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Tricia McKeever, PhD, Sarah Lewis, PhD and Richard Hubbard, MD

The authors are with the University of Nottingham, Nottingham, England.

Correspondence: Requests for reprints should be sent to Tricia M. McKeever, PhD, Clinical Science Building, City Hospital, Nottingham, England, NG5 1PB (e-mail: tricia.mckeever{at}nottingham.ac.uk).

We thank Hurwitz and Morgenstern for their interest in our recent work in what has become a controversial area of research with a number of interesting methodological problems.

The authors’ first point is that misclassification of both asthma and eczema status would have to be severely differential by vaccination status to produce the results we reported. In fact, our data demonstrate that this is likely to be the case, since the incidence of asthma among children not vaccinated with diphtheria, polio, pertussis, and tetanus (DPPT) vaccine in the lowest general practitioner (GP)–visit stratum was 0.3 per 100 person-years, which is very low and out of keeping with the other data. A similar pattern for rate of disease has been demonstrated for measles-mumps-rubella (MMR) vaccine, as well as for eczema and vaccination status, and we believe the most likely explanation is a marked under-diagnosis of allergic disease in children who do not regularly visit their GPs. In other words, children who do not visit their GPs are the ones who are not vaccinated and are not being diagnosed with other diseases.

We agree with Hurwitz and Morgenstern’s second point, that being diagnosed with an allergic disease might have increased an individual’s frequency of GP visits and biased our results. For this reason, we excluded any visits for allergic disease when determining the level of GP visits. In addition, only GP consultations before diagnosis of allergic disease were counted. It seems unlikely to us that frequency of GP consultation reflects a true biological modifier of the vaccination effect; it seems far more likely that the difference in effect by level of health care use is due to bias.

In their own study, Hurwitz and Morgenstern found a significant impact of vaccination on allergy symptoms and history.¹ However, they found no evidence of an association between vaccination status and asthma, hay fever, severe allergic reaction, any allergy or allergic reaction, sinusitis or sinus problems, or wheezing or whistling. These findings are consistent with the conclusion of the Institute of Medicine review (cited by Hurwitz and Morgenstern) that the evidence for a link between vaccination and allergic disease is at best weak.² Furthermore, this review did not include an ecological study,³ a case–control study,⁴ and a longitudinal study,⁵ all of which failed to demonstrate a relationship between vaccination and allergic disease.

In summary, we believe the most likely explanation for our finding is that routine vaccination against DPPT and MMR does not increase the incidence of allergic disease, and this conclusion is consistent with the bulk of the available evidence.

References

1. Hurwitz EL, Morgenstern H. The effects of diphtheria-tetanus-pertussis (DTP) or tetanus vaccination on allergies and allergy-related symptoms among children and adolescents in the United States. J Manipulative Physiol Ther. 2000;23;81–90.[CrossRef][Web of Science][Medline]

2. Stratton K, Wilson CB, McCormick MC, eds. Immunization Safety Review: Multiple Immunizations and Immune Dysfunction. Washington, DC: National Academy Press; 2002.

3. Kuehni CE, Brooke AM, Davis A, Silverman M. Vaccinations as risk factors for wheezing disorders [letter response]. Lancet. 2001;358(9288):1186.[Web of Science][Medline]

4. Mullooly JP, Pearson J, Drew L, et al. Wheezing lower respiratory disease and vaccination of full-term infants. Pharmacoepidemiol Drug Saf. 2002;11(1): 21–30.[CrossRef][Web of Science][Medline]

5. Henderson J, North K, Griffiths M, Harvey I, Golding J. Pertussis vaccination and wheezing illnesses in young children: prospective cohort study. The Longitudinal Study of Pregnancy and Childhood Team. BMJ. 1999;318(7192):1173–1176.[Abstract/Free Full Text]

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