Causality Argument

All of the available information in the literature regarding mononeuropathies and brachial neuritis and their relation with tetanus toxoid, DT, or Td come from case reports or uncontrolled observational studies. The evidence found in the literature relating receipt of tetanus toxoid, DT, or Td and mononeuropathy caused by direct injection into the radial nerve comes from two case reports (Ling and Loong, 1976; VAERS). This type of injury is most likely due to the intraneural nature of the injection rather than to some characteristic of the vaccine itself. The committee does not consider this an adverse event related to the vaccine.

The evidence for peripheral mononeuropathy in association with administration of tetanus toxoid, DT, or Td not related to direct injection into the nerve is less clear. Three case reports of transient cranial mononeuropathies that developed 5, 8, and 10 days following administration of tetanus toxoid have been reported in the literature. The authors speculated that these neuropathies were related to a "neuroallergic" phenomenon following injection of tetanus toxoid. Less is known about the etiology or pathogenesis of this type of phenomenon, rendering the evidence for this type of association solely on the basis of three case reports more speculative than conclusive.

Although little is understood regarding the pathogenesis of brachial neuritis as a distinct clinical syndrome, it is well described in the literature. In a large case series a significant portion of the cases were temporally related to vaccine administration, particularly to tetanus toxoid (Tsairis et al., 1972). Likewise, review of individual case reports revealed four well-documented case reports of brachial plexus neuropathy following administration of tetanus toxoid (Baust et al., 1979; Bensasson et al., 1977; Getsbach and Waridel, 1976; Kiwit, 1984), with latencies ranging from 4 to 21 days. Although the mechanisms of brachial neuritis are not well understood, there is biologic plausibility that vaccines could cause an allergic or hypersensitivity reaction that manifests as brachial neuritis. This provides reasonably good, although sparse, evidence that brachial neuritis can occur in relation to tetanus toxoid, although controlled epidemiologic studies designed to look at this relation do not exist.

If one presumes that, on average, the predominantly adult population of Rochester, Minnesota, was receiving tetanus toxoid approximately once every 10 years (120 months) during the periods covered by the Tsairis et al. and Beghi et al. studies, then an "expected" rate of receipt of tetanus toxoid within the month prior to onset of brachial plexus neuropathy can be estimated as 1/120. Based on reported exposure to tetanus toxoid alone in the Tsairis et al. study. the exposure odds ratio (OR) can be roughly estimated as 4.8. For the Beghi et al. study, the corresponding OR is 10.1. Thus the relative risk of brachial plexus neuropathy is on the order of 5 to 10. Given



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