Search Results (38)

The detection of “silent” poliovirus (PV) circulation among clinically healthy populations is an important component of supplementary surveillance for poliomyelitis. Migrants from countries or regions where polio is endemic, affected by outbreaks, or at risk may contribute to the introduction of PVs of epidemic significance: wild poliovirus type 1, vaccine-derived polioviruses (VDPVs), or poliovirus type 2 into polio-free countries. Migrant children, refugees under 5 years of age, are considered a “risk group” in Russia and are subject to testing for PVs. During 2014–2023, guided by the algorithm of virological and molecular investigation of acute flaccid paralysis cases recommended by the WHO, 51,548 migrant children, arriving from 40 countries, were examined. Among 4% of children excreting various cytopathogenic viruses, polio excretors accounted for 20.8%. Among the PVs, PV3 was predominant (41.7%), and PV types 2, 1, and a mixture of PVs accounted for, respectively, 28.2%, 18.8%, and 11.3%. All isolates of PVs 1 and 3 were identified as Sabin-like. The detection of five children excreting epidemically significant PV2 (four VDPV2 and one Sabin-like) required an assessment of the risk of dissemination and additional immunization activities. Among 580 identified isolates of NPEV, the most abundant was the E. betacoxsakie species at 73.8% (CVB1–6, E11, E6, E13, E7). Information on NPEVs expands our knowledge of the spectrum of NPEVs circulating among healthy children worldwide, but its prognostic significance is still unclear. The detection of PVs in children from the “risk group” allows targeted anti-epidemic measures and is a significant advantage of this type of supplementary surveillance for polio. Full article

Background: Polio is an infectious viral disease that can cause paralytic complications and death. Despite global efforts to eradicate wild poliovirus, there are ongoing outbreaks globally and the mutated form of paralytic polio, i.e., circulating vaccine-derived poliovirus, is present in Nigeria. Low vaccination uptake and poor sanitation are responsible for outbreaks in countries where polio had previously been eliminated. This review identifies policies, strategies and interventions for polio eradication and assesses their impact on polio vaccine uptake and eradication efforts in Nigeria. Methods: A systematic literature review was conducted and guided by the Population, Intervention, Comparator and Outcome (PICO) framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart, with identified articles appraised using the Critical Appraisal Skills Program appraisal tool. Results: A total of 393 articles were identified, of which 26 articles were included. Key findings indicate polio intervention services, policies and mass campaigns have had a significant impact on eradicating WPV in Nigeria. However, there are gaps in variant polio eradication efforts, with low vaccination uptake, poor surveillance, vaccine hesitancy, lack of community engagement, weaknesses in the healthcare system and other challenges in Nigeria regionally and nationally, posing a risk to public health that threatens the eradication of all forms of polio in Nigeria. Conclusions: Recommendations are suggested for changes to practice and policy to improve polio vaccination uptake in Nigeria and globally in the short-term (1–2 years), mid-term (3–4 years) and long-term (5+ years). Collaborative targeted polio vaccination programs and funding of public health infrastructure are imperative globally alongside national strategic policy intervention frameworks to strengthen the World Health Organization Global Polio Eradication Initiative and improve vaccine uptake and monitoring of vaccine hesitancy. Simultaneous health-literate community engagement is needed to achieve and maintain polio eradication efforts, which must be integrated into national health frameworks and coordinated across the African continent. Full article

Individuals with certain primary immunodeficiency disorders (PID) may be unable to clear poliovirus infection after exposure to oral poliovirus vaccine (OPV). Over time, vaccine-related strains can revert to immunodeficiency-associated vaccine-derived poliovirus (iVDPVs) that can cause paralysis in the patient and potentially spread in communities with low immunity. We reviewed the efforts for detection and management of PID patients with iVDPV infections and the epidemiology through an analysis of 184 cases reported to the World Health Organization (WHO) during 1962–2024 and a review of polio program and literature reports. Most iVDPV patients (79%) reported in the WHO Registry were residents in middle-income countries and almost half (48%) in the Eastern Mediterranean Region. Type 2 iVDPV was most frequently isolated (53%), but a sharp decline was observed after the switch to bivalent OPV in 2016, with only six cases reported during 2017–2024 compared to 63 during 2009–2016. Patients with common variable immunodeficiency have longer excretion of iVDPV than with other PID types. Implementation of sensitive sentinel surveillance to detect cases of iVDPV infection in high-risk countries and offer antiviral treatment to patients is challenged by competition with other health priorities and regulatory hurdles to the compassionate use of investigational antiviral drugs. Full article

In the context of the near-global eradication of wild poliovirus, the significance of non-polio enteroviruses (NPEVs) in causing acute flaccid paralysis (AFP) and their impact on public health has gained increased attention. This research, conducted from 2001 to 2021, examined stool samples from 1597 children under 15 years in São Paulo, Brazil, through the AFP/Poliomyelitis Surveillance Program, detecting NPEVs in 6.9% of cases. Among the 100 NPEV-positive strains analyzed, 90 were genotyped through genomic sequencing of the partial VP1 region, revealing a predominance of EV-B species (58.9%), followed by EV-A (27.8%) and EV-C (13.3%). This study identified 31 unique NPEV types, including EV-A71, CVB2, and E11, as the most prevalent, along with the first documented occurrence of CVA19 in Brazil. These findings emphasize the importance of NPEV genotyping in distinguishing AFP from poliomyelitis, enhancing understanding of these viruses’ epidemiology. Moreover, it ensures that AFP cases are correctly classified, contributing to the effective surveillance and eradication efforts for poliomyelitis. Full article

Background/Objectives: Although wild poliovirus type 2 has been eradicated, the prolonged transmission of the live- attenuated virus contained in the type-2 oral polio vaccine (OPV2) in under-immunized populations has led to the emergence of circulating vaccine-derived poliovirus type 2 (cVDPV2). The novel OPV2 (nOPV2) was designed to be more genetically stable and reduce the chance of cVDPV2 emergence while retaining comparable immunogenicity to the Sabin monovalent OPV2 (mOPV2). This study aimed to estimate the relative reduction in the emergence risk due to the use of nOPV2 instead of mOPV2. Methods: Data on OPV2 vaccination campaigns from May 2016 to 1 August 2024 were analyzed to estimate type-2 OPV-induced immunity in children under 5 years of age. Poliovirus surveillance data were used to estimate seeding dates and classify cVDPV2 emergences as mOPV2- or nOPV2-derived. The expected number of emergences if mOPV2 was used instead of nOPV2 was estimated, accounting for the timing and volume of nOPV2 doses, the known risk factors for emergence from mOPV2, and censoring due to the incomplete observation period for more recent nOPV2 doses. Results: As of 1 August 2024, over 98% of the approximately 1.19 billion nOPV2 doses administered globally were in Africa. We estimate that approximately 76 (95% confidence interval 69–85) index isolates of cVDPV2 emergences would be expected to be detected by 1 August 2024 if mOPV2 had been used instead of nOPV2 in Africa. The 18 observed nOPV2-derived emergences represent a 76% (74–79%) lower risk of emergence by nOPV2 than mOPV2 in Africa. The crude global analysis produced similar results. Key limitations include the incomplete understanding of the drivers of heterogeneity in emergence risk across geographies and variance in the per-dose risk of emergence may be incompletely captured using known risk factors. Conclusions: These results are consistent with the accumulating clinical and field evidence showing the enhanced genetic stability of nOPV2 relative to mOPV2, and this approach has been implemented in near-real time to contextualize new findings during the roll-out of this new vaccine. While nOPV2 has resulted in new emergences of cVDPV2, the number of cVDPV2 emergences is estimated to be approximately four-fold lower than if mOPV2 had been used instead. Full article

The Global Polio Eradication Initiative was adopted by Ghana in 1996, and through robust AFP surveillance was able to interrupt the circulation of wild poliovirus in 2008. However, the country suffered vaccine-derived poliovirus type 2 outbreaks in 2019 and 2022. We conducted a retrospective analysis of all AFP surveillance data received by the polio program in Ghana from 2018 to 2022. An analysis of the WHO performance indicators for evaluating a surveillance system was conducted using Epi Info 3.5.4 and Microsoft Excel. Of the 4832 cases investigated, 56.3% were males, 71.1% comprised children aged 5 years and below, and more than half (65.2%) had received a maximum of three doses of OPV. Over 77% (3028) had a fever at the onset of paralysis, and 67.8% had paralysis progression within 3 days. The non-polio AFP rate of ≥2 and the stool adequacy rate exceeded the target of ≥80% in nearly every study year. The proportion of non-polio enteroviruses isolated surpassed the target of ≥10% in all years except 2018. The AFP surveillance system in Ghana is sensitive and representative. Though the surveillance became more intensive and proactive during the outbreak, the system needs to focus on improving the completeness of the data as well as the timeliness of the arrival of stool specimens within 3 days of collection. Full article

In order to maintain the polio eradication status, it has become evident that the surveillance of cases with acute flaccid paralysis and of environmental samples must be urgently supplemented with the surveillance of poliovirus excretions among individuals with inborn errors of immunity (IEI). All children with IEI were screened for the excretion of poliovirus during a collaborative study conducted by the ICMR-National Institute of Virology, Mumbai Unit, ICMR-National Institute of Immunohaematology, and World Health Organization, India. A seven-month -old male baby who presented with persistent pneumonia and lymphopenia was found to have severe combined immune deficiency (SCID) due to a missense variant in the RAG1 gene. He had received OPV at birth and at 20 weeks. Four stool samples collected at 4 weekly intervals yielded iVDPV type 1. The child’s father, an asymptomatic 32-year-old male, was also found to be excreting iVDPV. A haploidentical hematopoietic stem cell transplant was performed, but the child succumbed due to severe myocarditis and pneumonia three weeks later. We report a rare case of transmission of iVDPV from an individual with IEI to a healthy household contact, demonstrating the threat of the spread of iVDPV from persons with IEI and the necessity to develop effective antivirals. Full article

Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral poliovirus vaccine (OPV) to replace the conventional CCID₅₀ assay, which is both time-consuming and laborious. The MPBT assay was shown to be reproducible, robust and sensitive. The conventional and MPBT assays showed similar results and sensitivity. The MPBT assay can be completed in two to three days, instead of ten days for the conventional assay. To prevent attenuated vaccine strains of poliovirus from reversion to virulence, a novel, genetically stable OPV (nOPV) was developed by modifying the genomes of conventional Sabin strains used in OPV. In this work, we evaluated the MPBT assay as a rapid screening tool to support trivalent nOPV (tnOPV) formulation development by simultaneous titration of the three nOPV strains to confirm stability as needed, for the selection of the lead tnOPV formulation candidate. We first assessed the ability of the MPBT assay to discriminate a 0.5 log₁₀ titer difference by titrating the two tnOPV samples (undiluted and threefold-diluted) on the same plate. Once the assay was shown to be discriminating, we then tested different formulations of tnOPV drug products (DPs) that were subjected to different exposure times at 37 °C (untreated group and treated groups: 2 and 7 days at 37 °C), and to three freeze and thaw (FT) cycles. Final confirmation of the down selected formulation candidates was achieved by performing the conventional CCID₅₀ assay, comparing the stability of untreated and treated groups and FT stability testing on the top three candidates. The results showed that the MPBT assay generates similar titers as the conventional assay. By testing two trivalent samples in the same plate, the assay can differentiate a 0.5 log₁₀ difference between the titers of the tested nOPV samples. Also, the assay was able to detect the gradual degradation of nOPV viruses with different formulation compositions and under different time/temperature conditions and freeze/thaw cycles. We found that there were three tnOPV formulations which met the stability criteria of less than 0.5 log₁₀ loss after 2 days’ exposure to 37 ℃ and after three FT cycles, maintaining the potency of all three serotypes in these formulations. The ability of the MPBT assay to titrate two tnOPV lots (six viruses) in the same plate makes it cheaper and gives it a higher throughput for rapid screening. The assay detected the gradual degradation of the tnOPV and was successful in the selection of optimal formulations for the tnOPV. The results demonstrated that the MPBT method can be used as a stability indicating assay to assess the thermal stability of the nOPV. It can be used for rapid virus titer determination during the vaccine manufacturing process, and in clinical trials. The MPBT assay can be automated and applied for other viruses, including those with no cytopathic effect. Full article

Despite coordinated efforts at global level, through the Global Polio Eradication Initiative (GPEI), poliomyelitis disease (Polio) is still a major public health issue. The wild poliovirus type-1 (WPV1) is still endemic in Afghanistan and Pakistan, and new circulations of the WPV1 were confirmed in southeast Africa in 2021, in Malawi and Mozambique. The circulating vaccine derived polioviruses (cVDPV) are also causing outbreaks worldwide. The Task Force for Global Health (TFGH)’s Polio Surge Capacity Support Program, established in 2019, is an effort to reinforce the existing partnership with the GPEI to strengthen countries’ capacities for polio outbreak preparedness and response. In four years, its coordinated efforts with GPEI partners have resulted in a remarkable improvement in the early detection of poliovirus circulation and reducing the missed children gaps in many countries. However, these encouraging results cannot hide an increasingly complex programmatic environment with numerous funding and operational challenges. Full article

As the Global Polio Eradication Initiative (GPEI) strategizes towards the final steps of eradication, routine immunization schedules evolve, and high-quality vaccination campaigns and surveillance systems remain essential. New tools are consistently being developed, such as the novel oral poliovirus vaccine to combat outbreaks more sustainably, as well as non-infectiously manufactured vaccines such as virus-like particle vaccines to eliminate the risk of resurgence of polio on the eve of a polio-free world. As the GPEI inches towards eradication, re-strategizing in the face of evolving challenges and preparing for unknown risks in the post-certification era are critical. Full article

Polio-associated paralysis is one of the diseases under national surveillance in the Democratic Republic of the Congo (DRC). Although it has become relatively rare due to control measures, non-polio paralysis cases are still reported and constitute a real problem, especially for etiological diagnosis, which is necessary for better management and response. From September 2022 to April 2023, we investigated acute flaccid paralysis (AFP) cases in Kinshasa following an alert from the Provincial Division of Health. All suspected cases and their close contacts were investigated and sampled. Among the 57 sampled patients, 21 (36.8%) were suspects, and 36 (63.2%) were contacts. We performed several etiological tests available in the laboratory, targeting viruses, including Poliovirus, Influenza virus, SARS-CoV-2, Enterovirus, and arboviruses. No virus material was detected, but the serological test (ELISA) detected antibodies against Chikungunya Virus, i.e., 47.4% (27/57) for IgM and 22.8% (13/57) for IgG. Among suspected cases, we detected 33.3% (7/21) with anti-Chikungunya IgM and 14.3% (3/21) of anti-Chikungunya IgG. These results highlight the importance of enhancing the epidemiological surveillance of Chikungunya. Full article

More than 100 types of non-polio enteroviruses (NPEVs) are ubiquitous in the human population and cause a variety of symptoms ranging from very mild to meningitis and acute flaccid paralysis (AFP). Much of the information regarding diverse pathogenic properties of NPEVs comes from the surveillance of poliovirus, which also yields NPEV. The analysis of 265 NPEV isolations from 10,433 AFP cases over 24 years of surveillance and more than 2500 NPEV findings in patients without severe neurological lesions suggests that types EV-A71, E13, and E25 were significantly associated with AFP. EV-A71 was also significantly more common among AFP patients who had fever at the onset and residual paralysis compared to all AFP cases. In addition, a significant disparity was noticed between types that were common in humans (CV-A2, CVA9, EV-A71, E9, and E30) or in sewage (CVA7, E3, E7, E11, E12, and E19). Therefore, there is significant evidence of non-polio viruses being implicated in severe neurological lesions, but further multicenter studies using uniform methodology are needed for a definitive conclusion. Full article

Recently, genetically stable novel OPVs (nOPV) were developed by modifying the genomes of Sabin viruses of conventional OPVs to reduce the risk of reversion to neurovirulence and therefore the risk of generating circulating vaccine-derived polioviruses. There is a need for specific and sensitive methods for the identification and quantification of nOPV viruses individually and in mixtures for clinical trials and potentially for manufacturing quality control and environmental surveillance. In this communication, we evaluated and improved the quantitative multiplex one-step reverse transcriptase polymerase chain reaction (qmosRT-PCR) assay for the identification and quantification of nOPV viruses in samples with different formulations and virus concentrations and in virus-spiked stool samples. The assay was able to specifically identify at least 1 log₁₀ CCID₅₀/mL of each serotype in the presence of the two other serotypes at high concentrations (6–7 log₁₀ CCID₅₀/mL) in the same sample. In addition, the lowest viral concentration that the assay was able to detect in stool samples was 17 CCID₅₀/mL for nOPV1 and nOPV2 viruses and 6 CCID₅₀/mL for nOPV3. We also found high correlation between the expected and observed (by qmosRT-PCR) concentrations of spiked viruses in stool samples for all three nOPV viruses, with R-squared values above 0.95. The analysis of samples collected from an nOPV2 clinical trial showed that 100% of poliovirus type 2 was detected and few samples showed the presence of type 1 and 3 residuals from previous vaccinations with bOPV (at least 4 weeks prior vaccination with nOPV2), confirming the high sensitivity of the method. The qmosRT-PCR was specific and sensitive for the simultaneous identification and quantification of all three nOPV viruses. It can be used as an identity test during the nOPV manufacturing process and in evaluation of virus excretion in nOPV clinical trials. Full article

Polio surveillance in the Global Polio Eradication Initiative has been conducted with virus isolation from stool samples of acute flaccid paralysis (AFP) cases. Under the current biorisk management/regulations, challenges arise in the timelines of the report, sensitivity of the test and containment of poliovirus (PV) isolates. In the present study, we evaluated protocols of previously reported direct detection (DD) methods targeting the VP1 or VP4–VP2 regions of the PV genome in terms of sensitivity and sequencability. An optimized protocol targeting the entire-capsid region for the VP1 sequencing showed a high sensitivity (limit of detection = 82 copies of PV genome) with a simpler and faster reaction than reported ones (i.e., with the addition of all the primers at the start of the reaction, the RT-PCR reaction finishes within 2.5 h). The DD methods targeting the VP1 region detected PV in 60 to 80% of PV-positive stool samples from AFP cases; however, minor populations of PV strains in the samples with virus mixtures were missed by the methods. Sequencability of the DD methods was primarily determined by the efficiency of the PCRs for both Sanger and nanopore sequencing. The DD method targeting the VP4–VP2 region showed higher sensitivity than that targeting the VP1 region (limit of detection = 25 copies of PV genome) and successfully detected PV from all the stool samples examined. These results suggest that DD methods are effective for the detection of PV and that further improvement of the sensitivity is essential to serve as an alternative to the current polio surveillance algorithm. Full article

Wastewater surveillance (WWS) was developed in the early 1960s for the detection of poliovirus (PV) circulation in the population. It has been used to monitor several pathogens, including non-polio enteroviruses (NPEVs), which are increasingly recognised as causes of morbidity in children. However, when applying WWS to a new pathogen, it is important to consider the purpose of such a study as well as the suitability of the chosen methodology. With this purpose, the European Non-Polio Enterovirus Network (ENPEN) organised an expert webinar to discuss its history, methods, and applications; its evolution from a culture-based method to molecular detection; and future implementation of next generation sequencing (NGS). The first simulation experiments with PV calculated that a 400 mL sewage sample is sufficient for the detection of viral particles if 1:10,000 people excrete poliovirus in a population of 700,000 people. If the method is applied correctly, several NPEV types are detected. Despite culture-based methods remaining the gold standard for WWS, direct methods followed by molecular-based and sequence-based assays have been developed, not only for enterovirus but for several pathogens. Along with case-based sentinel and/or syndromic surveillance, WWS for NPEV and other pathogens represents an inexpensive, flexible, anonymised, reliable, population-based tool for monitoring outbreaks and the (re)emergence of these virus types/strains within the general population. Full article