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.

Report offers harsh verdict on global polio vaccine switch.

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

Medial Hoffa Fracture: A Case Report and Literature Review of Approach and Management.

BACKGROUND Hoffa fractures are an uncommon form of coronal fracture that impact the femoral condyle. As a result, they are not very prevalent. It is necessary to perform anatomical reduction and rigorous fixation on these fractures; however, there is no consensus among medical professionals on the surgical procedure and implant that would be the most successful in treating these fractures. CASE REPORT A 50-year-old woman who had poliomyelitis in her right lower limb presented with a displaced medial Hoffa fracture of her left knee. She had fallen and was suffering from poliomyelitis. The trauma that caused this fracture had a modest energy level. Open reduction and internal fixation with 2 retrograde cannulated screws were included in her surgical procedure. An approach known as the medial parapatellar route was used for this treatment. As part of her postoperative rehabilitation, she participated in physiotherapy, exercises that did not require weight bearing, exercises that used passive and active assistance, activities that involved partial and full weight bearing, and exercises that involved complete weight bearing. At the 2-year follow-up, the patient's left knee continued to be painless and stable, and it had unrestricted range of motion across the whole extremity. It was determined via radiographs that the fracture had healed without any problems or arthritic changes developing. She was able to walk without help and carry out her daily tasks since she was able to walk with the use of a cane. CONCLUSIONS Retrograde cannulated screws can be a reliable and successful choice for treatment of medial Hoffa fractures, with positive results according to both clinical and radiographic characteristics. Further research is needed to analyze the outcomes over a longer period of time and make comparisons between this technique and others.

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.

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.

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.

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).

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.

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.

Poliomyelitis and COVID-19: a repeated history.

The measurement of the enterovirus and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in sewage water is relevant in the early detection of the introduction or disappearance of these viruses in the ecosystem. We evaluated the co-circulation of the enteroviruses and SARS-CoV-2 in 81 sewage water samples collected between September 2021 and April 2023 from different regions of north and southeast Romania, at the border with Ukraine. We used, for the molecular detection of the pathogens, the multiplex real-time polymerase chain reaction (PCR) assay produced for respiratory samples and the Respiratory 2.1 Plus panel Biofire Film array. The isolation of enteroviruses was performed on cell culture lines, in accordance with the World Health Organization (WHO) recommendations. By molecular investigations, we detected the SARS-CoV-2 in 22 (27%) samples, and the human rhinovirus/enterovirus in 64 (79%) samples. By isolation on cell culture lines, 27 samples (33,33%) were positive for non-polio enteroviruses, and no poliovirus strains were isolated, proving the maintenance of the polio-free status in Romania. In an emergency situation, the molecular detection of the pathogens in sewage water using a PCR system integrating sample preparation, amplification, detection, and analysis in 1 h could be implemented.

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.

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.

Two-year course of walking adaptability in persons living with late effects of polio.

OBJECTIVE: To evaluate the 2-year course of walking adaptability in persons with late effects of polio. DESIGN: Prospective cohort study. PATIENTS: A total of 48 persons with late effects of polio (69% female, mean age 63.1 years) with a fall history and/or fear of falling. METHODS: Walking adaptability (i.e. variable target-stepping and reactive obstacle-avoidance) was assessed on an interactive treadmill at baseline, 1 year and 2 years. Further, leg-muscle strength and balance were assessed at baseline. The course of walking adaptability was analysed with linear mixed models. Based on median values, subgroups were defined for low vs high baseline walking-adaptability and for clinical characteristics. Tme by subgroup interactions were analysed. RESULTS: Variable target-stepping and reactive obstacle-avoidance did not change (p > 0.285). Reactive obstacle-avoidance improved for persons with a high balance score at baseline (p = 0.037), but not for those with lower scores (p = 0.531). No other time by subgroup interactions were found (p > 0.126). CONCLUSION: Walking adaptability did not change in persons with late effects of polio over 2 years, and walking adaptability course did not differ between subgroups stratified for walking adaptability determinants, except for balance. Since falls are a major problem among persons with late effects of polio, future studies should investigate whether walking adaptability declines over a longer time and which persons are most at risk.

Occurrence of poliovirus and non-polio enterovirus among children with acute flaccid paralysis in Cameroon from 2015 to 2020.

INTRODUCTION: Poliovirus (PV) and non-polio enteroviruses (NPEV) belong to the Picornaviridae family. They are found worldwide and are responsible for a wide range of diseases such as acute flaccid paralysis (AFP). This study aimed to evaluate the detection rate of PV and NPEV in stool samples from children under fifteen years of age presenting with AFP in Cameroon and their distribution over time. METHODOLOGY: Stool samples were collected as part of poliovirus surveillance throughout Cameroon from 2015 to 2020. Virus isolation was performed using RD and L20B cells maintained in culture. Molecular methods such as intratypic differentiation were used to identify PVs serotypes and analysis of the VP1 genome was performed. RESULTS: A total of 12,354 stool samples were analyzed. The EV detection rate by virus isolation was 11.42% (1411/12354). This rate varied from year to year with a mean distribution of 11.41 with a 95% confidence interval [11.37; 11.44]. Of the viruses detected, suspected poliovirus accounted for 31.3% (442/1411) and NPEV 68.67% (969/1411). No wild poliovirus (WPV) was isolated. Sabin types 1 and 3 were continuously isolated. Surprisingly, from February 2020, vaccine-derived PV type 2 (VDPV2) was detected in 19% of cases, indicating its resurgence. CONCLUSIONS: This study strongly supports the successful elimination of WPV in Cameroon and the resurgence of VDPV2. However, as long as VDPV outbreaks continue to be detected in Africa, it remains essential to monitor how they spread.

Validation of improved automated nucleic acid extraction methods for direct detection of polioviruses for global polio eradication.

Polioviruses (PV), the main causative agent of acute flaccid paralysis (AFP), are positive-sense single-stranded RNA viruses of the family Picornaviridae. As we approach polio eradication, accurate and timely detection of poliovirus in stool from AFP cases becomes vital to success for the eradication efforts. Direct detection of PV from clinical diagnostic samples using nucleic acid (NA) extraction and real-time reverse transcriptase polymerase chain reaction (rRT-PCR) instead of the current standard method of virus isolation in culture, eliminates the long turn-around time to diagnosis and the need for high viral titer amplification in laboratories. An essential component of direct detection of PV from AFP surveillance samples is the efficient extraction of NA. Potential supply chain issues and lack of vendor presence in certain areas of the world necessitates the validation of multiple NA extraction methods. Using retrospective PV-positive surveillance samples (n=104), two extraction kits were compared to the previously validated Zymo Research Quick-RNA™ Viral Kit. The Roche High Pure Viral RNA Kit, a column-based manual extraction method, and the MagMaX™ Pathogen RNA/DNA kit used in the automated Kingfisher Flex system were both non-inferior to the Zymo kit, with similar rates of PV detection in pivotal rRT-PCR assays, such as pan-poliovirus (PanPV), poliovirus serotype 2 (PV2), and wild poliovirus serotype 1 (WPV1). These important assays allow the identification and differentiation of PV genotypes and serotypes and are fundamental to the GPLN program. Validation of two additional kits provides feasible alternatives to the current piloted method of NA extraction for poliovirus rRT-PCR assays.