Wild poliovirus makes comeback in Afghanistan and Pakistan.

2024 target of ending all transmission will likely be missed.

Application of MPBT Assay for Multiplex Determination of Infectious Titers and for Selection of the Optimal Formulation for the Trivalent Novel Oral Poliovirus Vaccine.

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.

Intestinal mucosal immunity is unimportant for polio eradication: the failure of oral polio vaccination.

AIMS: To explore if intestinal immunity induced by infection with live viruses in the oral poliovirus vaccine (OPV) is essential, necessary or even helpful in interrupting transmission of wild poliovirus (WPV) for global polio eradication. METHODS: We reviewed the biology of virus-host interactions in WPV infection and its alterations by OPV-induced immunity for direct evidence of the usefulness of intestinal immunity. We also explored indirect evidence by way of the effect of the inactivated poliovirus vaccine (IPV) on the biology and on transmission dynamics of WPV. RESULTS: Immunity, systemic and intestinal, induced by infection with WPV or vaccine viruses, does not prevent re-infection with WPV or vaccine viruses respectively, when exposed. Such re-infected hosts shed virus in the throat and in faeces and are sources of further transmission. Immunity protects against polio paralysis-hence reinfection always remain asymptommatic and silent. CONCLUSION: Vaccine virus-induced intestinal immunity is not necessary for polio eradication. The continued and intensive vaccination efforts using OPV under the assumption of its superiority over IPV have resulted in the well-known undesirable effects, namely vaccine associated paralytic polio and the emergence of de-attenuated circulating vaccine-derived polioviruses, in addition to the delay in completing global WPV eradication.

Persistent Transmission of Circulating Vaccine-Derived Poliovirus - Somalia, January 2017-March 2024.

Since the launch of the Global Polio Eradication Initiative in 1988, substantial progress has been made in the interruption of wild poliovirus (WPV) transmission worldwide: global eradication of WPV types 2 and 3 were certified in 2015 and 2019, respectively, and endemic transmission of WPV type 1 continues only in Afghanistan and Pakistan. After the synchronized global withdrawal of all serotype 2 oral poliovirus vaccines (OPVs) in 2016, widespread outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2) have occurred, which are linked to areas with low population immunity to poliovirus. Officials in Somalia have detected ongoing cVDPV2 transmission since 2017. Polio vaccination coverage and surveillance data for Somalia were reviewed to assess this persistent transmission. During January 2017-March 2024, officials in Somalia detected 39 cVDPV2 cases in 14 of 20 regions, and transmission has spread to neighboring Ethiopia and Kenya. Since January 2021, 28 supplementary immunization activities (SIAs) targeting cVDPV2 were conducted in Somalia. Some parts of the country are security-compromised and inaccessible for vaccination campaigns. Among 1,921 children with nonpolio acute flaccid paralysis, 231 (12%) had not received OPV doses through routine immunization or SIAs, 95% of whom were from the South-Central region, and 60% of whom lived in inaccessible districts. Enhancing humanitarian negotiation measures in Somalia to enable vaccination of children in security-compromised areas and strengthening campaign quality in accessible areas will help interrupt cVDPV2 transmission.

Progress Toward Poliomyelitis Eradication - Worldwide, January 2022-December 2023.

In 1988, poliomyelitis (polio) was targeted for eradication. Global efforts have led to the eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3), with only WPV type 1 (WPV1) remaining endemic, and only in Afghanistan and Pakistan. This report describes global polio immunization, surveillance activities, and poliovirus epidemiology during January 2022-December 2023, using data current as of April 10, 2024. In 2023, Afghanistan and Pakistan identified 12 total WPV1 polio cases, compared with 22 in 2022. WPV1 transmission was detected through systematic testing for poliovirus in sewage samples (environmental surveillance) in 13 provinces in Afghanistan and Pakistan, compared with seven provinces in 2022. The number of polio cases caused by circulating vaccine-derived polioviruses (cVDPVs; circulating vaccine virus strains that have reverted to neurovirulence) decreased from 881 in 2022 to 524 in 2023; cVDPV outbreaks (defined as either a cVDPV case with evidence of circulation or at least two positive environmental surveillance isolates) occurred in 32 countries in 2023, including eight that did not experience a cVDPV outbreak in 2022. Despite reductions in paralytic polio cases from 2022, cVDPV cases and WPV1 cases (in countries with endemic transmission) were more geographically widespread in 2023. Renewed efforts to vaccinate persistently missed children in countries and territories where WPV1 transmission is endemic, strengthen routine immunization programs in countries at high risk for poliovirus transmission, and provide more effective cVDPV outbreak responses are necessary to further progress toward global polio eradication.

Vaccine-associated paralytic poliomyelitis in oral polio vaccine recipients: disproportionality analysis using VAERS and systematic review.

BACKGROUND: Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of oral poliovirus vaccines (OPV), particularly affecting immunodeficient individuals. RESEARCH DESIGN AND METHODS: This study aimed to (1) Assess the association between OPV and VAPP using Vaccine Adverse Event Reporting System (VAERS) database (2) Outline patient characteristics and risk factors associated with the occurrence of VAPP in OPV recipients through a systematic review of case reports and case series. A disproportionality analysis was conducted using the data from VAERS, encompassing adverse events reported from 1990 till February 2023. Additionally, we conducted a systematic review of case reports and case series using PubMed, Scopus, and Embase databases. RESULTS: The VAERS data revealed 130 VAPP reports among 1,739,903 OPV linked adverse events, with year 2010 reporting the strongest association. The systematic review of 37 studies highlighted VAPP occurrence within 2 months to 4 years post-vaccination, typically with acute flaccid paralysis. Immunodeficiency and perianal abscess emerged as major risk factors. Out of the 37 included studies, 27 showed consistent causal association of VAPP with OPV using WHO-AEFI causality assessment tool. CONCLUSION: The study emphasized the seriousness of VAPP and highlights its association with OPV, identifying immunodeficiency as a prominent contributor to VAPP manifestation.

The history of polio vaccination with "Sabin's OPV" 60 years after its introduction in Italy: an unforgivable "delay".

In the spring of 1964, polio vaccination with the oral vaccine developed by Albert Sabin began in Italy. Polio was feared in the world and in Italy. Thus, between 1957 and the beginning of 1958, Italian children began receiving the "Salk vaccine", though the results were not particularly convincing. In July 1960, the international scientific community was able to verify the data from the mass testing of the Sabin vaccine. It became clear that the OPV, could prevent the virus from multiplying, thereby providing greater protection and determining the eradication of the disease. In 1960 over 70 million people in the USSR alone had already received the oral vaccine and mass vaccination in the USA would start in March 1961. However, in Italy there was no similar initiative; only later the new vaccine was accepted but was not made compulsory at the beginning. As a result of the commission's report, registration of the "Polioral" vaccine, was authorized in September 1962 but the sale of the vaccine was not authorized until November 1963. At the beginning of 1964, the production of "Polioral" started and the product was marketed and on the 1 st of March 1964, anti-polio vaccination with the "Sabin anti-polio vaccine" also began in Italy. This manuscript focuses on a crucial issue about a historical delay for public health and it points out as the preparation and diffusion of the Sabin polio vaccine demonstrates that decisions regarding health treatments, and specifically vaccination campaigns, must be based exclusively on the results of clinical studies and on independent evaluation by the scientific community. This process ensures trust in vaccines, adequate protection of public health andcitizens' well-being.

Immunogenicity evaluation of primary polio vaccination schedule with inactivated poliovirus vaccines and bivalent oral poliovirus vaccine.

BACKGROUND: To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). METHODS: A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. RESULTS: There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group. CONCLUSIONS: Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.

Report offers harsh verdict on global polio vaccine switch.

Draft evaluation calls 2016 decision to change oral vaccines a "failure".

Impact of COVID -19 on expanded programme on Immunisation in District Dir lower Khyber Pakhtunkhwa.

Objectives: To study the impact of coronavirus disease-2019 on Expanded Programme on Immunisation in a rural setting. METHODS: The descriptive, cross-sectional study was conducted in five union councils of District Dir Lower, in the Khyber Pakhtunkhwa province of Pakistan. Data was collected from March to August 2020, which was a period of lockdowns in the wake of the coronavirus disease-2019, and then from March to August 2021. The sample comprised children aged <2 years. Data was analysed using SPSS 25. RESULTS: Of the 330 children, 210(63.6%) were boys, and 120(36.4%) were girls, and all 330(100%) were located in rural areas. First-phase data showed that the maximum coverage rate of immunisation was 258(78.2%) noted in OPV1(Oral Polio Vaccine) Penta1(Pentavalent vaccine), PCV10-1 (Pneumococcal pneumonia) and Rota 1(Rota Vaccine), and the least vaccination rate was 68.2% for Measle-1. In the second phase, 23% incline was noted in Measles-2 vaccination, followed by 16.3% in OPV2, Penta 2, PCV10-2 and Rota 2, 16% in Measles-1, 14% in OPV-3, Penta-3, PCV10-3, Rota-3 and IPV, 11.5% in OPV-1, Penta-1, PCV10-1, and Rota-1, and 10.6% in OPV-0 and BCG-0. CONCLUSIONS: Immunisation programme was affected by lockdowns during the active phase of the coronavirus disease-2019 pandemic.

Monitoring the evolution of vaccine-derived poliovirus in East and Southern African countries, 2010 - 2021.

Introduction: the Africa region was certified indigenous wild poliovirus-free in August 2020. Countries in East and Southern Africa have, during acute flaccid paralysis (AFP) and environmental surveillance (ES), detected equally concerning vaccine-derived polioviruses (VDPVs) that have not been systematically documented to guide programming in the sub-region. The study documents trends and salient observations of the VDPVs by country of detection, for 11 years from 2010 to 2021. Methods: we conducted secondary data analysis, a descriptive study design, by deploying field and laboratory of AFP and environmental surveillance databases of the 20 East and Southern African countries from 2010 to 2021. Results: a total of 318 VDPVs were reported over the study period. The majority were from AFP cases (58.8%) and the rest equally distributed between healthy community children and environmental surveillance sources. More polioviruses were detected after 2016 than during the period before. We observed that more boys were affected by VDPVs compared to girls. Children under 5 years were more affected than other age groups, with a mean age of 3.6 years. Delay of samples in the field seemed to increase the likelihood of not reporting VDPVs and not mounting timely public health detailed investigations and vaccination responses. Conclusion: the study provides useful evolutional trends of VDPVs for surveillance and vaccination programming. We also noted that the VDPV2s have been increasing after the 2016 tOPV to oral polio vaccine (bOPV) switch. The COVID-19 pandemic emergence in 2020, led to a decline in AFP, ES surveillance, and immunization activities. Our findings point to the need to implement enhanced tailored childhood immunization recovery strategies and to speed up the use of inactivated polio vaccine (IPV) to boost population immunity.

Exploring the path to polio eradication: insights from consecutive seroprevalence surveys among Pakistani children.

Introduction: After trivalent oral poliovirus vaccine (tOPV) cessation, Pakistan has maintained immunity to type 2 poliovirus by administering inactivated polio vaccine (IPV) in routine immunization, alongside monovalent OPV type 2 (mOPV2) and IPV in supplementary immunization activities (SIAs). This study assesses the change in poliovirus type 2 immunity after tOPV withdrawal and due to SIAs with mOPV2 and IPV among children aged 6-11 months. Methods: Three cross-sectional sequential serological surveys were conducted in 12 polio high-risk areas of Pakistan. 25 clusters from each geographical stratum were selected utilizing probability proportional to size. Results: Seroprevalence of type 2 poliovirus was 49%, with significant variation observed among surveyed areas; <30% in Pishin, >80% in Killa Abdullah, Mardan & Swabi, and Rawalpindi. SIAs with IPV improved immunity from 38 to 57% in Karachi and 60 to 88% in Khyber. SIAs with IPV following mOPV2 improved immunity from 62 to 65% in Killa Abdullah, and combined mOPV2 and IPV SIAs in Pishin improved immunity from 28 to 89%. Results also reflected that immunity rates for serotypes 1 and 3 were consistently above 90% during all three phases and across all geographical areas. Conclusion: The study findings highlight the importance of implementing effective vaccination strategies to prevent the re-emergence of poliovirus. Moreover, the results provide crucial information for policymakers working toward achieving global polio eradication.

High throughput AS LNA qPCR method for the detection of a specific mutation in poliovirus vaccine strains.

Sabin Inactivated Poliovirus Vaccine (sIPV) has become one of the preferred vaccination options for the last step in the Poliovirus eradication program. Sequencing of poliovirus samples is needed during the manufacturing of poliovirus vaccines to assure the safety and immunogenicity of these vaccines. Next-generation sequencing analysis is the current costly and time-consuming gold standard for monitoring the manufacturing processes. We developed a low-cost and quick, highly sensitive, and allele-specific locked nucleic acid-probe-based reverse transcription quantitative PCR alternative that can accurately detect mutations in poliovirus vaccine samples during process development, scaling up, and release. Using the frequently in vitro occurring and viral replication-impacting VP1-E295K mutation as a showcase, we show that this technology can accurately detect E295K mutations in poliovirus 2 samples to similar levels as NGS. The qPCR technology was developed employing a synthetic dsDNA fragment-based standard curve containing mixes of E295K-WT (wildtype) and Mut (mutant) synthetic dsDNA fragments ranging from 1 × 107 copies/µL to 1 × 102 copies/µL to achieve a linear correlation with R2 > 0.999, and PCR efficiencies of 95-105 %. Individual standard concentration levels achieved accuracies of ≥92 % (average 96 %) and precisions of ≤17 % (average 3.3 %) RSD. Specificity of locked nucleic acid (LNA)-probes was confirmed in the presence and absence of co-mutations in the probe-binding region. Application of the developed assay to Sabin Poliovirus type 2 production run samples, illustrated a linear relationship with an R2 of 0.994, and an average accuracy of 97.2 % of the variant (allele)-specific AS LNA qPCR result, compared to NGS. The assay showed good sensitivity for poliovirus samples, containing E295K mutation levels between 0 % and 95 % (quantification range). In conclusion, the developed AS LNA qPCR presents a valuable low-cost, and fast tool, suitable for the process development and quality control of polio vaccines.

Novel Oral Poliovirus Vaccine 2 Safety Evaluation during Nationwide Supplemental Immunization Activity, Uganda, 2022.

Given its enhanced genetic stability, novel oral poliovirus vaccine type 2 was deployed for type 2 poliovirus outbreak responses under World Health Organization Emergency Use Listing. We evaluated the safety profile of this vaccine. No safety signals were identified using a multipronged approach of passive and active surveillance.

[Eradication of poliomyelitis in Spain: What has happened in the last decade?] / Erradicación de la poliomielitis en España: ¿qué ha pasado en la última década?

On the 60th anniversary of the initiation of the polio vaccination campaign in Spain, the significant milestone in achieving disease control is highlighted. There has been a shift from an incidence of over 2,000 yearly cases in the 1960s to a sustained absence of wild poliovirus (WPV) since 1988. Despite the observed negative impact on polio vaccination coverage at the onset of the COVID-19 pandemic, these rates gradually recovered, reaching 98.2% in primary vaccination in 2022. Over the past decade, two essential elements have been identified to maintain the goal of polio elimination and that reinforces the importance of sustaining high vaccination coverage: robust epidemiological surveillance systems and a swift response to alerts to protect the vulnerable population and prevent virus reintroduction. In order to achieve eradication, it is crucial to interrupt international transmission and maintain continuous high-quality surveillance and effective coordination across different levels in response to any detection of PV, wild or vaccine derived. This article aimed to provide a comprehensive view of the polio eradication situation in Spain, focusing on the key events that occurred in the last decade and the present and future challenges.

hito en el control de la enfermedad que ha supuesto el cambio desde una incidencia de más de 2.000 casos anuales en la década de los 60 a una ausencia mantenida de poliovirus (PV) salvaje desde 1988. A pesar del impacto negativo observado en las coberturas de vacunación de poliomielitis al inicio de la pandemia de la COVID-19, estas se fueron recuperando, alcanzando un 98,2% en la primovacunación en 2022. En la última década se han identificado dos elementos esenciales para mantener el objetivo de eliminación de la poliomielitis y que, además, refuerzan la importancia de mantener altas coberturas de vacunación: los sistemas de vigilancia epidemiológica robustos y la respuesta rápida a las alertas para proteger a la población vulnerable y evitar la circulación del virus. Es crucial interrumpir la transmisión a nivel internacional para lograr la erradicación, manteniendo una vigilancia continua de alta calidad y una coordinación efectiva entre los diferentes niveles frente a cualquier detección de PV, ya sea salvaje o derivado de la vacuna. Este artículo tuvo como objetivo proporcionar una visión integral sobre la situación de erradicación de la poliomielitis en España, centrándose en los eventos clave ocurridos en la última década y en los retos presentes y futuros.

Circulating vaccine derived polio virus type 2 outbreak and response in Yemen, 2021-2022, a retrospective descriptive analysis.

BACKGROUND: The outbreaks of circulating Vaccine Derived Polio Viruses (cVDPVs) have emerged as a major challenge for the final stage of polio eradication. In Yemen, an explosive outbreak of cVDPV2 was reported from August 2021 to December 2022. This study aims to compare the patterns of cVDPV2 outbreak, response measures taken by health authorities, and impacts in southern and northern governorates. METHOD: A retrospective descriptive study of confirmed cases of VDPV2 was performed. The data related to cVDPV2 as well as stool specimens and environmental samples that were shipped to WHO-accredited labs were collected by staff of surveillance. Frequencies and percentages were used to characterize and compare the confirmed cases from the southern and northern governorates. The average delayed time as a difference in days between the date of sample collection and lab confirmation was calculated. RESULTS: The cVDPV2 was isolated from 227 AFP cases reported from 19/23 Yemeni governorates and from 83% (39/47) of environmental samples with an average of 7 months delayed from sample collection. However, the non-polio AFP (NPAFP) and adequate stool specimen rates in the north were 6.7 and 87% compared to 6.4 and 87% in the south, 86% (195) and 14%(32) out of the total 227 confirmed cases were detected from northern and southern governorates, respectively. The first and second cases of genetically linked isolates experienced paralysis onset on 30 August and 1st September 2021. They respectively were from Taiz and Marib governorates ruled by southern authorities that started vaccination campaigns as a response in February 2022. Thus, in contrast to 2021, the detected cases in 2022 from the total cases detected in the south were lower accounting for 22% (7 of 32) of compared to 79% (155 of 195) of the total cases the north. CONCLUSION: A new emerging cVDPV2 was confirmed in Yemen. The result of this study highlighted the impact of vaccination campaigns in containing the cVDPV2 outbreak. Maintaining a high level of immunization coverage and switching to nOPV2 instead of tOPV and mOPV2 in campaigns are recommended and environmental surveillance should be expanded in such a risky country.