Chronic virus excreters may complicate polio eradication efforts
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Other so-called "chronic excreters" may be out there, and they may complicate the World Health Organization's (WHO) plans to eradicate polio, said senior investigator Javier Martin, PhD, of the U.K.'s National Institute for Biological Standards and Control in Potters Bar, and colleagues.
Chronic excreters are extremely rare. Only 73 have been identified since 1962. The man described in the study is the only one known to be excreting virus at present, and the only one to have produced vaccine-derived virus for such a long period of time, Martin and colleagues said.
However, vaccine-derived virus strains likely originating from immunodeficient individuals have been discovered in sewage samples in Slovakia, Finland, Estonia, and Israel, "indicating that an unknown number of these chronic excreters exist elsewhere," Martin and colleagues said.
The patient is a white male from the U.K. who received a full course of childhood immunizations, including the oral polio vaccine at 5, 7, and 12 months with a booster at age 7. He was later diagnosed with common variable immunodeficiency and started on immunoglobulin therapy.
The virus isolated from the man's stool samples is a highly antigenically drifted type 2 strain derived from the original Sabin 2 strain used in the oral vaccine. More than 90% of vaccine-derived polioviruses arise from the type 2 strain, which has not been found in the wild since 1999 and is believed to be eradicated, the scientists said.
Virus samples from the patient caused paralysis in unimmunized transgenic mice with the human poliovirus receptor. The conventional inactivated polio vaccine, based on wild poliovirus strains, protected these mice. Another vaccine, based on the Sabin oral vaccine strain, was less effective, having a variable response, the researchers reported.
Human sera from vaccinated individuals readily neutralized the most antigenically divergent strain of the vaccine-derived virus. "These results are reassuring in that they indicate that vaccinated humans are well protected against infection from these highly drifted ... strains," the scientists said.
The investigators concluded that "while maintaining high immunization coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunization strategies might be required to effectively stop their occurrence and potential widespread transmission."
"Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era," they said.
Other infectious disease experts said that monitoring for vaccine-derived viruses from immunocompromised individuals is important, but these viruses pose a minimal public health threat because they are typically unable to infect other people and circulate through a population.
Amesh Adalja, MD, of the University of Pittsburgh and spokesperson for the Infectious Disease Society of America, noted that the viruses obtained from the patient in the study were not able to recombine with other enteroviruses, which is how such viruses gain the ability to spread to and infect other people.
In addition, the mice in the study were challenged with the equivalent of 25 times the PD50 of live poliovirus, Adalja pointed out.
"That is a very high dose that doesn't mimic a natural infection," Adalja said. "It demonstrates the proof-of-concept that the virus could be virulent, but would a human that came into contact with the virus get what the mouse got? Probably not."
As long as the live oral polio vaccine is used, there will be some chance of outbreaks of circulating vaccine-derived polioviruses. However, the WHO reports that after more than 10 billion doses of the live vaccine were administered around the world, only 20 instances of vaccine-derived outbreaks were identified, resulting in 758 actual cases, Adalja said.
The more important task for public health officials is to eliminate wild poliovirus from the planet, he said. "Then we can tackle circulating vaccine-derived viruses."
The wild virus has mostly been eliminated, with some small pockets still existing in Pakistan and Afghanistan, said Cara Burns, PhD, of the CDC in Atlanta.
Public health officials are hopeful the wild virus will be completely eradicated in the next few years, though political turmoil in those countries has complicated the effort.
Vaccine-derived viruses from immunodeficient individuals "obviously could be a challenge post-eradication, but it's a relatively minor issue," Burns said. The occurrence is extremely rare, and vaccine-derived viruses rarely spread from the immunocompromised individual to the community, she said.
Scientists are studying the use of antiviral drugs to stop the replication of vaccine-derived virus in immunocompromised patients, Burns said.
But the key to defending against vaccine-derived viruses is immunization, because immunized individuals are protected, she said.
"We will have to keep our guard up for some time to come," Burns said.
The study had no commercial funding. Authors reported no relevant financial interests.
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