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Applied and Environmental Microbiology Jul 2020The Polio Endgame Strategy 2019-2023 has been developed. However, more effective and efficient surveillance activities should be conducted with the preparedness of...
The Polio Endgame Strategy 2019-2023 has been developed. However, more effective and efficient surveillance activities should be conducted with the preparedness of emergence for vaccine-derived poliovirus (VDPV) or wild poliovirus (WPV). We reviewed the impact of the case-based acute flaccid paralysis (AFP) surveillance (1991 to 2018) and environmental surveillance (2011 to 2018) in polio eradication in Shandong province of China. Clinical characteristics of AFP cases and enterovirus (EV) investigation of research samples were assessed. During the period, 10,224 AFP cases were investigated, and 352 sewage samples were collected. The nonpolio AFP rate sustained at over 2.0/100,000 since 1997. Of 10,224 cases, males and young children experienced a higher risk of severe diseases, and 68.5% suffered lower limb paralysis. We collected 1,707 EVs from AFP cases, including 763 polioviruses and 944 nonpolio enteroviruses (NPEVs). No WPV was isolated since 1992. The AFP surveillance showed high sensitivity in detecting 143 vaccine-associated paralytic poliomyelitis (VAPP) cases and 6 VDPVs. For environmental surveillance, 217 (61.6%) samples were positive for poliovirus, and altogether, 838 polioviruses and 2,988 NPEVs were isolated. No WPV was isolated in environmental surveillance, although one VDPV2 was identified. Phylogenetic analysis revealed environmental surveillance had the capacity to detect a large scope of NPEVs. The case-based AFP surveillance will be indispensable for detecting VAPP cases and VDPV circulation in countries using oral polio vaccine. Environmental surveillance is advantageous in identifying EV circulation and responding to ongoing circulating VDPV outbreaks and should be expanded to complement the AFP surveillance. Interrupting wild poliovirus transmission and stopping circulating vaccine-derived poliovirus (cVDPV) outbreaks have been proposed as two global goals by the World Health Organization in the Global Polio Eradication Initiative (GPEI). This analysis, based on the 28-year acute flaccid paralysis (AFP) surveillance and 8-year environmental surveillance, provides continued high-quality surveillance performance in achieving the GPEI and detecting the circulation of enterovirus. Given the ongoing cVDPV outbreaks in the world, we present the surveillance capacity of environmental surveillance in capturing enterovirus circulation. The final poliovirus (especially VDPV) elimination has become increasingly complex, and the case-based AFP surveillance alone will lead to difficulties in early detecting dynamics of poliovirus transmission and monitoring the extent of environmental circulation. This study goes beyond previous work to provide a detailed comprehensive evaluation of the enterovirus surveillance and can be used to formulate a set of implementation plan and performance indicators for environmental surveillance.
Topics: China; Enterovirus; Environmental Monitoring; Humans; Paralysis; Poliomyelitis; Poliovirus; Population Surveillance
PubMed: 32444474
DOI: 10.1128/AEM.00702-20 -
Virology Journal Aug 2023Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine but can be associated with outbreaks and permanent disability in patients harboring...
Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine but can be associated with outbreaks and permanent disability in patients harboring circulating vaccine-derived polioviruses (cVDPVs). With the advancement of polio abolition in a glimpse, cVDPVs are causing outbreaks and slowing the polio eradication process. The polio virus protein 1 (VP1) contains the binding site that is key for virus transmission. Understanding the evolution of VP1 among AFP patients could yield more insight into the early events of cVDPVs. Polioviruses were identified from stool specimens of AFP patients using cell culture; and confirmed by the real time RT PCR intra-typic differentiation and vaccine-derived poliovirus assays. Seventy-nine (79) Sabin-like poliovirus 1 (SL1) and 86 Sabin-like poliovirus 3 (SL3) were sequenced. The VP1 amino acid substitutions T106A in Sabin poliovirus 1 and A54V in Sabin poliovirus 3 were common among the AFP patients as has been found in previous studies. Other substitutions that were associated with AFP were: T290A and A54T in SL1 and SL3 respectively. Nucleotide mutations that were common among the AFP patients included T402C, C670A, and T816C in SL1, and G22A, C375Y, A472R, and A694T in SL3 polioviruses. Characterizing mutations that are associated with AFP could contribute to efforts pursued to mitigate the risk of vaccine-derived polioviruses and promote development of safer vaccines.
Topics: Humans; Poliovirus; Uganda; alpha-Fetoproteins; Enterovirus; Poliomyelitis; Poliovirus Vaccine, Oral; Paralysis
PubMed: 37533043
DOI: 10.1186/s12985-023-02143-7 -
Expert Review of Vaccines Jul 2019: The inability to successfully stop all use of oral poliovirus vaccine (OPV) as part of the polio endgame and/or the possibilities of reintroduction of live... (Review)
Review
: The inability to successfully stop all use of oral poliovirus vaccine (OPV) as part of the polio endgame and/or the possibilities of reintroduction of live polioviruses after successful OPV cessation may imply the need to restart OPV production and use, either temporarily or permanently. : Complementing prior work that explored the risks of potential OPV restart, we discuss the logistical challenges and implications of restarting OPV in the future, and we develop appropriate assumptions for modeling the possibility of OPV restart. The complexity of phased cessation of the three OPV serotypes implies different potential combinations of OPV use long term. We explore the complexity of polio vaccine choices and key unresolved policy questions that may impact continuing and future use of OPV and/or inactivated poliovirus vaccine (IPV). We then characterize the assumptions required to quantitatively model OPV restart in prospective global-integrated economic policy models for the polio endgame. : Depending on the timing, restarting production of OPV would imply some likely delays associated with ramp-up, re-licensing, and other logistics that would impact the availability and costs of restarting the use of OPV in national immunization programs after globally coordinated cessation of one or more OPV serotypes.
Topics: Disease Eradication; Global Health; Humans; Immunization Programs; Models, Theoretical; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 31248293
DOI: 10.1080/14760584.2019.1635463 -
PloS One 2017The key role of cell cultures in different scientific fields is worldwide recognized, both as in vitro research models alternative to laboratory animals and substrates...
The key role of cell cultures in different scientific fields is worldwide recognized, both as in vitro research models alternative to laboratory animals and substrates for biological production. However, many safety concerns rise from the use of animal/human cell lines that may be tumorigenic, leading to potential adverse contaminations in cell-derived biologicals. In order to evaluate the suitability of 13 different cell lines for Poliovirus vaccine production, safety and quality, in vitro/in vivo tumorigenicity and Poliovirus propagation properties were evaluated. Our results revealed that non-human primate cell lines CYNOM-K1, FRhK-4, 4MBr-5 and 4647 are free of tumorigenic features and represent highly susceptible substrates for attenuated Sabin Poliovirus strains. In particular, FRhK-4 and 4647 cell lines are characterized by a higher in vitro replication, resulting indicated for the use in large-scale production field.
Topics: Animals; Biological Assay; Carcinogenesis; Cell Line; Cell Transformation, Neoplastic; Poliovirus; Primates; Virus Replication
PubMed: 28046048
DOI: 10.1371/journal.pone.0169391 -
Journal of Virology Jul 2019Template-dependent RNA replication mechanisms render picornaviruses susceptible to error catastrophe, an overwhelming accumulation of mutations incompatible with...
Template-dependent RNA replication mechanisms render picornaviruses susceptible to error catastrophe, an overwhelming accumulation of mutations incompatible with viability. Viral RNA recombination, in theory, provides a mechanism for viruses to counteract error catastrophe. We tested this theory by exploiting well-defined mutations in the poliovirus RNA-dependent RNA polymerase (RDRP), namely, a G64S mutation and an L420A mutation. Our data reveal two distinct mechanisms by which picornaviral RDRPs influence error catastrophe: fidelity of RNA synthesis and RNA recombination. A G64S mutation increased the fidelity of the viral polymerase and rendered the virus resistant to ribavirin-induced error catastrophe, but only when RNA recombination was at wild-type levels. An L420A mutation in the viral polymerase inhibited RNA recombination and exacerbated ribavirin-induced error catastrophe. Furthermore, when RNA recombination was substantially reduced by an L420A mutation, a high-fidelity G64S polymerase failed to make the virus resistant to ribavirin. These data indicate that viral RNA recombination is required for poliovirus to evade ribavirin-induced error catastrophe. The conserved nature of L420 within RDRPs suggests that RNA recombination is a common mechanism for picornaviruses to counteract and avoid error catastrophe. Positive-strand RNA viruses produce vast amounts of progeny in very short periods of time via template-dependent RNA replication mechanisms. Template-dependent RNA replication, while efficient, can be disadvantageous due to error-prone viral polymerases. The accumulation of mutations in viral RNA genomes leads to error catastrophe. In this study, we substantiate long-held theories regarding the advantages and disadvantages of asexual and sexual replication strategies among RNA viruses. In particular, we show that picornavirus RNA recombination counteracts the negative consequences of asexual template-dependent RNA replication mechanisms, namely, error catastrophe.
Topics: Amino Acid Substitution; Animals; HeLa Cells; Humans; Mice; Mutation, Missense; Poliovirus; RNA; RNA, Viral; RNA-Dependent RNA Polymerase; Recombination, Genetic; Ribavirin; Viral Proteins
PubMed: 31068422
DOI: 10.1128/JVI.00652-19 -
Vaccine Sep 2016In September 2015, Nigeria was removed from the list of polio-endemic countries after more than 12months had passed since the detection of last wild poliovirus case in...
INTRODUCTION
In September 2015, Nigeria was removed from the list of polio-endemic countries after more than 12months had passed since the detection of last wild poliovirus case in the country on 24 July 2014. We are presenting here a report of two polio seroprevalence surveys conducted in September 2013 and October 2014, respectively, in the Kano state of northern Nigeria.
METHODS
Health facility based seroprevalence surveys were undertaken at Murtala Mohammad Specialist Hospital, Kano. Parents or guardians of children aged 6-9months, 36-47months, 5-9years and 10-14years in 2013 and 6-9months and 19-22months (corresponding to 6-9months range at the time of 2013 survey) in 2014 presenting to the outpatient department, were approached for participation, screened for eligibility and asked to provide informed consent. A questionnaire was administered and a blood sample collected for polio neutralization assay.
RESULTS
Among subjects aged 6-9months in the 2013 survey, seroprevalence was 58% (95% confidence interval [CI] 51-66%) to poliovirus type 1, 42% (95% CI 34-50%) to poliovirus type 2, and 52% (95% CI 44-60%) to poliovirus type 3. Among children 36-47months and older, seroprevalence was 85% or higher for all three serotypes. In 2014, seroprevalence in 6-9month infants was 72% (95% CI 65-79%) for type 1, 59% (95% CI 52-66%) for type 2, and 65% (95% CI 57-72%) for type 3 and in 19-22months, 80% (95% CI 74-85%), 57% (49-63%) and 78% (71-83%) respectively. Seroprevalence was positively associated with history of increasing oral poliovirus vaccine doses.
CONCLUSIONS
There was significant improvement in seroprevalence in 2014 over the 2013 levels indicating a positive impact of recent programmatic interventions. However the continued low seroprevalence in 6-9month age is a concern and calls for improved immunization efforts to sustain the polio-free Nigeria.
Topics: Adolescent; Antibodies, Viral; Child; Child, Preschool; Disease Eradication; Female; Humans; Infant; Male; Nigeria; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Seroepidemiologic Studies; Serogroup; Surveys and Questionnaires
PubMed: 27591950
DOI: 10.1016/j.vaccine.2016.08.058 -
The Enzymes 2016Using poliovirus (PV) and its RNA-dependent RNA polymerase (RdRp) as our primary model system, we have advanced knowledge fundamental to the chemistry and fidelity of... (Review)
Review
Using poliovirus (PV) and its RNA-dependent RNA polymerase (RdRp) as our primary model system, we have advanced knowledge fundamental to the chemistry and fidelity of nucleotide addition by nucleic acid polymerase. Two fidelity checkpoints exist prior to nucleotide addition. The first toggles the enzyme between a nucleotide binding-occluded state and a nucleotide binding-competent state. The second represents an ensemble of conformational states of conserved structural motifs that permits retention of the incoming nucleotide in a state competent for phosphoryl transfer long enough for chemistry to occur. Nucleophilic attack of the alpha-phosphorous atom of the incoming nucleotide produces a pentavalent transition state, collapse of which is facilitated by protonation of the pyrophosphate leaving group by a general acid. All of the relevant conformational states of the enzyme are controlled by a network of interacting residues that permits remote-site residues to control active-site function. The current state of the art for PV RdRp enzymology is such that mechanisms governing fidelity of this enzyme can now be targeted genetically and chemically for development of attenuated viruses and antiviral agents, respectively. Application of the knowledge obtained with the PV RdRp to the development of vaccines and antivirals for emerging RNA viruses represents an important goal for the future.
Topics: Nucleotides; Poliovirus; RNA-Dependent RNA Polymerase
PubMed: 27241934
DOI: 10.1016/bs.enz.2016.02.002 -
PloS One 2021Surveillance and detection of polioviruses (PV) remain crucial to monitoring eradication progress. Intratypic differentiation (ITD) using the real-time RT-PCR kit is key...
Surveillance and detection of polioviruses (PV) remain crucial to monitoring eradication progress. Intratypic differentiation (ITD) using the real-time RT-PCR kit is key to the surveillance workflow, where viruses are screened after cell culture isolation before a subset are verified by sequencing. The ITD kit is a series of real-time RT-PCR assays that screens cytopathic effect (CPE)-positive cell cultures using the standard WHO method for virus isolation. Because ITD screening is a critical procedure in the poliovirus identification workflow, validation of performance of real-time PCR platforms is a core requirement for the detection of poliovirus using the ITD kit. In addition, the continual update and improvement of the ITD assays to simplify interpretation in all platforms is necessary to ensure that all real-time machines are capable of detecting positive real-time signals. Four platforms (ABI7500 real-time systems, Bio-Rad CFX96, Stratagene MX3000P, and the Qiagen Rotor-Gene Q) were validated with the ITD kit and a redesigned poliovirus probe. The poliovirus probe in the real-time RT-PCR pan-poliovirus (PanPV) assay was re-designed with a double-quencher (Zen™) to reduce background fluorescence and potential false negatives. The updated PanPV probe was evaluated with a panel consisting of 184 polioviruses and non-polio enteroviruses. To further validate the updated PanPV probe, the new assay was pilot tested in five Global Polio Laboratory Network (GPLN) laboratories (Madagascar, India, Philippines, Pakistan, and Democratic Republic of Congo). The updated PanPV probe performance was shown to reduce background fluorescence and decrease the number of false positives compared to the standard PanPV probe.
Topics: Feces; Laboratories; Poliovirus; Real-Time Polymerase Chain Reaction; Sewage
PubMed: 34358268
DOI: 10.1371/journal.pone.0255795 -
Viruses Apr 2022Genetic recombination in RNA viruses is an important evolutionary mechanism. It contributes to population diversity, host/tissue adaptation, and compromises vaccine...
Genetic recombination in RNA viruses is an important evolutionary mechanism. It contributes to population diversity, host/tissue adaptation, and compromises vaccine efficacy. Both the molecular mechanism and initial products of recombination are relatively poorly understood. We used an established poliovirus-based in vitro recombination assay to investigate the roles of sequence identity and RNA structure, implicated or inferred from an analysis of circulating recombinant viruses, in the process. In addition, we used next-generation sequencing to investigate the early products of recombination after cellular coinfection with different poliovirus serotypes. In independent studies, we find no evidence for a role for RNA identity or structure in determining recombination junctions location. Instead, genome function and fitness are of greater importance in determining the identity of recombinant progeny. These studies provide further insights into this important evolutionary mechanism and emphasize the critical nature of the selection process on a mixed virus population.
Topics: Antigens, Viral; Enterovirus; Enterovirus Infections; Genome, Viral; Humans; Poliovirus; RNA; Recombination, Genetic
PubMed: 35632658
DOI: 10.3390/v14050916 -
Frontiers in Cellular and Infection... 2023In 2021, a type 2 vaccine-derived poliovirus (VDPV2) was isolated from the stool of a patient with acute flaccid paralysis (AFP) admitted to Spain from Senegal. A...
INTRODUCTION
In 2021, a type 2 vaccine-derived poliovirus (VDPV2) was isolated from the stool of a patient with acute flaccid paralysis (AFP) admitted to Spain from Senegal. A virological investigation was conducted to characterize and trace the origin of VDPV2.
METHODS
We used an unbiased metagenomic approach for the whole-genome sequencing of VDPV2 from the stool (pre-treated with chloroform) and from the poliovirus-positive supernatant. Phylogenetic analyses and molecular epidemiological analyses relying on the Bayesian Markov Chain Monte Carlo methodology were used to determine the geographical origin and estimate the date of the initiating dose of the oral poliovirus vaccine for the imported VDPV2.
RESULTS
We obtained a high percentage of viral reads per total reads mapped to the poliovirus genome (69.5% for pre-treated stool and 75.8% for isolate) with a great depth of sequencing coverage (5,931 and 11,581, respectively) and complete genome coverage (100%). The two key attenuating mutations in the Sabin 2 strain had reverted (A481G in the 5'UTR and Ile143Thr in VP1). In addition, the genome had a recombinant structure between type-2 poliovirus and an unidentified non-polio enterovirus-C (NPEV-C) strain with a crossover point in the protease-2A genomic region. VP1 phylogenetic analysis revealed that this strain is closely related to VDPV2 strains circulating in Senegal in 2021. According to Bayesian phylogenetics, the most recent common ancestor of the imported VDPV2 could date back 2.6 years (95% HPD: 1.7-3.7) in Senegal. We suggest that all VDPV2s circulating in 2020-21 in Senegal, Guinea, Gambia, and Mauritania have an ancestral origin in Senegal estimated around 2015. All 50 stool samples from healthy case contacts collected in Spain (n = 25) and Senegal (n = 25) and four wastewater samples collected in Spain were poliovirus negative.
DISCUSSION
By using a whole-genome sequencing protocol with unbiased metagenomics from the clinical sample and viral isolate with high sequence coverage, efficiency, and throughput, we confirmed the classification of VDPV as a circulating type. The close genomic linkage with strains from Senegal was consistent with their classification as imported. Given the scarce number of complete genome sequences for NPEV-C in public databases, this protocol could help expand poliovirus and NPEV-C sequencing capacity worldwide.
Topics: Humans; Poliovirus; Phylogeny; Poliomyelitis; Spain; Bayes Theorem; Poliovirus Vaccine, Oral
PubMed: 37201115
DOI: 10.3389/fcimb.2023.1168355