Polio Eradication Research Articles

The Fight against Poliovirus Is Not Over.

Poliovirus (PV), the virus that causes both acute poliomyelitis and post-polio syndrome, is classified within the Enterovirus C species, and there are three wild PV serotypes: WPV1, WPV2 and WPV3. The launch of the Global Polio Eradication Initiative (GPEI) in 1988 eradicated two of the three serotypes of WPV (WPV2 and WPV3). However, the endemic transmission of WPV1 persists in Afghanistan and Pakistan in 2022. There are cases of paralytic polio due to the loss of viral attenuation in the oral poliovirus vaccine (OPV), known as vaccine-derived poliovirus (VDPV). Between January 2021 and May 2023, a total of 2141 circulating VDPV (cVDPV) cases were reported in 36 countries worldwide. Because of this risk, inactivated poliovirus (IPV) is being used more widely, and attenuated PV2 has been removed from OPV formulations to obtain bivalent OPV (containing only types 1 and 3). In order to avoid the reversion of attenuated OPV strains, the new OPV, which is more stable due to genome-wide modifications, as well as sabin IPV and virus-like particle (VLP) vaccines, is being developed and offers promising solutions for eradicating WP1 and VDPV.

Halting vaccine-derived poliovirus circulation: the novel type 2 oral vaccine might not be enough

Halting vaccine-derived poliovirus circulation: the novel type 2 oral vaccine might not be enough

Progress Toward Poliomyelitis Eradication - Worldwide, January 2021-March 2023.

Since the World Health Assembly established the Global Polio Eradication Initiative (GPEI) in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated, and global WPV cases have decreased by more than 99.9%. Afghanistan and Pakistan remain the only countries where indigenous WPV type 1 (WPV1) transmission has not been interrupted. This report summarizes progress toward global polio eradication during January 1, 2021-March 31, 2023, and updates previous reports (1,2). In 2022, Afghanistan and Pakistan reported 22 WPV1 cases, compared with five in 2021; as of May 5, 2023, a single WPV1 case was reported in Pakistan in 2023. A WPV1 case was reported on the African continent for the first time since 2016, when officials in Malawi confirmed a WPV1 case in a child with paralysis onset in November 2021; neighboring Mozambique subsequently reported eight genetically linked cases. Outbreaks of polio caused by circulating vaccine-derived polioviruses (cVDPVs) can occur when oral poliovirus vaccine (OPV) strains circulate for a prolonged time in underimmunized populations, allowing reversion to neurovirulence (3). A total of 859 cVDPV cases occurred during 2022, an increase of 23% from 698 cases in 2021. cVDPVs were detected in areas where poliovirus transmission had long been eliminated (including in Canada, Israel, the United Kingdom, and the United States). In addition, cocirculation of multiple poliovirus types occurred in multiple countries globally (including Democratic Republic of the Congo [DRC], Israel, Malawi, Mozambique, Republic of the Congo, and Yemen). The 2022-2026 GPEI strategic plan targeted the goal of detecting the last cases of WPV1 and cVDPV in 2023 (4). The current global epidemiology of poliovirus transmission makes the likelihood of meeting this target date unlikely. The detections of poliovirus (WPV1 and cVDPVs) in areas where it had been previously eliminated underscore the threat of continued poliovirus spread to any area where there is insufficient vaccination to poliovirus (3). Mass vaccination and surveillance should be further enhanced in areas of transmission to interrupt poliovirus transmission and to end the global threat of paralytic polio in children.

National Surveillance of Poliovirus Excretion among Children with Primary Immune Deficiency in Pakistan & Assessment of Sensitivity of JMF Signs for Screening of Suspected PID Children (2018-To Date)

Background and objectivesPolio is an infectious viral disease that invades a child’s nervous system. Children with PID disorder exposed to the oral polio vaccine have chronic poliovirus excretion. This project aims to develop a national surveillance system to identify and monitor vaccine-derived poliovirus excretion among children diagnosed with PID. It will also assess whether Jeffery Modell Foundation warning signs are appropriate for screening PIDs in Pakistan. MethodsThe surveillance is currently being undertaken at tertiary healthcare facilities around Pakistan. In the initial stage, mapping was executed to identify hospitals and their consultant pediatricians. Master training workshops were conducted for the pediatricians from the selected hospitals of each province of Pakistan who agreed to participate in iVDPV surveillance. The suspected PID cases were tested for the confirmatory PID status and poliovirus excretion in the fecal specimen. Children who were excreting poliovirus were followed on the monthly basis until the two negative stool samples are obtained. ResultsThe surveillance for poliovirus was initiated in December 2018. Till date, 444 children (17 days-15 years; 264 males and 180 females) have been enrolled in the surveillance. Immunodeficiencies affecting cellular and humoral immunity were the most frequent, accounting for 113/444 cases. The second most prevalent immunodeficiency were antibody deficiencies, which accounted for 75/444 cases. Additionally, congenital disabilities of phagocyte number or function accounted for 18/444 of the cases. The surveillance system also included uncategorized suspected PIDs 114/444 and Children with normal investigations but considered suspected PID 124/444. The serotype of the excreted virus was predominantly SL3 in 10/358 cases, followed by SL1 in 4/358 cases and SL2 in 1/358 patients. During the four-year surveillance period, two AFP cases were tested for PID after isolation of VDPV 1 (1/358) and VDPV 3 (1/358) whom were later confirmed as Primary Immunodeficient. The JMF signs 8, 5 & 3 are the most frequently occurring signs amongst enrolled PIDs. [Display omitted] ConclusionThe poliovirus excretion in PID children should be the programmatic priority for the polio eradication initiative. The JMF proved to be adequate screening tool for the identification of PID individuals.

Poliovirus surveillance in patients with primary immunodeficiencies, India.

Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by surveillance programmes of acute flaccid paralysis. These patients therefore pose a risk of initiating poliovirus outbreaks that jeopardize efforts towards global polio eradication. To identify these individuals, we designed a study protocol for the establishment of a network for surveillance of immunodeficiency-related vaccine-derived poliovirus in India. In the first step we identified recognized centres in India that could diagnose and enrol patients with primary immunodeficiency disorder into the study. Stool sample collection from study sites, culture, isolation, characterization of enteroviruses and reporting to study sites was carried out at the National Institute of Virology Mumbai Unit, as per the WHO national polio surveillance project protocol. In the first phase of the study from January 2020 to December 2021, we implemented the protocol at seven study sites at different medical institutes to determine the proportion of poliovirus infections in primary immunodeficiency disorder patients of India. We later expanded the study by including an additional 14 medical institutes across the country in the second phase running from January 2022 to December 2023. We believe this study protocol will help other countries to initiate immunodeficiency-related vaccine-derived poliovirus surveillance to identify and follow up patients who are long-term excretors of vaccine-derived poliovirus. Integration of immunodeficiency-related poliovirus surveillance with acute flaccid paralysis surveillance of the existing poliovirus network will enhance continuous screening of patients with primary immunodeficiency disorder in the future.

Threat of resurgence or hope for global eradication of poliovirus?

Recent outbreaks of poliomyelitis in countries that have been free of cases for decades highlight the challenges of eradicating polio in a globalized interconnected world beset with a novel viral pandemic. We provide an epidemiological update, advancements in vaccines, and amendments in public health strategy of poliomyelitis in this review. Last year, new cases of wild poliovirus type 1 (WPV1) were documented in regions previously documented to have eradicated WPV1 and reports of circulating vaccine-derived poliovirus type 2 (cVDPV2) and 3 (cVDPV3) in New York and Jerusalem made international headlines. Sequencing of wastewater samples from environmental surveillance revealed that the WPV1 strains were related to WPV1 lineages from endemic countries and the cVDPV2 strains from New York and Jerusalem were not only related to each other but also to environmental isolates found in London. The evidence of importation of WPV1 cases from endemic countries, and global transmission of cVDPVs justifies renewed efforts in routine vaccination programs and outbreak control measures that were interrupted by the COVID-19 pandemic. After the novel oral poliovirus vaccine type 2 (nOPV2) received emergency authorization for containment of cVDPV2 outbreaks in 2021, subsequent reduced incidence, transmission rates, and vaccine adverse events, alongside increased genetic stability of viral isolates substantiates the safety and efficacy of nOPV2. The nOPV1 and nOPV3 vaccines, against type 1 and 3 cVDPVs, and measures to increase accessibility and efficacy of inactivated poliovirus vaccine (IPV) are in development. A revised strategy utilizing more genetically stable vaccine formulations, with uninterrupted vaccination programs and continued active surveillance optimizes the prospect of global poliomyelitis eradication.

Complexity of options related to restarting oral poliovirus vaccine (OPV) in national immunization programs after OPV cessation.

Background: The polio eradication endgame continues to increase in complexity. With polio cases caused by wild poliovirus type 1 and circulating vaccine-derived polioviruses of all three types (1, 2 and 3) reported in 2022, the number, formulation, and use of poliovirus vaccines poses challenges for national immunization programs and vaccine suppliers. Prior poliovirus transmission modeling of globally-coordinated type-specific cessation of oral poliovirus vaccine (OPV) assumed creation of Sabin monovalent OPV (mOPV) stockpiles for emergencies and explored the potential need to restart OPV if the world reached a specified cumulative threshold number of cases after OPV cessation. Methods: We document the actual experience of type 2 OPV (OPV2) cessation and reconsider prior modeling assumptions related to OPV restart. We develop updated decision trees of national immunization options for poliovirus vaccines considering different possibilities for OPV restart. Results: While OPV restart represented a hypothetical situation for risk management and contingency planning to support the 2013-2018 Global Polio Eradication Initiative (GPEI) Strategic Plan, the actual epidemiological experience since OPV2 cessation raises questions about what, if any, trigger(s) could lead to restarting the use of OPV2 in routine immunization and/or plans for potential future restart of type 1 and 3 OPV after their respective cessation. The emergency use listing of a genetically stabilized novel type 2 OPV (nOPV2) and continued evaluation of nOPV for types 1 and/or 3 add further complexity by increasing the combinations of possible OPV formulations for OPV restart. Conclusions: Expanding on a 2019 discussion of the logistical challenges and implications of restarting OPV, we find a complex structure of the many options and many issues related to OPV restart decisions and policies as of early 2023. We anticipate many challenges for forecasting prospective vaccine supply needs during the polio endgame due to increasing potential combinations of poliovirus vaccine choices.

Update on Wild Poliovirus Type 1 Outbreak — Southeastern Africa, 2021–2022

Since the Global Polio Eradication Initiative (GPEI) began in 1988, the number of wild poliovirus (WPV) cases has declined by >99.99%. Five of the six World Health Organization (WHO) regions have been certified free of indigenous WPV, and WPV serotypes 2 and 3 have been declared eradicated globally (1). WPV type 1 (WPV1) remains endemic only in Afghanistan and Pakistan (2,3). Before the outbreak described in this report, WPV1 had not been detected in southeastern Africa since the 1990s, and on August 25, 2020, the WHO African Region was certified free of indigenous WPV (4). On February 16, 2022, WPV1 infection was confirmed in one child living in Malawi, with onset of paralysis on November 19, 2021. Genomic sequence analysis of the isolated poliovirus indicated that it originated in Pakistan (5). Cases were subsequently identified in Mozambique. This report summarizes progress in the outbreak response since the initial report (5). During November 2021-December 2022, nine children and adolescents with paralytic polio caused by WPV1 were identified in southeastern Africa: one in Malawi and eight in Mozambique. Malawi, Mozambique, and three neighboring countries at high risk for WPV1 importation (Tanzania, Zambia, and Zimbabwe) responded by increasing surveillance and organizing up to six rounds of national and subnational polio supplementary immunization activities (SIAs).* Although no cases of paralytic WPV1 infection have been reported in Malawi since November 2021 or in Mozambique since August 2022, undetected transmission might be ongoing because of poliovirus surveillance gaps and testing delays. Efforts to further enhance poliovirus surveillance sensitivity, improve SIA quality, and strengthen routine immunization are needed to ensure that WPV1 transmission has been interrupted within 12 months of the first case, thereby preserving the WHO African Region's WPV-free status.

Facilitators and barriers to community engagement in the Global Polio Eradication Initiative-A mixed methods study.

Community engagement (CE) is an important component of public health research and program implementation, especially in low- and middle-income countries. More recently, CE activities have been utilized to develop partnerships in research and program implementation processes, and advocate for policy recommendations with the aim to improve acceptance and reduce disparities of public health research activities and benefits in the involved communities. Utilizing the tacit knowledge gained from the Global Polio Eradication Initiative, this paper highlights the contributors and challenges to the implementation of the GPEI program's community engagement initiatives from an implementers' perspective. The study took a mixed methods approach to analyze data collected from the Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) project, which conducted an online survey and hosted key informant interviews with individuals who had been engaged with the GPEI program from 1988 onwards for at least 12 or more continuous months. An analysis of data limited to individuals (32%, N = 3659) who were primarily involved in CE activities revealed that around 24% were front-line healthcare workers, 21% were supervisors and 8% were surveillance officers. CE activities mainly focused on building trust within the communities, addressing misinformation, myths and fears around vaccinations, mobilization to reach high-risk or hard to reach populations, as well as building ownership and buy in from the communities. The strength of the implemental process of a program (38.7%) was among the key drivers of success, coupled with personal beliefs and characteristics of the implementers (25.3%). Social, political, and financial forces received mixed opinions as to their importance, depending on the stage of execution and readiness of the communities to accept the programs. Lessons learnt from the GPEI program provide tried and tested best practices and evidence for strategies that would work in diverse backgrounds with some customization to suit the needs of the situation.

Addressing Immunization Inequity-What Have the International Community and India Learned over 35 Years?

Countries around the world established immunization programs over 40 years ago to reach all infants. The maturity of these preventive health programs offers some useful learning on the importance of, and components needed for, population-based services to reach all communities. A public health success, ensuring equity in immunization, requires a multi-faceted approach that includes sustained government and partner commitment and human, financial, and program operational resources. Evidence from India's Universal Immunization Program (UIP) across stabilizing vaccine supply and services, enhancing access, and generating demand for vaccines in the community provides a useful case study. The political leadership in India took advantage of the two decades of learning from polio eradication and focused initiatives, such as the National Health Mission and Intensified Mission Indradhanush, to reach populations with immunization services. With a goal of leaving no one behind, India's UIP and partners are bringing essential rotavirus and pneumococcal vaccines nationwide, upgrading vaccine cold chain and supply systems with technologies, such as the electronic Vaccine Intelligence Network (eVIN), and optimizing funding for local needs through the Program Implementation Plan (PIP) budgetary processes and building health worker capacities through training, awareness, and e-learning.

Outbreak response strategies with type 2-containing oral poliovirus vaccines.

Despite exhaustive and fully-financed plans to manage the risks of globally coordinated cessation of oral poliovirus vaccine (OPV) containing type 2 (OPV2) prior to 2016, as of 2022, extensive, continued transmission of circulating vaccine-derived polioviruses (cVDPVs) type 2 (cVDPV2) remains. Notably, cumulative cases caused by cVDPV2 since 2016 now exceed 2,500. Earlier analyses explored the implications of using different vaccine formulations to respond to cVDPV2 outbreaks and demonstrated how different properties of novel OPV2 (nOPV2) might affect its performance compared to Sabin monovalent OPV2 (mOPV2). These prior analyses used fixed assumptions for how outbreak response would occur, but outbreak response implementation can change. We update an existing global poliovirus transmission model to explore different options for responding with different vaccines and assumptions about scope, delays, immunization intensity, target age groups, and number of rounds. Our findings suggest that in order to successfully stop all cVDPV2 transmission globally, countries and the Global Polio Eradication Initiative need to address the deficiencies in emergency outbreak response policy and implementation. The polio program must urgently act to substantially reduce response time, target larger populations - particularly in high transmission areas - and achieve high coverage with improved access to under-vaccinated subpopulations. Given the limited supplies of nOPV2 at the present, using mOPV2 intensively immediately, followed by nOPV2 intensively if needed and when sufficient quantities become available, substantially increases the probability of ending cVDPV2 transmission globally.

Vaccine-derived poliovirus serotype 2 outbreaks and response in the Democratic Republic of the Congo, 2017-2021.

Vaccine-derived polioviruses (VDPVs) can emerge from Sabin strain poliovirus serotypes 1, 2, and 3 contained in oral poliovirus vaccine (OPV) after prolonged person-to-person transmission where population vaccination immunity against polioviruses is suboptimal. VDPVs can cause paralysis indistinguishable from wild polioviruses and outbreaks when community circulation ensues. VDPV serotype 2 outbreaks (cVDPV2) have been documented in The Democratic Republic of the Congo (DRC) since 2005. The nine cVDPV2 outbreaks detected during 2005-2012 were geographically-limited and resulted in 73 paralysis cases. No outbreaks were detected during 2013-2016. During January 1, 2017-December 31, 2021, 19 cVDPV2 outbreaks were detected in DRC. Seventeen of the 19 (including two first detected in Angola) resulted in 235 paralysis cases notified in 84 health zones in 18 of DRC's 26 provinces; no notified paralysis cases were associated with the remaining two outbreaks. The DRC-KAS-3 cVDPV2 outbreak that circulated during 2019-2021, and resulted in 101 paralysis cases in 10 provinces, was the largest recorded in DRC during the reporting period in terms of numbers of paralysis cases and geographic expanse. The 15 outbreaks occurring during 2017-early 2021 were successfully controlled with numerous supplemental immunization activities (SIAs) using monovalent OPV Sabin-strain serotype 2 (mOPV2); however, suboptimal mOPV2 vaccination coverage appears to have seeded the cVDPV2 emergences detected during semester 2, 2018 through 2021. Use of the novel OPV serotype 2 (nOPV2), designed to have greater genetic stability than mOPV2, should help DRC's efforts in controlling the more recent cVDPV2 outbreaks with a much lower risk of further seeding VDPV2 emergence. Improving nOPV2 SIA coverage should decrease the number of SIAs needed to interrupt transmission. DRC needs the support of polio eradication and Essential Immunization (EI) partners to accelerate the country's ongoing initiatives for EI strengthening, introduction of a second dose of inactivated poliovirus vaccine (IPV) to increase protection against paralysis, and improving nOPV2 SIA coverage.

Assessing country compliance with circulating vaccine-derived poliovirus type 2 outbreak response standard operating procedures: April 2016 to December 2020.

Trivalent oral poliovirus vaccine (tOPV) was globally replaced with bivalent oral poliovirus vaccine (bOPV) in April 2016 ("the switch"). Many outbreaks of paralytic poliomyelitis associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) have been reported since this time. The Global Polio Eradication Initiative (GPEI) developed standard operating procedures (SOPs) to guide countries experiencing cVDPV2 outbreaks to implement timely and effective outbreak response (OBR). To assess the possible role of compliance with SOPs in successfully stopping cVDPV2 outbreaks, we analyzed data on critical timelines in the OBR process. Data were collected on all cVDPV2 outbreaks detected for the period April 1, 2016 and December 31, 2020 and all outbreak responses to those outbreaks between April 1, 2016 and December 31, 2021. We conducted secondary data analysis using the GPEI Polio Information System database, records from the U.S. Centers for Disease Control and Prevention Polio Laboratory, and meeting minutes of the monovalent OPV2 (mOPV2) Advisory Group. Date of notification of circulating virus was defined as Day 0 for this analysis. Extracted process variables were compared with indicators in the GPEI SOP version 3.1. One hundred and eleven cVDPV2 outbreaks resulting from 67 distinct cVDPV2 emergences were reported during April 1, 2016-December 31, 2020, affecting 34 countries across four World Health Organization Regions. Out of 65 OBRs with the first large-scale campaign (R1) conducted after Day 0, only 12 (18.5%) R1s were conducted by the target of 28days after Day 0. Of the 89 OBRs with the second large-scale campaign (R2) conducted after Day 0, 30 (33.7%) R2s were conducted by the target of 56days after Day 0. Twenty-three (31.9%) of the 72 outbreaks with isolates dated after Day 0 were stopped within the 120-day target. Since "the switch", delays in OBR implementation were evident in many countries, which may be related to the persistence of cVDPV2 outbreaks >120days. To achieve timely and effective response, countries should follow GPEI OBR guidelines.

Analysis of population immunity to poliovirus following cessation of trivalent oral polio vaccine.

The global withdrawal of trivalent oral poliovirus vaccine (OPV) (tOPV, containing Sabin poliovirus strains serotypes 1, 2 and 3) from routine immunization, and the introduction of bivalent OPV (bOPV, containing Sabin poliovirus strains serotypes 1 and 3) and trivalent inactivated poliovirus vaccine (IPV) into routine immunization was expected to improve population serologic and mucosal immunity to types 1 and 3 poliovirus, while population mucosal immunity to type 2 poliovirus would decline. However, over the period since tOPV withdrawal, the implementation of preventive bOPV supplementary immunization activities (SIAs) has decreased, while outbreaks of type 2 circulating vaccine derived poliovirus (cVDPV2) have required targeted use of monovalent type 2 OPV (mOPV2). We develop a dynamic model of OPV-induced immunity to estimate serotype-specific, district-level immunity for countries in priority regions and characterize changes in immunity since 2016. We account for the changes in routine immunization schedules and varying implementation of preventive and outbreak response SIAs, assuming homogenous coverages of 50% and 80% for SIAs. In areas with strong routine immunization, the switch from tOPV to bOPV has likely resulted in gains in population immunity to types 1 and 3 poliovirus. However, we estimate that improved immunogenicity of new schedules has not compensated for declines in preventive SIAs in areas with weak routine immunization. For type 2 poliovirus, without tOPV in routine immunization or SIAs, mucosal immunity has declined nearly everywhere, while use of mOPV2 has created highly heterogeneous population immunity for which it is important to take into account when responding to cVDPV2 outbreaks. The withdrawal of tOPV and declining allocations of resources for preventive bOPV SIAs have resulted in reduced immunity in vulnerable areas to types 1 and 3 poliovirus and generally reduced immunity to type 2 poliovirus in the regions studied, assuming homogeneous coverages of 50% and 80% for SIAs. The very low mucosal immunity to type 2 poliovirus generates substantially greater risk for further spread of cVDPV2 outbreaks. Emerging gaps in immunity to all serotypes will require judicious targeting of limited resources to the most vulnerable populations by the Global Polio Eradication Initiative (GPEI).

Exploring public perceptions of vaccine-derived poliovirus and a novel oral polio vaccine in the Democratic Republic of the Congo, Kenya, and Nigeria.

The Global Polio Eradication Initiative introduced novel oral polio vaccine Type 2 (nOPV2) to address circulating vaccine-derived poliovirus Type 2 (cVDPV2). Although nOPV2 is a more genetically stable vaccine, it may not have the immediate trust of communities and health workers due to its novelty, potential side effects, and introduction under an Emergency Use Listing (EUL). We explored how nOPV2 introduction might be perceived by stakeholders and identified communications barriers related to nOPV2 hesitancy. This work was conducted in the Democratic Republic of the Congo, Kenya, and Nigeria between January and March 2020. We used a rapid qualitative approach to conduct focus group discussions and in-depth interviews with four stakeholder groups: caregivers of children under 5, polio frontline workers, healthcare practitioners, and social/health influencers. Data are presented according to awareness, attitudes/beliefs, and concerns about cVDPV2 and nOPV2. Stakeholders were largely unaware of cVDPV2. The causes of recent polio outbreaks were characterized as poor sanitation, under-immunization/in-migration, or poor vaccine management procedures. Caregivers were aware of and concerned by repeated vaccination campaigns. All stakeholder groups anticipated initial hesitancy, fear, and suspicion from caregivers due to nOPV2 introduction, with primary concerns linked to vaccine testing, safety, effectiveness, side effects, and support from authorities. Stakeholders thought the term "genetic modification" could be controversial but that introduction under an EUL would be acceptable given the emergency nature of cVDPV2 outbreaks. Stakeholders called for adequate and timely information to counter concerns. Despite initial concerns, stakeholders felt nOPV2 would ultimately be accepted by caregivers. However, public health officials have a small window for "getting things right" when introducing nOPV2. Strategic communication interventions addressing key concerns and targeted communications with stakeholder groups, especially frontline workers, could improve community acceptance of nOPV2.

Enabling accelerated vaccine roll-out for Public Health Emergencies of International Concern (PHEICs): Novel Oral Polio Vaccine type 2 (nOPV2) experience.

To address the evolving risk of circulating vaccine-derived poliovirus type 2 (cVDPV2), Global Polio Eradication Initiative (GPEI) partners are working closely with countries to deploy an additional innovative tool for outbreak response - novel oral polio vaccine type 2 (nOPV2). The World Health Organization's (WHO) Prequalification program issued an Emergency Use Listing (EUL) recommendation for nOPV2 on 13 November 2020. The WHO's EUL procedure was created to assess and list unlicensed vaccines, therapeutics and diagnostics to enable their use in response to a Public Health Emergency of International Concern (PHEIC). nOPV2 was the first vaccine to receive an EUL, paving the way for other emergency vaccines. In this report, we summarise the pathway for nOPV2 roll-out under EUL.

Real-time prediction model of cVDPV2 outbreaks to aid outbreak response vaccination strategies.

Circulating vaccine-derived poliovirus outbreaks are spreading more widely than anticipated, which has generated a crisis for the global polio eradication initiative. Effectively responding with vaccination activities requires a rapid risk assessment. This assessment is made difficult by the low case-to-infection ratio of type 2 poliovirus, variable transmissibility, changing population immunity, surveillance delays, and limited vaccine supply from the global stockpile. The geographical extent of responses have been highly variable between countries. We develop a statistical spatio-temporal model of short-term, district-level poliovirus spread that incorporates known risk factors, including historical wild poliovirus transmission risk, routine immunization coverage, population immunity, and exposure to the outbreak virus. We find that proximity to recent cVDPV2 cases is the strongest risk factor for spread of an outbreak, and find significant associations between population immunity, historical risk, routine immunization, and environmental surveillance (p<0.05). We examine the fit of the model to type 2 vaccine derived poliovirus spread since 2016 and find that our model predicts the location of cVDPV2 cases well (AUC=0.96). We demonstrate use of the model to estimate appropriate scope of outbreak response activities to current outbreaks. As type 2 immunity continues to decline following the cessation of tOPV in 2016, outbreak responses to new cVDPV2 detections will need to be faster and larger in scope. We provide a framework that can be used to support decisions on the appropriate size of a vaccination response when new detections are identified. While the model does not account for all relevant local factors that must be considered in the overall vaccination response, it enables a quantitative basis for outbreak response size.

Commentary: In the Post-COVID-19 Era, Poliomyelitis is Making a Comeback.

During the COVID-19 pandemic, measures such as “physical prevention and control” of the novel coronavirus have reduced children’s exposure to pathogens. Additionally, the pandemic has significantly disrupted routine vaccination programs in many countries. Official data released by the World Health Organization (WHO) and the United Nations Children’s Fund show that the number of children receiving vaccinations is experiencing the most significant decline in 30 years (https://www.who.int/news/item/15-07-2022-covid-19-pandemic-fuels-largest-continued-backslide-in-vaccinations-in-three-decades). In the postpandemic era, there is a significant gap in the level of immunity among children compared to prepandemic times. Polio is an acute infectious disease caused by the wild poliovirus (WPV), which includes 3 serotypes: type 1, type 2 and type 3. It can lead to permanent flaccid paralysis of the limbs, and all reported cases of polio worldwide are currently caused by WPV type 1. As of 2022, Pakistan and Afghanistan remain the only countries with indigenous WPV epidemics (https://www.who.int/health-topics/poliomyelitis#tab=tab_1). However, it is important to note that polio is highly contagious, and until the world achieves complete eradication of polio, countries and regions that have already achieved polio-free status remain at risk of WPV importation and spread. According to WHO estimates, between 2002 and 2009, 39 polio-free countries reported WPV importations.1–3 In the postpandemic era of 2022, Malawi and Mozambique in Africa reported their first cases of WPV infection in 30 years. In addition to the risk of WPV importation, countries such as Israel and the United States (especially New York) have reported cases of polio caused by circulating vaccine-derived poliovirus (cVDPV). In London, UK, cVDPV was detected in routine sewage monitoring despite no cases of paralysis being reported, indicating possible local transmission (Fig. 1).4 The re-emergence of infection in previously declared polio-free countries is a wake-up call to the Global Polio Eradication Initiative.FIGURE 1.: A map showing the latest number of WPV1 and cVDPV cases in each affected. country from 01 Mar.2022 to 28 Feb.2023. Data are from WHO (https://polioeradication.org/polio-today/polio-now/). cVDPV indicates circulating vaccine-derived poliovirus; WPV1, wild poliovirus.In the postpandemic era, with the resumption of international exchanges and tourism, polio returns in ways we did not anticipate. Vaccinating against polio is the most cost-effective means of preventing and controlling the disease, and all countries must raise their vaccination coverage to 95% to block the spread of the virus. There are currently two types of polio vaccines widely used: inactivated polio vaccine (IPV), administered by intramuscular injection, and oral polio vaccine (OPV). Both vaccines have been certified as safe and effective by the WHO. However, we agree with Farahat et al.5 that the attenuated viruses in OPV can sometimes mutate into transmissible live viruses in areas with low vaccination rates. These viruses can be transmitted from vaccinated individuals’ feces to their environment, leading to outbreaks of cVDPV in unvaccinated populations.5 Therefore, under the context of immunity debt in the postpandemic era, we strongly recommend a complete shift from OPV to inactivated polio vaccine to avoid such risks. It is also worth noting that timely and strengthened environmental and wastewater monitoring should be carried out to detect early “silent” poliovirus transmission in the population rather than relying solely on clinical monitoring of acute flaccid paralysis.

Determinants of parental knowledge and attitude towards poliomyelitis and its immunization in Sialkot city: a mix method study

&lt;p&gt;&lt;strong&gt;Background and Objectives&lt;/strong&gt;: Poliomyelitis still remains a significant public health concern in developing countries though it has been eradicated from most of the world. Illiteracy, cultural constraints, and skepticism of the general public regarding vaccination are considered major impediments to its successful eradication from developing countries. In this study, the authors aimed to evaluate parental knowledge and attitudes about poliomyelitis and its immunization in a local population as well as to elucidate the determinants and barriers relating to the immunization process.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This mixed-method study was conducted on 350 consenting parents who accompanied their children under 5 years of age at the pediatric outdoors of a tertiary care hospital in Sialkot, Pakistan. Parents of only those children were included for the study who had failed to receive a polio dose during the last two supplementary immunization activities The parents were interviewed on a pre-tested, semi structured questionnaire. Statistical Package for the Social Sciences was used for statistical analysis considering p-value &amp;lt;0.05 as significant.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Among 350 parents, 91.7% lacked knowledge about polio vaccination and 82% reported a negative attitude towards the disease and its immunization. A total of 11.4% of subjects completely refused to get their child vaccinated. The socioeconomic status, religious myths, level of literacy, and occupation of the parents significantly influenced their level of knowledge and attitude toward the disease and its vaccination (p &amp;lt; 0.05).&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Poor knowledge and negative attitudes of parents towards poliomyelitis vaccination were observed. Fear of side effects and religious beliefs were identified as the most common barriers to immunization toward achieving polio eradication.&lt;/p&gt;

Comparison of Eleven RNA Extraction Methods for Poliovirus Direct Molecular Detection in Stool Samples.

Direct detection by PCR of poliovirus RNA in stool samples provides a rapid diagnostic and surveillance tool that can replace virus isolation by cell culture in global polio surveillance. The sensitivity of direct detection methods is likely to depend on the choice of RNA extraction method and sample volume. We report a comparative analysis of 11 nucleic acid extraction methods (7 manual and 4 semiautomated) for poliovirus molecular detection using stool samples (n = 59) that had been previously identified as poliovirus positive by cell culture. To assess the effect of RNA recovery methods, extracted RNA using each of the 11 methods was tested with a poliovirus-specific reverse transcription-quantitative PCR (RT-qPCR), a pan-poliovirus RT-PCR (near-whole-genome amplification), a pan-enterovirus RT-PCR (entire capsid region), and a nested VP1 PCR that is the basis of a direct detection method based on nanopore sequencing. We also assessed extracted RNA integrity and quantity. The overall effect of extraction method on poliovirus PCR amplification assays tested in this study was found to be statistically significant (P < 0.001), thus indicating that the choice of RNA extraction method is an important component that needs to be carefully considered for any diagnostic based on nucleic acid amplification. Performance of the methods was generally consistent across the different assays used. Of the 11 extraction methods tested, the MagMAX viral RNA isolation kit used manually or automatically was found to be the preferable method for poliovirus molecular direct detection considering performance, cost, and processing time. IMPORTANCE Poliovirus, the causative agent of poliomyelitis, is a target of global eradication led by the World Health Organization since 1988. Direct molecular detection and genomic sequencing without virus propagation in cell culture is arguably a critical tool in the final stages of polio eradication. Efficient recovery of good-quality viral RNA from stool samples is a prerequisite for direct detection by nucleic acid amplification. We tested 11 nucleic acid extraction methods to identify those facilitating sensitive, fast, simple, and cost-effective extraction, with flexibility for manual and automated protocols considered. Several different PCR assays were used to compare the recovered viral RNA to test suitability for poliovirus direct molecular detection. Our findings highlight the importance of choosing a suitable RNA extraction protocol and provide useful information to diagnostic laboratories and researchers facing the choice of RNA extraction method for direct molecular virus detection from stool.