Challenges associated with the recent outbreaks of wild-type Poliovirus in previously polio-free countries

During the last five years, outbreaks of wild-type polio infections following importation of wild-type poliovirus were reported from 39 countries that had been polio-free previously.¹ The contributions through different host genetic profiles and/or any upsurge in neurovirulence of imported isolates might have been crucial for the sudden outburst of disease. For example, such profiles of adults with either a laboratory-confirmed / clinical or non-polio acute flaccid paralysis during the 2010 outbreak of wild poliovirus in the Republic of Congo² might have contributed toward their increased susceptibility to wild poliovirus.

During the two outbreaks of paralytic poliomyelitis in a vaccine-protected infant population in the Gaza Strip in 1974 and 1976, the frequency of histocompatibility leukocyte antigen (HLA) antigens in 58 of the affected children was compared with 113 control vaccinated subjects. HLA-AW19 and -B7 were found more frequently in the affected children. This difference, although not statistically significant, was consistent with the possibility that patients with paralytic disease had an HLA genetic makeup that was different from the rest of the population.³

Furthermore, following a single epidemic of paralytic poliomyelitis in 17 families in the Netherlands, different genetic factors encoded by the HLA complex influencing resistance to poliomyelitis were studied, including the pattern of inheritance of HLA haplotypes within the affected families. Whereas none of 17 other polymorphic markers deviated from the expected Mendelian pattern of inheritance, the inheritance pattern of HLA haplotypes was different in sib pairs consisting of a patient with paralytic poliomyelitis and a non-paralytic control sib. A significantly reduced amount of sharing of HLA haplotypes was observed than would have been expected by chance alone (p = 0.014). The sharing of HLA haplotypes between patients with non-paralytic poliomyelitis and healthy controls did not deviate significantly from the expected value, which suggested that HLA-encoded genetic factors may control resistance to the paralytic form of poliomyelitis.⁴

In Pointe Noire, Republic of Congo, 80% polio cases and an 82% fatality rate were recorded in those aged ≥ 15 y.⁵ The in vitro testing for poliovirus isolates showed that their genetic components were not significantly different from the Angolan parent virus and from related cases from neighboring countries.² In vivo testing in animals would be desirable to assess the neurovirluance potential of poliovirus isolates from acute flaccid paralysis cases aged ≥ 15 y, including both fatal cases and survivors.

The paralytogenic potential of wild poliovirus was established during the 1940s in the central nervous system using experimental monkeys following an intra-cerebral inoculation of virus.⁶ During the 1960s, the distribution, extent and characteristics of lesions in nervous tissues following intra-cerebral and intra-spinal inoculation of three attenuated strains of poliovirus were characterized in cynomolgus monkeys.⁷ The virus-induced lesions at the site of inoculation and their spread to different regions in brain were quantified as the number of tissue culture infective doses that were required to produce neuronal lesions in the lumbar cord and brain in 50% of inoculated monkeys. The percentages of both the ‘brain levels’ showing neuronal lesions as well as the brain segments/regions/nuclei showing neuronal lesions were calculated.⁸

With no prejudice toward the competence of molecular tests for the characterization of poliovirus virulence, the monkey neurovirulence test has remained the definitive reference test to re-qualify vaccine production and to evaluate any new seed materials or vaccines produced on a new substrate or lots prepared for consistency testing from the new seed or substrate.⁹ Recently, WHO proposed an intra-spinal inoculation of monkeys in lumbar region, with analysis of tissues and evaluation of lesions in the lumbar enlargement, cervical enlargement, medulla oblongata, cerebellum, midbrain, thalamus and cerebral cortex.¹⁰

To conclude, elucidation of host factors and poliovirus neurovirluance in adults afflicted with wild-type polio^1,2 would be useful to understand the pathogenesis of emergent wild-type polio in otherwise polio-free locations.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.