Did Thalidomide Promote Poliomyelitis following Oral Poliovirus Vaccination in West Berlin in 1960?

DID THAUDOMIDE PROMOTE POLIOMYELITIS FOLLOWING ORAL POUOVIRUS VACCINATION IN WEST BERUN IN 1960? H. V. WYATT* When the Cox-Lederle oral poliovaccine (OPV) was used in West Berlin, there were a number ofapparently coincident vaccine-associated cases (VAC) [I]. The Cox-Lederle vaccine was abandoned, but the explanations of the incident are unconvincing [2, 3]. In this paper, a new explanation is offered: that drugs or other agents may promote entry of poliovirus to the CNS and that provocation by injection is a special type of promotion. The West Berlin Incident, 1960 About 290,000 people were given OPV between May 1 1 and 20, 1960, and 25 cases ofpoliomyelitis occurred within the next 4 weeks [I]. These cases occurred 2-3 months earlier than the usual epidemic season [4, fig. 1], and the opinion has been that these cases were associated in some way with the vaccine [3, 4]. Raettig did not think that the vaccine was virulent enough to cause the cases [4], and virus recovered from cases was similar to or only very slightly changed from the vaccine virus [5]. Raettig considered that the vaccine virus stimulated wild virus to invade the bloodstream and CNS. There is no evidence that this invasion occurred in Berlin or anywhere else: Wilson was not convinced [3]. The peculiar features of the incident are puzzling and fit no simple explanation (table 1)· Nevertheless, let us consider the following hypothesis: (1) the vaccine virus caused the cases of illness, but the virus had not become more virulent; (2) the cases occurred in nonimmune persons who were tem- * Reader in microbiology, University of Bradford, Bradford, BD7 IDP, United Kingdom . On sabbatical as honorary research associate, Department of Bacteriology and Virology , University of Manchester, Manchester M13 9PT, United Kingdom. Present address : 1 Hollyshaw Terrace, Leeds LSI5 7BG, United Kingdom.© 1983 by The University of Chicago. All rights reserved. 0031-5982/84/2701-0364$01.00 Perspectives in Biology and Medicine, 27, 1 ¦ Autumn 1983 | 93 TABLE 1 Features of the West Berlin Incident Following Use of the Cox-Lederle OPV Berlin, I960 OPV Implicated 25 cases within 30 days of OPV Cases 2-3 months early ........ Abrupt cessation after 30 days . Cases more severe in contacts . . Cases randomly distributed Ages of the cases did not correspond with the age groups receiving OPV .......... Virus from cases still vaccine-like .......... First cases were vaccinées ................. No secondary cases from initial cases ...... Attack rate x 15 in vaccinées ............. Two-thirds of cases in adults .............. Yes Yes ? ? ? No No ? ? Yes ? Comments But cases also early in West Germany [1] Expected because contacts were mainly adults [1] Implicates OPV rather than wild virus but suggests no reversion of OPV Vaccinées were groups with low immunity Suggests no reversion to virulence Unexpected because more adults would be immune porarily more susceptible to vaccine virus; and (3) persons temporarily more susceptible were present in both West Berlin and West Germany. Most of the peculiar features of the incident would then be explained. It has recently been proposed that there is genetic susceptibility to poliomyelitis, and the model [6] has been tested against data from many epidemics [7]. Burnet has suggested that "there is good reason to believe that paralytic polio . . . dependfs] more on the presence of individual genetic susceptibility to an initiated infection than to the virulence or dose of the infecting strain" [8]. The genetic model predicts that more people become susceptible with age; this might explain the other peculiarities. A few hypogammaglobulinemics and perhaps those people who have a very slow synthesis of antibody are peculiarly susceptible to paralysis from vaccine strains of poliovirus [9, 10] and to infections of the CNS by ECHO virus [10]. An immunosuppressive agent might therefore allow entry ofvaccine virus to the CNS. It has also been suggested that entry of poliovirus to the CNS occurs following inflammatory reactions at peripheral nerve endings [H]. The chance reading that thalidomide caused peripheral neuritis [12] and immunosuppression [13, 14] and was widely sold in 1960 in West Berlin [12] suggested that thalidomide might have been associated with the use of the OPV in West Berlin. The hypothesis and the mechanism are tested in this...