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Research Letters |

Nasopharyngeal Carriage of Streptococcus Pneumoniae in Very Low-Birth-Weight Infants After Administration of Heptavalent Pneumococcal Conjugate Vaccine FREE

Jocelyn Y. Ang, MD; Jorge L. Lua, MD; Basim I. Asmar, MD; Seetha Shankaran, MD; Roy J. Heyne, MD; Robert L. Schelonka, MD; Abhik Das, PhD; Lei Li, PhD; Delois M. Jackson, MSc; Rosemary D. Higgins, MD; Carl T. D'Angio, MD; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network
[+] Author Affiliations

Author Affiliations: Divisions of Infectious Diseases (Drs Ang and Asmar) and Neonatal-Perinatal Medicine (Drs Lua and Shankaran), Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan; Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical Center, Dallas (Dr Heyne); Department of Pediatrics, Division of Neonatology, University of Alabama at Birmingham (Dr Schelonka); Statistics and Epidemiology Unit, Research Triangle Institute International, Rockville, Maryland (Dr Das); Statistics and Epidemiology Unit, Research Triangle Institute International, Research Triangle Park, North Carolina (Dr Li); Streptococcus Laboratory, Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia (Ms Jackson); Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Dr Higgins); Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Strong Children's Research Center, University of Rochester School of Medicine and Dentistry, Rochester, New York (Dr D'Angio).


Arch Pediatr Adolesc Med. 2010;164(12):1173-1175. doi:10.1001/archpediatrics.2010.233.
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Published online

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 Streptococcus pneumoniae in a group of VLBW infants (weight, 401-1500 g) before administration of the first PCV-7 vaccine (prevaccine) and at 4 to 6 weeks after a 3-dose PCV-7 primary series (postvaccine). We also investigated the correlation between vaccine-induced pneumococcal IgG antibody level and pneumococcal NP carriage after PCV-7 (postvaccine).

Very low-birth-weight infants who participated in a PCV-7 immunogenicity study1 were enrolled from 4 National Institute of Child Health and Human Development Neonatal Research Network sites (Detroit, Michigan, Rochester, New York, Dallas, Texas, and Birmingham, Alabama). The study was approved by Neonatal Research Network 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.

Nasopharyngeal cultures were obtained at the prevaccine and postvaccine visits. Antimicrobial susceptibility testing of all pneumococcal isolates was performed.

Pneumococcal isolates were serotyped at the Centers for Disease Control and Prevention, Atlanta, Georgia. Serotypes 4, 6B, 9V, 14,18C, 19F, and 23F were classified as vaccine serotypes (VT). Other serotypes were classified as non-VT (NVT).

Antipneumococcal antibodies2 against 7 VT were measured at the postvaccine visit, and 0.15 μg/mL or greater 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, and chronologic age at swab collection, as well as serotype and antimicrobial susceptibilities of pneumococcal isolates.

A total of 123 of 135 infants enrolled had at least 1 NP swab obtained; 71 had prevaccine and 102 had postvaccine NP swab cultures. Fifty infants had both prevaccine and postvaccine NP swabs. Most (44 of 71; 62%) had a prevaccine NP swab done while in the neonatal intensive care unit, whereas all but 1 had postvaccine NP swab done after hospital discharge.

The median gestational age of 123 infants was 28 weeks (range, 23-32). The median chronologic ages at prevaccine and postvaccine NP swab collections were 2 (range, 1-3) and 8 months (range, 6-10), respectively.

S pneumoniae was isolated in 4.2% (3 of 71) prevaccine and 12.7% (13 of 102) postvaccine samples. One infant had positive prevaccine and postvaccine NP cultures with 2 different serotypes; another colonized at prevaccine had a negative postvaccine NP culture. Of the 50 infants with both prevaccine and postvaccine NP swabs, 49 had negative prevaccine NP cultures, of whom 8 became colonized at the postvaccine visit (all NVT) (Table).

Table Graphic Jump LocationTable. Pneumococcal Nasopharyngeal Isolates: Time and Place of Collection, Birth Weight, Serotype, and Antimicrobial Susceptibility

Serotyping was done on 15 of 16 isolates (Table). One prevaccine isolate was a VT; all 12 postvaccine isolates were NVT. Antibiotic susceptibility4 (Table) revealed 1 prevaccine isolate that was resistant to erythromycin. Of 12 postvaccine isolates, 2 (19A) were resistant to 4 antibiotics, 1 (35B) to penicillin, and 1 (nontypeable) to erythromycin.

Serum anticapsular IgG antibody levels to 7 VT were available for 100 infants who had postvaccine NP swabs. Antipneumococcal antibody levels greater than 0.15 μg/mL were achieved in 88% to 99% of participants and varied by serotype. Since all postvaccine pneumococcal isolates were NVT, assessment of NP carriage status based on antibody levels could not be performed.

The pneumococcal NP carriage rate of 12.7% in our very low-birth-weight infants after PCV-7 vaccination was lower than previously reported during the pre–PCV-75 and early post–PCV-76 eras and was exclusively owing 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 anticapsular antibody levels, all postvaccine pneumococcal NP isolates were NVT, suggesting protection against VT NP carriage at 4 to 6 weeks after the vaccine period.

Correspondence: Dr Ang, Carman and Ann Adams Department of Pediatrics, Division of Infectious Diseases, Children's Hospital of Michigan, Wayne State University School of Medicine, 3901 Beaubien Blvd, Detroit, MI 48201 (jang@med.wayne.edu).

Author Contributions: Drs Das (Data Coordinating Center Principal Investigator) and Li (Data Coordinating Center 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. Study concept and design: Ang, Asmar, Shankaran, Higgins, and D'Angio. Acquisition of data: Lua, Shankaran, Heyne, Li, Jackson, Higgins, and D'Angio. Analysis and interpretation of data: Ang, Asmar, Shankaran, Heyne, Schelonka, Das, Higgins, and D'Angio. Drafting of the manuscript: Ang, Lua, Asmar, Shankaran, Schelonka, and Li. Critical revision of the manuscript for important intellectual content: Ang, Lua, Shankaran, Heyne, Schelonka, Das, Jackson, Higgins, and D'Angio. Statistical analysis: Shankaran, Das, Li, and D'Angio. Obtained funding: Ang, Shankaran, and D'Angio. Administrative, technical, and material support: Lua, Shankaran, Jackson, and Higgins. Study supervision: Asmar, Shankaran, Heyne, Das, and D'Angio.

Eunice Kennedy Shriver NICHD Neonatal Research Network Investigators: Alan Jobe, MD, PhD, University of Cincinnati (Chair, 2001-2006), Michael S. Caplan, MD, Northwestern University (Chair, 2006-2011); Stephanie Wilson Archer, MA, Eunice Kennedy Shriver National Institute of Child Health and Human Development; 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, Research Triangle Institute International (U01 HD36790); 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 Alabama at Birmingham Health System and Children's Hospital of Alabama (GCRC M01 RR32, U10 HD34216); Dale L. Phelps, MD, Gary J. Myers, MD, Cassandra A. Horihan, MS, Rosemary L. Jensen, Diane L. Hust, RN, PNP, University of Rochester Golisano Children's Hospital at Strong (GCRC M01 RR44, U10 HD40521); 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, University of Texas Southwestern Medical Center at Dallas Parkland Health & Hospital System and Children's Medical Center Dallas (GCRC M01 RR633, U10 HD40689); Athina Pappas, MD; Rebecca Bara, RN, BSN, Wayne State University Hutzel Women's Hospital and Children's Hospital of Michigan (U10 HD21385).

Financial Disclosure: None reported.

Funding/Support: This study was supported by the National Institutes of Health and the Eunice Kennedy Shriver NICHD and Children's Research Center of Michigan (CRCM).

Role of the Sponsor: The National Institutes of Health and the Eunice Kennedy Shriver NICHD provided grant support for the Neonatal Research Network's PCV-7 Study. The agencies provided overall oversight for study conduct but all data analyses and interpretation were independent of the funding agencies. The CRCM, Detroit, Michigan, provided funding for the nasopharyngeal swab cultures and compensation for nurse coordinators' time.

Additional Information: Data collected at participating Neonatal Research Network sites were transmitted to Research Triangle Institute International, the data coordinating center for the Neonatal Research Network, which stored, managed, and analyzed the data for this study. Serotyping of pneumococcal isolates was performed in the Streptococcus Laboratory at the Centers for Disease Control and Prevention.

Additional Contributions: We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. We thank Cynthia G. Whitney, MD, MPH, and Bernard Beall, PhD, Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, for their assistance; Theresa Painter, MA, MT, and Christine Wollenweber, MT, Detroit Medical Center University Laboratory, Wayne State University for their assistance in processing nasopharyngeal specimens for culture, storage, and shipment; and William Lyman, PhD, Director of the CRCM, Detroit, Michigan, for his support.

D’Angio  CTHeyne  RJO’Shea  TM  et al. NICHD Neonatal Research Network, Heptavalent pneumococcal conjugate vaccine immunogenicity in very-low-birth-weight, premature infants. Pediatr Infect Dis J 2010;29 (7) 600- 606
PubMed Link to Article
Wernette  CMFrasch  CEMadore  D  et al.  Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides. Clin Diagn Lab Immunol 2003;10 (4) 514- 519
PubMed
Black  SShinefield  HFireman  B  et al. Northern California Kaiser Permanente Vaccine Study Center Group, Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000;19 (3) 187- 195
PubMed Link to Article
Wikler  MABush  KCockerill  FR  III  et al.  Performance Standards for Antimicrobial Susceptibility Testing: Eighteenth Informational Supplement.  Wayne, PA Clinical and Laboratory Standards Institute2008;
Ghaffar  FFriedland  IR McCracken  GH  Jr Dynamics of nasopharyngeal colonization by Streptococcus pneumoniae. Pediatr Infect Dis J 1999;18 (7) 638- 646
PubMed Link to Article
Pelton  SILoughlin  AMMarchant  CD Seven valent pneumococcal conjugate vaccine immunization in two Boston communities: changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr Infect Dis J 2004;23 (11) 1015- 1022
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable. Pneumococcal Nasopharyngeal Isolates: Time and Place of Collection, Birth Weight, Serotype, and Antimicrobial Susceptibility

References

D’Angio  CTHeyne  RJO’Shea  TM  et al. NICHD Neonatal Research Network, Heptavalent pneumococcal conjugate vaccine immunogenicity in very-low-birth-weight, premature infants. Pediatr Infect Dis J 2010;29 (7) 600- 606
PubMed Link to Article
Wernette  CMFrasch  CEMadore  D  et al.  Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides. Clin Diagn Lab Immunol 2003;10 (4) 514- 519
PubMed
Black  SShinefield  HFireman  B  et al. Northern California Kaiser Permanente Vaccine Study Center Group, Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000;19 (3) 187- 195
PubMed Link to Article
Wikler  MABush  KCockerill  FR  III  et al.  Performance Standards for Antimicrobial Susceptibility Testing: Eighteenth Informational Supplement.  Wayne, PA Clinical and Laboratory Standards Institute2008;
Ghaffar  FFriedland  IR McCracken  GH  Jr Dynamics of nasopharyngeal colonization by Streptococcus pneumoniae. Pediatr Infect Dis J 1999;18 (7) 638- 646
PubMed Link to Article
Pelton  SILoughlin  AMMarchant  CD Seven valent pneumococcal conjugate vaccine immunization in two Boston communities: changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr Infect Dis J 2004;23 (11) 1015- 1022
PubMed Link to Article

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