Dataset Information

Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

ABSTRACT: Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the threshold permitting VDPV2 circulation. A failure to implement this risk-based approach could mean these SIAs actually increase the risk of VDPV2 emergence and spread.

SUBMITTER: Pons-Salort M

PROVIDER: S-EPMC4934862 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

Pons-Salort Margarita M Burns Cara C CC Lyons Hil H Blake Isobel M IM Jafari Hamid H Oberste M Steven MS Kew Olen M OM Grassly Nicholas C NC

PLoS pathogens 20160706 7

Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by in ...[more]

PMID: 27384947

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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:BackgroundVaccine-derived poliovirus (VDPV) is a potential threat to polio eradication because they can reintroduce into the general population and cause paralytic polio outbreaks, a phenomenon that has recently emerged as a prominent public health concern at the end of global polio eradication. This study aimed to describe the epidemiology and genetic characteristics of the first VDPV identified from a patient with acute flaccid paralysis (AFP), with four doses of inactivated polio vaccine immunization in Henan Province, China in 2017.MethodsThe patient was diagnosed with type 3 VDPV. Subsequently, a series of epidemiological approaches was implemented, including a retrospective search of AFP cases, rate of vaccination assessment, study of contacts, and supplementary immunization activities. Fecal samples were collected, viral isolation was performed, and the viral isolates were characterized using full-length genomic sequencing and bioinformatic analysis.ResultsPhylogenetic analysis showed that the viral isolates from the patient were different from other reported genetic clusters of type 3 VDPV worldwide. They were identified as a Sabin 3/Sabin 1 recombinant VDPV with a crossover site in the P2 region. Nucleotide substitutions, including U → C (472) and C → U (2493), have been identified, both of which are frequently observed as reversion mutations in neurovirulent type 3 poliovirus. A unique aspect of this case is that the patient had been vaccinated with four doses of inactive polio vaccine, and the serum neutralizing antibody for Sabin types 1 and 3 were 1∶16 and 1∶512, respectively. Thus, the patient was speculated to have been infected with type 3 VDPV, and the virus continued to replicate and be excreted for at least 41 d.ConclusionsThe existence of this kind of virus in human population is a serious risk and poses a severe challenge in maintaining a polio-free status in China. To the best of our knowledge, this is the first report of VDPV identified in the Henan province of China. Our results highlight the importance of maintaining a high-level vaccination rate and highly sensitive AFP case surveillance system in intercepting VDPV transmission.

Dataset Information

Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

Publications

Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

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