Workshop on Neurologic Complications of Pertussis and Pertussis Vaccination

Abstract

A multidisciplinary workshop held from September 29 to October 1, 1989, at Airlie House, Warrenton, Virginia, considered the neurologic complications of whooping cough and pertussis vaccine.

Pertussis mortality in the U.S. in 2-3/1000 cases. Seizures occur in 1.9% of cases, and encephalopathy in 0.3 %. Reviewing all data, it appears likely that a combination of one or more bacterial toxins, asphyxia, CO₂ retention and loss of cerebral vascular autoregulation is responsible for neurologic symptoms. The timing of the encephalopathy suggests that it results from increased lysis of bacteria, and release of endotoxin. The encephalopathy is not confined to the paroxysmal phase.

In evaluating side-reactions to the vaccine, the following must be kept in mind:
1. Vaccines are not standardized between manufacturers.
2. For a given manufacturer, vaccines are not standard from one batch to the next.
3. Unless the vaccine is properly prepared and refrigerated, its potency and reactivity varies with shelf life.

In fact, the whole question of vaccine detoxification has never been systematically investigated.

Listed in order of increasing severity, observed adverse reactions include irritability, persistent, unusually high pitched crying, somnolence, seizures, a shock-like "hypotensive, hyporesponsive" state, and an encephalopathy. Since the neurologic picture is not specific for pertussis vaccination, its temporal relationship to the vaccination is the critical variable for determining causation.

Although the majority of seizures following pertussis vaccination are associated with fever, it was the consensus of the neurologists attending the workshop, that these do not represent febrile convulsions, but are non-benign convulsions.

The incidence of post-vaccine encephalopathy is difficult to ascertain. The most carefully conducted retrospective case-control study reported that the relative risk of a previously normal infant for the onset of an illness leading to encephalopathy with permanent subsequent disability was 4.2 times greater during the first 72 hours following DPT vaccination than in controls. From this study, the risk for permanent brain damage following DPT has been calculated as 1:310,000 doses.

It was the consensus of the workshop, and in particular of the participating neurologists, that although the vaccine may possibly accelerate neurologic signs or symptoms in some children, and a small proportion of apparent complications may be coincidental, there was no inherent difficulty in assigning cause and effect to the vaccine and subsequent permanent neurologic residua.

It was also the consensus that there was no demonstrated association between DPT vaccination and SIDS, because sudden death after pertussis vaccination is too rare to be detectable in the context of presently available series. Sudden death may occur in infants in the course of whooping cough, and following pertussis vaccination.

As was pointed out by several pediatric neurologists, the inherent problem in linking pertussis vaccination to infantile spasms is the extreme difficulty in determining the exact timing of their onset.

In implicating pertussis vaccination in the evolution of subsequent neurologic residua, a careful consideration of the mechanism for vaccine-induced brain damage plays an important supporting role. Pertussis toxin has been shown to alter cellular signalling. It also affects the catecholaminergic and GABAergic systems in brain. Although normally a protein of the size of PT would not be able to cross the blood-brain barrier, factors known to disrupt the blood-brain barrier include brief hypertensive episodes such as might occur during a coughing paroxysm, hypoxia, and prolonged seizures, whether or not they are accompanied by hypoxia. In addition, a direct, endotoxin-mediated attack on the endothelial cells could create a local defect of the bloodbrain barrier.

In summary, it was the consensus that there is sufficient experimental data to implicate both endotoxin and PT in adverse neurologic reactions to pertussis vaccine.

Key words

Pertussis vaccination - Post-vaccination encephalopathy - Pertussis