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Bulletin of the World Health... Jan 2004Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines... (Review)
Review
Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence.
Topics: Child; Disease Outbreaks; Dominican Republic; Egypt; Haiti; Humans; Immunization Programs; Madagascar; Philippines; Poland; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; RNA, Viral; Risk Factors; Virus Shedding; World Health Organization
PubMed: 15106296
DOI: No ID Found -
Vaccine Aug 2017The European Region, certified polio-free in 2002, remains at risk of wild poliovirus reintroduction and emergence of circulating vaccine-derived polioviruses (cVDPV)... (Review)
Review
BACKGROUND
The European Region, certified polio-free in 2002, remains at risk of wild poliovirus reintroduction and emergence of circulating vaccine-derived polioviruses (cVDPV) until global polio eradication is achieved, as demonstrated by the cVDPV1 outbreak in Ukraine in 2015.
METHODS
We reviewed epidemiologic, clinical and virology data on cVDPV cases, surveillance and immunization coverage data, and reports of outbreak-related surveys, country missions, and expert group meetings.
RESULTS
In Ukraine, 3-dose polio vaccine coverage declined from 91% in 2008 to 15% by mid-2015. In summer, 2015, two unrelated children from Zakarpattya province were paralyzed by a highly divergent cVDPV1. The isolates were 20 and 26 nucleotide divergent from prototype Sabin strain (with 18 identical mutations) consistent with their common origin and ∼2-year evolution. Outbreak response recommendations developed with international partner support included conducting three nationwide supplementary immunization activities (SIAs) with tOPV, strengthening surveillance and implementing communication interventions. SIAs were conducted during October 2015-February 2016 (officially reported coverage, round 1-64.4%, round 2-71.7%, and round 3-80.7%). Substantial challenges to outbreak response included lack of high-level support, resistance to OPV use, low perceived risk of polio, widespread vaccine hesitancy, anti-vaccine media environment, economic crisis and military conflict. Communication activities improved caregiver awareness of polio and confidence in vaccination. Surveillance was enhanced but did not consistently meet applicable performance standards. Post-outbreak assessments concluded that cVDPV1 transmission in Ukraine has likely stopped following the response, but significant gaps in population immunity and surveillance remained.
CONCLUSIONS
Chronic under-vaccination in Ukraine resulted in the accumulation of children susceptible to polioviruses and created favorable conditions for VDPV1 emergence and circulation, leading to the outbreak. Until programmatic gaps in immunization and surveillance are addressed, Ukraine will remain at high-risk for VDPV emergence and circulation, as well as at risk for other vaccine-preventable diseases.
Topics: Adolescent; Child; Disease Eradication; Disease Outbreaks; Female; Humans; Infant; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Ukraine; Vaccination; Vaccination Refusal
PubMed: 28528761
DOI: 10.1016/j.vaccine.2017.04.036 -
Journal of Clinical Microbiology Feb 2018With poliovirus eradication nearing, few pockets of active wild poliovirus (WPV) transmission remain in the world. Intratypic differentiation (ITD) plays a crucial part...
With poliovirus eradication nearing, few pockets of active wild poliovirus (WPV) transmission remain in the world. Intratypic differentiation (ITD) plays a crucial part in laboratory surveillance as the molecular detection method that can identify and distinguish wild and vaccine-like polioviruses isolated from acute flaccid paralysis cases or environmental sources. The need to detect new variants of WPV serotype 1 (WPV1) and the containment of all serotype 2 polioviruses (PV2) in 2015 required changes to the previous version of the method. The ITD version 5.0 is a set of six real-time reverse transcription-PCR (rRT-PCR) assays that serve as accurate diagnostic tools to easily detect and differentiate PV serotypes and genotypes. We describe the creation and properties of quantitation standards, including 16 control RNA transcripts and nine plaque-isolated viruses. All ITD rRT-PCR assays were validated using these standards, and the limits of detection were determined for each assay. We designed and pilot tested two new assays targeting recently circulating WPV1 genotypes and all PV2 viruses. The WPV1 assay had 99.1% specificity and 100% sensitivity, and the PV2 assay had 97.7% specificity and 92% sensitivity. Before proceeding to the next step in the global poliovirus eradication program, we needed to gain a better understanding of the performance of the ITD 5.0 suite of molecular assays and their limits of detection and specificities. The findings and conclusions in this evaluation serve as building blocks for future development work.
Topics: Disease Eradication; Epidemiological Monitoring; Genotype; Humans; Molecular Typing; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; RNA, Viral; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Serogroup
PubMed: 29212703
DOI: 10.1128/JCM.01624-17 -
Lancet (London, England) Jan 2021Two novel type 2 oral poliovirus vaccine (OPV2) candidates, novel OPV2-c1 and novel OPV2-c2, designed to be more genetically stable than the licensed Sabin monovalent... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in healthy adults: two clinical trials.
BACKGROUND
Two novel type 2 oral poliovirus vaccine (OPV2) candidates, novel OPV2-c1 and novel OPV2-c2, designed to be more genetically stable than the licensed Sabin monovalent OPV2, have been developed to respond to ongoing polio outbreaks due to circulating vaccine-derived type 2 polioviruses.
METHODS
We did two randomised studies at two centres in Belgium. The first was a phase 4 historical control study of monovalent OPV2 in Antwerp, done before global withdrawal of OPV2, and the second was a phase 2 study in Antwerp and Ghent with novel OPV2-c1 and novel OPV2-c2. Eligible participants were healthy adults aged 18-50 years with documented history of at least three polio vaccinations, including OPV in the phase 4 study and either OPV or inactivated poliovirus vaccine (IPV) in the novel OPV2 phase 2 study, with no dose within 12 months of study start. In the historical control trial, participants were randomly assigned to either one dose or two doses of monovalent OPV2. In the novel OPV2 trial, participants with previous OPV vaccinations were randomly assigned to either one or two doses of novel OPV2-c1 or to one or two doses of novel OPV2-c2. IPV-vaccinated participants were randomly assigned to receive two doses of either novel OPV2-c1, novel OPV2-c2, or placebo. Vaccine administrators were unmasked to treatment; medical staff performing safety and reactogenicity assessments or blood draws for immunogenicity assessments were masked. Participants received the first vaccine dose on day 0, and a second dose on day 28 if assigned to receive a second dose. Primary objectives were assessments and comparisons of safety up to 28 days after each dose, including solicited adverse events and serious adverse events, and immunogenicity (seroprotection rates on day 28 after the first vaccine dose) between monovalent OPV2 and the two novel OPV2 candidates. Primary immunogenicity analyses were done in the per-protocol population. Safety was assessed in the total vaccinated population-ie, all participants who received at least one dose of their assigned vaccine. The phase 4 control study is registered with EudraCT (2015-003325-33) and the phase 2 novel OPV2 study is registered with EudraCT (2018-001684-22) and ClinicalTrials.gov (NCT04544787).
FINDINGS
In the historical control study, between Jan 25 and March 18, 2016, 100 volunteers were enrolled and randomly assigned to receive one or two doses of monovalent OPV2 (n=50 in each group). In the novel OPV2 study, between Oct 15, 2018, and Feb 27, 2019, 200 previously OPV-vaccinated volunteers were assigned to the four groups to receive one or two doses of novel OPV2-c1 or novel OPV2-c2 (n=50 per group); a further 50 participants, previously vaccinated with IPV, were assigned to novel OPV2-c1 (n=17), novel OPV2-c2 (n=16), or placebo (n=17). All participants received the first dose of assigned vaccine or placebo and were included in the total vaccinated population. All vaccines appeared safe; no definitely vaccine-related withdrawals or serious adverse events were reported. After first doses in previously OPV-vaccinated participants, 62 (62%) of 100 monovalent OPV2 recipients, 71 (71%) of 100 recipients of novel OPV2-c1, and 74 (74%) of 100 recipients of novel OPV2-c2 reported solicited systemic adverse events, four (monovalent OPV2), three (novel OPV2-c1), and two (novel OPV2-c2) of which were considered severe. In IPV-vaccinated participants, solicited adverse events occurred in 16 (94%) of 17 who received novel OPV2-c1 (including one severe) and 13 (81%) of 16 who received novel OPV2-c2 (including one severe), compared with 15 (88%) of 17 placebo recipients (including two severe). In previously OPV-vaccinated participants, 286 (97%) of 296 were seropositive at baseline; after one dose, 100% of novel OPV2 vaccinees and 97 (97%) of monovalent OPV2 vaccinees were seropositive.
INTERPRETATION
Novel OPV2 candidates were as safe, well tolerated, and immunogenic as monovalent OPV2 in previously OPV-vaccinated and IPV-vaccinated adults. These data supported the further assessment of the vaccine candidates in children and infants.
FUNDING
University of Antwerp and Bill & Melinda Gates Foundation.
Topics: Adult; Belgium; Female; Humans; Immunogenicity, Vaccine; Male; Middle Aged; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Vaccination
PubMed: 33308429
DOI: 10.1016/S0140-6736(20)32541-1 -
The Indian Journal of Medical Research May 2013India's success in eliminating wild polioviruses (WPVs) has been acclaimed globally. Since the last case on January 13, 2011 success has been sustained for two years. By... (Review)
Review
India's success in eliminating wild polioviruses (WPVs) has been acclaimed globally. Since the last case on January 13, 2011 success has been sustained for two years. By early 2014 India could be certified free of WPV transmission, if no indigenous transmission occurs, the chances of which is considered zero. Until early 1990s India was hyperendemic for polio, with an average of 500 to 1000 children getting paralysed daily. In spite of introducing trivalent oral poliovirus vaccine (tOPV) in the Expanded Programme on Immunization (EPI) in 1979, the burden of polio did not fall below that of the pre-EPI era for a decade. One of the main reasons was the low vaccine efficacy (VE) of tOPV against WPV types 1 and 3. The VE of tOPV was highest for type 2 and WPV type 2 was eliminated in 1999 itself as the average per-capita vaccine coverage reached 6. The VE against types 1 and 3 was the lowest in Uttar Pradesh and Bihar, where the force of transmission of WPVs was maximum on account of the highest infant-population density. Transmission was finally interrupted with sustained and extraordinary efforts. During the years since 2004 annual pulse polio vaccination campaigns were conducted 10 times each year, virtually every child was tracked and vaccinated - including in all transit points and transport vehicles, monovalent OPV types 1 and 3 were licensed and applied in titrated campaigns according to WPV epidemiology and bivalent OPV (bOPV, with both types 1 and 3) was developed and judiciously deployed. Elimination of WPVs with OPV is only phase 1 of polio eradication. India is poised to progress to phase 2, with introduction of inactivated poliovirus vaccine (IPV), switch from tOPV to bOPV and final elimination of all vaccine-related and vaccine-derived polioviruses. True polio eradication demands zero incidence of poliovirus infection, wild and vaccine.
Topics: Disease Eradication; Humans; Immunization Programs; Incidence; India; Paralysis; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Population Density
PubMed: 23760372
DOI: No ID Found -
Current Protocols in Microbiology 2013Poliovirus (PV) is the prototypical picornavirus. It is a non-enveloped RNA virus with a small (~7.5-kb) genome of positive polarity. cDNA clones of several strains are...
Poliovirus (PV) is the prototypical picornavirus. It is a non-enveloped RNA virus with a small (~7.5-kb) genome of positive polarity. cDNA clones of several strains are available, and infectious virus can be produced by the transfection of in vitro-transcribed viral genomes into an appropriate host cell. The ease of genetic studies in poliovirus is a primary reason that it has long served as a model to study RNA virus biology, pathogenesis, and evolution. Protocols for the generation and characterization of PV mutants are presented.
Topics: Genetics, Microbial; Mutation; Poliovirus; Virology
PubMed: 23686829
DOI: 10.1002/9780471729259.mc15h02s29 -
MMWR. Morbidity and Mortality Weekly... May 2022In 1988, the World Health Assembly established the Global Polio Eradication Initiative (GPEI). Since then, wild poliovirus (WPV) cases have decreased approximately...
In 1988, the World Health Assembly established the Global Polio Eradication Initiative (GPEI). Since then, wild poliovirus (WPV) cases have decreased approximately 99.99%, and WPV types 2 and 3 have been declared eradicated. Only Afghanistan and Pakistan have never interrupted WPV type 1 (WPV1) transmission. This report describes global progress toward polio eradication during January 1, 2020-April 30, 2022, and updates previous reports (1,2). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.* Five WPV1 cases were reported from Afghanistan and Pakistan in 2021, compared with 140 in 2020. In 2022 (as of May 5), three WPV1 cases had been reported: one from Afghanistan and two from Pakistan. WPV1 genetically linked to virus circulating in Pakistan was identified in Malawi in a child with paralysis onset in November 2021. Circulating vaccine-derived polioviruses (cVDPVs), with neurovirulence and transmissibility similar to that of WPV, emerge in populations with low immunity following prolonged circulation of Sabin strain oral poliovirus vaccine (OPV) (3). During January 2020-April 30, 2022, a total of 1,856 paralytic cVDPV cases were reported globally: 1,113 in 2020 and 688 in 2021, including cases in Afghanistan and Pakistan. In 2022 (as of May 5), 55 cVDPV cases had been reported. Intensified programmatic actions leading to more effective outbreak responses are needed to stop cVDPV transmission. The 2022-2026 GPEI Strategic Plan objective of ending WPV1 transmission by the end of 2023 is attainable (4). However, the risk for children being paralyzed by polio remains until all polioviruses, including WPV and cVDPV, are eradicated.
Topics: Child; Disease Eradication; Humans; Immunization Programs; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Population Surveillance
PubMed: 35552352
DOI: 10.15585/mmwr.mm7119a2 -
The Journal of Infectious Diseases Jan 2021
Topics: Child; Humans; Lithuania; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 32621744
DOI: 10.1093/infdis/jiaa393 -
Polish Journal of Microbiology Mar 2018As a complement to the active search for cases of acute flaccid paralysis, environmental sampling was conducted from January to December 2011, to test for any putative...
As a complement to the active search for cases of acute flaccid paralysis, environmental sampling was conducted from January to December 2011, to test for any putative polio revertants and recombinants in sewage. A total of 165 environmental samples were obtained and analyzed for the presence of polioviruses by use of cell culture (L20B, RD and Caco-2) followed by neutralization and reverse-transcription polymerase chain reaction. Out of the 31 CPE positive samples, 26 contained one and 5 two different serotypes, yielding a total of 36 PVs. The microneutralization test revealed the presence of 7, 10 and 19 strains belonging to poliovirus serotype 1, 2 and 3, respectively. The genomic variability of 36 poliovirus strains was examined by the restriction fragment length polymorphism assay (RFLP). By combined analyses of two distant, polymorphic segments of the viral genome, one situated in the capsid protein VP1 coding region and the other in the 3D-polymerase coding region, we screened for the putative poliovirus revertants and recombinants. All detected PVs were classified as vaccine strains on the basis of RFLP-VP1 test. None of wild-type PVs or vaccine derived polioviruses were detected. RFLP assay also revealed the presence of 11 recombinants in 3D-polymerase coding region. Nine isolates appeared to be S3/S2, one S3/S1 and S1/S2 recombinant in analyzed 3Dpol region. This study revealed, through environmental monitoring, the introduction of SL PVs into the population associated with the routine use of OPV in Poland before the April 2016. Our findings demonstrate the usefulness of environmental surveillance in the overall polio eradication program.
Topics: Capsid Proteins; Environmental Monitoring; Genome, Viral; Humans; Neutralization Tests; Poland; Poliovirus; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Sequence Analysis, DNA; Serogroup; Sewage
PubMed: 30015429
DOI: 10.5604/01.3001.0011.6147 -
Applied and Environmental Microbiology Mar 2017In the context of poliomyelitis eradication, a reinforced supplementary laboratory surveillance of enteroviruses was implemented in Greece. Between 2008 and 2014, the...
In the context of poliomyelitis eradication, a reinforced supplementary laboratory surveillance of enteroviruses was implemented in Greece. Between 2008 and 2014, the Hellenic Polioviruses/Enteroviruses Reference Laboratory performed detailed supplementary surveillance of circulating enteroviruses among healthy individuals in high-risk population groups, among immigrants from countries in which poliovirus is endemic, and in environmental samples. In total, 722 stool samples and 179 sewage water samples were included in the study. No wild-type polioviruses were isolated during these 7 years of surveillance, although two imported vaccine polioviruses were detected. Enterovirus presence was recorded in 25.3 and 25.1% of stool and sewage water samples, respectively. Nonpolio enteroviruses isolated from stool samples belonged to species A, B, or C; coxsackievirus A24 was the most frequently identified serotype. Only enteroviruses of species B were identified in sewage water samples, including four serotypes of echoviruses and four serotypes of coxsackie B viruses. Phylogenetic analysis revealed close genetic relationships among virus isolates from sewage water samples and stool samples, which in most cases fell into the same cluster. To the best of our knowledge, this is the first study to compare enterovirus serotypes circulating in fecal specimens of healthy individuals and environmental samples, emphasizing the burden of enterovirus circulation in asymptomatic individuals at high risk. Given that Greece continues to receive a large number of short-term arrivals, students, migrants, and refugees from countries in which poliovirus is endemic, it is important to guarantee high-quality surveillance in order to maintain its polio-free status until global eradication is achieved. This article summarizes the results of supplementary poliovirus surveillance in Greece and the subsequent characterization of enteroviral circulation in human feces and the environment. The examination of stool samples from healthy refugees and other individuals in "high-risk" groups for poliovirus enables the identification of enterovirus cases and forms the basis for further investigation of the community-level risk of viral transmission. In addition, the examination of composite human fecal samples through environmental surveillance links poliovirus and nonpoliovirus isolates from unknown individuals to populations served by the sewage or wastewater system. Supplementary surveillance is necessary to comply with the prerequisites imposed by the World Health Organization for monitoring the emergence of vaccine-derived polioviruses, reemergence of wild polioviruses, or disappearance of all vaccine-related strains in order for countries such as Greece to maintain their polio-free status and contribute to global poliovirus eradication.
Topics: Enterovirus; Enterovirus B, Human; Enterovirus Infections; Environment; Environmental Monitoring; Feces; Greece; Humans; Laboratories; Molecular Typing; Phylogeny; Poliomyelitis; Poliovirus; Population Surveillance; Sewage; Wastewater
PubMed: 28039136
DOI: 10.1128/AEM.02872-16