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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Arch Pediatr Adolesc Med. Author manuscript; available in PMC Jan 25, 2012.
Published in final edited form as:
PMCID: PMC3266167
NIHMSID: NIHMS346674
Nasopharyngeal carriage of Streptococcus pneumoniae in very low birth weight infants after administration of heptavalent pneumococcal conjugate vaccine
Jocelyn Y. Ang, MD,1 Jorge L. Lua, MD,2 Basim I. Asmar, MD,1 Seetha Shankaran, MD,2 Roy J. Heyne, MD,3 Robert L. Schelonka, MD,4 Abhik Das, PhD,5 Lei Li, PhD,6 Delois M. Jackson, MSc,7 Rosemary D. Higgins, MD,8 Carl T. D'Angio, MD,9 and on behalf of the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network
1Division of Infectious Diseases, Department of Pediatrics/ Children's Hospital of Michigan/ Wayne State University, Detroit, Michigan
2Division of Neonatal-Perinatal Medicine, Department of Pediatrics/ Children's Hospital of Michigan/ Wayne State University, Detroit, Michigan
3University of Texas Southwestern Medical Center, Department of Pediatrics/ Division of Neonatal-Perinatal Medicine, Dallas, Texas
4 University of Alabama at Birmingham, Department of Pediatrics/ Division of Neonatology, Birmingham, Alabama
5Research Triangle Institute (RTI) International, Statistics and Epidemiology Unit, Rockville, MD
6Research Triangle Institute (RTI) International, Statistics and Epidemiology Unit, Research Triangle Park, North Carolina
7Streptococcus Laboratory, Respiratory Diseases Branch, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia
8Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
9Strong Children's Research Center, University of Rochester School of Medicine and Dentistry, Department of Pediatrics/ Division of Neonatal-Perinatal Medicine, Rochester, New York
Correspondence: Jocelyn Y. Ang, MD Children's Hospital of Michigan Carman and Ann Adams Department of Pediatrics Division of Infectious Diseases Wayne State University School of Medicine 3901 Beaubien Blvd. Detroit, MI 48201 Tel: (313) 745-5863 Fax: (313) 996-8846 ; jang/at/med.wayne.edu
Introduction
The effect of pneumococcal conjugate vaccine-7 (PCV-7) in reducing pneumococcal nasopharyngeal (NP) carriage in very low birth weight (VLBW) infants has not been studied. Our primary objective was to characterize NP carriage of S. pneumoniae in a group of VLBW infants (401-1500 grams) before administration of first PCV-7 (PRE) and at 4-6 weeks after a 3-dose PCV-7 primary series (POST). We also investigated the correlation between vaccine induced pneumococcal IgG antibody level and pneumococcal NP carriage POST PCV-7.
VLBW infants participating in a PCV-7 immunogenicity study1 were enrolled from 4 NICHD Neonatal Research Network (NRN) sites (Detroit, MI, Rochester, NY, Dallas, TX and Birmingham, AL). The study was approved by NRN and each site's institutional review board. Written informed consent was obtained from each subject's parent/guardian. Infants received PCV-7 at approximately 2, 4 and 6 months of age.
NP cultures were obtained at the PRE and POST visits. Antimicrobial susceptibility testing of all pneumococcal isolates was performed.
Pneumococcal isolates were serotyped at the Centers for Disease Control and Prevention, Atlanta, GA. Serotypes 4, 6B, 9V, 14,18C, 19F, and 23F were classified as vaccine serotypes (VT). Other serotypes were classified as non-VT (NVT).
Anti-pneumococcal antibodies2 against seven VT were measured at POST visit and ≥0.15μg/ml was chosen as a possible measure of protective level.3
Descriptive statistics were used to characterize the study subjects with regard to birth weight, gestational age at birth (GA) and chronologic age (CA) at swab collection, as well as serotype and antimicrobial susceptibilities of pneumococcal isolates.
123 of 135 infants enrolled had at least one NP swab obtained; 71 had PRE and 102 had POST NP swab cultures. 50 infants had both PRE and POST NP swabs. Most (44/71=62%) had PRE NP swab done while in NICU, whereas all but one had POST NP swab done after hospital discharge.
The median GA of 123 infants was 28 weeks (range 23-32). The median CA at PRE and POST NP swab collections were 2 months (range 1-3) and 8 months (range 6-10) respectively.
S. pneumoniae was isolated in 4.2% (3/71) PRE and 12.7% (13/102) POST samples. One infant had positive PRE and POST NP cultures with 2 different serotypes; another colonized at PRE had a negative POST NP culture. Among the 50 infants with both PRE and POST NP swabs, 49 had negative PRE NP cultures of whom 8 became colonized at POST (all NVT) (Table 1).
Table 1
Table 1
Pneumococcal nasopharyngeal (NP) isolates: time and place of collection, birth weight, serotype and antimicrobial susceptibility
Serotyping was done on 15 of 16 isolates (Table 1). One PRE isolate was a VT; all 12 POST isolates were NVT. Antibiotic susceptibility (Table1) showed one PRE isolate resistant to erythromycin. Of 12 POST isolates, 2 (19A) were resistant to 4 antibiotics, 1 (35B) resistant to penicillin and 1 (non-typeable) resistant to erythromycin.
Serum anti-capsular IgG antibody levels to 7 VT were available for 100 infants who had POST NP swabs. Anti-pneumococcal antibody ≥0.15 μg/ml were achieved in 88-99% and varied by serotype. Since all POST pneumococcal isolates were NVT, assessment of NP carriage status based on antibody levels could not be performed.
Comment
The pneumococcal NP carriage rate of 12.7 % in our VLBW infants post-PCV-7 vaccination was lower than previously reported during the pre-PCV-74 and early post-PCV-75 eras and was exclusively due to NVT. Our findings also support the recent observation that NVT serotype 19A is becoming more prevalent. An expanded PCV such as PCV-13 which includes 6 additional serotypes (1, 3, 5, 6A, 7F and 19A) may change that. Regardless of serum pneumococcal anti-capsular antibody levels, all POST pneumococcal NP isolates were NVT, suggesting protection against VT NP carriage at 4-6 weeks POST period.
Acknowledgements
Funding /Support: The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Children's Research Center of Michigan (CRCM).
Role of Sponsor: The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provided grant support for the Neonatal Research Network's (NRN) PCV-7 Study. The agencies provided overall oversight for study conduct, but all data analyses and interpretation were independent of the funding agencies. The Children's Research Center of Michigan (CRCM) in Detroit, MI provided funding for the nasopharyngeal swab cultures and compensation for nurse coordinators’ time.
Data collected at participating NRN sites were transmitted to Research Triangle Institute (RTI) International, the data coordinating center (DCC) for the NRN, which stored, managed, and analyzed the data for this study.
Footnotes
Role of Authors: On behalf of the network, Drs. Abhik Das (DCC PI) and Lei Li (DCC Statistician) had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. All authors are involved in the interpretation of data, and in the preparation, review, and approval of the manuscript.
We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. The following investigators participated in this study:
NRN Chairs: Alan Jobe, MD PhD, University of Cincinnati (2001-2006); Michael S. Caplan, MD, Northwestern University (2006-2011).
Eunice Kennedy Shriver National Institute of Child Health and Human Development – Stephanie Wilson Archer, MA.
RTI International (U01 HD36790) – W. Kenneth Poole, PhD; Betty K. Hastings; Elizabeth McClure, MEd; Rebecca L. Perritt, MS; Steve Emrich, MS; Kristin Zaterka-Baxter, RN; Carolyn Petrie Huitema, MS; Jamie E. Newman, MPH; Scott E. Schaefer, MS; Jeanette O'Donnell Auman, BS.
University of Alabama at Birmingham Health System and Children's Hospital of Alabama (GCRC M01 RR32, U10 HD34216) – Waldemar A. Carlo, MD; Myriam Peralta-Carcelen, MD MPH; Monica V. Collins, RN BSN MaEd; Shirley S. Cosby, RN BSN; Vivien A. Phillips, RN BSN.
University of Rochester Golisano Children's Hospital at Strong (GCRC M01 RR44, U10 HD40521) – Dale L. Phelps, MD; Gary J. Myers, MD; Cassandra A. Horihan, MS; Rosemary L. Jensen; Diane L. Hust, RN PNP.
University of Texas Southwestern Medical Center at Dallas Parkland Health & Hospital System and Children's Medical Center Dallas (GCRC M01 RR633, U10 HD40689) – Charles R. Rosenfeld, MD; Walid A. Salhab, MD; Pablo J. Sanchez, MD; Janet S. Morgan, RN; Jackie F. Hickman, RN; Alicia Guzman; Nancy A. Miller, RN; Gaynelle Hensley, RN.
Wayne State University Hutzel Women's Hospital and Children's Hospital of Michigan (U10 HD21385) – Athina Pappas, MD; Rebecca Bara, RN BSN.
We thank Cynthia G. Whitney, MD, MPH and Bernard Beall, PhD from the Respiratory Diseases Branch, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia for their assistance. Serotyping of pneumococcal isolates was performed in the Streptococcus Laboratory at CDC.
We thank Theresa Painter MA, MT and Christine Wollenweber MT from Detroit Medical Center University Laboratory/ Wayne State University for their assistance in processing nasopharyngeal specimens for culture, storage and shipment.
We thank William Lyman, PhD, Director of Children's Research Center of Michigan (CRCM) Detroit, Michigan for his support.
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