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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. [ABSTRACT FROM AUTHOR]

The article presents the discussion on poliovirus in the US. Topics include rapid improvement in vaccine coverage with the attenuated oral poliovirus vaccine (OPV) sustaining person-to-person transmission like that of WPV; and acute flaccid paralysis as a presenting condition having many causes considered in the differential diagnosis.

Background: Pakistan and Afghanistan remain the only reservoirs of wild poliovirus transmission. Prior modeling suggested that before the coronavirus disease 2019 (COVID-19) pandemic, plans to stop the transmission of serotype 1 wild poliovirus (WPV1) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2) did not appear on track to succeed.Methods: We updated an existing poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model for Pakistan and Afghanistan to characterize the impacts of immunization disruptions and restrictions on human interactions (ie, population mixing) due to the COVID-19 pandemic. We also consider different options for responding to outbreaks and for preventive supplementary immunization activities (SIAs).Results: The modeling suggests that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on 1 January 2021 of all polio immunization activities to pre-COVID-19 levels, Pakistan and Afghanistan would remain off-track for stopping all transmission through 2023 without improvements in quality.Conclusions: Using trivalent OPV (tOPV) for SIAs instead of serotype 2 monovalent OPV offers substantial benefits for ending the transmission of both WPV1 and cVDPV2, because tOPV increases population immunity for both serotypes 1 and 2 while requiring fewer SIA rounds, when effectively delivered in transmission areas. [ABSTRACT FROM AUTHOR]

Background The Global Polio Eradication Initiative (GPEI) Strategic Plan for 2019–2023 includes commitments to monitor the quality of immunization campaigns using lot quality assurance sampling surveys (LQAS) and to support poliovirus surveillance in Pakistan and Afghanistan. Methods We analyzed LQAS and poliovirus surveillance data between 2016 and 2020, which included both acute flaccid paralysis (AFP) case-based detection and the continued expansion of environmental surveillance (ES). Using updated estimates for unit costs, we explore the costs of different options for future poliovirus monitoring and surveillance for Pakistan and Afghanistan. Results The relative value of the information provided by campaign quality monitoring and surveillance remains uncertain and depends on the design, implementation, and performance of the systems. Prospective immunization campaign quality monitoring (through LQAS) and poliovirus surveillance will require tens of millions of dollars each year for the foreseeable future for Pakistan and Afghanistan. Conclusions LQAS campaign monitoring as currently implemented in Pakistan and Afghanistan provides limited and potentially misleading information about immunization quality. AFP surveillance in Pakistan and Afghanistan provides the most reliable evidence of transmission, whereas ES provides valuable supplementary information about the extent of transmission in the catchment areas represented at the time of sample collection. [ABSTRACT FROM AUTHOR]

Background: Following successful eradication of wild polioviruses and planned globally-coordinated cessation of oral poliovirus vaccine (OPV), national and global health leaders may need to respond to outbreaks from reintroduced live polioviruses, particularly vaccine-derived polioviruses (VDPVs). Preparing outbreak response plans and assessing potential vaccine needs from an emergency stockpile require consideration of the different national risks and conditions as they change with time after OPV cessation.Methods: We used an integrated global model to consider several key issues related to managing poliovirus risks and outbreak response, including the time interval during which monovalent OPV (mOPV) can be safely used following homotypic OPV cessation; the timing, quality, and quantity of rounds required to stop transmission; vaccine stockpile needs; and the impacts of vaccine choices and surveillance quality. We compare the base case scenario that assumes aggressive outbreak response and sufficient mOPV available from the stockpile for all outbreaks that occur in the model, with various scenarios that change the outbreak response strategies.Results: Outbreak response after OPV cessation will require careful management, with some circumstances expected to require more and/or higher quality rounds to stop transmission than others. For outbreaks involving serotype 2, using trivalent OPV instead of mOPV2 following cessation of OPV serotype 2 but before cessation of OPV serotypes 1 and 3 would represent a good option if logistically feasible. Using mOPV for outbreak response can start new outbreaks if exported outside the outbreak population into populations with decreasing population immunity to transmission after OPV cessation, but failure to contain outbreaks resulting in exportation of the outbreak poliovirus may represent a greater risk. The possibility of mOPV use generating new long-term poliovirus excretors represents a real concern. Using the base case outbreak response assumptions, we expect over 25% probability of a shortage of stockpiled filled mOPV vaccine, which could jeopardize the achievement of global polio eradication. For the long term, responding to any poliovirus reintroductions may require a global IPV stockpile. Despite the risks, our model suggests that good risk management and response strategies can successfully control most potential outbreaks after OPV cessation.Conclusions: Health leaders should carefully consider the numerous outbreak response choices that affect the probability of successfully managing poliovirus risks after OPV cessation. [ABSTRACT FROM AUTHOR]

The article focuses on the challenges of the organization, World Health Assembly to make policy changes post the decision to end the use of oral polio vaccines (OPV), considering the successful efforts of poliovirus eradication. Topics discussed include outbreak of circulating vaccine-derived poliovirus (cVDPV) due to wild poliovirus (WPV), role of Global Polio Eradication Initiative (GPEI), and need for research on better surveillance tools and vaccines for complete eradication of the virus.

Background: The Global Polio Eradication Initiative plans for coordinated cessation of oral poliovirus vaccine (OPV) after interrupting all wild poliovirus (WPV) transmission, but many questions remain related to long-term poliovirus risk management policies.Methods: We used an integrated dynamic poliovirus transmission and stochastic risk model to simulate possible futures and estimate the health and economic outcomes of maintaining the 2013 status quo of continued OPV use in most developing countries compared with OPV cessation policies with various assumptions about global inactivated poliovirus vaccine (IPV) adoption.Results: Continued OPV use after global WPV eradication leads to continued high costs and/or high cases. Global OPV cessation comes with a high probability of at least one outbreak, which aggressive outbreak response can successfully control in most instances. A low but non-zero probability exists of uncontrolled outbreaks following a poliovirus reintroduction long after OPV cessation in a population in which IPV-alone cannot prevent poliovirus transmission. We estimate global incremental net benefits during 2013-2052 of approximately $16 billion (US$2013) for OPV cessation with at least one IPV routine immunization dose in all countries until 2024 compared to continued OPV use, although significant uncertainty remains associated with the frequency of exportations between populations and the implementation of long term risk management policies.Conclusions: Global OPV cessation offers the possibility of large future health and economic benefits compared to continued OPV use. Long-term poliovirus risk management interventions matter (e.g., IPV use duration, outbreak response, containment, continued surveillance, stockpile size and contents, vaccine production site requirements, potential antiviral drugs, and potential safer vaccines) and require careful consideration. Risk management activities can help to ensure a low risk of uncontrolled outbreaks and preserve or further increase the positive net benefits of OPV cessation. Important uncertainties will require more research, including characterizing immunodeficient long-term poliovirus excretor risks, containment risks, and the kinetics of outbreaks and response in an unprecedented world without widespread live poliovirus exposure. [ABSTRACT FROM AUTHOR]

Background: A small number of individuals with B-cell-related primary immunodeficiency diseases (PIDs) may exhibit long-term (prolonged or chronic) excretion of immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) following infection with oral poliovirus vaccine (OPV). These individuals pose a risk of live poliovirus reintroduction into the population after global wild poliovirus eradication and subsequent OPV cessation. Treatment with polio antiviral drugs may potentially stop excretion in some of these individuals and thus may reduce the future population risk.Methods: We developed a discrete event simulation model to characterize the global prevalence of long-term iVDPV excretors based on the best available evidence. We explored the impact of different assumptions about the effectiveness of polio antiviral drugs and the fraction of long-term excretors identified and treated.Results: Due to the rarity of long-term iVDPV excretion and limited data on the survival of PID patients in developing countries, uncertainty remains about the current and future prevalence of long-term iVDPV excretors. While the model suggests only approximately 30 current excretors globally and a rapid decrease after OPV cessation, most of these excrete asymptomatically and remain undetected. The possibility that one or more PID patients may continue to excrete iVDPVs for several years after OPV cessation represents a risk for reintroduction of live polioviruses after OPV cessation, particularly for middle-income countries. With the effectiveness of a single polio antiviral drug possibly as low as 40% and no system in place to identify and treat asymptomatic excretors, the impact of passive use of a single polio antiviral drug to treat identified excretors appears limited. Higher drug effectiveness and active efforts to identify long-term excretors will dramatically increase the benefits of polio antiviral drugs.Conclusions: Efforts to develop a second polio antiviral compound to increase polio antiviral effectiveness and/or to maximize the identification and treatment of affected individuals represent important risk management opportunities for the polio endgame. Better data on the survival of PID patients in developing countries and more longitudinal data on their exposure to and recovery from OPV infections would improve our understanding of the risks associated with iVDPV excretors and the benefits of further investments in polio antiviral drugs. [ABSTRACT FROM AUTHOR]

Background: Frequent supplemental immunization activities (SIAs) with the oral poliovirus vaccine (OPV) represent the primary strategy to interrupt poliovirus transmission in the last endemic areas. Materials and Methods: Using a differential-equation based poliovirus transmission model tailored to high-risk areas in Nigeria, we perform one-way and multi-way sensitivity analyses to demonstrate the impact of different assumptions about routine immunization (RI) and the frequency and quality of SIAs on population immunity to transmission and persistence or emergence of circulating vaccine-derived polioviruses (cVDPVs) after OPV cessation. Results: More trivalent OPV use remains critical to avoid serotype 2 cVDPVs. RI schedules with or without inactivated polio vaccine (IPV) could significantly improve population immunity if coverage increases well above current levels in under-vaccinated subpopulations. Similarly, the impact of SIAs on overall population immunity and cVDPV risks depends on their ability to reach under-vaccinated groups (i.e., SIA quality). Lower SIA coverage in the under-vaccinated subpopulation results in a higher frequency of SIAs needed to maintain high enough population immunity to avoid cVDPVs after OPV cessation. Conclusions: National immunization program managers in northwest Nigeria should recognize the benefits of increasing RI and SIA quality. Sufficiently improving RI coverage and improving SIA quality will reduce the frequency of SIAs required to stop and prevent future poliovirus transmission. Better information about the incremental costs to identify and reach under-vaccinated children would help determine the optimal balance between spending to increase SIA and RI quality and spending to increase SIA frequency. [ABSTRACT FROM AUTHOR]

Highlights: [•] We measured anti-poliovirus (PV) antibodies among 1–24 year-olds in Tajikistan after the 2010 wild PV1 outbreak. [•] PV3 results used as surrogate for the pre-outbreak PV1 immunity suggest suboptimal coverage over time led to the outbreak. [•] PV1 seroprevalence >98% indicates mOPV1 supplementary immunization activities (SIAs) succeeded in closing the immunity gap. [•] PV3-susceptibility across wide age range (<90% seroprevalence in most age groups) justifies SIA age expansion to 15 years. [•] Widespread PV3-susceptibility supports the need for tOPV SIAs after the initial mOPV1 response. [Copyright &y& Elsevier]

• Timeliness, scope, and quality of cVDPV2 outbreak response campaigns substantially impact global risks. • Countries and GPEI could stop cVDPV2 transmission with existing vaccines if they improve campaigns. • The properties of nOPV2 use in the field remain uncertain, and GPEI needs to manage expectations. 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. [ABSTRACT FROM AUTHOR]

Following the global declaration of indigenous wild poliovirus type 2 eradication in 2015, the world switched to oral polio vaccine (OPV) that removed the type 2 component. This 'switch' included the widespread introduction of inactivated poliovirus vaccine and the creation of a stockpile of monovalent type 2 OPV (mOPV2) to respond to potential polio virus Type 2 (PV2) outbreaks and events. With subsequent detection of outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2), it was necessary to use this stockpile for outbreak response. Not only were more outbreaks detected than anticipated in the first few years after the switch, but the number of supplemental immunization activities (SIAs) used to stop transmission was often high, and in many cases did not stop wider transmission. Use of mOPV type 2 led in some locations to the emergence of new outbreaks that required further use of the vaccine from the stockpile. In the following years, stockpile management became a critical element of the cVDPV2 outbreak response strategy and continued to evolve to include trivalent OPV and genetically stabilized 'novel OPV type 2' vaccines in the stockpile. An overview of this process and its evolution is presented to highlight several of these management challenges. The unpredictable vaccine demand, fixed production and procurement timelines, resource requirements, and multiple vaccine types contributes to the complexity of assuring appropriate vaccine availability for this critical programmatic need to stop outbreaks. [ABSTRACT FROM AUTHOR]

• The COVID-19 pandemic disrupted polio immunization activities. • Response to COVID-19 included substantial reductions in people mixing and traveling. • Early resumption of polio immunization activities could mitigate the impacts on poliovirus transmission. 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. [ABSTRACT FROM AUTHOR]

Abstract: The global polio eradication initiative (GPEI), which started in 1988, represents the single largest, internationally coordinated public health project to date. Completion remains within reach, with type 2 wild polioviruses apparently eradicated since 1999 and fewer than 2000 annual paralytic poliomyelitis cases of wild types 1 and 3 reported since then. This economic analysis of the GPEI reflects the status of the program as of February 2010, including full consideration of post-eradication policies. For the GPEI intervention, we consider the actual pre-eradication experience to date followed by two distinct potential future post-eradication vaccination policies. We estimate GPEI costs based on actual and projected expenditures and poliomyelitis incidence using reported numbers corrected for underreporting and model projections. For the comparator, which assumes only routine vaccination for polio historically and into the future (i.e., no GPEI), we estimate poliomyelitis incidence using a dynamic infection transmission model and costs based on numbers of vaccinated children. Cost-effectiveness ratios for the GPEI vs. only routine vaccination qualify as highly cost-effective based on standard criteria. We estimate incremental net benefits of the GPEI between 1988 and 2035 of approximately 40–50billion dollars (2008 US dollars; 1988 net present values). Despite the high costs of achieving eradication in low-income countries, low-income countries account for approximately 85% of the total net benefits generated by the GPEI in the base case analysis. The total economic costs saved per prevented paralytic poliomyelitis case drive the incremental net benefits, which become positive even if we estimate the loss in productivity as a result of disability as below the recommended value of one year in average per-capita gross national income per disability-adjusted life year saved. Sensitivity analysis suggests that the finding of positive net benefits of the GPEI remains robust over a wide range of assumptions, and that consideration of the additional net benefits of externalities that occurred during polio campaigns to date, such as the mortality reduction associated with delivery of Vitamin A supplements, significantly increases the net benefits. This study finds a strong economic justification for the GPEI despite the rising costs of the initiative. [Copyright &y& Elsevier]

Abstract: Eradication of a disease promises significant health and financial benefits. Preserving those benefits, hopefully in perpetuity, requires preparing for the possibility that the causal agent could re-emerge (unintentionally or intentionally). In the case of a vaccine-preventable disease, creation and planning for the use of a vaccine stockpile becomes a primary concern. Doing so requires consideration of the dynamics at different levels, including the stockpile supply chain and transmission of the causal agent. This paper develops a mathematical framework for determining the optimal management of a vaccine stockpile over time. We apply the framework to the polio vaccine stockpile for the post-eradication era and present examples of solutions to one possible framing of the optimization problem. We use the framework to discuss issues relevant to the development and use of the polio vaccine stockpile, including capacity constraints, production and filling delays, risks associated with the stockpile, dynamics and uncertainty of vaccine needs, issues of funding, location, and serotype dependent behavior, and the implications of likely changes over time that might occur. This framework serves as a helpful context for discussions and analyses related to the process of designing and maintaining a stockpile for an eradicated disease. [Copyright &y& Elsevier]

For the final stages in the eradication of poliovirus type 1 (P1), the World Health Organization advocates the selective use of monovalent type 1 oral poliovirus vaccine (mOPV1). To compare the immunogenicity of mOPV1 with that of trivalent OPV (tOPV) in infants, a study was performed in Egypt in 2005. Newborns were vaccinated with mOPV1 or tOPV immediately after birth and were challenged with mOPV1 after 1 month. Vaccination with mOPV1 at birth resulted in significantly higher seroconversion against P1 viruses and lower excretion of P1 viruses than vaccination with tOPV. Intratypic differentiation of the viruses shed by the newborns revealed the presence of remarkably high numbers of antigenically divergent (AD) P1 isolates, especially in the mOPV1 study group. The majority of these AD P1 isolates (71%) were mOPV1 challenge derived and were shed by newborns who did not seroconvert to P1 after the birth dose. Genetic characterization of the viruses revealed that amino acid 60 of the VP3 region was mutated in all AD P1 isolates. Isolates with substitution of residue 99 of the VP1 region had significantly higher numbers of nonsynonymous mutations in the VP1 region than isolates without this substitution and were preferentially shed in the mOPV1 study group. The widespread use of mOPV1 has proven to be a powerful tool for fighting poliovirus circulation in the remaining areas of endemicity. This study provides another justification for the need to achieve high vaccination coverage in order to prevent the circulation of AD strains. [ABSTRACT FROM AUTHOR]

The authors discuss a study led by Feng-Cai Zhu and published within the issue, regarding a phase 2 clinical trial of an inactivated enterovirus 71 (EV71) vaccine to prevent severe outcomes of EV71 infection in young children. It mentions the large number of deaths in Asia caused by EV71 infections. The possibility that the vaccine's immunogenicity may have been overestimated is also addressed.

The article focuses on three books related to poliomyelitis. These are "Polio: An American Story," by David M. Oshinsky; "Splendid Solution: Jonas Salk and the Conquest of Polio," by Jeffrey Kluger; and "Living With Polio: The Epidemic and Its Survivors," by Daniel J. Wilson. Oshinsky offers an easily approachable yet factually rich narrative. Discussing the key events and characters that shaped the steady progression of the scientific search for a vaccine to vanquish polio, Oshinsky places them in the social context of the times. By weaving together the threads of stories of afflicted individuals, affected communities, and effective leaders while also chronicling the establishment of the organizations that championed the fight against the disease, he provides a solid backdrop for the philanthropic and scientific efforts. Kluger reveals in more detail the individuals who most closely influenced and interacted with the scientist credited with the first licensed polio vaccine. The book stays close to the strand of the polio story that begins with Salk living through the New York polio outbreak of 1916 and continues until the use of his vaccine becomes routine, 40 years later.

To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6–10–14 weeks/fIPV at 6 weeks (A); mOPV1 at 6–10–14 weeks/fIPV at 10 weeks (B); mOPV1 at 6–10–14 weeks (C); and bOPV at 6–10–14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). During 18 December 2018 – 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91–97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93–98%]) or 10 weeks (96% [93–98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. U.S. Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Novel oral poliovirus vaccine type 2 (nOPV2) was developed by modifying the Sabin strain to increase genetic stability and reduce risk of seeding new circulating vaccine-derived poliovirus type 2 outbreaks. Bivalent oral poliovirus vaccine (bOPV; containing Sabin types 1 and 3) is the vaccine of choice for type 1 and type 3 outbreak responses. We aimed to assess immunological interference between nOPV2 and bOPV when administered concomitantly. We conducted an open-label, non-inferiority, randomised, controlled trial at two clinical trial sites in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomly assigned (1:1:1) using block randomisation, stratified by site, to receive nOPV2 only, nOPV2 plus bOPV, or bOPV only, at the ages of 6 weeks, 10 weeks, and 14 weeks. Eligibility criteria included singleton and full term (≥37 weeks' gestation) birth and parents intending to remain in the study area for the duration of study follow-up activities. Poliovirus neutralising antibody titres were measured at the ages of 6 weeks, 10 weeks, 14 weeks, and 18 weeks. The primary outcome was cumulative immune response for all three poliovirus types at the age of 14 weeks (after two doses) and was assessed in the modified intention-to-treat population, which was restricted to participants with adequate blood specimens from all study visits. Safety was assessed in all participants who received at least one dose of study product. A non-inferiority margin of 10% was used to compare single and concomitant administration. This trial is registered with ClinicalTrials.gov , NCT04579510. Between Feb 8 and Sept 26, 2021, 736 participants (244 in the nOPV2 only group, 246 in the nOPV2 plus bOPV group, and 246 in the bOPV only group) were enrolled and included in the modified intention-to-treat analysis. After two doses, 209 (86%; 95% CI 81–90) participants in the nOPV2 only group and 159 (65%; 58–70) participants in the nOPV2 plus bOPV group had a type 2 poliovirus immune response; 227 (92%; 88–95) participants in the nOPV2 plus bOPV group and 229 (93%; 89–96) participants in the bOPV only group had a type 1 response; and 216 (88%; 83–91) participants in the nOPV2 plus bOPV group and 212 (86%; 81–90) participants in the bOPV only group had a type 3 response. Co-administration was non-inferior to single administration for types 1 and 3, but not for type 2. There were 15 serious adverse events (including three deaths, one in each group, all attributable to sudden infant death syndrome); none were attributed to vaccination. Co-administration of nOPV2 and bOPV interfered with immunogenicity for poliovirus type 2, but not for types 1 and 3. The blunted nOPV2 immunogenicity we observed would be a major drawback of using co-administration as a vaccination strategy. The US Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Background. The Strategic Advisory Group of Experts on Immunization (SAGE) has recommended introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) at ≥14 weeks of age through the routine immunization program in countries currently not using IPV.Methods. We analyzed all available unrestricted data obtained from the Demographic and Health Surveys since 2005 in sub-Saharan Africa (31 countries) and in South and Southeast Asia (9 countries) to determine coverage of the following injectable vaccines delivered through the routine immunization schedule: diphtheria-tetanus-pertussis vaccine dose 1 (DTP1), DTP2, DTP3, and measles vaccine. Coverage with these vaccines was used as a proxy measure of likely 1- and 2-dose IPV coverage.Results. Coverage with 1 dose of IPV is expected to be lowest when offered with DTP3 (median coverage, 73%) and highest when offered with DTP1 (median coverage, 90%). The median DTP1-DTP3 drop-out rate was 14%, which equates to an additional 12 million children not receiving IPV if IPV is offered with DTP3, rather than with DTP1. An increased geographical clustering of children who have not received IPV is expected in sub-Saharan Africa and Asia if IPV is offered with DTP3, rather than with DTP1. Coverage with 2 doses of IPV is expected to be lowest if IPV is administered with DTP3 and measles vaccine (69%) and highest if administered with DTP1 and DTP2 (84%).Conclusions. Coverage with 1 dose of IPV is expected to be lowest if it is administered at the DTP3 visit. At present, there is insufficient evidence to determine whether the SAGE-recommended IPV schedule for the polio endgame would maximize population immunity to type 2 poliovirus. [ABSTRACT FROM PUBLISHER]

Nonpolio enteroviruses are diverse and common viruses that can circulate year-round but tend to peak in summer. Although most infections are asymptomatic, they can result in a wide range of neurological and other diseases. Many serotypes circulate every year, and different serotypes predominate in different years, but the drivers of their geographical and temporal dynamics are not understood. We use national enterovirus surveillance data collected by the US Centers for Disease Control and Prevention during 1983-2013, as well as demographic and climatic data for the same period, to study the patterns and drivers of the seasonality of these infections. We find that the seasonal pattern of enterovirus cases is spatially structured in the United States and similar to that observed for historical prevaccination poliomyelitis (1931-1954). We identify latitudinal gradients for the amplitude and the timing of the peak of cases, meaning that those are more regularly distributed all year-round in the south and have a more pronounced peak that arrives later toward the north. The peak is estimated to occur between July and September across the United States, and 1 month earlier than that for historical poliomyelitis. Using mixed-effects models, we find that climate, but not demography, is likely to drive the seasonal pattern of enterovirus cases and that the dew point temperature alone explains ~30% of the variation in the intensity of transmission. Our study contributes to a better understanding of the epidemiology of enteroviruses, demonstrates important similarities in their circulation dynamics with polioviruses, and identifies potential drivers of their seasonality. [ABSTRACT FROM AUTHOR]

Introduction The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries. Methods We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV. Results Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19–42% (median: 37%, p < 0.001) and relative increase of 53–125% (median: 82%), and antibody titer to type 2 increasing by 2–32-fold (median: 10-fold). Early age of administration and shorter intervals between doses were associated with lower immunogenicity. Discussion Overall, two fIPV doses are more immunogenic than a single full-dose, associated with significantly increased seroconversion rates and antibody titers. Two fIPV doses together use two-fifth of the vaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14 weeks has been endorsed by technical oversight committees and has been introduced in some affected countries. [ABSTRACT FROM AUTHOR]

• Successful outbreak response requires timely supplemental immunization activities. • There are numerous sources of delayed response beyond the vaccine approval process. • Several countries met multiple target indicators for successful outbreak response. 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 28 days 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 56 days 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 >120 days. To achieve timely and effective response, countries should follow GPEI OBR guidelines. [ABSTRACT FROM AUTHOR]

The article explores the challenges and the progress made in the global eradication of polio. It states that poliovirus circulation still persists in countries where the virus is endemic and that outbreaks are occurring in previously polio-free areas. It cites some of the major accomplishments of the global polio eradication program, including the establishment of a global integrated virologic surveillance network and the use of genetic sequencing in studying polio.

In 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) recommended introduction of at least one inactivated poliovirus vaccine (IPV) dose in essential immunization programs. We evaluated systemic humoral and intestinal mucosal immunity of a sequential IPV-bivalent oral poliovirus vaccine (bOPV) schedule compared with a co-administration IPV + bOPV schedule in an open-label, randomized, controlled, non-inferiority, inequality trial in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomized to either: (A) IPV and bOPV at 6 and bOPV at 10 and 14 weeks (IPV + bOPV-bOPV-bOPV); or (B) IPV at 6 and bOPV at 10 and 14 weeks (IPV-bOPV-bOPV). Of 456 participants enrolled and randomly assigned during May–August 2015, 428 (94%) were included in the modified intention-to-treat analysis (arm A: 211, arm B: 217). Humoral immune responses did not differ at 18 weeks between study arms: type 1 (98% versus 96%; p = 0.42), type 2 (37% versus 39%; p = 0.77), and type 3 (97% versus 93%; p = 0.07). Virus shedding one week after the bOPV challenge dose in arm B was non-inferior to arm A (type 1 difference = −3% [90% confidence interval: −6 − 0.4%]; type 3 difference: −3% [−6 to −0.2%]). Twenty-six adverse events including seven serious adverse events were reported among 25 participants including one death; none were attributed to study vaccines. An IPV-bOPV-bOPV sequential schedule induced comparable systemic humoral immunity to all poliovirus types and types 1 and 3 intestinal mucosal immunity as an IPV + bOPV-bOPV-bOPV co-administration schedule. [ABSTRACT FROM AUTHOR]

Background: Most poliovirus infections occur with no symptoms and this leads to the possibility of silent circulation, which complicates the confirmation of global goals to permanently end poliovirus transmission. Previous simple models based on hypothetical populations assumed perfect detection of symptomatic cases and suggested the need to observe no paralytic cases from wild polioviruses (WPVs) for approximately 3-4 years to achieve 95% confidence about eradication, but the complexities in real populations and the imperfect nature of surveillance require consideration. Methods: We revisit the probability of undetected poliovirus circulation using a more comprehensive model that reflects the conditions in a number of places with different characteristics related to WPV transmission, and we model the actual environmental WPV detection that occurred in Israel in 2013. We consider the analogous potential for undetected transmission of circulating vaccine-derived polioviruses. The model explicitly accounts for the impact of different vaccination activities before and after the last detected case of paralytic polio, different levels of surveillance, variability in transmissibility and neurovirulence among serotypes, and the possibility of asymptomatic participation in transmission by previously-vaccinated or infected individuals. Results: We find that prolonged circulation in the absence of cases and thus undetectable by case-based surveillance may occur if vaccination keeps population immunity close to but not over the threshold required for the interruption of transmission, as may occur in northwestern Nigeria for serotype 2 circulating vaccine-derived poliovirus in the event of insufficient tOPV use. Participation of IPV-vaccinated individuals in asymptomatic fecal-oral transmission may also contribute to extended transmission undetectable by case-based surveillance, as occurred in Israel. We also find that gaps or quality issues in surveillance could significantly reduce confidence about actual disruption. Maintaining high population immunity and high-quality surveillance for several years after the last detected polio cases will remain critical elements of the polio end game. Conclusions: Countries will need to maintain vigilance in their surveillance for polioviruses and recognize that their risks of undetected circulation may differ as a function of their efforts to manage population immunity and to identify cases or circulating live polioviruses. [ABSTRACT FROM AUTHOR]

The article presents an interim U.S. Centers for Disease Control and Prevention (CDC) guidance for polio vaccination for travel to from countries affected by wild poliovirus (WPV) released in July 2014. Topics discussed include the three countries which are still endemic for polio, namely Afghanistan, Nigeria and Pakistan, the recommendations for travelers to ensure that they have completed the necessary polio vaccine series and the minor side effects of inactivated polio vaccine (IPV).

Abstract: The use of inactivated poliovirus vaccines (IPV) will be required to achieve, world-wide eradication of polio. The current expense of IPV is however prohibitive for, some countries, and therefore efforts to decrease the costs of the vaccine are a high, priority. Our results show that the addition of oil-in-water emulsion adjuvants to an, inactivated trivalent poliovirus vaccine are dose-sparing and are capable of enhancing, neutralizing antibody titers in the rat potency model. [ABSTRACT FROM AUTHOR]

Abstract: Background: The Parechovirus genus (Picornaviridae) contains two known species, Human parechovirus (HPeV) and Ljungan virus (LV). HPeVs cause a wide spectrum of disease, including meningitis, gastroenteritis, encephalitis, respiratory illness, and neonatal sepsis-like disease. LVs are associated with diabetes and myocarditis in bank voles and have been proposed to cause disease in humans. The ability to rapidly and accurately type parechoviruses is critical to understanding their role in human disease. Objectives: For parechovirus molecular typing, we sought to develop reverse transcription, nested polymerase chain reaction (RT-PCR) assays to amplify the sequence encoding the VP1 capsid protein from all known members of the Parechovirus genus. Study design: The assays consist of a two-step RT-PCR with primers flanking VP1 (PCR1), followed by semi-nested PCR2A and PCR2B reactions that produce overlapping amplicons, encompassing the complete VP1 gene, as well as a nested PCR2C that amplifies a shorter internal VP1 amplicon. Results: All primer sets are 100% sensitive and 100% specific for the 77 parechovirus culture isolates tested. The semi-nested and nested PCR primer sets are 94% sensitive and 100% specific for detection of parechovirus in original specimens. Viral genotype can be deduced from analysis of amplicon sequences. Parechoviruses of the same type share ≥77% complete VP1 nucleotide sequence identity or ≥87% amino acid identity, while those of different types share ≤73% nucleotide identity and ≤81% amino acid identity. Conclusions: The PCR primers described here amplify VP1 sequences from all known parechoviruses, providing a sensitive, reliable system for molecular typing directly from original clinical specimens. [Copyright &y& Elsevier]

Objectives. We assessed the costs, risks, and benefits of possible future major policy decisions on vaccination, surveillance, response plans, and containment following global eradication of wild polioviruses. Methods. We developed a decision analytic model to estimate the incremental cost-effectiveness ratios and net benefits of risk management options for polio for the 20-year period and stratified the world according to income level to capture important variability between nations. Results. For low-, lower-middle-, and upper-middle-income groups currently using oral poliovirus vaccine (OPV), we found that after successful eradication of wild polioviruses, OPV cessation would save both costs and lives when compared with continued use of OPV without supplemental immunization activities. We found cost-effectiveness ratios for switching from OPV to inactivated poliovirus vaccine to be higher (i.e., less desirable) than other health investment opportunities, depending on the actual inactivated poliovirus vaccine costs and assumptions about whether supplemental immunization activities with OPV would continue. Conclusions. Eradication promises billions of dollars of net benefits, although global health policy leaders face difficult choices about future policies. Until successful eradication and coordination of posteradication policies, health authorities should continue routine polio vaccination and supplemental immunization activities. [ABSTRACT FROM AUTHOR]

RNA recombination has been shown to occur during circulation of enteroviruses, but most studies have focused on poliovirus. To examine the role of recombination in the evolution of the coxsackie B viruses (CVB), we determined the partial sequences of four genomic intervals for multiple clinical isolates of each of the six CVB serotypes isolated from 1970 to 1996. The regions sequenced were the 5'-nontranslated region (5'-NTR) (350 nucleotides [nt]), capsid (VP4.VP2, 416 nt, and VP1, ∼320 nt), and polymerase (3D, 491 nt). Phylogenetic trees were constructed for each genome region, using the clinical isolate sequences and those of the prototype strains of all 65 enterovirus serotypes. The partial VP1 sequences of each CVB serotype were monophyletic with respect to serotype, as were the VP4-VP2 sequences, in agreement with previously published studies. In some cases, however, incongruent tree topologies suggested that intraserotypic recombination had occurred between the sequenced portions of VP2 and VP1. Outside the capsid region, however, isolates of the same serotype were not monophyletic, indicating that recombination had occurred between the 5'-NTR and capsid, the capsid and 3D, or both. Almost all clinical isolates were recombinant relative to the prototype strain of the same serotype. All of the recombination partners appear to be members of human enterovirus species B. These results suggest that recombination is a frequent event during enterovirus evolution but that there are genetic restrictions that may influence recombinational compatibility. [ABSTRACT FROM AUTHOR]

The species Human enterovirus B (HEV-B) in the family Picornaviridae consists of coxsackievirus A9; coxsackieviruses B1 to B6; echoviruses 1 to 7, 9, 11 to 21, 24 to 27, and 29 to 33; and enteroviruses 69 and 73. We have determined complete genome sequences for the remaining 22 HEV-B serotypes whose sequences were not represented in public databases and analyzed these in conjunction with previously available complete sequences in GenBank. Members of HEV-B were monophyletic relative to all other human enterovirus species in all regions of the genome except in the 5'-nontranslated region (NTR), where they are known to cluster with members of HEV-A. Within HEV-B, phylogenies constructed from the structural (P1) and nonstructural regions of the genome (P2 and P3) are incongruent, suggesting that recombination had occurred. Similarity plots and bootscanning analysis across the complete genome identified multiple sites at which the phylogeny of a given strain's sequence shifted, indicating potential recombination points. These points are distributed in the 5'-NTR and throughout P2 and P3, but no sites with >80% bootstrap support were identified within the capsid. Individual sequence comparisons and phylogenetic analyses suggest that members of HEV-B have recombined with one another on multiple occasions, resulting in a complex mosaic of sequences derived from multiple parental viruses in the nonstructural regions of the genome. We conclude that RNA recombination is a common mechanism for enterovirus evolution and that recombination within the nonstructural regions of the genome (P2 and P3) has been observed only among members of the same species. [ABSTRACT FROM AUTHOR]

Analysis of the VP1 capsid protein coding region of simian virus (SV) 2, SV16, SV18, SV42, SV44, SV45, and SV49 demonstrates that they are clearly distinct from members of the Enterovirus genus and from members of other existing picornavirus genera. To further characterize this group of viruses and to clarify their classification within the Picornaviridae, we have determined the complete genomic sequence of SV2 (8126 nucleotides). The genome was typical of members of Picornaviridae, encoding a single open reading frame. The putative polyprotein contained typical picornavirus protease cleavage sites, yielding mature proteins homologous to each of the known picornavirus proteins. SV2 contained an amino-terminal extension of the reading frame, which was analogous to the leader protein of members of the Aphthovirus, Cardiovirus, Erbovirus, Kobuvirus, and Teschovirus genera, but there was no significant amino acid homology with any of these known leader proteins. The 2A protein also aligned poorly with the 2A proteins of other picornaviruses. The deduced amino acid sequences of the SV2 structural and nonstructural proteins were related to but phylogenetically distinct from those of enteroviruses and human rhinoviruses. The major distinguishing features of SV2 were the presence of a type 2 internal ribosome entry site in the 5′-NTR, a putative leader protein encoded upstream of the structural proteins, and an unusually large 2A protein. On the basis of the molecular analysis, we propose that SV2, SV16, SV18, SV42, SV44, SV45, SV49, and porcine enterovirus 8 be classified as members of a new genus in Picornaviridae and that SV2 (strain 2383) be designated as the type strain. [Copyright &y& Elsevier]

• Poliovirus eradication endgame requires IPV-only immunization schedules. • A 14-week/9-month IPV schedule is superior to a 6 and 14-week schedule. • A 14-week/9-month and 6-week/9-month schedules achieved a cumulative immune response of >=98%. • Findings support current SAGE guidelines for IPV immunization schedules. After global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age. We conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age. Of the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77–81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98–99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C. Results support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks. [ABSTRACT FROM AUTHOR]

Since 1988, when World Health Organization (WHO) Member States and partners launched the Global Polio Eradication Initiative, the number of wild poliovirus (WPV) cases has declined from 350,000 in 125 countries to 176 in only two countries in 2019 (1). The Global Commission for the Certification of Poliomyelitis Eradication (GCC) declared two of the three WPV types, type 2 (WPV2) and type 3 (WPV3), eradicated globally in 2015 and 2019, respectively (1). Wild poliovirus type 1 (WPV1) remains endemic in Afghanistan and Pakistan (1). Containment under strict biorisk management measures is vital to prevent reintroduction of eradicated polioviruses into communities from poliovirus facilities. In 2015, Member States committed to contain type 2 polioviruses (PV2) in poliovirus-essential facilities (PEFs) certified in accordance with a global standard (2). Member states agreed to report national PV2 inventories annually, destroy unneeded PV2 materials, and, if retaining PV2 materials, establish national authorities for containment (NACs) and a PEF auditing process. Since declaration of WPV3 eradication in October 2019, these activities are also required with WPV3 materials. Despite challenges faced during 2019-2020, including the coronavirus disease 2019 (COVID-19) pandemic, the global poliovirus containment program continues to work toward important milestones. To maintain progress, all WHO Member States are urged to adhere to the agreed containment resolutions, including officially establishing legally empowered NACs and submission of PEF Certificates of Participation. [ABSTRACT FROM AUTHOR]

The use of the oral poliovirus vaccine (OPV) in developing countries has reduced the incidence of poliomyelitis by >99% since 1988 and is the primary tool for global polio eradication. Spontaneous reversions of the vaccine virus to a neurovirulent form can impede this effort. In persons with primary B-cell immunodeficiencies, exposure to OPV can result in chronic infection, mutation, and excretion of immunodeficiency-associated vaccine-derived polioviruses, (iVDPVs). These iVDPVs may have the potential for transmission in a susceptible population and cause paralysis. The extent to which sera from OPV recipients are able to neutralize iVDPVs with varying degrees of antigenic site substitutions is investigated here. We tested sera from a population immunized with a combination vaccine schedule (both OPV and inactivated polio vaccine) against a panel of iVDPVs and found that increases in amino acid substitution in the P1 capsid protein resulted in a decrease in the neutralizing capacity of the sera. This study underscores the importance of maintaining high vaccine coverage in areas of OPV use as well as active surveillance of those known to be immunocompromised. [ABSTRACT FROM AUTHOR]

An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection. [ABSTRACT FROM AUTHOR]

Certification of global eradication of indigenous wild poliovirus type 2 occurred in 2015 and of type 3 in 2019. Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988 and broad use of live, attenuated oral poliovirus vaccine (OPV), the number of wild poliovirus cases has declined >99.99% (1). Genetically divergent vaccine-derived poliovirus* (VDPV) strains can emerge during vaccine use and spread in underimmunized populations, becoming circulating VDPV (cVDPV) strains, and resulting in outbreaks of paralytic poliomyelitis.† In April 2016, all oral polio vaccination switched from trivalent OPV (tOPV; containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV; containing types 1 and 3) (2). Monovalent type 2 OPV (mOPV2) is used in response campaigns to control type 2 cVDPV (cVDPV2) outbreaks. This report presents data on cVDPV outbreaks detected during January 2018-June 2019 (as of September 30, 2019). Compared with January 2017-June 2018 (3), the number of reported cVDPV outbreaks more than tripled, from nine to 29; 25 (86%) of the outbreaks were caused by cVDPV2. The increase in the number of outbreaks in 2019 resulted from VDPV2 both inside and outside of mOPV2 response areas. GPEI is planning future use of a novel type 2 OPV, stabilized to decrease the likelihood of reversion to neurovirulence. However, all countries must maintain high population immunity to decrease the risk for cVDPV emergence. Cessation of all OPV use after certification of polio eradication will eliminate the risk for VDPV emergence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acute flaccid myelitis (AFM) is a neurologic condition characterized by flaccid limb weakness. After a large number of reports of AFM in 2014, the Centers for Disease Control and Prevention began standardized surveillance in the United States to characterize the disease burden and explore potential etiologies and epidemiologic associations. METHODS: Persons meeting the clinical case criteria of acute flaccid limb weakness from January 1, 2015, through December 31, 2017, were classified as confirmed (spinal cord gray matter lesions on MRI) or probable (white blood cell count >5 cells per mm³ in cerebrospinal fluid [CSF]). We describe clinical, radiologic, laboratory, and epidemiologic findings of pediatric patients (age ≤21 years) confirmed with AFM. RESULTS: Of 305 children reported from 43 states, 193 were confirmed and 25 were probable. Of confirmed patients, 61% were male, with a median age of 6 years (range: 3 months to 21 years; interquartile range: 3 to 10 years). An antecedent respiratory or febrile illness was reported in 79% with a median of 5 days (interquartile range: 2 to 7 days) before limb weakness. Among 153 sterile-site specimens (CSF and serum) submitted to the Centers for Disease Control and Prevention, coxsackievirus A16 was detected in CSF and serum of one case patient and enterovirus D68 was detected in serum of another. Of 167 nonsterile site (respiratory and stool) specimens, 28% tested positive for enterovirus or rhinovirus. CONCLUSIONS: AFM surveillance data suggest a viral etiology, including enteroviruses. Further study is ongoing to better characterize the etiology, pathogenesis, and risk factors of this rare condition. [ABSTRACT FROM AUTHOR]

Background: Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response.Methods: We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0·5 mL), and fIPV was administered intradermally (0·1 mL of the IPV formulation was administered using the 0·1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12·5%. This trial is registered with ClinicalTrials.gov, number NCT02847026.Findings: Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0·0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73-83]) versus 305 (57% [53-61]) participants, the type 2 response comprised 173 (64% [58-70]) versus 249 (46% [42-51]) participants, and the type 3 response comprised 196 (73% [67-78]) versus 196 (36% [33-41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vs group A) for serotype 1 (-1·12% [90% CI -2·18 to -0·06]), serotype 2 (0·40%, [-2·22 to 1·42]), and serotype 3 (1·51% [-3·23 to -0·21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV.Interpretation: fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses.Funding: US Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

The need for closer linkages between scientific and programmatic areas focused on addressing vaccine-preventable and acute respiratory infections led to establishment of the National Center for Immunization and Respiratory Diseases (NCIRD) at the Centers for Disease Control and Prevention. During its first 10 years (2006-2015), NCIRD worked with partners to improve preparedness and response to pandemic influenza and other emergent respiratory infections, provide an evidence base for addition of 7 newly recommended vaccines, and modernize vaccine distribution. Clinical tools were developed for improved conversations with parents, which helped sustain childhood immunization as a social norm. Coverage increased for vaccines to protect adolescents against pertussis, meningococcal meningitis, and human papillomavirus-associated cancers. NCIRD programs supported outbreak response for new respiratory pathogens and oversaw response of the Centers for Disease Control and Prevention to the 2009 influenza A(H1N1) pandemic. Other national public health institutes might also find closer linkages between epidemiology, laboratory, and immunization programs useful. [ABSTRACT FROM AUTHOR]

Background: Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2.Methods: We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 105 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual.Findings: Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune responses after two mOPV2 doses were observed in 161 (93%) of 173 infants with testable serum samples in the 1 week group, 169 (96%) of 177 in the 2 week group, and 176 (97%) of 181 in the 4 week group. 1 week and 2 week intervals between two mOPV2 doses were non-inferior to 4 week intervals because the lower bound of the absolute differences in the percentage of immune responses were greater than -10% (-4·2% [90% CI -7·9 to -0·4] in the 1 week group and -1·8% [-5·0 to 1·5] in the 2 week group vs the 4 week group). The immune response elicited by two mOPV2 doses 4 weeks apart was not different when IPV was added to the first dose (176 [97%] of 182 infants with IPV vs 176 [97%] of 181 without IPV; p=1·0). During the trial, two serious adverse events (pneumonia; one [1%] of 186 patients in the 1 week group and one [1%] of 182 in the 4 week group) and no deaths were reported; the adverse events were not attributed to the vaccines.Interpretation: Administration of mOPV2 at short intervals does not interfere with its immunogenicity. The addition of IPV to the first mOPV2 dose did not improve poliovirus type 2 immune response.Funding: US Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Background: More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection. Methods: Genetic, geographic and temporal data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan from January 2011 through December 2013. We used viral genetics to assess gaps in AFP surveillance and ES as measured by detection of ‘orphan viruses’ (≥1.5% different in VP1 capsid nucleotide sequence). We compared preceding detection of closely related circulating isolates (≥99% identity) detected by AFP surveillance or ES to determine which surveillance system first detected circulation before the presentation of each polio case. Findings: A total of 1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011–2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively). ES detected circulation before AFP surveillance in nearly 60% of polio cases (200 of 346). For polio cases reported from provinces conducting ES, ES detected circulation nearly four months sooner on average (117.6 days) than did AFP surveillance. Interpretation: Our findings suggest ES in Pakistan is providing earlier, more sensitive detection of wild polioviruses than AFP surveillance alone. Overall, targeted ES through strategic selection of sites has important implications in the eradication endgame strategy. [ABSTRACT FROM AUTHOR]

The Global Polio Laboratory Network (GPLN) began building in the late 1980s on a 3-tiered structure of 146 laboratories with different and complementary technical and support capacities (poliovirus isolation, molecular strain characterization including sequencing, quality assurance, and research). The purpose of this network is to provide timely and accurate laboratory results to the Global Polio Eradication Initiative. Deeply integrated with field case-based surveillance, it ultimately provides molecular epidemiological data from polioviruses used to inform programmatic and immunization activities. This network of global coverage requires substantial investments in laboratory infrastructure, equipment, supplies, reagents, quality assurance, staffing and training, often in resource-limited settings. The GPLN has not only developed country capacities, but it also serves as a model to other global laboratory networks for vaccine-preventable diseases that will endure after the polio eradication goal is achieved. Leveraging lessons learned during past 27 years, the authors discuss options for transitioning GPLN assets to support control of other viral vaccine-preventable, emerging, and reemerging diseases. [ABSTRACT FROM AUTHOR]

In August 2018, CDC noted an increased number of reports of patients having symptoms clinically compatible with acute flaccid myelitis (AFM), a rare condition characterized by rapid onset of flaccid weakness in one or more limbs and spinal cord gray matter lesions, compared with August 2017. Since 2014, CDC has conducted surveillance for AFM using a standardized case definition (1,2). An Epi-X* notice was issued on August 23, 2018, to increase clinician awareness and provide guidance for case reporting. [ABSTRACT FROM AUTHOR]

Background. During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the United States, coincident with a national outbreak of enterovirus D68 (EV-D68)-associated severe respiratory illness. Methods. Clinicians and health departments reported standardized clinical, epidemiologic, and radiologic information on AFM cases to the Centers for Disease Control and Prevention (CDC), and submitted biological samples for testing. Cases were ≤21 years old, with acute onset of limb weakness 1 August-31 December 2014 and spinal magnetic resonance imaging (MRI) showing lesions predominantly restricted to gray matter. Results. From August through December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but 1 case was hospitalized; none died. Cerebrospinal fluid (CSF) pleocytosis (>5 white blood cells/μL) was common (81%). At CDC, 1 CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time polymerase chain reaction, although the specimen had >3000 red blood cells/μL. The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 16 AFM cases reported from 13 states. Conclusions. Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology, and etiology of AFM. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a novel respiratory pathogen first reported in 2012. During September 2014-January 2015, an outbreak of 38 cases of MERS was reported from 4 healthcare facilities in Taif, Saudi Arabia; 21 of the 38 case-patients died. Clinical and public health records showed that 13 patients were healthcare personnel (HCP). Fifteen patients, including 4 HCP, were associated with 1 dialysis unit. Three additional HCP in this dialysis unit had serologic evidence of MERS-CoV infection. Viral RNA was amplified from acute-phase serum specimens of 15 patients, and full spike gene-coding sequencing was obtained from 10 patients who formed a discrete cluster; sequences from specimens of 9 patients were closely related. Similar gene sequences among patients unlinked by time or location suggest unrecognized viral transmission. Circulation persisted in multiple healthcare settings over an extended period, underscoring the importance of strengthening MERS-CoV surveillance and infection-control practices. [ABSTRACT FROM AUTHOR]