Pertussis Vaccination Triggers Dravet Syndrome in Predisposed Children

Fran Lowry

May 05, 2010

May 5, 2010 — Pertussis vaccination may trigger an earlier onset of Dravet syndrome in children who are destined to develop the disease because they possess a genetic abnormality.

However, this does not affect their clinical outcome, and therefore vaccination in these children should not be withheld, researchers conclude in a study published online May 4 in Lancet Neurology.

Dravet syndrome, also known as severe myoctonic epilepsy of infancy, is characterized by seizures that start around 6 months of age and intellectual disability that starts from the second year of life. About 70% to 80% of children with Dravet syndrome have mutations in the gene for the sodium channel SCN1A.

"Amongst these children, [diphtheria, pertussis, and tetanus (DPT)] vaccination appears to be associated with a slightly earlier onset of the disorder in some cases," lead author of the study, Anne McIntosh, MD, from the Epilepsy Research Centre, University of Melbourne, Victoria, Australia, told Medscape Neurology.

"However, proximity to vaccination did not affect outcome for these children, and there is no evidence to suggest that DPT vaccination should be withheld. In fact, even if the vaccination was withheld, it is extremely unlikely this would prevent onset of the disorder, given the presence of a gene that causes Dravet syndrome," she added.

Lower Age of Seizure Onset

Pertussis vaccination has been alleged to cause an encephalopathy that involves seizures and subsequent intellectual disability, and this proposed link has led some parents to deny vaccination to their children.

In earlier work, the researchers discovered that 11 of 14 patients who developed vaccine encephalopathy turned out to have Dravet syndrome, which was associated with mutations of the SCN1A gene.

The researchers undertook the current study to establish whether the apparent association between DTP vaccination and Dravet syndrome was a result of recall bias and, if not, whether vaccination affected the onset or clinical outcome of the disorder.

They retrospectively studied 40 patients with Dravet syndrome. All of the patients had mutations in SCN1A, a first seizure that was a convulsion, and validated source data. Medical and vaccination records were examined for links between vaccination and onset of seizures, and a peak in the number of patients who had seizure onset within 2 days after vaccination was identified.

The patients were separated into 2 groups: a vaccination-proximate group (n = 12), with seizure onset occurring on the day or the day after vaccination, and a vaccination-distant group (n = 28), with seizure onset 2 days or more after vaccination (n = 25) or before vaccination (n = 3).

The average age at seizure onset was significantly lower in the vaccination-proximate group (18.4 weeks) compared with the vaccination-distant group (26.2 weeks; difference, 7.8 weeks; 95% confidence interval, 2.6 - 13.1 weeks; P = .004).

No Effect on Outcome

There were no differences in intellectual outcome, subsequent seizure type, or mutation type between the 2 groups (all P values > .3). In addition, a post hoc analysis showed no difference in intellectual outcome between patients who received vaccinations after seizure onset and those who did not.

"Stories about children who were healthy and then developed severe seizures and brain damage after a vaccination are an understandable source of anxiety for parents," Dr. McIntosh said. "What the current study shows is that in some of these children, the DPT vaccine might trigger the onset of Dravet syndrome at a slightly earlier time. However, this is not a reason to withhold or delay the vaccination."

The study also shows that vaccination does not affect outcome, she added.

"The important message to come from this and other scientific evidence is that vaccination may occur around the time that some severe disorders become obvious, but it is not the vaccination itself that causes the disorder. In fact, vaccine is a relatively safe way to prevent the sort of childhood illnesses that can have very severe consequences. In the case of these children who have the genetic abnormality, Dravet syndrome would have developed anyway."

In an accompanying editorial, Max Wiznitzer, MD, from Rainbow Babies & Childrens Hospital and Case Western Reserve University, Cleveland, Ohio, told Medscape Neurology: "It is reassuring that, for children with Dravet syndrome, vaccination has not been shown to aggravate this disorder."

He added that the findings should make the primary care provider comfortable in giving vaccinations with antipyretic medication to ensure protection against these childhood illnesses. "It is important to protect the child from the natural infection, which can cause fever lasting days and puts the child at risk for recurrent seizures," said Dr. Wiznitzer.

Dr. McIntosh has disclosed no relevant financial relationships. Dr. Wiznitzer reports that he has received money for expert testimony from the US Department of Health and Human Services.

Lancet Neurol. Published online May 4, 2010.

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