Abstract
There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation 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.
Highlights
Despite difficulties in interrupting wild poliovirus transmission in the last few remaining endemic countries and recent drawbacks due to international spread of poliovirus in central Asia, central Africa and the Middle East [1], the global polio eradication appears to be within reach
Of the three serotypes types 2 and 3 appear to have been eradicated in the wild and type 1 is mostly confined to a region of Pakistan and Afghanistan
We describe virological studies of a patient deficient in humoral immunity who has been excreting type 2 vaccine-derived poliovirus for 28 years
Summary
Despite difficulties in interrupting wild poliovirus transmission in the last few remaining endemic countries and recent drawbacks due to international spread of poliovirus in central Asia, central Africa and the Middle East [1], the global polio eradication appears to be within reach. Vaccine-derived poliovirus (VDPV) strains, defined as those with more than 1% (0.6% for serotype 2 poliovirus) sequence drift in the capsid VP1 gene with respect to the corresponding Sabin strain, can be generated and transmitted from person to person in populations with low immunity and have been associated with a number of poliomyelitis outbreaks around the world [5,6,7,8,9]. These circulating VDPVs (cVDPVs) behave very to wild polioviruses and should be eliminated by the same immunisation methods. This represents a major change after more than 50 years of trivalent OPV use for routine immunisation monovalent and bivalent vaccines are commonly used for campaigns on national immunisation days
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