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.

Report offers harsh verdict on global polio vaccine switch.

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

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.

From legacy to integration in the Global Polio Eradication Initiative: looking back to look forward.

INTRODUCTION: The Global Polio Eradication Initiative (GPEI) is a global single-disease programme with an extensive infrastructure in some of the world's most underserved areas. It provides a key example of the opportunities and challenges of transition efforts-the process of shifting from donor-funded, single-disease programmes to programmes with more integrated and sustainable programmatic and funding streams. Our goal is to closely analyse the social and political dynamics of the polio transition in the 2010s to provide insights into today, as well as lessons for other programmes. METHODS: We conducted semistructured interviews with GPEI officials involved in transition planning across GPEI partner agencies (n=11). We also drew on document review and interviews with national and subnational actors in Nigeria, India, Ethiopia and the Democratic Republic of the Congo. We inductively analysed this material to capture emergent themes in the evolution of transition activities in the GPEI. RESULTS: Since the mid-2010s, GPEI actors expressed concern that polio's assets should not be lost when polio was eradicated. Planning for polio's legacy, however, proved complicated. The GPEI's commitment to and focus on eradication had taken precedence over strong collaborations outside the polio programme, making building alliances for transition challenging. There were also complex questions around who should be responsible for the transition process, and which agencies would ultimately pay for and deliver polio-funded functions. Current efforts to achieve 'integration' both have great promise and must grapple with these same issues. DISCUSSION: Within the GPEI, relinquishing control to other programmes and planning for significant, long-term funding for transition will be central to achieving successful integration and eventual transition. Beyond polio, other vertical programmes can benefit from going beyond transition 'planning' to integrate transition into the initial design of vertical programmes.

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.

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.

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.

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.

Immunogenicity and safety of adsorbed diphtheria-purified pertussis-tetanus-inactivated polio (Sabin strain)-Haemophilus type b conjugate combined vaccine (DPT-IPV-Hib) in healthy Japanese Infants ≥ 2 and < 43 months of Age: A phase III, multicenter, active controlled, assessor-blinded, randomized, parallel-group study.

OBJECTIVE: This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator. METHODS: This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 µg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization. RESULTS: In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 µg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified. CONCLUSION: A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik).

Building confidence in the COVID-19 vaccine in a polio-endemic country: strategic communication lessons from Pakistan.

In a health emergency, governments rely on public trust in their policy, and anticipate its compliance to protect health and save lives. Vaccine hesitancy compromises this process when an emergency involves infections. The prevailing discourse on vaccine hesitancy often describes it as a static phenomenon, ignoring its expanse and complexity, and neglecting the exploration of tools to address it. This article diverges from the conventional perspective by explaining the case of Pakistan and its communication strategy for the COVID-19 vaccine. Decades of polio vaccine hesitancy, rooted in the country's fight against terrorism, constitute its history. On the other hand, the first-ever launch of typhoid conjugate vaccine involving 35 million kids during 2019-2021 was a success. Against this backdrop, the country considered vaccine hesitancy as a dynamic phenomenon, interwoven with the social ecology and the responsiveness of the healthcare system. Its communication strategy facilitated those willing to receive the vaccine, while being responsive to the information needs of those still in the decision-making process. In the face of both hesitancy and a scarcity of vaccine doses, the country successfully inoculated nearly 70% (160 million) of its population in just over 1 year. People's perceptions about the COVID-19 vaccine also improved over time. This achievement offers valuable insights and tools for policymakers and strategists focused on the demand side of vaccine programmes. The lessons can significantly contribute to the global discourse on improving vaccine confidence and bolstering global health security.

Surveillance To Track Progress Toward Polio Eradication - Worldwide, 2022-2023.

The reliable and timely detection of poliovirus cases through surveillance for acute flaccid paralysis (AFP), supplemented by environmental surveillance of sewage samples, is a critical component of the polio eradication program. Since 1988, the number of polio cases caused by wild poliovirus (WPV) has declined by >99.9%, and eradication of WPV serotypes 2 and 3 has been certified; only serotype 1 (WPV1) continues to circulate, and transmission remains endemic in Afghanistan and Pakistan. This surveillance update evaluated indicators from AFP surveillance, environmental surveillance for polioviruses, and Global Polio Laboratory Network performance data provided by 28 priority countries for the program during 2022-2023. No WPV1 cases have been detected outside of Afghanistan and Pakistan since August 2022, when an importation into Malawi and Mozambique resulted in an outbreak during 2021-2022. During 2022-2023, among 28 priority countries, 20 (71.4%) met national AFP surveillance indicator targets, and the number of environmental surveillance sites increased. However, low national rates of reported AFP cases in priority countries in 2023 might have resulted from surveillance reporting lags; substantial national and subnational AFP surveillance gaps persist. Maintaining high-quality surveillance is critical to achieving the goal of global polio eradication. Monitoring surveillance indicators is important to identifying gaps and guiding surveillance-strengthening activities, particularly in countries at high risk for poliovirus circulation.

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.

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.

A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China.

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.

Safety of incidental exposure to the novel oral poliovirus vaccine type 2 in pregnancy: A longitudinal observational study in Mozambique, 2022-2023

To minimize the risk of vaccine-derived poliovirus emergences, the novel oral poliovirus vaccine type 2 (nOPV2), was bioengineered to have increased genetic stability compared to Sabin OPV and recommended for outbreak response Emergency Use Listing by WHO. Although pregnant women are not a target population for this vaccine, a theoretical risk of incidental exposure exists via pharyngeal or faecal shedding from vaccinated children in the household or close community. Methods: This was an observational study of pregnant women conducted in Nampula (exposed cohort) and Maputo (non-exposed cohort) in Mozambique from August 2022 to June 2023. Two nOPV2 campaigns were conducted in Nampula and none in Maputo. Women were followed-up during routine prenatal consultation, delivery, and 28-day neonate visits for obstetric anomalies and pregnancy outcomes. Sociodemographic, medical, and obstetric history was captured. Results: Three hundred twenty-six pregnant women were enrolled from Nampula and 940 from Maputo City. Stillbirth prevalence (2·3% vs 1·6%, p = 0·438), low birth weight (8·9% vs 8·2%, p = 0·989), congenital anomalies (1 % vs 0·5%, p = 0·454), neonatal death (2·3% vs 1·6%, p = 0·08), and maternal death (0 % vs 0·2%, p = 0·978) did not differ amongst exposed and non-exposed cohorts. There was an increased rate of pre-term delivery in the exposed cohort (18·4% vs 11·0%, p = 0·011). Conclusion: We did not observe an increased frequency of adverse pregnancy outcomes due to passive nOPV2 exposure. A higher frequency of preterm delivery needs to be further investigated. The data reported herein support the continued use of nOPV2 for poliovirus outbreak response and full licensure of the vaccine.

2022 Polio outbreak, Rockland County, NY: Cost evaluation of strategies to prevent future outbreaks of vaccine-preventable diseases.

In 1994, the World Health Organization Region of the Americas was declared polio-free. In July 2022, a confirmed case of paralytic polio in an unvaccinated adult resident of Rockland County, New York was reported by the New York State Department of Health (NYSDOH) and Rockland County Department of Health (RCDOH). While only one case was identified, a single case of paralytic polio represents a public health emergency in the United States. The patient's county of residence was identified to have low vaccination coverage indicating that the community was at risk for additional cases. Disease outbreaks are resource-intensive and incur high costs to the patient, local health departments, and to society. These costs are potentially avoidable for vaccine-preventable diseases and thus, highlight the urgency to not only interrupt transmission but to prevent future vaccine-preventable disease outbreaks by improving vaccination coverage. Following case confirmation, an investigation and response was initiated by NYSDOH, along with local health departments and the Centers for Disease Control and Prevention (CDC). After the initial investigation and response, collaborative efforts to mitigate risk and strengthen routine immunization continued, which included provider outreach and immunization record assessments of Head Start and licensed childcare facilities (primarily those with missing or incomplete required vaccination coverage reports from the previous year) in Rockland County. We estimated the costs of (1) provider outreach and (2) childcare and pre-kindergarten immunization record assessments of select licensed childcare and Head Start facilities in Rockland County. The total labor cost incurred for these activities was $138,514 with a total of 2,555 h incurred. Often there are unique opportunities in the midst of an outbreak for public health to implement activities to proactively address low vaccination and strengthen vaccination coverage and possibly prevent future outbreaks. Understanding the cost of these activities might help inform future outbreak planning.