Published online October 31, 2008
PEDIATRICS Vol. 122 No. 5 November 2008, pp. 1153-1154 (doi:10.1542/peds.2008-2152)

This Article Extract Full Text (PDF) An erratum has been published Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Anderson, E. J. Search for Related Content PubMed PubMed Citation Articles by Anderson, E. J. Related Collections Adolescent Medicine Social Bookmarking                         What's this?

LETTER TO THE EDITOR

Importance of On-time RotaTeq Vaccination and Long-term Active Surveillance

Evan J. Anderson, MD
Divisions of Infectious Diseases,
Departments of Pediatrics and Medicine,
Children's Memorial and Northwestern Memorial Hospitals,
Northwestern University Feinberg School of Medicine,
Chicago, IL 60614

To the Editor.—

I read with great interest the article by Haber et al,¹ who studied intussusception after implementation of RotaTeq vaccination by using the passive Vaccine Adverse Event Reporting System (VAERS) and the active Vaccine Safety Datalink (VSD) surveillance systems. Two important points bear mentioning.

First, data from this study should not be misconstrued to support RotaTeq administration outside the US Food and Drug Administration (FDA)–licensed window.² Although debated, reanalysis of the RotaShield data suggests that much of the risk of intussusception occurred in patients receiving RotaShield late (eg, first dose at 4 or 6 months).^3–5 Compliance with recommendations to administer the first dose of RotaTeq at 6 to 12 weeks has been high (92%).¹ Thus, although fewer than 8% of children received their first dose at >90 days, a relatively large percentage (19% [3 of 16]) of children with intussusception from the VAERS received the first RotaTeq dose at >90 days (P .3). Time of administration of RotaTeq was not included for the 3 children with intussusception in the VSD.

Second, although Haber et al¹ provided important early safety information, it will be much more important to assess intussusception at 2 years with more active surveillance systems (eg, the VSD).⁶ Wild-type rotavirus has inconsistently been linked with intussusception.^7–9 The primary end point of intussusception events after Rotarix or RotaTeq vaccination versus placebo was almost identical at 31 and 42 days, respectively.^10,11 Data from subjects followed beyond the primary end point suggest vaccine protection against intussusception. Intussusception occurred in 9 Rotarix and 16 placebo recipients (P = .16) at a median of 100 days after dose 1 and in 4 of 10159 Rotarix and 14 of 10010 placebo recipients followed to 1 year (relative risk: 0.28 [95% confidence interval: 0.10–0.81]).^11,12 In addition, intussusception occurred in 12 of 34837 RotaTeq and 19 of 34788 placebo recipients followed to the end of the trial (P .3) (written communication, Merck & Co [REST Safety Update Report, unpublished data, data on file with Merck & Co], 2008).¹⁰ Thus, the overall risk of intussusception may be lower in Rotarix and RotaTeq recipients.

Although the passive reporting surveillance system VAERS notes lower-than-expected intussusception rates,¹ such a result should be questioned because of potential subtle underreporting of events.⁶ The VSD notes a relative risk of 0.84 (95% confidence interval: 0.14–3.92) within 30 days after vaccination¹; assessment of active surveillance VSD data⁶ in a cohort receiving RotaTeq vaccination to 2 years of life will be necessary to determine the net impact on intussusception.

The article by Haber et al¹ has provided important postlicensure data for RotaTeq supporting its safety when administered within its FDA-licensed window.² The VSD and other active surveillance systems should monitor children for 2 years after RotaTeq (and the newly FDA-licensed Rotarix) vaccination. Long-term surveillance after vaccine implementation is important in detecting both adverse reactions and unexpected benefits.

FOOTNOTES

Financial Disclosure: Dr Anderson has served as a consultant and on the speaker's bureau for Merck regarding rotavirus, receives grant support from Merck for rotavirus research, has served as a consultant for GlaxoSmithKline, and has received grant support from Meridian Biosciences, Inc.

Statements appearing here are those of the writers and do not represent the offcial position of the American Academy of Pediatrics or its Committees. Comments on any topic, including the contents of PEDIATRICS, are invited from all members of the profession; those accepted for publication will not be subject to major editorial revision but generally must be no more than 400 words in length. The editors reserve the right to publish replies and may solicit responses from authors and others.

Please see www.pediatrics.org for instructions on submitting letters.

REFERENCES

1. Haber P, Patel M, Izurieta HS, et al. Postlicensure monitoring of intussusception after RotaTeq vaccination in the United States, February 1, 2006, to September 25, 2007. Pediatrics. 2008;121 (6):1206 –1212[Abstract/Free Full Text]
2. RotaTeq [prescribing information]. Whitehouse Station, NJ: Merck & Co; 2008
3. Rothman KJ, Young-Xu Y, Arellano F. Age dependence of the relation between reassortant rotavirus vaccine (RotaShield) and intussusception. J Infect Dis. 2006;193 (6):898; author reply 898–899[Web of Science][Medline]
4. Murphy BR, Morens DM, Simonsen L, Chanock RM, La Montagne JR, Kapikian AZ. Reappraisal of the association of intussusception with the licensed live rotavirus vaccine challenges initial conclusions. J Infect Dis. 2003;187 (8):1301 –1308[CrossRef][Web of Science][Medline]
5. Simonsen L, Viboud C, Elixhauser A, Taylor RJ, Kapikian AZ. More on RotaShield and intussusception: the role of age at the time of vaccination. J Infect Dis. 2005;192 (suppl 1):S36 –S43[CrossRef][Web of Science][Medline]
6. Davis RL, Kolczak M, Lewis E, et al. Active surveillance of vaccine safety: a system to detect early signs of adverse events. Epidemiology. 2005;16 (3):336 –341[CrossRef][Medline]
7. Buettcher M, Baer G, Bonhoeffer J, Schaad UB, Heininger U. Three-year surveillance of intussusception in children in Switzerland. Pediatrics. 2007;120 (3):473 –480[Abstract/Free Full Text]
8. Kombo LA, Gerber MA, Pickering LK, Atreya CD, Breiman RF. Intussusception, infection, and immunization: summary of a workshop on rotavirus. Pediatrics. 2001;108 (2). Available at: www.pediatrics.org/cgi/content/full/108/2/e37
9. Robinson CG, Hernanz-Schulman M, Zhu Y, Griffin MR, Gruber W, Edwards KM. Evaluation of anatomic changes in young children with natural rotavirus infection: is intussusception biologically plausible? J Infect Dis. 2004;189 (8):1382 –1387[CrossRef][Web of Science][Medline]
10. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med. 2006;354 (1):23 –33[Abstract/Free Full Text]
11. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006;354 (1):11 –22[Abstract/Free Full Text]
12. Rotarix [summary of product characteristics]. Rixensart, Belgium: GlaxoSmithKline Biologicals; 2008

---

PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Extract Full Text (PDF) An erratum has been published Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Anderson, E. J. Search for Related Content PubMed PubMed Citation Articles by Anderson, E. J. Related Collections Adolescent Medicine Social Bookmarking                         What's this?