Oral poliovirus vaccine type 3 from a patient with transverse myelitis is neurovirulent in a transgenic mouse model.

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, > or = 4.96 for the poliovirus known to have caused VAPP and > or = 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.

Annual report of the Australian National Poliovirus Reference Laboratory, 2006.

The Australian National Poliovirus Reference Laboratory (NPRL), located within the Victorian Infectious Diseases Reference Laboratory, is the national laboratory for Australia, the Pacific Islands and Brunei Darussalam, and is accredited by the World Health Organization (WHO) as the Regional Reference Laboratory for the WHO Western Pacific Region. The NPRL, in collaboration with the Australian Paediatric Surveillance Unit, co-ordinates surveillance for acute flaccid paralysis (AFP), the major clinical presentation of poliovirus infection. After classification of AFP cases by the Polio Expert Committee, the non-polio AFP rate for Australia in 2006 was 1.1, meeting the WHO surveillance requirement of detecting more than one AFP case per 100,000 children aged less than 15 years. During 2006, 80 specimens were referred to the NPRL, 59 from AFP cases and 21 from other sources. Poliovirus type 3 was isolated from two patients without AFP and the isolates were characterised as Sabin-like using WHO accredited methodologies. Echovirus 30 was isolated from two cases of AFP and coxsackievirus B5 and adenovirus were isolated from individual cases. During 2006, 1,998 cases of poliomyelitis due to wild poliovirus infection were reported world-wide, of which, only 6.8% (127) were due to importation of wild poliovirus.

Annual report of the Australian National Poliovirus Reference Laboratory 2005.

In May 1988 the World Health Assembly adopted a resolution for the global eradication of poliomyelitis. Since then two target dates for eradication (2000 and 2003) have passed and the struggle to eradicate the poliovirus continues. Australia's commitment to the worldwide campaign began in December 1994 with the designation of the National Poliovirus Reference Laboratory at the Victorian Infectious Diseases Reference Laboratory and the initiation of acute flaccid paralysis (AFP) surveillance in March 1995. During 2005 the National Poliovirus Reference Laboratory did not isolate any wild or vaccine derived polioviruses from the 42 samples collected from eighteen cases of acute flaccid paralysis in Australian residents. Three Sabin-like polioviruses were isolated from three cases of acute flaccid paralysis but all were considered incidental isolations by the Polio Expert Committee and not implicated in the disease of the patients. After exceeding the World Health Organization target of one case of AFP per 100,000 children aged less than 15 years in 2004, Australia's non-polio AFP rate in 2005 fell to 0.75 cases per 100,000 children. The high number of wild poliovirus importations reported globally in 2005 into previously polio free countries, highlights the need for a sensitive AFP surveillance system within Australia and for specimens from AFP cases to be forwarded to the National Poliovirus Reference Laboratory.

Annual report of the Australian National Poliovirus Reference Laboratory, 2004.

The Australian National Poliovirus Reference Laboratory at the Victorian Infectious Diseases Reference Laboratory is the World Health Organization designated laboratory for the isolation and testing of poliovirus from clinical specimens within Australia, the Pacific Island countries and Brunei Darussalam. Surveillance for acute flaccid paralysis (AFP) within Australia, the main clinical manifestation of poliomyelitis, is also coordinated at the Victorian Infectious Diseases Reference Laboratory in conjunction with the Australian Paediatric Surveillance Unit. The annual non-polio acute flaccid paralysis rate after classification of cases by the Polio Expert Committee was 1.0 per 100,000 population, reaching the expected World Health Organization annual target for a non-polio endemic country. During 2004, 64 specimens from 30 AFP cases were referred to the National Polio Reference Laboratory. A mixture of poliovirus types 1 and 2 was isolated from an infant with AFP from New South Wales. Both isolates tested as Sabin-like and the case was subsequently classified as infant botulism by the Polio Expert Committee. The laboratory isolated adenoviruses from seven AFP cases. A coxsackievirus B5 and an echovirus 18 were identified from a further two AFP cases. During 2004, 1,266 cases of poliomyelitis due to wild poliovirus were reported world-wide. Many of these resulted from wild poliovirus importations, which continued in 2005, including to Indonesia. This highlights the need for maintaining high poliovirus vaccination coverage to prevent the transmission of poliovirus and high quality AFPand laboratory surveillance for the detection of poliomyelitis due to an imported wild poliovirus.

Annual report of the Australian National Poliovirus Reference Laboratory, 2003.

The Australian National Poliovirus Reference Laboratory was established in late 1994, as part of Australia's commitment to the World Health Organization's (WHO) polio eradication program. The laboratory continues to play a pivotal role in maintaining Australia's polio-free status through surveillance for cases of acute flaccid paralysis (AFP), the main clinical presentation of poliomyelitis, and the testing of specimens from these cases. The annual notification rate for eligible cases of AFP in Australia for 2003 was 0.83 per 100,000 children less than 15 years of age. The annual non-polio AFP rate after classification of cases by the polio expert committee was 0.68 per 100,000, 32 per cent below WHO's annual target. While no polioviruses were isolated from the specimens tested from the 27 cases of AFP in 2003, a novel enterovirus (enterovirus 75) was isolated from one case and enterovirus 71 was isolated from another. During the same period 12 polioviruses, referred from cases other than AFP, tested as Sabin-like by the WHO approved methods of intratypic differentiation. The importation of wild polioviruses from endemic Nigeria into surrounding countries of Africa during 2003, highlights the importance of the continuation of AFP surveillance and high quality laboratory activities throughout the world until global eradication of polio is certified.

Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001.

In 2001, highly evolved type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from three acute flaccid paralysis patients and one contact from three separate communities in the Philippines. Complete genomic sequencing of these four cVDPV isolates revealed that the capsid region was derived from the Sabin 1 vaccine strain but most of the noncapsid region was derived from an unidentified enterovirus unrelated to the oral poliovirus vaccine (OPV) strains. The sequences of the cVDPV isolates were closely related to each other, and the isolates had a common recombination site. Most of the genetic and biological properties of the cVDPV isolates were indistinguishable from those of wild polioviruses. However, the most recently identified cVDPV isolate from a healthy contact retained the temperature sensitivity and partial attenuation phenotypes. The sequence relationships among the isolates and Sabin 1 suggested that cVDPV originated from an OPV dose given in 1998 to 1999 and that cVDPV circulated along a narrow chain of transmission. Type 1 cVDPV was last detected in the Philippines in September 2001, and population immunity to polio was raised by extensive OPV campaigns in late 2001 and early 2002.

Annual report of the Australian National Poliovirus Reference Laboratory, 2002.

Acute flaccid paralysis is the main clinical manifestation of poliomyelitis. Faecal specimens from cases of acute flaccid paralysis in Australia are referred to the National Poliovirus Reference Laboratory for virus culture to determine if poliovirus is the causative agent. Isolations of poliovirus are tested to determine whether they have characteristics of the Sabin oral polio vaccine virus strains or wild type polioviruses. In 2002, a poliovirus type 3, which tested as Sabin vaccine-like, was isolated from an Australian patient with acute flaccid paralysis. A non-polio enterovirus, Echovirus type 18, was isolated from the faecal specimens of another case of acute flaccid paralysis. In the same period, the laboratory identified 35 Sabin-like polioviruses from 52 referred specimens and isolates from cases without acute flaccid paralysis. Australia is a member nation of the World Health Organization's Western Pacific region that was declared free of endemic wild poliovirus in October 2000. Poliomyelitis remains endemic in three of the WHO regions of the world and wild poliovirus may be re-introduced to Australia. While the number of polio-endemic countries has been reduced to seven, the total number of wild polioviruses identified increased in 2002 compared to 2001 due to a sharp rise in isolations of wild virus from Northern India. Until global eradication of poliomyelitis is achieved, it is essential that a high level of poliovirus vaccination coverage, and surveillance for cases of acute flaccid paralysis, be maintained in Australia.

Annual report of the Australian National Poliovirus Reference Laboratory and summary of acute flaccid paralysis surveillance, 2001.

The National Poliovirus Reference Laboratory at the Victorian Infectious Diseases Reference Laboratory (VIDRL) is responsible for poliovirus testing for Australia and the Pacific Island countries. It is also a regional reference laboratory for the Western Pacific Region of the World Health Organization. Surveillance for acute flaccid paralysis, a clinical manifestation of poliomyelitis, is coordinated at VIDRL in collaboration with the Australian Paediatric Surveillance Unit. There were 60 unique notifications of acute flaccid paralysis (AFP) in 2001, of which 44 were classified by the polio expert committee as eligible non-polio AFP cases, that is, from patients resident in Australia and aged less than 15 years. Polioviruses were Isolated from one AFP patient and characterised as Sabin oral poliovirus vaccine-like for all 3 serotypes. In the same period, the National Poliovirus Reference Laboratory identified 40 Sabin-like viruses from 74 referred isolates and specimens, and an additional five non-Sabin-like polioviruses as part of the laboratory containment of poliovirus. The Western Pacific Region, of which Australia is a member nation, was declared free of circulating wild poliovirus in October 2000. However, during 2001, viruses derived from the Sabin oral poliovirus vaccine caused 3 cases of poliomyelitis in the Philippines, also a member nation of the Western Pacific Region. The identification of circulating vaccine-derived poliovirus in the Philippines has emphasised the necessity of maintaining a high level of vaccination coverage within Australia and an effective surveillance system to detect cases of poliomyelitis.