Poliovirus Serotypes Research Articles

A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation

Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.

Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021

Novel oral poliovirus vaccine type 2 (nOPV2) was used to control an outbreak of type 2 circulating vaccine derived poliovirus (cVDPV2) in Tajikistan, in 2021. We measured seroconversion and seroprevalence of type 2 polio antibodies in children who were reported to have received two doses of nOPV2 in outbreak response campaigns. In this community serosurvey, children born after Jan 1, 2016 were enrolled from seven districts in Tajikistan. Dried blood spot cards were collected before nOPV2 campaigns and after the first and second rounds of the campaigns and were sent to the Centers for Disease Control and Prevention (Atlanta, GA, USA) for microneutralisation assay to determine presence of polio antibodies. The primary endpoint was to assess change in seroprevalence and seroconversion against poliovirus serotype 2 after one and two doses of nOPV2. 228 (97%) of 236 enrolled children were included in the analysis. The type 2 antibody seroprevalence was 26% (53/204; 95% CI 20 to 33) before nOPV2, 77% (161/210; 70 to 82) after one dose of nOPV2, and 83% (174/209; 77 to 88) after two doses of nOPV2. The increase in seroprevalence was statistically significant between baseline and after one nOPV2 dose (51 percentage points [42 to 59], p<0·0001), but not between the first and second doses (6 percentage points [-2 to 15], p=0·12). Seroconversion from the first nOPV2 dose, 67% (89/132; 59 to 75), was significantly greater than that from the second nOPV2 dose, 44% (20/45; 30 to 60; χ2 p=0·010). Total seroconversion after two nOPV2 doses was 77% (101/132; 68 to 83). Our study demonstrated strong immune responses following nOPV2 outbreak response campaigns in Tajikistan. Our results support previous clinical trial data on the generation of poliovirus type 2 immunity by nOPV2 and provide evidence that nOPV2 can be appropriate for the cVDPV2 outbreak response. The licensure and WHO prequalification of nOPV2 should be accelerated to facilitate wider use of the vaccine. World Health Organization, Centers for Disease Control and Prevention, and Rotary International.

The fight against poliomyelitis through the history: past, present and hopes for the future. Albert Sabin's missing Nobel and his “gift to all the world's children”

Polio, or poliomyelitis, is a disabling and life-threatening disease caused by three poliovirus (PV) serotypes. The virus spreads from person to person and can infect a person’s spinal cord, causing paralysis. In 1988, when the WHO registered 350,000 cases of poliomyelitis in the world and 70,000 which occurred in Africa alone, global poliomyelitis eradication was proposed by the World Health Organization to its member States. On 25 August 2020, while the world was waging war against the Coronavirus pandemic, a historic milestone was reached: Africa was officially declared polio-free.It is an important result obtained thanks to an intensive large-scale vaccination campaign.The road was far from smooth, nevertheless, according to the WHO, a great effort needs to be made in order to facilitate access to vaccination and to promote its implementation in those countries where coverage is low and vaccine hesitancy is high because the risk of the spread of poliomyelitis is still relevant. Eradication of the virus in Africa provides us with an excellent opportunity to commemorate the many scientists who contributed to achieving this epoch-making goal: first of all, Jonas Salk, who developed a killed-virus vaccine in 1952, and, especially, Albert Sabin, who in 1961 launched programs of mass immunisation with his oral vaccine against poliomyelitis.

Importation and Circulation of Vaccine-Derived Poliovirus Serotype 2, Senegal, 2020-2021.

Environmental surveillance for poliovirus is increasingly used in poliovirus eradication efforts as a supplement to acute flaccid paralysis (AFP) surveillance. Environmental surveillance was officially established in 2017 in Senegal, where no poliovirus had been detected since 2010. We tested sewage samples from 2 sites in Dakar monthly for polioviruses. We identified a vaccine-derived poliovirus serotype 2 on January 19, 2021, from a sample collected on December 24, 2020; by December 31, 2021, we had detected 70 vaccine-derived poliovirus serotype 2 isolates circulating in 7 of 14 regions in Senegal. Sources included 18 AFP cases, 20 direct contacts, 17 contacts in the community, and 15 sewage samples. Phylogenetic analysis revealed the circulation of 2 clusters and provided evidence on the virus introduction from Guinea. Because novel oral polio vaccine serotype 2 was used for response activities throughout Senegal, we recommend expanding environmental surveillance into other regions.

Strengthened surveillance revealed a rapid disappearance of the poliovirus serotype 2 vaccine strain in Madagascar after its removal from the oral polio vaccine.

To assess circulation of the Sabin 2 poliovirus vaccine strain in Madagascar after its withdrawal from the oral polio vaccine in April 2016, a reinforced poliovirus surveillance was implemented in three regions of Madagascar from January 2016 toDecember 2017. Environmental samples and stool specimens from healthy children were screened using the Global Polio Laboratory Network algorithm to detect the presence of polioviruses. Detected polioviruses were molecularly typed and their genomes fully sequenced. Polioviruses were detected during all but 4months of the study period. All isolates were related to the vaccine strains and no wild poliovirus was detected. The majority of isolates belong to the serotype 3. The last detection of Sabin 2 occurred in July 2016, 3months after its withdrawal. No vaccine-derived poliovirus of any serotype was observed during the study. Only few poliovirus isolates contained sequences from non-polio origin. The genetic characterization of all the poliovirus isolates did not identify isolates that were highly divergent compared to the vaccine strains. This observation is in favor of a good vaccine coverage that efficiently prevented long-lasting transmission chains between unvaccinated persons. This study underlines that high commitment in the fight against polioviruses can succeed in stopping their circulation even in countries where poor sanitation remains a hurdle.

Inactivated Poliovirus Vaccine Closing the Type 2 Immunity Gap in Vietnam

This was a cross-sectional community-based serological survey of polio antibodies assessing the immunogenicity of inactivated poliovirus vaccine (IPV) focusing on poliovirus serotype 2. IPV was administered to 5-month-old children. Type 2 antibody seroprevalence when measured 1 month after IPV administration was >95%. One IPV dose successfully closed the immunity gap.

Generated Randomly and Selected Functionally? The Nature of Enterovirus Recombination.

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.

Intradermal fractional-dose inactivated polio vaccine (fIPV) adjuvanted with double mutant Enterotoxigenic Escherichia coli heat labile toxin (dmLT) is well-tolerated and augments a systemic immune response to all three poliovirus serotypes in a randomized placebo-controlled trial

Eradication of poliomyelitis globally is constrained by fecal shedding of live polioviruses, both wild-type and vaccine-derived strains, into the environment. Although inactivated polio vaccines (IPV) effectively protect the recipient from clinical poliomyelitis, fecal shedding of live virus still occurs following infection with either wildtype or vaccine-derived strains of poliovirus. In the drive to eliminate the last cases of polio globally, improvements in both oral polio vaccines (OPV) (to prevent reversion to virulence) and injectable polio vaccines (to improve mucosal immunity and prevent viral shedding) are underway. The E. coli labile toxin with two or “double” attenuating mutations (dmLT) may boost immunologic responses to IPV, including at mucosal sites. We performed a double-blinded phase I controlled clinical trial to evaluate safety, tolerability, as well as systemic and mucosal immunogenicity of IPV adjuvanted with dmLT, given as a fractional (1/5th) dose intradermally (fIPV-dmLT). Twenty-nine volunteers with no past exposure to OPV were randomized to a single dose of fIPV-dmLT or fIPV alone. fIPV-dmLT was well tolerated, although three subjects had mild but persistent induration and hyperpigmentation at the injection site. A ≥ 4-fold rise in serotype-specific neutralizing antibody (SNA) titers to all three serotypes was seen in 84% of subjects receiving fIPV-dmLT vs. 50% of volunteers receiving IPV alone. SNA titers were higher in the dmLT-adjuvanted group, but only differences in serotype 1 were significant. Mucosal immune responses, as measured by polio serotype specific fecal IgA were minimal in both groups and differences were not seen. fIPV-dmLT may offer a benefit over IPV alone. Beyond NAB responses protecting the individual, studies demonstrating the ability of fIPV-dmLT to prevent viral shedding are necessary. Studies employing controlled human infection models, using monovalent OPV post-vaccine are ongoing. Studies specifically in children may also be necessary and additional biomarkers of mucosal immune responses in this population are needed.Clinicaltrials.gov Identifer: NCT03922061.

Achieving high immunogenicity against poliovirus with fractional doses of inactivated poliovirus vaccine in Ecuador-results from a cross-sectional serological survey

SummaryBackgroundIn January 2018, Ecuador changed its routine immunization schedule by replacing one full dose of inactivated poliovirus vaccine (IPV) administered intramuscularly at 2 months of age with two doses of fractional IPV (1/5th of full dose, fIPV) administered intradermally at 2 and 4 months of age; and bivalent oral poliovirus vaccine (serotypes 1 and 3, bOPV) continues to be used. We compared seroprevalence and titres of polio antibodies achieved by the past and the current immunization schedules.MethodsThis was a cross-sectional serological survey in children in Ecuador who received bOPV and either one IPV dose in 2017 or two fIPV doses in 2018. One blood sample was collected between October 2020 and March 2021 and analysed for presence of poliovirus neutralizing antibodies at CDC, Atlanta by microneutralization assay.FindingsWe obtained 321 analysable samples from 329 (97·6%) enrolled children (160 received IPV and 161 fIPV). For serotype 2, seroprevalence was 50·0% (CI95%= 44·2-55·8%) for IPV and 83·2% (CI95%=78·5-87·1%) for fIPV recipients (p<0·001). Median antibody titers for serotype 2 were significantly lower for IPV than for fIPV recipients (3·0, CI95%= 3 – 3·5 vs. 4·8, CI95%= 4·5 – 5·2, p<0·001). Seroprevalence for serotypes 1 and 3 was above 90% and was not significantly different between IPV and fIPV recipients.InterpretationEcuador achieved significantly better poliovirus serotype 2 immunogenicity with two fIPV doses than with one IPV dose, while preserving vaccine supply and reducing costs. Our data provide further evidence that fIPV is a beneficial and potentially a cost-effective option in polio immunization.FundingWHO obtained funds for the study from Rotary International.

VaxArray immunoassay for the multiplexed quantification of poliovirus D-antigen

Next generation poliovirus vaccines are critical to reaching global poliovirus eradication goals. Recent efforts have focused on creating inactivated vaccines using attenuated Sabin strains that maintain patient safety benefits and immunogenicity of conventional inactivated vaccines while increasing manufacturing safety and lowering production costs, and on developing novel oral vaccines using modified Sabin strains that provide critical mucosal immunity but are further attenuated to minimize risk of reversion to neurovirulence. In addition, there is a push to improve the analytical tools for poliovirus vaccine characterization. Conventional and Sabin inactivated poliovirus vaccines typically rely on standard plate-based ELISA as in vitro D-antigen potency assays in combination with WHO international standards as calibrants. While widely utilized, the current D-antigen ELISA assays have a long time to result (up to 72 h), can suffer from lab-to-lab inconsistency due to non-standardized protocols and reagents, and are inherently singleplex. For D-antigen quantitation, we have developed the VaxArray Polio Assay Kit, a multiplexed, microarray-based immunoassay that uses poliovirus-specific human monoclonal antibodies currently under consideration as standardized reagents for characterizing inactivated Sabin and Salk vaccines. The VaxArray assay can simultaneously quantify all 3 poliovirus serotypes with a time to result of less than 3 h. Here we demonstrate that the assay has limits of quantification suitable for both bioprocess samples and final vaccines, excellent reproducibility and precision, and improved accuracy over an analogous plate-based ELISA. The assay is suitable for adjuvanted combination vaccines, as common vaccine additives and crude matrices do not interfere with quantification, and is intended as a high throughput, standardized quantitation tool to aid inactivated poliovirus vaccine manufacturers in streamlining vaccine development and manufacturing, aiding the global polio eradication effort.

New oral polio vaccine: A turning point for the global polio eradication initiative?

RésuméLancé en 1988, le programme d’éradication de la poliomyélite vise à éradiquer les poliovirus, agents étiologiques de la maladie. Coordonné par l'Organisation mondiale de la santé, le programme repose sur des campagnes de vaccination de routine ciblant les enfants et sur la surveillance active de la circulation des virus. Il a permis l’éradication de deux des trois sérotypes de poliovirus sauvages et a circonscrit la circulation du sérotype restant à deux pays seulement.Deux vaccins antipoliomyélitiques existent: le vaccin injectable et le vaccin oral. Si les deux vaccins offrent une protection similaire contre la maladie, seul le second est capable de bloquer la transmission des poliovirus. Le vaccin oral est donc indispensable pour endiguer les poliovirus et, finalement, les éradiquer. Dans certains contextes où la couverture vaccinale est faible, les souches atténuées qui composent le vaccin oral peuvent circuler durant des mois et recouvrer un phénotype pathogène par dérive génétique. Afin d’éviter ce phénomène, une nouvelle souche vaccinale a été développée par génie génétique: elle a été conçue pour être aussi immunogène que la souche vaccinale historique mais beaucoup plus stable génétiquement afin d’éviter la perte des déterminants génétiques de son atténuation. Après une phase d’évaluation in vitro et des essais cliniques visant à confirmer ses propriétés, la nouvelle souche a été mise en œuvre dans plusieurs pays africains et au Tadjikistan en 2021.

A Survey to Assess Serological Prevalence of Poliovirus Antibodies in Areas With High-Risk for Vaccine-Derived Poliovirus Transmission in Chad.

BackgroundWorld Health Organization African region is wild poliovirus-free; however, outbreaks of vaccine-derived poliovirus type 2 (VDPV2) continue to expand across the continent including in Chad. We conducted a serological survey of polio antibodies in polio high-risk areas of Chad to assess population immunity against poliovirus and estimate the risk of future outbreaks.MethodsThis was a community-based, cross-sectional survey carried out in September 2019. Children between 12 and 59 months were randomly selected using GIS enumeration of structures. Informed consent, demographic and anthropometric data, vaccination history, and blood spots were collected. Seropositivity against all 3 poliovirus serotypes was assessed using a microneutralization assay at Centers for Disease Control and Prevention, Atlanta, GA, USA.ResultsAnalyzable data were obtained from 236 out of 285 (82.8%) enrolled children. Seroprevalence of polio antibodies for serotypes 1, 2, and 3 was 214/236 (90.7%); 145/236 (61.4%); and 196/236 (86.2%), respectively. For serotype 2, the seroprevalence significantly increased with age (P = .004); chronic malnutrition was a significant risk factor for being type 2-seronegative.InterpretationPoliovirus type 2 seroprevalence in young children was considered insufficient to protect against the spread of paralytic diseases caused by VDPV2. Indeed, VDPV2 outbreaks were reported from Chad in 2019 and 2020. High-quality immunization response to these outbreaks is needed to prevent further spread.

Achieving High Immunogenicity Against Poliovirus With Fractional Doses of Inactivated Poliovirus Vaccine in Ecuador

Background: In January 2018, Ecuador changed its routine immunization schedule by replacing one full dose of inactivated poliovirus vaccine (IPV) administered intramuscularly at 2 months of age with two doses of fractional IPV (1/5th of full dose, fIPV) administered intradermally at 2 and 4 months of age; bivalent oral poliovirus vaccine (serotypes 1 and 3, bOPV) continues to be used. We compared seroprevalence and titers of polio antibodies achieved by the past and the current immunization schedules. Methods: This was a cross-sectional serological survey in children in Ecuador who received bOPV and either one IPV dose in 2017 or two fIPV doses in 2018. One blood sample was collected between October 2020 and March 2021 and analysed for presence of poliovirus neutralizing antibodies at CDC, Atlanta by microneutralization assay. Findings: We obtained 321 analyzable samples from 329 (97·6%) enrolled children (160 received IPV and 161 fIPV). For serotype 2, seroprevalence was 50.0% (CI95%= 44·2-55·8%) for IPV and 83·2% (CI95%=78·5-87·1%) for fIPV recipients (p<0·001). Median antibody titers for serotype 2 were significantly lower for IPV than for fIPV recipients (3·0, CI95%= 3 – 3·5 vs. 4·8, CI95%= 4·5 – 5·2, p<0·001). Seroprevalence for serotypes 1 and 3 was above 90% and was not significantly different between IPV and fIPV recipients. Interpretation: Ecuador achieved significantly better poliovirus serotype 2 immunogenicity with two fIPV doses than with one IPV dose, while preserving vaccine supply and reducing costs. Our data provide further evidence that fIPV is a beneficial and cost-effective option in polio immunization. Funding Information: The World Health Organization to the University of San Francisco. Declaration of Interests: All authors – no conflict of interest declared. Ethics Approval Statement: The protocol was reviewed and approved by the Human Research Ethics Committee - CEISH-USFQ and by the Ethics Review Committee at the WHO in Geneva. After obtaining informed consent the children were enrolled.

Progress Toward Polio Eradication - Worldwide, January 2019-June 2021.

In 1988, when the Global Polio Eradication Initiative (GPEI) began, polio paralyzed >350,000 children across 125 countries. Today, only one of three wild poliovirus serotypes, type 1 (WPV1), remains in circulation in only two countries, Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2019-June 30, 2021 and updates previous reports (1,2). In 2020, 140 cases of WPV1 were reported, including 56 in Afghanistan (a 93% increase from 29 cases in 2019) and 84 in Pakistan (a 43% decrease from 147 cases in 2019). As GPEI focuses on the last endemic WPV reservoirs, poliomyelitis outbreaks caused by circulating vaccine-derived poliovirus (cVDPV) have emerged as a result of attenuated oral poliovirus vaccine (OPV) virus regaining neurovirulence after prolonged circulation in underimmunized populations (3). In 2020, 32 countries reported cVDPV outbreaks (four type 1 [cVDPV1], 26 type 2 [cVDPV2] and two with outbreaks of both); 13 of these countries reported new outbreaks. The updated GPEI Polio Eradication Strategy 2022-2026 (4) includes expanded use of the type 2 novel oral poliovirus vaccine (nOPV2) to avoid new emergences of cVDPV2 during outbreak responses (3). The new strategy deploys other tactics, such as increased national accountability, and focused investments for overcoming the remaining barriers to eradication, including program disruptions and setbacks caused by the COVID-19 pandemic.

Achieving High Poliovirus Antibody Seroprevalence in Areas at Risk of Vaccine-Derived Poliovirus Transmission-Niger Experience.

Background Outbreaks of vaccine-derived poliovirus type 2 (VDPV2) continue to expand across Africa. We conducted a serological survey of polio antibodies in high–polio risk areas of Niger to assess risk of poliovirus outbreaks.MethodsChildren between 1 and 5 years of age were enrolled from structures randomly selected using satellite imaging enumeration in Diffa Province, Niger, in July 2019. After obtaining informed consent, dried blood spot cards were collected. Neutralizing antibodies against 3 poliovirus serotypes were detected using microneutralization assay at the Centers for Disease Control and Prevention.ResultsWe obtained analyzable data from 309/322 (95.9%) enrolled children. Seroprevalence of polio antibodies was 290/309 (93.9%), 272/309 (88.0%), and 254/309 (82.2%) for serotypes 1, 2, and 3, respectively. For serotypes 1 and 2, the seroprevalence did not significantly change with age (P = .09 and P = .44, respectively); for serotype 3, it increased with age (from 65% in 1–2-year-olds to 91.1% in 4–5-year olds; P < .001). We did not identify any risk factors for type 2 seronegativity.Conclusions With type 2 seroprevalence close to 90%, the risk of emergence of new cVDPV2 outbreaks in Niger is low; however, the risk of cVDPV2 importations from neighboring countries leading to local transmission persists. Niger should maintain its outbreak response readiness capacity and further strengthen its routine immunization.

The impact of disruptions caused by the COVID-19 pandemic on global polio eradication.

In early 2020, the COVID-19 pandemic led to substantial disruptions in global activities. The disruptions also included intentional and unintentional reductions in health services, including immunization campaigns against the transmission of wild poliovirus (WPV) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2). Building on a recently updated global poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model, we explored the implications of immunization disruption and restrictions of human interactions (i.e., population mixing) on the expected incidence of polio and on the resulting challenges faced by the Global Polio Eradication Initiative (GPEI). We demonstrate that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021 of all polio immunization activities to pre-COVID-19 levels, the GPEI could largely mitigate the impact of COVID-19 to the delays incurred. The relative importance of reduced mixing (leading to potentially decreased incidence) and reduced immunization (leading to potentially increased expected incidence) depends on the timing of the effects. Following resumption of immunization activities, the GPEI will likely face similar barriers to eradication of WPV and elimination of cVDPV2 as before COVID-19. The disruptions from the COVID-19 pandemic may further delay polio eradication due to indirect effects on vaccine and financial resources.

Updated Characterization of Poliovirus Transmission in Pakistan and Afghanistan and the Impacts of Different Outbreak Response Vaccine Options.

BackgroundPakistan and Afghanistan remain the only reservoirs of wild poliovirus transmission. Prior modeling suggested that before the COVID-19 pandemic, plans to stop the transmission of serotype 1 wild poliovirus (WPV1) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2) did not appear on track to succeed.MethodsWe updated an existing poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model for Pakistan and Afghanistan to characterize the impacts of immunization disruptions and restrictions on human interactions (i.e., population mixing) due to the COVID-19 pandemic. We also consider different options for responding to outbreaks and for preventive supplementary immunization activities (SIAs).ResultsThe modeling suggests that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021 of all polio immunization activities to pre-COVID-19 levels, Pakistan and Afghanistan would remain off-track for stopping all transmission through 2023 without improvements in quality.ConclusionsUsing trivalent OPV (tOPV) for SIAs instead of serotype 2 monovalent OPV (mOPV2) offers substantial benefits for ending the transmission of both WPV1 and cVDPV2, because tOPV increases population immunity for both serotypes 1 and 2 while requiring fewer SIA rounds, when effectively delivered in transmission areas.

Hypothetical emergence of poliovirus in 2020: part 1. Consequences of policy decisions to respond using nonpharmaceutical interventions

ABSTRACT Objectives As efforts to control COVID-19 continue, we simulate hypothetical emergence of wild poliovirus assuming an immunologically naïve population. This differs from the current global experience with polio and serves as a model for responding to future pandemics. Methods Applying an established global model, we assume a fully susceptible global population to polioviruses, independently introduce a virus with properties of each of the three stable wild poliovirus serotypes, and explore the impact of strategies that range from doing nothing to seeking global containment and eradication. Results We show the dynamics of paralytic cases as the virus spreads globally. We demonstrate the difficulty of eradication unless aggressive efforts begin soon after initial disease detection. Different poliovirus serotypes lead to different trajectories and burdens of disease. In the absence of aggressive measures, the virus would become globally endemic in 2–10 years, and cumulative paralytic cases would exceed 4–40 million depending on serotype, with the burden of disease shifting to younger ages. Conclusions The opportunity to eradicate emerging infections represents an important public policy choice. If the world first observed the emergence of wild poliovirus in 2020, adopting aggressive control strategies would have been required to prevent a devastating global pandemic.

Poliovirus-nonsusceptible Vero cell line for the World Health Organization global action plan

Polio or poliomyelitis is a disabling and life-threatening disease caused by poliovirus (PV). As a consequence of global polio vaccination efforts, wild PV serotypes 2 and 3 have been eradicated around the world, and wild PV serotype 1-transmitted cases have been largely eliminated except for limited regions. However, vaccine-derived PV, pathogenically reverted live PV vaccine strains, has become a serious issue. For the global eradication of polio, the World Health Organization is conducting the third edition of the Global Action Plan, which is requesting stringent control of potentially PV-infected materials. To facilitate the mission, we generated a PV-nonsusceptible Vero cell subline, which may serve as an ideal replacement of standard Vero cells to isolate emerging/re-emerging viruses without the risk of generating PV-infected materials.

Circulation and Molecular Epidemiology of Enteroviruses in Paralyzed, Immunodeficient and Healthy Individuals in Tunisia, a Country with a Polio-Free Status for Decades.

This report is an overview of enterovirus (EV) detection in Tunisian polio-suspected paralytic cases (acute flaccid paralysis (AFP) cases), healthy contacts and patients with primary immunodeficiencies (PID) during an 11-year period. A total of 2735 clinical samples were analyzed for EV isolation and type identification, according to the recommended protocols of the World Health Organization. Three poliovirus (PV) serotypes and 28 different nonpolio enteroviruses (NPEVs) were detected. The NPEV detection rate was 4.3%, 2.8% and 12.4% in AFP cases, healthy contacts and PID patients, respectively. The predominant species was EV-B, and the circulation of viruses from species EV-A was noted since 2011. All PVs detected were of Sabin origin. The PV detection rate was higher in PID patients compared to AFP cases and contacts (6.8%, 1.5% and 1.3% respectively). PV2 was not detected since 2015. Using nucleotide sequencing of the entire VP1 region, 61 strains were characterized as Sabin-like. Among them, six strains of types 1 and 3 PV were identified as pre-vaccine-derived polioviruses (VDPVs). Five type 2 PV, four strains belonging to type 1 PV and two strains belonging to type 3 PV, were classified as iVDPVs. The data presented provide a comprehensive picture of EVs circulating in Tunisia over an 11-year period, reveal changes in their epidemiology as compared to previous studies and highlight the need to set up a warning system to avoid unnoticed PVs.