The case of a patient in the United Kingdom with evidence of live poliovirus in his system for more than 20 years raises questions about how immunocompromised patients could potentially complicate disease eradication efforts, according to researchers.

Investigators from the National Institute for Biological Standards and Control in the United Kingdom relayed details of the case in a study published in PLOS Pathogens.

Beginning in November of 1995, they analyzed 185 stool samples from the patient, who had been fully immunized against polio as a child. He had received oral polio vaccine (OVP) at ages 5, 7, and 12 months and an additional booster dose at age 7 years. He was later diagnosed with an immunodeficiency that affected the ability of his immune system to kill the virus in the digestive tract and resulted in the accumulation of vaccine-derived poliovirus (VDPV) in his system.


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The researchers noted that scenarios like this may “represent a real risk of polio re-emergence in the post-eradication era, particularly considering there is currently no effective strategy to treat these patients.” Similar cases have been reported in Slovakia, Finland, Estonia, and Israel, where sewage samples containing all 3 poliovirus serotypes have been documented; poliovirus type 2 has been the most prevalent.

Stool samples collected in the current study showed that the UK patient had been excreting highly infectious type 2 poliovirus at high titers. The researchers found that over time, the OVP vaccine strains had mutated to reverse the effects of the vaccine and had acquired other mutations that changed the antigenic structure of the virus. 

They tested the infectious vaccine-derived poliovirus (iVDPV) strains from the UK patient’s stool samples on transgenic mice that had human poliovirus receptors and found that each of the strains paralyzed the mice.

Martin and colleagues estimated that the iVDPV strains had mutated approximately 28 years prior, which corresponded with the patient’s last date of OVP vaccination. This is the longest case of an individual known to be excreting iVDPV. 

Although the iVDPV strains examined in the current study showed evidence of antigenic changes, the researchers found that human sera from patients vaccinated with OPV were able to neutralize even the most divergent strain, suggesting continued protection. However, they only tested human sera from healthy adults who had received 4 doses of OPV and one additional dose of inactivated poliovirus vaccine (IPV). The researchers noted that it would be beneficial to test sera from individuals who had received only IPV to determine if there are differences in the level of protection the two types of vaccines provide.

Between 1962 and 2014, only 7 out of 73 documented cases of iVDPV have endured longer than 5 years, according to background information in the study. Although some areas of Pakistan and Afghanistan are not yet polio-free,  eradication of the virus still seems in reach.

These study findings emphasize the need to improve existing IPV products by measuring vaccine potency and defining the amount of antigen needed to adequately protect against the virus, according to the researchers.

The case could also have important implications for the World Health Organization’s (WHO) Global Polio Eradication Initiative, which includes eliminating  serotype 2 from OPV and  implementing global IPV administration. 

New measures are required to manage the possible risks of iVDPV, including sewage sampling and stool surveys to develop efficient antiviral treatments that can stop the spread of iVDPV strains to the general population, the researchers concluded.

“New polio vaccines such as those based on noninfectious virus-like particles with no associated risk of producing VDPVs might be required to resolve the ‘OPV paradox,’” they wrote.

Reference

1. Dunn G, Klapsa D, Wilton T, Stone L, Minor PD, Martin J.  Twenty-eight years of poliovirus replication in an immunodeficient individual: impact on the global polio eradication initiative.  PLOS Pathogens. 2015; Aug 27. doi: 10.1371/journal.ppat.1005114.