diphtheria, pertussis, tetanus vaccination is associated with risk of childhood asthma

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J Allergy Clin Immunol. 2008 Mar;121(3):626- 31. Epub 2008 Jan 18.

J Allergy Clin Immunol. 2008 Sep;122(3):656; author reply 657-8.

Delay in diphtheria, pertussis, tetanus vaccination is associated

with a reduced risk of childhood asthma.

Mc KL, Huq SI, Lix LM, Becker AB, Kozyrskyj AL.

Faculty of Medicine, Department of Community Health Sciences,

University of Manitoba, Winnipeg, Manitoba, Canada.

BACKGROUND: Early childhood immunizations have been viewed as

promoters of asthma development by stimulating a T(H)2-type immune

response or decreasing microbial pressure, which shifts the balance

between T(H)1 and T(H)2 immunity. OBJECTIVE: Differing time schedules

for childhood immunizations may explain the discrepant findings of an

association with asthma reported in observational studies. This

research was undertaken to determine whether timing of diphtheria,

pertussis, tetanus (DPT) immunization has an effect on the development

of childhood asthma by age 7 years. METHODS: This was a retrospective

longitudinal study of a cohort of children born in Manitoba in 1995.

The complete immunization and health care records of cohort children

from birth until age 7 years were available for analysis. The adjusted

odds ratio for asthma at age 7 years according to timing of DPT

immunization was computed from multivariable logistic regression.

RESULTS: Among 11, 531 children who received at least 4 doses of DPT,

the risk of asthma was reduced to (1/2) in children whose first dose

of DPT was delayed by more than 2 months. The likelihood of asthma in

children with delays in all 3 doses was 0.39 (95% CI, 0.18-0.86).

CONCLUSION: We found a negative association between delay in

administration of the first dose of whole-cell DPT immunization in

childhood and the development of asthma; the association was greater

with delays in all of the first 3 doses. The mechanism for this

phenomenon requires further research.

PMID: 18207561

J Manipulative Physiol Ther. 2000 Feb;23(2):81- 90. Effects of

diphtheria-tetanus- pertussis or tetanus vaccination on allergies and

allergy-related respiratory symptoms among children and adolescents in

the United States. Hurwitz EL, Morgenstern H.

UCLA School of Public Health, Department of Epidemiology, Los Angeles,

Calif 90095-1772, USA. ehurwitzucla (DOT) edu

BACKGROUND: Findings from animal and human studies confirm that

diphtheria and tetanus toxoids and pertussis (DTP) and tetanus

vaccinations induce allergic responses; associations between childhood

vaccinations and subsequent allergies have been reported recently.

OBJECTIVE: The association of DTP or tetanus vaccination with

allergies and allergy-related respiratory symptoms among children and

adolescents in the United States was assessed. METHODS: Data were used

from the Third National Health and Nutrition Examination Survey on

infants aged 2 months through adolescents aged 16 years. DTP or

tetanus vaccination, lifetime allergy history, and allergy symptoms in

the past 12 months were based on parental or guardian recall. Logistic

regression modeling was performed to estimate the effects of DTP or

tetanus vaccination on each allergy. RESULTS: The odds of having a

history of asthma was twice as great among vaccinated subjects than

among unvaccinated subjects (adjusted odds ratio, 2.00; 95% confidence

interval, 0.59 to 6.74). The odds of having had any allergy-related

respiratory symptom in the past 12 months was 63% greater among

vaccinated subjects than unvaccinated subjects (adjusted odds ratio,

1.63; 95% confidence interval, 1.05 to 2.54). The associations between

vaccination and subsequent allergies and symptoms were greatest among

children aged 5 through 10 years. CONCLUSIONS: DTP or tetanus

vaccination appears to increase the risk of allergies and related

respiratory symptoms in children and adolescents. Although it is

unlikely that these results are entirely because of any sources of

bias, the small number of unvaccinated subjects and the study design

limit our ability to make firm causal inferences about the true

magnitude of effect.

PMID: 10714532

Int J Hyg Environ Health. 2001 Jul;203(5-6) :479-81.Inhibiti on of the

human erythrocytic glutathione- S-transferase T1 (GST T1) by

thimerosal. Müller M, Westphal G, Vesper A, Bünger J, Hallier E.

Department of Occupational and Social Medicine,

Georg-August- University Göttingen, D-37073 Göttingen, Germany.

mmuelle3gwdg (DOT) de

We have investigated the interaction of thimerosal, a widely used

antiseptic and preservative, with the human erythrocytic GST T1

(glutathione- S-transferase T1). This detoxifying enzyme is expressed

in the erythrocytes of solely the human species and it displays a

genetic polymorphism. Due to this polymorphism about 25% of the

individuals of the caucasian population lack this activity

( " non-conjugators " ), while 75% show it ( " conjugators " ) (Hallier, E.,

et al., 1993). Using our newly developed HPLC-fluorescence detection

assay (Müller, M., et al., 2001) we have profiled the kinetics of

enzyme inhibition in erythrocyte lysates of two individuals previously

identified as " normal conjugator " (medium enzyme activity) and

" super-conjugator " (very high activity). For the normal conjugator we

have determined a 2.77 mM thimerosal concentration to inhibit 50% of

the GST T1 activity. In the case of the super-conjugator a 2.3 mM

thimerosal concentration causes a 50% inhibition of the enzyme

activity. For both phenotypes a 14.8 mM thimerosal concentration

results in residual enzyme activities equal to those typically

detected in non-conjugator lysates. Thus, sufficiently high doses of

thimerosal may be able to change the phenotypic status of an

individual-- at least in vitro--by inhibition of the GST T1 enzyme.

PMID: 11556154

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