0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Number and Order of Whole Cell Pertussis Vaccines in Infancy and Disease Protection FREE

Sarah L. Sheridan, BMed, MAppEpid; Robert S. Ware, PhD; Keith Grimwood, MB, ChB, MD; Stephen B. Lambert, MBBS, PhD
[+] Author Affiliations

Author Affiliations: Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Australia (s.sheridan@uq.edu.au).


Letters Section Editor: Jody W. Zylke, MD, Senior Editor.

More Author Information
JAMA. 2012;308(5):454-456. doi:10.1001/jama.2012.6364.
Text Size: A A A
Published online

To the Editor: Due to their lower rate of adverse events, acellular pertussis vaccines (diphtheria-tetanus-acellular pertussis; DTaP) replaced whole cell vaccines (diphtheria-tetanus-whole cell pertussis; DTwP) in many developed countries during the 1990s. DTaP became available in Queensland, Australia, in 1996 and replaced DTwP for publicly funded primary course immunizations delivered at ages 2 months, 4 months, and 6 months in March 1999. This meant children born in 1998 could receive a primary course consisting of only DTwP, only DTaP, or a mixed schedule.

Similar to North America,1 Australia is experiencing a sustained pertussis epidemic,2 with the highest incidence rates in Queensland during 2011 in children aged 6 to 11 years. The recent changes in pertussis epidemiology may be related to the shift from DTwP to DTaP. To test this hypothesis, we compared pertussis reporting rates by primary course vaccination in the 1998 birth cohort.

Reporting pertussis cases to the health department is mandatory in Queensland. For children born in 1998, we calculated pertussis reporting rates in both the preepidemic (1998-2008) and outbreak periods (2009-2011), by number and order of DTwP doses given before their first birthday. We linked data from the Queensland vaccination register (QVR) with case reports of pertussis. The QVR is not a population-based register so we could not construct a group of wholly unvaccinated children for comparison. Children were censored following initial reporting. We calculated average annual incidence rates, incidence rate differences, incidence rate ratios, and 95% confidence intervals using Stata version 12 (StataCorp). The Queensland Children's Health Services ethics committee approved the study.

Of 58 233 children born in 1998 identified in the QVR, 40 694 (69.9%) received at least 3 doses of any pertussis-containing vaccine during the first year from a Queensland vaccine service provider and were included in the analysis. Overall, 267 first pertussis cases were reported from this cohort between 1999 and 2011; 2 second reports were excluded.

Children who received a 3-dose DTaP primary course had higher rates of pertussis than those who received a 3-dose DTwP primary course in the preepidemic and outbreak periods (Table and Figure). Among those who received mixed courses, rates in the current epidemic were highest for children receiving DTaP as their first dose. This pattern remained when looking at subgroups with 1 or 2 DTwP doses in the first year of life, although it did not reach statistical significance (Table). Children who received a mixed course with DTwP as the initial dose had incidence rates that were between rates for the pure course DTwP and DTaP cohorts (Table).

Table Graphic Jump LocationTable. Pertussis Reports Between 1999 and 2011 for Children Born in 1998 (N = 40 694)a
Place holder to copy figure label and caption
Figure. Pertussis Reporting Rates Between 1999 and 2011 by Primary Course of Pertussis Vaccination for Children Born in 1998
Graphic Jump Location

DTaP indicates diphtheria-tetanus-acellular pertussis; DTwP, diphtheria-tetanus-whole cell pertussis.

Infant priming with DTwP was associated with a lower risk of subsequent pertussis than DTaP only primed children in this cohort. This difference persisted for more than a decade, being evident in preepidemic and outbreak periods. A primary course using even a moderately effective DTwP vaccine may be more protective than DTaP.3 In the preacellular era, Australia used a locally produced DTwP vaccine with very good to excellent effectiveness.4 Our findings suggest the most important factor, in this cohort, may be the initial vaccine received.

It is unlikely our findings during the current outbreak are the result of detection bias because this would require health care–seeking behavior, or the likelihood of laboratory testing or reporting, to be associated with the primary course received by children over a decade previously.

Possible explanations for our findings could include antigenic shifts in circulating Bordetella pertussis strains2 or the different immune responses from acellular and whole-cell priming.5 The lesser protection provided by DTaP, both as the initial vaccine or full primary course, may be due to linked epitope suppression, when the initial exposure locks in the immune response to certain epitopes and inhibits response to other linked epitopes on subsequent exposures.6

The challenge for future pertussis vaccine development is to address the benefit-risk trade-off highlighted by our study, and to develop vaccines that induce long-lasting protection from the first dose, without the adverse events associated with DTwP use.

Author Contributions: Dr Sheridan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Sheridan, Ware, Grimwood, Lambert.

Analysis and interpretation of data: Sheridan, Ware, Lambert.

Drafting of the manuscript: Sheridan, Lambert.

Critical revision of the manuscript for important intellectual content: Sheridan, Ware, Grimwood, Lambert.

Statistical analysis: Sheridan.

Administrative, technical, or material support: Sheridan, Ware.

Study supervision: Grimwood, Lambert.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Grimwood and Lambert reported receiving honoraria for serving on the GlaxoSmithKline advisory boards for pneumonia and pneumonia conjugate vaccine, serving as an investigator on clinical studies sponsored by GlaxoSmithKline and sanofi-pasteur (both manufacturers of pertussis-containing vaccines), and serving on GlaxoSmithKline and sanofi-pasteur advisory boards for pneumococcal and influenza vaccines, respectively. Drs Sheridan and Ware did not report any disclosures.

Funding/Support: Dr Sheridan is supported by an Australian postgraduate award from the Australian government and a clinical scholarship from Queensland Children's Medical Research Institute. Dr Lambert is supported by an early career fellowship from the National Health and Medical Research Council and is a Queensland Children's Medical Research Institute senior research fellow.

Role of the Sponsor: None of the funding sources had a role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

Additional Contributions: We recognize Christine E. Selvey, MBBS, MSc (senior director of Communicable Diseases Branch, Queensland Health), for supporting the research; Craig A. Davis, MAppSc, BA, MAppEpid, and Angela Wakefield, BHSc (both with Communicable Diseases Branch, Queensland Health), for data extraction; and Vicki Bryant, BNurs, and Madeline A. Hall, BNurs (both with the Immunisation Program, Queensland Health), for assisting in vaccination record interpretation. The persons listed in this section provided assistance while employed by Queensland Health and did not received additional financial compensation for their contributions.

This article was corrected for errors on September 14, 2012.

Witt MA, Katz PH, Witt DJ. Unexpected limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak.  Clin Infect Dis. 2012;54(12):1730-1735
Link to Article
Octavia S, Sintchenko V, Gilbert GL,  et al.  Newly emerging clones of Bordetella pertussis carrying prn2 and ptxP3 alleles implicated in Australian pertussis epidemic in 2008-2010.  J Infect Dis. 2012;205(8):1220-1224
PubMed   |  Link to Article
Zhang L, Prietsch SOM, Axelsson I, Halperin SA. Acellular vaccines for preventing whooping cough in children.  Cochrane Database Syst Rev. 2011;(1):CD001478
PubMed
Torvaldsen S, Simpson JM, McIntyre PB. Effectiveness of pertussis vaccination in New South Wales, Australia, 1996-1998.  Eur J Epidemiol. 2003;18(1):63-69
PubMed   |  Link to Article
Mascart F, Hainaut M, Peltier A, Verscheure V, Levy J, Locht C. Modulation of the infant immune responses by the first pertussis vaccine administrations.  Vaccine. 2007;25(2):391-398
PubMed   |  Link to Article
Cherry JD, Heininger U, Richards DM,  et al.  Antibody response patterns to Bordetella pertussis antigens in vaccinated (primed) and unvaccinated (unprimed) young children with pertussis.  Clin Vaccine Immunol. 2010;17(5):741-747
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure. Pertussis Reporting Rates Between 1999 and 2011 by Primary Course of Pertussis Vaccination for Children Born in 1998
Graphic Jump Location

DTaP indicates diphtheria-tetanus-acellular pertussis; DTwP, diphtheria-tetanus-whole cell pertussis.

Tables

Table Graphic Jump LocationTable. Pertussis Reports Between 1999 and 2011 for Children Born in 1998 (N = 40 694)a

References

Witt MA, Katz PH, Witt DJ. Unexpected limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak.  Clin Infect Dis. 2012;54(12):1730-1735
Link to Article
Octavia S, Sintchenko V, Gilbert GL,  et al.  Newly emerging clones of Bordetella pertussis carrying prn2 and ptxP3 alleles implicated in Australian pertussis epidemic in 2008-2010.  J Infect Dis. 2012;205(8):1220-1224
PubMed   |  Link to Article
Zhang L, Prietsch SOM, Axelsson I, Halperin SA. Acellular vaccines for preventing whooping cough in children.  Cochrane Database Syst Rev. 2011;(1):CD001478
PubMed
Torvaldsen S, Simpson JM, McIntyre PB. Effectiveness of pertussis vaccination in New South Wales, Australia, 1996-1998.  Eur J Epidemiol. 2003;18(1):63-69
PubMed   |  Link to Article
Mascart F, Hainaut M, Peltier A, Verscheure V, Levy J, Locht C. Modulation of the infant immune responses by the first pertussis vaccine administrations.  Vaccine. 2007;25(2):391-398
PubMed   |  Link to Article
Cherry JD, Heininger U, Richards DM,  et al.  Antibody response patterns to Bordetella pertussis antigens in vaccinated (primed) and unvaccinated (unprimed) young children with pertussis.  Clin Vaccine Immunol. 2010;17(5):741-747
PubMed   |  Link to Article
CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.