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:
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
