their clonal distribution, and antibiotic susceptibility.


METHODS
Post hoc per-protocol completer's analysis as part of a randomized controlled trial of nasopharyngeal Streptococcus pneumoniae carriage enrolling 1003 healthy newborns with follow-up to the age of 24 months in The Netherlands, which has low antibiotic resistance rates. The study was conducted before widespread PCV-7 implementation in infants, between July 7, 2005, and February 14, 2008. Nasopharyngeal swabs were obtained at the age of 6 weeks and at 6, 12, 18, and 24 months.


METHODS
Infants were randomly assigned to receive 2 doses of PCV-7 at 2 and 4 months; 2 + 1 doses of PCV-7 at 2, 4, and 11 months; or no dosage (unvaccinated control group).


METHODS
Cumulative proportion of children with nasopharyngeal acquisition of a new serotype 19A strain from 6 through 24 months of age.


RESULTS
Nine hundred forty-eight children completed the study. Fifty-four nasopharyngeal serotype 19A carriage isolates from 318 in the 2-dose group, 66 isolates from 327 in the 2 + 1-dose group, and 33 isolates from 303 in the unvaccinated were collected from 6 weeks through 24 months. The cumulative proportion who tested positive for new nasopharyngeal serotype 19A acquisition from 6 through 24 months of age was significantly higher in those having received the 2 + 1-dose PCV-7 schedule (16.2%; 95% confidence interval [CI], 12.6%-20.6%) vs those who were unvaccinated (9.2%; 95% CI, 6.5%-13.0%; relative risk [RR], 1.75; 95% CI, 1.14-2.70) but not after a 2-dose schedule (13.2%; 95% CI, 9.9%-17.4%; RR, 1.43; 95% CI, 0.91-2.25). There were 28 different sequence types identified, including 6 new types. The proportion of children with new 19A acquisition who had used antibiotics in the last 6 months (18.7%) did not differ among groups. Five isolates were penicillin-intermediate susceptible and another 3 were nonsusceptible to erythromycin and azithromycin, all in the vaccine groups.


CONCLUSIONS
A 2 + 1-dose PCV-7 schedule was associated with an increase in serotype 19A nasopharyngeal acquisition compared with unvaccinated controls.


BACKGROUND
clinicaltrials.gov Identifier: NCT00189020.
van Gils
Elske J M
EJ
University Medical Center Utrecht, Wilhelmina Children's Hospital, Department of Pediatric Immunology and Infectious Diseases, 3508 AB Utrecht, The Netherlands.
Veenhoven
Reinier H
RH
Hak
Eelko
E
Rodenburg
Gerwin D
GD
Keijzers
Wendy C M
WC
Bogaert
Debby
D
Trzcinski
Krzysztof
K
Bruin
Jacob P
JP
van Alphen
Loek
L
van der Ende
Arie
A
Sanders
Elisabeth A M
EA
D002353:Carrier State / Q000517:prevention & control*; D024881:Drug Resistance, Bacterial; D005260:Female; D005500:Follow-Up Studies; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000187:drug effects / Q000302:isolation & purification
D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines