Journal of Clinical Virology 44 (2009) 268–271 Contents lists available at ScienceDirect Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv Oral poliovirus vaccine type 3 from a patient with transverse myelitis is neurovirulent in a transgenic mouse model Bruce Thorley a,∗ , Heath Kelly a , Yorihiro Nishimura b , Yeon Kyung Yoon a , Kerri Anne Brussen a , Jason Roberts a , Hiroyuki Shimizu b a Polio Reference Laboratory and Epidemiology Unit, Victorian Infectious Diseases Reference Laboratory, 10 Wreckyn Street, North Melbourne, Australia b Section of Enteroviruses, Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan article info Article history: Received 30 October 2008 Received in revised form 27 January 2009 Accepted 28 January 2009 Keywords: Neurovirulence Oral polio vaccine Poliovirus Transgenic mice Transverse myelitis abstract Background: It is accepted that oral poliovirus vaccine (OPV) can cause vaccine-associated paralytic poliomyelitis (VAPP) and that wild poliovirus infection can rarely present as transverse myelitis. It is therefore possible that OPV could cause transverse myelitis. We previously reported a case of transverse myelitis that developed in a 6-month-old boy, 7 days after receiving his second dose of OPV. Objectives: Our aim was to test the virus from this patient with transverse myelitis for neurovirulence in a mouse model. Study design: The TgPVR21 transgenic mouse line, which expresses the human poliovirus receptor CD155, was used to assess neurovirulence of the viruses tested. Neurovirulence was expressed as the PD 50 , the dose of virus causing paralysis in 50% of the mice. Four type 3 polioviruses were tested: a prototype wild strain, a fully attenuated polio vaccine virus, a virus from a patient with VAPP and the virus from the patient with transverse myelitis. Results: The PD 50 for the wild poliovirus strain was 3.83 and for the fully attenuated vaccine strain, 7.63. The PD 50 for the two clinical isolates were between these values, ≧4.96 for the poliovirus known to have caused VAPP and ≧4.81 for the virus from the patient with transverse myelitis. Conclusions: The report of an OPV strain from a transverse myelitis case being neurovirulent in an in vivo mouse model provides further evidence for a causal association between OPV and transverse myelitis. Crown Copyright © 2009 Published by Elsevier B.V. All rights reserved. 1. Introduction The neurological presentation of poliovirus infection is charac- teristically of acute flaccid paralysis (AFP) in one or more limbs, or acute bulbar palsy. Poliovirus infection affects the motor neu- rons of the CNS. However, sensory deficits have been recorded and presentations of acute poliovirus infection with both sen- sory and motor deficits, manifesting as transverse myelitis, have been reported in a number of older case studies. 1–3 Standard text- books record wild poliovirus as a cause of encephalomyelitis 4 and myelitis. 5 We previously reported the case of a 6-month-old boy who, in 1996, developed transverse myelitis 7 days after the receipt of oral poliovirus vaccine (OPV). 6 The boy received his first scheduled OPV at the age of 4 months and developed immunity to poliovirus Abbreviations: AFP, acute flaccid paralysis; CCID, cell culture infective dose; OPV, oral polio vaccine; PD, paralysis dose; VAPP, vaccine-associated paralytic poliomyeli- tis; WHO, World Health Organization. ∗ Corresponding author. Tel.: +61 3 9342 3910; fax: +61 3 9342 2665. E-mail address: bruce.thorley@mh.org.au (B. Thorley). serotypes 1 and 2 but not to serotype 3 by the time he received his second dose of OPV. The onset of symptoms, confirmed later by a paediatric neurologist as transverse myelitis, occurred 7 days after receiving the second OPV dose. Two days later poliovirus serotype 3 was isolated from stool and throat specimens collected from the infant while CSF was negative for enterovirus culture. The virus tested as an OPV-like strain by nucleic acid probe hybridisation and enzyme-linked immunosorbent assay according to recommended procedures in a World Health Organization (WHO) poliovirus ref- erence laboratory. 7,8 The boy subsequently developed immunity to poliovirus serotype 3. We argued that there was strong evidence for a causal relation- ship between the OPV serotype 3 and transverse myelitis in this patient. From a review of the literature we estimated transverse myelitis to occur in 1:125–1:800 cases of symptomatic poliovirus infection. 6 It is also accepted that OPV can cause vaccine-associated paralytic polio (VAPP) with a frequency of approximately one case per 2.5 million doses of OPV distributed. 9 Based on the frequencies with which wild poliovirus infection causes transverse myelitis and vaccine virus causes VAPP, we estimated that a clinical entity of poliovirus vaccine-associated transverse myelitis could occur with a frequency of 1 in 300 million to 1 in two billion doses of OPV 1386-6532/$ – see front matter. Crown Copyright © 2009 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2009.01.014