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Nature Microbiology Sep 2023Timely detection of outbreaks is needed for poliovirus eradication, but gold standard detection in the Democratic Republic of the Congo takes 30 days (median). Direct...
Timely detection of outbreaks is needed for poliovirus eradication, but gold standard detection in the Democratic Republic of the Congo takes 30 days (median). Direct molecular detection and nanopore sequencing (DDNS) of poliovirus in stool samples is a promising fast method. Here we report prospective testing of stool samples from suspected polio cases, and their contacts, in the Democratic Republic of the Congo between 10 August 2021 and 4 February 2022. DDNS detected polioviruses in 62/2,339 (2.7%) of samples, while gold standard combination of cell culture, quantitative PCR and Sanger sequencing detected polioviruses in 51/2,339 (2.2%) of the same samples. DDNS provided case confirmation in 7 days (median) in routine surveillance conditions. DDNS enabled confirmation of three serotype 2 circulating vaccine-derived poliovirus outbreaks 23 days (mean) earlier (range 6-30 days) than the gold standard method. The mean sequence similarity between sequences obtained by the two methods was 99.98%. Our data confirm the feasibility of implementing DDNS in a national poliovirus laboratory.
Topics: Poliovirus; Nanopore Sequencing; Polymerase Chain Reaction; Dansyl Compounds
PubMed: 37591995
DOI: 10.1038/s41564-023-01453-4 -
Nature Communications Oct 2023Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of...
Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic structures of 9H2 fragments (Fab) bound to capsids of poliovirus serotypes 1, 2, and 3. The Fab-virus complexes show that Fab interacts with the same binding mode for each serotype and at the same angle of interaction relative to the capsid surface. For each of the Fab-virus complexes, we find that the binding site overlaps with the poliovirus receptor (PVR) binding site and maps across and into a depression in the capsid called the canyon. No conformational changes to the capsid are induced by Fab binding for any complex. Competition binding experiments between 9H2 and PVR reveal that 9H2 impedes receptor binding. Thus, 9H2 outcompetes the receptor to neutralize poliovirus. The ability to neutralize all three serotypes, coupled with the critical importance of the conserved receptor binding site make 9H2 an attractive antiviral candidate for future development.
Topics: Humans; Serogroup; Antibodies, Monoclonal; Capsid Proteins; Poliovirus; Binding Sites; Antibodies, Viral
PubMed: 37816742
DOI: 10.1038/s41467-023-41052-9 -
Risk Analysis : An Official Publication... Feb 2021Countries face different poliovirus risks, which imply different benefits associated with continued and future use of oral poliovirus vaccine (OPV) and/or inactivated...
Countries face different poliovirus risks, which imply different benefits associated with continued and future use of oral poliovirus vaccine (OPV) and/or inactivated poliovirus vaccine (IPV). With the Global Polio Eradication Initiative (GPEI) continuing to extend its timeline for ending the transmission of all wild polioviruses and to introduce new poliovirus vaccines, the polio vaccine supply chain continues to expand in complexity. The increased complexity leads to significant uncertainty about supply and costs. Notably, the strategy of phased OPV cessation of all three serotypes to stop all future incidence of poliomyelitis depends on successfully stopping the transmission of all wild polioviruses. Countries also face challenges associated with responding to any outbreaks that occur after OPV cessation, because stopping transmission of such outbreaks requires reintroducing the use of the stopped OPV in most countries. National immunization program leaders will likely consider differences in their risks and willingness-to-pay for risk reduction as they evaluate their investments in current and future polio vaccination. Information about the costs and benefits of future poliovirus vaccines, and discussion of the complex situation that currently exists, should prove useful to national, regional, and global decisionmakers and support health economic modeling. Delays in achieving polio eradication combined with increasing costs of poliovirus vaccines continue to increase financial risks for the GPEI.
Topics: Costs and Cost Analysis; Disease Eradication; Disease Outbreaks; Global Health; Health Care Costs; Humans; Immunization Programs; Models, Economic; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Risk; Risk Management; Serogroup; Vaccination
PubMed: 32645244
DOI: 10.1111/risa.13557 -
MMWR. Morbidity and Mortality Weekly... Jan 2022Wild poliovirus types 2 and 3 were declared eradicated in 2015 and 2019, respectively, and, since 2017, transmission of wild poliovirus type 1 (WPV1) has been detected...
Wild poliovirus types 2 and 3 were declared eradicated in 2015 and 2019, respectively, and, since 2017, transmission of wild poliovirus type 1 (WPV1) has been detected only in Afghanistan and Pakistan. In 2020, these countries reported their highest number of WPV1 cases since 2014 and experienced outbreaks of type 2 circulating vaccine-derived poliovirus (cVDPV2)* (1); in Afghanistan, the number of WPV1 cases reported increased 93%, from 29 in 2019 to 56 in 2020, with 308 cVDPV2 cases reported. This report describes the activities and progress toward polio eradication in Afghanistan during January 2020-November 2021 and updates previous reports (2-4). Despite restrictions imposed by antigovernment elements since 2018, disruption of polio eradication efforts by the COVID-19 pandemic, and civil and political instability, eradication activities have resumed. During January-November 2021, four WPV1 cases and 43 cVDPV2 cases were detected, representing decreases of 93% from 56 and 85% from 281, respectively, during the same period in 2020. After the assumption of nationwide control by the current de facto government of Afghanistan during August 2021, health officials committed to oral poliovirus vaccine (OPV) campaigns nationwide, with the potential to vaccinate approximately 2.5 million children against poliovirus who were previously not accessible for ≥2 years. Although challenges remain, vigorous, sustained polio eradication efforts in Afghanistan could result in substantial progress toward eradication during 2022-2023.
Topics: Adult; Afghanistan; Child; Child, Preschool; Disease Eradication; Disease Outbreaks; Humans; Immunization Programs; Infant; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Population Surveillance
PubMed: 35051135
DOI: 10.15585/mmwr.mm7103a3 -
MMWR. Morbidity and Mortality Weekly... May 2023Since the World Health Assembly established the Global Polio Eradication Initiative (GPEI) in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have...
Since the World Health Assembly established the Global Polio Eradication Initiative (GPEI) in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated, and global WPV cases have decreased by more than 99.9%. Afghanistan and Pakistan remain the only countries where indigenous WPV type 1 (WPV1) transmission has not been interrupted. This report summarizes progress toward global polio eradication during January 1, 2021-March 31, 2023, and updates previous reports (1,2). In 2022, Afghanistan and Pakistan reported 22 WPV1 cases, compared with five in 2021; as of May 5, 2023, a single WPV1 case was reported in Pakistan in 2023. A WPV1 case was reported on the African continent for the first time since 2016, when officials in Malawi confirmed a WPV1 case in a child with paralysis onset in November 2021; neighboring Mozambique subsequently reported eight genetically linked cases. Outbreaks of polio caused by circulating vaccine-derived polioviruses (cVDPVs) can occur when oral poliovirus vaccine (OPV) strains circulate for a prolonged time in underimmunized populations, allowing reversion to neurovirulence (3). A total of 859 cVDPV cases occurred during 2022, an increase of 23% from 698 cases in 2021. cVDPVs were detected in areas where poliovirus transmission had long been eliminated (including in Canada, Israel, the United Kingdom, and the United States). In addition, cocirculation of multiple poliovirus types occurred in multiple countries globally (including Democratic Republic of the Congo [DRC], Israel, Malawi, Mozambique, Republic of the Congo, and Yemen). The 2022-2026 GPEI strategic plan targeted the goal of detecting the last cases of WPV1 and cVDPV in 2023 (4). The current global epidemiology of poliovirus transmission makes the likelihood of meeting this target date unlikely. The detections of poliovirus (WPV1 and cVDPVs) in areas where it had been previously eliminated underscore the threat of continued poliovirus spread to any area where there is insufficient vaccination to poliovirus (3). Mass vaccination and surveillance should be further enhanced in areas of transmission to interrupt poliovirus transmission and to end the global threat of paralytic polio in children.
Topics: Child; Humans; Disease Eradication; Disease Outbreaks; Global Health; Immunization Programs; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Population Surveillance
PubMed: 37167156
DOI: 10.15585/mmwr.mm7219a3 -
Current Opinion in Virology Dec 2014The membrane landscape of a cell often changes drastically upon infection by a virus. In the case of the well-studied positive strand RNA virus poliovirus, the short... (Review)
Review
The membrane landscape of a cell often changes drastically upon infection by a virus. In the case of the well-studied positive strand RNA virus poliovirus, the short infection cycle induces vesicles and tubular structures early in infection, and double-membraned vesicles late in infection. In this review, the current understanding of membrane changes in a PV-infected cell, the host and viral factors that facilitate these changes, and how these changes may promote virus replication will be discussed. Host factors involved in membrane rearrangement during infection include components of the COPI and COPII secretory pathways, lipid kinases, and the autophagy pathway. The roles of cellular membranes include acting as a scaffold for the RNA replication complex and roles in exit of mature virus. Finally, recent studies suggesting that not all picornaviruses are truly 'non-enveloped' are discussed in the context of the field, raising the possibility that cell-derived membranes play a role in delivering poliovirus particles to the extracellular space.
Topics: Cell Membrane; Host-Pathogen Interactions; Intracellular Membranes; Poliovirus; Virus Release; Virus Replication
PubMed: 25310497
DOI: 10.1016/j.coviro.2014.09.007 -
Journal of Clinical Microbiology Feb 2017The poliovirus (PV) is currently targeted for worldwide eradication and containment. Sanger-based sequencing of the viral protein 1 (VP1) capsid region is currently the...
The poliovirus (PV) is currently targeted for worldwide eradication and containment. Sanger-based sequencing of the viral protein 1 (VP1) capsid region is currently the standard method for PV surveillance. However, the whole-genome sequence is sometimes needed for higher resolution global surveillance. In this study, we optimized whole-genome sequencing protocols for poliovirus isolates and FTA cards using next-generation sequencing (NGS), aiming for high sequence coverage, efficiency, and throughput. We found that DNase treatment of poliovirus RNA followed by random reverse transcription (RT), amplification, and the use of the Nextera XT DNA library preparation kit produced significantly better results than other preparations. The average viral reads per total reads, a measurement of efficiency, was as high as 84.2% ± 15.6%. PV genomes covering >99 to 100% of the reference length were obtained and validated with Sanger sequencing. A total of 52 PV genomes were generated, multiplexing as many as 64 samples in a single Illumina MiSeq run. This high-throughput, sequence-independent NGS approach facilitated the detection of a diverse range of PVs, especially for those in vaccine-derived polioviruses (VDPV), circulating VDPV, or immunodeficiency-related VDPV. In contrast to results from previous studies on other viruses, our results showed that filtration and nuclease treatment did not discernibly increase the sequencing efficiency of PV isolates. However, DNase treatment after nucleic acid extraction to remove host DNA significantly improved the sequencing results. This NGS method has been successfully implemented to generate PV genomes for molecular epidemiology of the most recent PV isolates. Additionally, the ability to obtain full PV genomes from FTA cards will aid in facilitating global poliovirus surveillance.
Topics: High-Throughput Nucleotide Sequencing; Humans; Molecular Epidemiology; Pilot Projects; Poliovirus; Specimen Handling
PubMed: 27927929
DOI: 10.1128/JCM.02121-16 -
Medical Decision Making : An... 2023Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear...
BACKGROUND
Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear the virus without therapeutic intervention. Although prolonged/chronic poliovirus excreters are rare, they represent a source of poliovirus reintroduction into the general population. Prior studies that assumed the successful cessation of all oral poliovirus vaccine (OPV) use estimated the potential upper bound of the incremental net benefits (INBs) of resource investments in research and development of PAVDs. However, delays in polio eradication, OPV cessation, and the development of PAVDs necessitate an updated economic analysis to reevaluate the costs and benefits of further investments in PAVDs.
METHODS
Using a global integrated model of polio transmission, immunity, vaccine dynamics, risks, and economics, we explore the risks of reintroduction of polio transmission due to immunodeficiency-related vaccine-derived poliovirus (iVDPV) excreters and reevaluate the upper bound of the INBs of PAVDs.
RESULTS
Under the current conditions, for which the use of OPV will likely continue for the foreseeable future, even with successful eradication of type 1 wild poliovirus by the end of 2023 and continued use of Sabin OPV for outbreak response, we estimate an upper bound INB of 60 million US$2019. With >100 million US$2019 already invested in PAVD development and with the introduction of novel OPVs that are less likely to revert to neurovirulence, our analysis suggests the expected INBs of PAVDs would not offset their costs.
CONCLUSIONS
While PAVDs could play an important role in the polio endgame, their expected economic benefits drop with ongoing OPV use and poliovirus transmissions. However, stakeholders may pursue the development of PAVDs as a desired product regardless of their economic benefits.HighlightsWhile polio antiviral drugs could play an important role in the polio endgame, their expected economic benefits continue to drop with delays in polio eradication and the continued use of oral poliovirus vaccines.The incremental net benefits of investments in polio antiviral drug development and screening for immunodeficiency-related circulating polioviruses are small.Limited global resources are better spent on increasing global population immunity to polioviruses to stop and prevent poliovirus transmission.
Topics: Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Disease Outbreaks; Antiviral Agents
PubMed: 37577803
DOI: 10.1177/0272989X231191127 -
International Journal of Molecular... Dec 2022The phenomenon of internal initiation of translation was discovered in 1988 on poliovirus mRNA. The prototypic -acting element in the 5' untranslated region (5'UTR) of... (Review)
Review
The phenomenon of internal initiation of translation was discovered in 1988 on poliovirus mRNA. The prototypic -acting element in the 5' untranslated region (5'UTR) of poliovirus mRNA, which is able to direct initiation at an internal start codon without the involvement of a cap structure, has been called an IRES (Internal Ribosome Entry Site or Segment). Despite its early discovery, poliovirus and other related IRES elements of type I are poorly characterized, and it is not yet clear which host proteins (a.k.a. IRES trans-acting factors, ITAFs) are required for their full activity in vivo. Here we discuss recent and old results devoted to type I IRESes and provide evidence that Poly(rC) binding protein 2 (PCBP2), Glycyl-tRNA synthetase (GARS), and Cold Shock Domain Containing E1 (CSDE1, also known as UNR) are major regulators of type I IRES activity.
Topics: Poliovirus; Internal Ribosome Entry Sites; Trans-Activators; Regulatory Sequences, Nucleic Acid; Codon, Initiator; RNA, Messenger; Protein Biosynthesis; 5' Untranslated Regions; RNA, Viral
PubMed: 36555135
DOI: 10.3390/ijms232415497 -
The Pan African Medical Journal 2023Polio is an infectious and disabling life-threatening disease caused by the poliovirus. This disease is prevented through vaccination. Though this viral infection has...
Polio is an infectious and disabling life-threatening disease caused by the poliovirus. This disease is prevented through vaccination. Though this viral infection has been eliminated in most parts of the world, a few countries are still endemic to wild poliovirus. In 2020, the World Health Organization (WHO) African Region, including Cameroon, was certified free of wild poliovirus. Some countries recurrently report circulating vaccine-derived poliovirus cases (cVDPV) despite recorded achievements. Also, the risk of importing poliovirus from endemic settings remains, particularly in the context of coronavirus disease (COVID-19). This study aimed to assess the state of polio in Cameroon and identify the situation during COVID-19. A data review was conducted from February to March 2023. Data on polio cases and vaccination coverage per region of Cameroon were reviewed from 2014 to 2022. Data were analyzed with Microsoft Excel, and the results were presented as proportions. The last wild poliovirus was reported in Cameroon in 2014, and the country benefitted from a response. No case of poliovirus was detected in the country from 2015 to 2018. After that, an increasing number of type two cVDPV were reported across 50% of the country's regions from 2019 to 2022. The outbreaks benefitted from responses with various oral polio vaccines, including the type two novel oral polio vaccine (nOPV-2). Though wild polioviruses have been eliminated in most countries, including Cameroon, cVDPV remains a significant problem. There is an urgent need to strengthen disease surveillance and vaccination to prevent cVDPV-2 in this country, particularly in the COVID-19 context.
Topics: Humans; Cameroon; Pandemics; COVID-19; Poliomyelitis; Poliovirus; Disease Outbreaks; Poliovirus Vaccine, Oral; Blindness
PubMed: 37663631
DOI: 10.11604/pamj.2023.45.90.35332