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Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

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.

SUBMITTER: Dunn G

PROVIDER: S-EPMC4552295 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

Dunn Glynis G Klapsa Dimitra D Wilton Thomas T Stone Lindsay L Minor Philip D PD Martin Javier J

PLoS pathogens 20150827 8

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 l ...[more]

PMID: 26313548

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Project description:BackgroundVaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV which may serve as sources of poliovirus reintroduction after the eradication of wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV cases published in the scientific literature from 1962 to 2012, and describes clinically relevant trends in reported iVDPV cases worldwide.MethodsWe conducted a systematic review of published iVDPV case reports from January 1960 to November 2012 from four databases. We included cases in which the patient had a primary immunodeficiency, and the vaccine virus isolated from the patient either met the sequencing definition of VDPV (>1% divergence for serotypes 1 and 3 and >0.6% for serotype 2) and/or was previously reported as an iVDPV by the World Health Organization.ResultsWe identified 68 iVDPV cases in 49 manuscripts reported from 25 countries and the Palestinian territories. 62% of case patients were male, 78% presented clinically with acute flaccid paralysis, and 65% were iVDPV2. 57% of cases occurred in patients with predominantly antibody immunodeficiencies, and the overall all-cause mortality rate was greater than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median percent divergence for iVDPV1 cases. More cases were reported from high income countries, which also had a larger age variation and different distribution of immunodeficiencies compared to upper and lower middle-income countries.ConclusionOur study describes the incidence and characteristics of global iVDPV cases reported in the literature in the past five decades. It also highlights the regional and economic disparities of reported iVDPV cases.

Project description:ObjectiveThis study employed the Consolidated Framework for Implementation Research (CFIR) to assess factors that enhanced or impeded the implementation of community engagement strategies using the Nigerian polio programme as a point of reference.DesignThis study was a part of a larger descriptive cross-sectional survey. The CFIR was used to design the instrument which was administered through face-to-face and phone interviews as well as a web-based data collection platform, Qualtrics.SettingThe study took place in at least one State from each of the six geopolitical zones in Nigeria (Nasarawa, Borno, Kano, Sokoto, Anambra, Bayelsa, Lagos, Ondo and Oyo States as well as the Federal Capital Territory).ParticipantsThe respondents included programme managers, policy-makers, researchers and frontline field implementers affiliated with the Global Polio Eradication Initiative (PEI) core partner organisations, the three tiers of the government health parastatals (local, state and federal levels) and academic/research institutions.ResultsData for this study were obtained from 364 respondents who reported participation in community engagement activities in Nigeria's PEI. Majority (68.4%) had less than 10 years' experience in PEI, 57.4% were involved at the local government level and 46.9% were team supervisors. Almost half (45.0%) of the participants identified the process of conducting the PEI program and social environment (56.0%) as the most important internal and external contributor to implementing community engagement activities in the community, respectively. The economic environment (35.7%) was the most frequently reported challenge among the external challenges to implementing community engagement activities.ConclusionCommunity engagement strategies were largely affected by the factors relating to the process of conducting the polio programme, the economic environment and the social context. Therefore, community engagement implementers should focus on these key areas and channel resources to reduce obstacles to achieve community engagement goals.

Dataset Information

Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

Publications

Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

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