The Hygiene Hypothesis
Developed countries have seen an increase in the incidence of allergic diseases during the same time that many new vaccines have been introduced, leading some to believe there is a relationship. The theoretical basis for this belief has to do with the hygiene hypothesis, which holds that “clean living” brought on in part by the elimination of vaccine-preventable diseases creates an immunologic environment during ontogeny that is replete with Th2-cells and deficient in T regulator cells (see Chapter 1: Introduction to Vaccinology—The Germinal Center Reaction), an environment that promotes allergy and autoimmunity.
However, several large epidemiologic studies favor rejection of this hypothesis. For vaccines to cause allergies by this mechanism, unimmunized children would have to receive the “benefit” of vaccine-preventable diseases; few studies, however, offer data on this. There’s also an inherent inconsistency in the idea that by preventing infections, vaccines cause allergies—for live vaccines, anyway, vaccination is infection!
A well-controlled study in the United States identified 18,407 children with asthma who were born between 1991 and 1997 and compared them with a control group without asthma. Relative risks of asthma in vaccinated compared to unvaccinated children were 0.92 for DTwP, 1.09 for OPV, and 0.97 for MMR. In children who had at least two medical encounters during their first year of life, the RR for asthma following receipt of Hib was 1.07, and for HepB it was 1.09. Another large, population-based cohort study was performed in Leicestershire, United Kingdom. A total of 6811 children were enrolled between 1993 and 1997 and questioned about respiratory symptoms repeatedly until 2003.
Data on pertussis vaccinations were independently acquired, and the study included 23,201 person-years of follow-up. No association between vaccination and wheezing or asthma was seen. In a subsequent analysis, it was shown that delaying the first immunization beyond the first 2 months of life did not protect against wheezing at 5 to 10 years of age. Other studies also refute an association between vaccinations and the development of asthma.
Other Forms of Atopy
A well-controlled study of over 600 children prospectively evaluated the risk of allergies following receipt of the pertussis vaccine. Infants were randomized to receive a 2-component DTaP vaccine, a 5-component DTaP, DTwP, or DT beginning at 2 months of age. They were followed for the first few years of life and the presence of allergies at 7 years of age was determined by parent questionnaires. The disorders studied included asthma, atopic dermatitis, allergic rhinoconjunctivitis, urticaria, and food allergies. No difference in the incidence of allergic diseases was observed in children who did or did not receive pertussis vaccine.
Of interest, children with natural pertussis infections were more likely to develop allergic diseases than children not infected with pertussis. A cohort study from Tasmania published in 2007 showed small and inconsistent associations between receipt of diphtheria toxoid and asthma, eczema, and food allergies. The authors, however, acknowledged the problems with this and other similar studies: the possibility of recall bias (wherein parents of children with allergies may falsely recall immunizations that were not actually given), difficulty ascertaining the timing of vaccination and types of vaccines that were given, inaccurate reporting of allergies by parents, and health care-seeking behavior on the part of parents (certain parents may seek both immunizations and diagnoses of allergy).
Many of these factors could have led to an increased association between immunizations and atopic conditions. One of the strongest studies to date was the PARSIFAL (Prevention of Allergy-Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle) study, conducted in five European countries and involving over 12,000 children born between 1987 and 1996. No association between measles vaccination and allergy was seen (interestingly, measles infection was associated with a reduced risk of allergy). One strength of this study was the inclusion of allergen-specific serum IgE levels as a marker of allergic sensitization in a subset of children.
Several uncontrolled observational studies claimed that the introduction of vaccines, particularly Hib, into certain populations caused an increase in the incidence of type 1 diabetes. The purported link is vaccine-induced enhancement of preexisting subclinical islet cell autoimmunity. Once again, the data do not support an association. One study from the VSD compared 252 cases of type 1 diabetes with 768 matched controls without diabetes. The odds ratio was 0.28 for the association between diabetes and DTwP, 1.36 for MMR, 1.14 for Hib, 0.81 for HepB, 1.16 for VAR, and 0.92 for DTaP.
For children vaccinated at birth with HepB, the odds ratio for diabetes was 0.51 and for those vaccinated at 2 months of age or later was 0.86. In another study, 21,421 children who received Hib between 1988 and 1990 in the United States were followed for 10 years and the risk of type 1 diabetes was 0.78 when compared with a group of 22,557 children who did not receive the vaccine. Several other well-controlled retrospective studies also found that immunizations are not associated with an increased risk of developing type 1 diabetes.
—Marshall, Gary S. “Addressing Concerns About Vaccines.” The Vaccine Handbook: A Practical Guide for Clinicians. 3rd ed. New York: Professional Communications, Inc., 2010. 215-217. Print.
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