Global polio eradication; can we replicate the smallpox success story?

Although the Global Polio Eradication Initiative has been largely successful in elimination of polio from various parts of the world, sporadic local outbreaks in non-endemic areas continue to pose a threat to global polio eradication efforts. In the two endemic countries, Pakistan and Afghanistan, a staggering 176 cases of wild poliovirus 1 (WPV1) were reported in 2019. In 2020 alone, 959 cases of Circulating Vaccine Derived Poliovirus 2 were reported globally from 27 countries. After staying polio-free for years, cases of WPV were detected in Malawi and Mozambique in 2022. The roots of the reported strains matched with the WPV strain from Pakistan. The emergence of WPV cases in Malawi and Mozambique underscores the fact that WPV still has the chance to spread beyond the Afghanistan-Pakistan region and sustained efforts are required for its complete eradication. In the case of smallpox, surveillance-containment was the key to eradication as many countries had already eradicated smallpox and the bigger concern was to track and contain any new cases emerging. Smallpox eradication followed a comprehensive plan which included elements like quality control and standardisation of vaccination protocols. Governments all over the world should prioritise immunisation drives, surveillance, and awareness campaigns to achieve the dream of a polio-free world.

Increasing polio coverage with safer vaccines: a pressing need in Latin America

Given the actual risk of poliomyelitis outbreaks in the region due to poliovirus derived from the Sabin vaccine or the importation of wild poliovirus, the Latin American Society of Pediatric Infectious Diseases commissioned an ad hoc group of experts from the institution's Vaccines and Biologicals Committee, to draft an official position paper on the urgent need to increase immunization levels against the disease in the region and incorporate inactivated polio vaccine exclusive schedules in all national immunization programs. This publication discusses the main conclusions and recommendations generated as a result of such activity.Copyright © 2022, Sociedad Chilena de Infectologia. All rights reserved.

My Uncle Charlie.

This is a story about my uncle Charlie, who contracted paralytic polio at an early age, and the remembrances on my career trajectory as a virologist that will never be forgotten.

Modeling undetected live type 1 wild poliovirus circulation after apparent interruption of transmission: Pakistan and Afghanistan.

Since 2013, wild poliovirus (WPV) transmission occurred only for type 1 (WPV1). Following several years of increasing reported incidence (2017-2019) and programmatic disruptions caused by COVID-19 (early 2020), Pakistan and Afghanistan performed a large number of supplementary immunization activities (late 2020-2021). This increased intensity of immunization, following widespread transmission, substantially decreased WPV1 cases and positive environmental samples during 2021. Modeling the potential for undetected circulation of WPV1 after apparent interruption can support regional and global decisions about certification of the eradication of indigenous WPV1 transmission. We apply a stochastic model to estimate the confidence about no circulation (CNC) of WPV1 in Pakistan and Afghanistan as a function of time since the last reported case and/or positive environmental sample. Exploration of different assumptions about surveillance quality suggests a range for CNC for WPV1 as a function of time since the last positive surveillance signal, and supports the potential use of a time with no evidence of transmission of less than 3 years as sufficient to assume die out in the context of good acute flaccid paralysis (AFP) surveillance. We show high expected CNC based on AFP surveillance data alone, even with imperfect surveillance and some use of inactivated poliovirus vaccine masking the ability of AFP surveillance to detect transmission. Ensuring high quality AFP and environmental surveillance may substantially shorten the time required to reach high CNC. The time required for high CNC depends on whether immunization activities maintain high population immunity and the quality of surveillance data.

Enhancing vaccination of key populations: lessons and actions

Vaccination is effective in preventing the increase of disease, especially emerging infectious diseases (EIDs), and it is particularly important for people in close contact with infected sources and susceptible populations who are at increased risk of getting infectious diseases due to behavior, occupation or health. Despite targeted vaccination guidelines, inadequate vaccination of the key populations fails to receive widespread attention, resulting in a high-risk transition of disease from key populations to general populations. Strengthening the vaccination of the susceptible groups can effectively block the spread of pathogens to general populations, and reduce the consumption of medical resources in universal vaccination, which has significant economic value. In this review, we describe the prevalence of EIDs, analyze the experience and lessons of infectious disease vaccination in key populations through several cases, and further explore the causes for the decline in vaccination rates of key populations. According to the trends of EIDs, a plan to strengthen the vaccination of key populations is proposed to effectively prevent the transition of EIDs from key populations to general populations.

The impact of disruptions caused by the COVID-19 pandemic on global polio eradication.

In early 2020, the COVID-19 pandemic led to substantial disruptions in global activities. The disruptions also included intentional and unintentional reductions in health services, including immunization campaigns against the transmission of wild poliovirus (WPV) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2). Building on a recently updated global poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model, we explored the implications of immunization disruption and restrictions of human interactions (i.e., population mixing) on the expected incidence of polio and on the resulting challenges faced by the Global Polio Eradication Initiative (GPEI). We demonstrate that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021 of all polio immunization activities to pre-COVID-19 levels, the GPEI could largely mitigate the impact of COVID-19 to the delays incurred. The relative importance of reduced mixing (leading to potentially decreased incidence) and reduced immunization (leading to potentially increased expected incidence) depends on the timing of the effects. Following resumption of immunization activities, the GPEI will likely face similar barriers to eradication of WPV and elimination of cVDPV2 as before COVID-19. The disruptions from the COVID-19 pandemic may further delay polio eradication due to indirect effects on vaccine and financial resources.

Serotype 2 oral poliovirus vaccine (OPV2) choices and the consequences of delaying outbreak response.

The Global Polio Eradication Initiative (GPEI) faces substantial challenges with managing outbreaks of serotype 2 circulating vaccine-derived polioviruses (cVDPV2s) in 2021. A full five years after the globally coordinated removal of serotype 2 oral poliovirus vaccine (OPV2) from trivalent oral poliovirus vaccine (tOPV) for use in national immunization programs, cVDPV2s did not die out. Since OPV2 cessation, responses to outbreaks caused by cVDPV2s mainly used serotype 2 monovalent OPV (mOPV2) from a stockpile. A novel vaccine developed from a genetically stabilized OPV2 strain (nOPV2) promises to potentially facilitate outbreak response with lower prospective risks, although its availability and properties in the field remain uncertain. Using an established global poliovirus transmission model and building on a related analysis that characterized the impacts of disruptions in GPEI activities caused by the COVID-19 pandemic, we explore the implications of trade-offs associated with delaying outbreak response to avoid using mOPV2 by waiting for nOPV2 availability (or equivalently, delayed responses waiting for national validation of meeting the criteria for nOPV2 initial use). Consistent with prior modeling, responding as quickly as possible with available mOPV2 promises to reduce the expected burden of disease in the outbreak population and to reduce the chances for the outbreak virus to spread to other areas. Delaying cVDPV2 outbreak response (e.g., modeled as no response January-June 2021) to wait for nOPV2 can considerably increase the total expected cases (e.g., by as many as 1,300 cVDPV2 cases in the African region during 2021-2023) and increases the likelihood of triggering the need to restart widescale preventive use of an OPV2-containing vaccine in national immunization programs that use OPV. Countries should respond to any cVDPV2 outbreaks quickly with rounds that achieve high coverage using any available OPV2, and plan to use nOPV2, if needed, once it becomes widely available based on evidence that it is as effective but safer in populations than mOPV2.

The immediate impact of the COVID-19 pandemic on polio immunization and surveillance activities.

In addition to affecting individual health the COVID-19 pandemic has disrupted efforts to deliver essential health services around the world. In this article we present an overview of the immediate programmatic and epidemiologic impact of the pandemic on polio eradication as well as the adaptive strategic and operational measures taken by the Global Polio Eradication Initiative (GPEI) from March through September 2020. Shortly after the World Health Organization (WHO) declared a global pandemic on 11 March 2020, the GPEI initially redirected the programme's assets to tackle COVID-19 and suspended house-to-house supplementary immunization activities (SIAs) while also striving to continue essential poliovirus surveillance functions. From March to May 2020, 28 countries suspended a total of 62 polio vaccine SIAs. In spite of efforts to continue poliovirus surveillance, global acute flaccid paralysis (AFP) cases reported from January-July 2020 declined by 34% compared with the same period in 2019 along with decreases in the mean number of environment samples collected per active site in the critical areas of the African and Eastern Mediterranean regions. The GPEI recommended countries should resume planning and implementation of SIAs starting in July 2020 and released guidelines to ensure these could be done safely for front line workers and communities. By the end of September 2020, a total of 14 countries had implemented circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreak response vaccination campaigns and Afghanistan and Pakistan restarted SIAs to stop ongoing wild poliovirus type 1 (WPV1) transmission. The longer-term impacts of disruptions to eradication efforts remain to be determined, especially in terms of the effect on poliovirus epidemiology. Adapting to the pandemic situation has imposed new considerations on program implementation and demonstrated not only GPEI's contribution to global health security, but also identified potential opportunities for coordinated approaches across immunization and health services.

Prevalence of Non-Polio Enteroviruses in the Sewage of Guangzhou City, China, from 2013 to 2021.

Continuous surveillance of enteroviruses (EVs) in urban domestic sewage can timely reflect the circulation of EVs in the environment and crowds, and play a predictive and early warning role in EV-related diseases. To better understand the long-term epidemiological trends of circulating EVs and EV-related diseases, we conducted a 9-year (2013 to 2021) surveillance study of non-polio EVs (NPEVs) in urban sewage in Guangzhou city, China. After concentrating and isolating the viruses from the sewage samples, NPEVs were detected and molecular typing was performed. Twenty-one different NPEV serotypes were identified. The most isolated EVs were echovirus 11 (E11), followed by coxsackievirus (CV) B5, E6, and CVB3. EV species B prevailed in sewage samples, but variations in the annual frequency of different serotypes were also observed in different seasons, due to spatial and temporal factors. E11 and E6 were detected continuously before 2017, and the number of isolates was relatively stable during the surveillance period. However, after their explosive growth in 2018 and 2019, their numbers suddenly decreased significantly. CVB3 and CVB5 had alternating trends; CVB5 was most frequently detected in 2013 to 2014 and 2017 to 2018, while CVB3 was most frequently detected in 2015 to 2016 and 2020 to 2021. Phylogenetic analysis showed that at least two different transmission chains of CVB3 and CVB5 were prevalent in Guangzhou City. Our results show that in the absence of a comprehensive and systematic EV-related disease surveillance system in China, environmental surveillance is a powerful and effective tool to strengthen and further investigate the invisible transmission of EVs in the population. IMPORTANCE This study surveilled urban sewage samples from north China for 9 years to monitor enteroviruses. Samples were collected, processed, and viral identification and molecular typing were performed. We detected 21 different non-polio enteroviruses (NPEVs) with yearly variations in prevalence and peak seasons. In addition, this study is very important for understanding the epidemiology of EVs during the COVID-19 pandemic, as the detection frequency and serotypes of EVs in sewage changed considerably around 2020. We believe that our study makes a significant contribution to the literature because our results strongly suggest that environmental surveillance is an exceptionally important tool, which can be employed to detect and monitor organisms of public health concern, which would otherwise be missed and under-reported by case-based surveillance systems alone.

Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection.

The global polio eradication campaign has had remarkable success in reducing wild-type poliovirus infection, largely built upon the live attenuated Sabin oral poliovirus vaccine. Whilst rare, vaccine poliovirus strains may cause infection and subsequently revert to a neurovirulent type, termed vaccine-derived poliovirus (VDPV). Persistent, vaccine derived infection may occur in an immunocompromised host (iVDPV), where it is a recognised complication following receipt of the Sabin vaccine. This has significant implications for the global polio eradication campaign and there is currently no agreed global strategy to manage such patients.Here we describe a case of a 50-year-old man with common variable immune deficiency, persistently infected with a neurovirulent vaccine-derived type 2 poliovirus following vaccination in childhood. iVDPV infection had proven resistant to multiple prior attempts at treatment with human breast milk, ribavirin and oral administration of a normal human pooled immunoglobulin product. His iVDPV infection subsequently resolved after 12 days treatment with remdesivir, an adenosine analogue prodrug that is an inhibitor of viral RNA-dependent RNA polymerase, administered as treatment for a prolonged, moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. iVDPV from the patient, isolated prior to treatment, was subsequently demonstrated to be sensitive to remdesivir in vitro. Based on the observations made in this case, and the mechanistic rationale for use with iVDPV, there is strong justification for further clinical studies of remdesivir treatment as a potentially curative intervention in patients with iVDPV infection.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Design and molecular docking studies of {N1-[2-(amino)ethyl]ethane-1,2-diamine}-[tris(oxido)]-molybdenum(VI) complex as a potential antivirus drug: from synthesis to structure

The aim of this study was to synthesize and examine the molecular docking of a Mo(VI) complex [Mo(dien)O3] (1), {N1-[2-(amino)ethyl]ethane-1,2-diamine}-[tris(oxido)]-molybdenum(VI) as a potential antivirus drug against the SARS-CoV-2, HIV and polio viruses. [Mo(dien)O3] (1) was fully characterized, including single crystal x-ray crystallography. The complex was crystallized in the orthorhombic crystal system with Pbcm space group and has distorted octahedral coordination geometry. DFT calculations have been explored for structure-property relationships. The Hirshfeld surface analysis and 2D fingerprint plots were also performed to investigate intermolecular interactions in the crystal structure. Antibacterial activities of 1 were also studied. In order to have insight into the potential application of 1 as an effective antivirus agent, we have examined the molecular docking of 1 with SARS-CoV-2 Mpro (PDB ID: 7N0I), HIV virus (PDB ID: 6MCF), Polio virus (PDB ID: 1HXS), and DNA duplex dodecamer (PDB ID: 1BNA). The molecular docking results reveal that 1 with Mpro of SARS-CoV-2, HIV-1 RNA and Polio virus resulted in binding energies (ΔG) of −9.9 kcal/mol, −8.8 kcal/mol and −8.4 kcal/mol with good inhibition constant (Ki) of 6.539 µM, 5.113 µM and 4.237 µM, respectively. Overall, in silico molecular docking predicts potential antivirus effects of 1 against the virus of SARS CoV-2, HIV, and Polio. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

ASVAC2022 : 8th Asian Vaccine Conference.

Aiming to further the Immunization Partners in Asia Pacific (IPAP)'s vision of a world where no one suffers from a vaccine preventable disease, the 8th Asian Vaccine Conference (ASVAC 2022) was held in Colombo, Sri Lanka and virtually from 15 to 18, September 2022 (www.asianvaccine.com). This conference followed those held in Siem Reap, Cambodia (2009), Manila, Philippines (2010), Jakarta, Indonesia (2011), Cebu, Philippines (2013), Hanoi, Vietnam (2015), Singapore (2017) and Naypyidaw and Yangon, Myanmar (2019). The ASVAC2022 themed "Immunization: in Era of Pandemics," commenced with the EPI Managers' Workshop, followed by pre-conference workshops and Vaccinology Masterclass, followed by the main conference featuring 5 plenary lectures, 6 partner-led symposia, free paper and poster presentations, and industry-supported lunch and evening sessions. There were over 1830 registered participants, with 112 attending in person and 998 virtually from 63 countries. The conference was organized by IPAP and hosted by the Vaccine and Infectious Disease Forum of Sri Lanka, Sri Lanka College of Pediatricians, Sri Lanka College of Microbiologists and College of General Practitioners of Sri Lanka, with the support of the Ministry of Health, Sri Lanka. The 9th ASVAC is scheduled to be held in Davao City, Philippines in late 2023.

Leveraging Lessons Learned from Yellow Fever and Polio Immunization Campaigns during COVID-19 Pandemic, Ghana, 2021.

Ghana is a yellow fever-endemic country and experienced a vaccine-derived polio outbreak in July 2019. A reactive polio vaccination campaign was conducted in September 2019 and preventive yellow fever campaign in November 2020. On March 12, 2020, Ghana confirmed its first COVID-19 cases. During February-August 2021, Ghana received 1,515,450 COVID-19 vaccines through the COVID-19 Vaccines Global Access initiative and other donor agencies. We describe how systems and infrastructure used for polio and yellow fever vaccine deployment and the lessons learned in those campaigns were used to deploy COVID-19 vaccines. During March-August 2021, a total of 1,424,008 vaccine doses were administered in Ghana. By using existing vaccination and health systems, officials in Ghana were able to deploy COVID-19 vaccines within a few months with <5% vaccine wastage and minimal additional resources despite the short shelf-life of vaccines received. These strategies were essential in saving lives in a resource-limited country.

Wastewater Surveillance for SARS-CoV-2 RNA in Canada

Wastewater surveillance for SARS-CoV-2 RNA is a relatively recent adaptation of long-standing wastewater surveillance for infectious and other harmful agents. Individuals infected with COVID-19 were found to shed SARS-CoV-2 in their faeces. Researchers around the world confirmed that SARS-CoV-2 RNA fragments could be detected and quantified in community wastewater. Canadian academic researchers, largely as volunteer initiatives, reported proof-of-concept by April 2020. National collaboration was initially facilitated by the Canadian Water Network.Many public health officials were initially skeptical about actionable information being provided by wastewater surveillance even though experience has shown that public health surveillance for a pandemic has no single, perfect approach. Rather, different approaches provide different insights, each with its own strengths and limitations. Public health science must triangulate among different forms of evidence to maximize understanding of what is happening or may be expected. Well-conceived, resourced, and implemented wastewater-based platforms can provide a cost-effective approach to support other conventional lines of evidence. Sustaining wastewater monitoring platforms for future surveillance of other disease targets and health states is a challenge. Canada can benefit from taking lessons learned from the COVID-19 pandemic to develop forward-looking interpretive frameworks and capacity to implement, adapt, and expand such public health surveil-lance capabilities.

Implications of COVID-19 and "super floods" for routine vaccination in Pakistan: The reemergence of vaccine preventable-diseases such as polio and measles.

With multiple waves and variants, the coronavirus disease 2019 (COVID-19) pandemic has affected routine vaccination programs globally. Its impact is also visible in Pakistan as routine health services continue to be disrupted. Consequently, thousands of children have emerged as vulnerable in the face of vaccine-preventable diseases (VPDs), which have already started causing outbreaks in the country. Infections with polio and measles have been significantly reported, especially during the last few years. This reemergence of both diseases is posing great challenges for the country at local, national, and global levels. These impacts are being multiplied by the 2022 flooding - called "super floods" - in the country. Hence, relevant stakeholders, such as the Pakistani government and the World Health Organization (WHO), need to revisit the entire vaccination program to address and resolve issues occurring at the management or local levels. It is highly important to pay attention to the context that provides a fertile ground to negatively affect vaccine uptake.

Effects of COVID-19 on Vaccine-Preventable Disease Surveillance Systems in the World Health Organization African Region, 2020.

Global emergence of the COVID-19 pandemic in 2020 curtailed vaccine-preventable disease (VPD) surveillance activities, but little is known about which surveillance components were most affected. In May 2021, we surveyed 214 STOP (originally Stop Transmission of Polio) Program consultants to determine how VPD surveillance activities were affected by the COVID-19 pandemic throughout 2020, primarily in low- and middle-income countries, where program consultants are deployed. Our report highlights the responses from 154 (96%) of the 160 consultants deployed to the World Health Organization African Region, which comprises 75% (160/214) of all STOP Program consultants deployed globally in early 2021. Most survey respondents observed that VPD surveillance activities were somewhat or severely affected by the COVID-19 pandemic in 2020. Reprioritization of surveillance staff and changes in health-seeking behaviors were factors commonly perceived to decrease VPD surveillance activities. Our findings suggest the need for strategies to restore VPD surveillance to prepandemic levels.

A 5-year look-back at the notification and management of vaccine supply shortages in Germany.

BackgroundUnavailability of vaccines endangers the overall goal to protect individuals and whole populations against infections.MethodsThe German notification system includes the publication of vaccine supply shortages reported by marketing authorisation holders (MAH), information on the availability of alternative vaccine products, guidance for physicians providing vaccinations and an unavailability reporting tool to monitor regional distribution issues.AimThis study provides a retrospective analysis of supply issues and measures in the context of European and global vaccine supply constraints.Resultsbetween October 2015 and December 2020, the 250 notifications concerned all types of vaccines (54 products). Most shortages were caused by increased demand associated with immigration in Germany in 2015 and 2016, new or extended vaccine recommendations, increased awareness, or changes in global immunisation programmes. Shortages of a duration up to 30 days were mitigated using existing storage capacities. Longer shortages, triggered by high demand on a national level, were mitigated using alternative products and re-allocation; in a few cases, vaccines were imported. However, for long lasting supply shortages associated with increased global demand, often occurring in combination with manufacturing issues, few compensatory mechanisms were available. Nevertheless, only few critical incidents were identified: (i) shortage of hexavalent vaccines endangering neonatal immunisation programmes in 2015;(ii) distribution issues with influenza vaccines in 2018; and (iii) unmet demand for pneumococcal and influenza vaccines during the coronavirus disease (COVID)-19 pandemic.ConclusionVaccine product shortages in Germany resemble those present in neighbouring EU states and often reflect increased global demand not matched by manufacturing capacities.

Oral Polio Vaccine to Mitigate the Risk of Illness and Mortality During the Coronavirus Disease 2019 Pandemic: A Cluster-Randomized Trial in Guinea-Bissau.

Background: Oral polio vaccine (OPV) may improve resistance to non-polio-infections. We tested whether OPV reduced the risk of illness and mortality before coronavirus disease 2019 (COVID-19) vaccines were available. Methods: During the early COVID-19 pandemic, houses in urban Guinea-Bissau were randomized 1:1 to intervention or control. Residents aged 50+ years were invited to participate. Participants received bivalent OPV (single dose) or nothing. Rates of mortality, admissions, and consultation for infections (primary composite outcome) during 6 months of follow-up were compared in Cox proportional hazards models adjusted for age and residential area. Secondary outcomes included mortality, admissions, consultations, and symptoms of infection. Results: We followed 3726 participants (OPV, 1580; control, 2146) and registered 66 deaths, 97 admissions, and 298 consultations for infections. OPV did not reduce the risk of the composite outcome overall (hazard ratio [HR] = 0.97; 95% confidence interval [CI], .79-1.18). OPV reduced the risk in males (HR = 0.71; 95% CI, .51-.98) but not in females (HR = 1.18; 95% CI, .91-1.52) (P for same effect = .02). OPV also reduced the risk in Bacillus Calmette-Guérin scar-positive (HR = 0.70; 95% CI, .49-.99) but not in scar-negative participants (HR = 1.13; 95% CI, .89-1.45) (P = .03). OPV had no overall significant effect on mortality (HR = 0.96; 95% CI, .59-1.55), admissions (HR = 0.76; 95% CI, .49-1.17) or recorded consultations (HR = 0.99; 95% CI, .79-1.25), but the OPV group reported more episodes with symptoms of infection (6050 episodes; HR = 1.10 [95% CI, 1.03-1.17]). Conclusions: In line with previous studies, OPV had beneficial nonspecific effects in males.