Correspondence

More on Rotavirus Vaccination and Intussusception

N Engl J Med 2002; 346:211-212January 17, 2002

Article

To the Editor:

In the February 22 issue of the Journal, we reported a strong and temporal association between vaccination with rhesus–human reassortant rotavirus vaccine (RRV-TV) and intussusception, which we found by examining the rate of intussusception during predefined periods after vaccination.1 Excess cases of intussusception above the base-line rate were evident when the number of occurrences was averaged over the maximal available follow-up period, a mean of 3.7 months per infant (adjusted odds ratio for intussusception, 2.2; 95 percent confidence interval, 1.5 to 3.3). During days 3 to 7 after dose 1, the adjusted odds ratio was 37.2 (95 percent confidence interval, 12.6 to 110.1). We presented odds ratios for other periods up to 21 days after each dose, on the premise that the rate of intussusception returned to base-line levels after 21 days.

Subsequent examination of the period beyond 21 days after vaccination suggested that the rate of intussusception decreased below the base-line level (adjusted odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.5). One possible explanation is that excess cases of intussusception were prematurely triggered by RRV-TV among infants who were predisposed to have intussusception,2 a pattern that has been described as a temporal shift in cases of infantile spasm after the administration of diphtheria–tetanus–pertussis vaccine.3 Alternatively, if the infants who received RRV-TV had a lower base-line rate of intussusception than unvaccinated infants, the low odds ratio more than 21 days after vaccination could be the result of a reference rate that was measured largely in unvaccinated infants. Our data support this alternative hypothesis. We found that markers of higher socioeconomic status were strongly associated with a lower rate of intussusception.1 We also found, as data from the National Immunization Survey indicated (Smith P, Centers for Disease Control and Prevention: personal communication), that markers of higher socioeconomic status were strongly associated with receipt of RRV-TV.

To evaluate the disparity between base-line rates of intussusception among the infants given RRV-TV and unvaccinated infants, we used data for the infants with intussusception in our study to calculate crude incidence rates of intussusception before vaccination and more than 21 days after vaccination among infants who were given RRV-TV and during analogous periods among unvaccinated infants. We calculated the number of cases of intussusception per 1000 child-months, and we compared the rates in terms of a ratio — the incidence among vaccinated infants to the incidence among unvaccinated infants. The base-line rate of intussusception among infants given RRV-TV was about one half the base-line rate among unvaccinated infants, both before vaccination (at two to five months of age; ratio, 0.52) and more than 21 days after vaccination (ratio, 0.50; 95 percent confidence interval, 0.3 to 0.9). These data suggest that the odds ratio for intussusception more than 21 days after vaccination was below 1.0 because the normal (expected) base-line rate of intussusception was lower among infants given RRV-TV than among unvaccinated infants, who formed the primary group on the basis of which the reference rate was established. Thus, our results provide no evidence of temporal shift or compensatory decrease in occurrence of intussusception after the initial excess of intussusception among infants who received RRV-TV.

Trudy V. Murphy, M.D.
Paul M. Gargiullo, Ph.D.
Melinda Wharton, M.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 30333
tkm4@cdc.gov

3 References

1. 1

   Murphy TV, Gargiullo PM, Massoudi MS, et al. Intussusception among infants given an oral rotavirus vaccine. N Engl J Med 2001;344:564-572
   Full Text | Web of Science | Medline

2. 2

   Simonsen L, Morens D, Elixhauser A, Gerber M, Van Raden M, Blackwelder W. Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception. Lancet 2001;358:1224-1229
   CrossRef | Web of Science | Medline

3. 3

   Goodman M, Lamm SH, Bellman MH. Temporal relationship modeling: DTP or DT immunizations and infantile spasms. Vaccine 1998;16:225-231
   CrossRef | Web of Science | Medline

Citing Articles (7)

Citing Articles

1. 1

   Juan J. Picazo, Javier de Arístegui Fernández, Jose M. Arteagoitia Axpe, Dolores Barranco Ordóñez, Aurelio Barricarte Gurrea, Xavier Bosch José, Javier Díez Domingo, Fernando González Romo, Teresa Hernández-Sampelayo Matos, Jesús Ruiz Contreras, Lluís Salleras. (2011) Evidencias científicas disponibles sobre la seguridad de las vacunas. Vacunas 12:1, 3-34
   CrossRef

2. 2

   Julie Bines. (2006) Intussusception and rotavirus vaccines. Vaccine 24:18, 3772-3776
   CrossRef

3. 3

   L. Simonsen, C. Viboud, A. Elixhauser, R. J. Taylor, A. Z. Kapikian. (2005) More on RotaShield and Intussusception: The Role of Age at the Time of Vaccination. The Journal of Infectious Diseases 192:s1, S36-S43
   CrossRef

4. 4

   D. A. Salmon, L. H. Moulton, N. A. Halsey. (2004) Enhancing Public Confidence in Vaccines Through Independent Oversight of Postlicensure Vaccine Safety. American Journal of Public Health 94:6, 947-950
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5. 5

   Robert T. Chen. (2004) Evaluation of vaccine safety after the events of 11 September 2001: role of cohort and case-control studies. Vaccine 22:15-16, 2047-2053
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6. 6

   Karla Soares-Weiser, Elad Goldberg, Ghandi Tamimi, Leonard Leibovici, Femi Pitan, Karla Soares-Weiser. 2004. Rotavirus vaccine for preventing diarrhoea. .
   CrossRef

7. 7

   Lone Simonsen, David M Morens, William C Blackwelder. (2002) Ecological studies, rotavirus vaccination, and intussusception. The Lancet 359:9311, 1066-1067
   CrossRef