Coordinated global cessation of oral poliovirus vaccine use: Options and potential consequences.

Due to the very low, but nonzero, paralysis risks associated with the use of oral poliovirus vaccine (OPV), eradicating poliomyelitis requires ending all OPV use globally. The Global Polio Eradication Initiative (GPEI) coordinated cessation of Sabin type 2 OPV (OPV2 cessation) in 2016, except for emergency outbreak response. However, as of early 2023, plans for cessation of bivalent OPV (bOPV, containing types 1 and 3 OPV) remain undefined, and OPV2 use for outbreak response continues due to ongoing transmission of type 2 polioviruses and reported type 2 cases. Recent development and use of a genetically stabilized novel type 2 OPV (nOPV2) leads to additional potential vaccine options and increasing complexity in strategies for the polio endgame. Prior applications of integrated global risk, economic, and poliovirus transmission modeling consistent with GPEI strategic plans that preceded OPV2 cessation explored OPV cessation dynamics and the evaluation of options to support globally coordinated risk management efforts. The 2022-2026 GPEI strategic plan highlighted the need for early bOPV cessation planning. We review the published modeling and explore bOPV cessation immunization options as of 2022, assuming that the GPEI partners will not support restart of the use of any OPV type in routine immunization after a globally coordinated cessation of such use. We model the potential consequences of globally coordinating bOPV cessation in 2027, as anticipated in the 2022-2026 GPEI strategic plan. We do not find any options for bOPV cessation likely to succeed without a strategy of bOPV intensification to increase population immunity prior to cessation.

Health Economic Analysis of Antiviral Drugs in the Global Polio Eradication Endgame.

BACKGROUND: Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear the virus without therapeutic intervention. Although prolonged/chronic poliovirus excreters are rare, they represent a source of poliovirus reintroduction into the general population. Prior studies that assumed the successful cessation of all oral poliovirus vaccine (OPV) use estimated the potential upper bound of the incremental net benefits (INBs) of resource investments in research and development of PAVDs. However, delays in polio eradication, OPV cessation, and the development of PAVDs necessitate an updated economic analysis to reevaluate the costs and benefits of further investments in PAVDs. METHODS: Using a global integrated model of polio transmission, immunity, vaccine dynamics, risks, and economics, we explore the risks of reintroduction of polio transmission due to immunodeficiency-related vaccine-derived poliovirus (iVDPV) excreters and reevaluate the upper bound of the INBs of PAVDs. RESULTS: Under the current conditions, for which the use of OPV will likely continue for the foreseeable future, even with successful eradication of type 1 wild poliovirus by the end of 2023 and continued use of Sabin OPV for outbreak response, we estimate an upper bound INB of 60 million US$2019. With >100 million US$2019 already invested in PAVD development and with the introduction of novel OPVs that are less likely to revert to neurovirulence, our analysis suggests the expected INBs of PAVDs would not offset their costs. CONCLUSIONS: While PAVDs could play an important role in the polio endgame, their expected economic benefits drop with ongoing OPV use and poliovirus transmissions. However, stakeholders may pursue the development of PAVDs as a desired product regardless of their economic benefits.HighlightsWhile polio antiviral drugs could play an important role in the polio endgame, their expected economic benefits continue to drop with delays in polio eradication and the continued use of oral poliovirus vaccines.The incremental net benefits of investments in polio antiviral drug development and screening for immunodeficiency-related circulating polioviruses are small.Limited global resources are better spent on increasing global population immunity to polioviruses to stop and prevent poliovirus transmission.

The ghost of polio haunts us once again. The appeal of the scientific community is clear: "Vaccinate your kids today!"

INTRODUCTION: In the summer of 2022, a vaccination campaign for the prevention of poliomyelitis was launched and "The CDC recommend that all children be vaccinated against polio, or poliomyelitis". The scientific community is on the alert for new cases of polio, which is spreading. Although polio seemed to have been almost completely eradicated throughout the world, the disease has surprisingly reappeared in some Western countries. The risk of international spread of poliovirus remains a Public Health Emergency of International Concern (PHEIC). METHOD: The authors reviewed recent polio cases in some western countries which have caused significant public health concern and they underline the meaning and weight of this issue emphasizing the importance of vaccination. DISCUSSION: In June 2022, the British authorities announced that they had detected traces of a form of polio derived from a vaccine strain in the wastewater of some London boroughs. Although no cases of disease were identified, the British government immediately announced that it was proceeding to reinstate polio vaccination for all children. A few weeks later, on July 18, 2022, the New Jersey Department of Health notified the CDCP of the detection of type-2 poliovirus in an unvaccinated young man in the New York metropolitan area. This case immediately triggered an appeal from the CDCP to get vaccinated and, above all, to vaccinate children. Low vaccination coverage means that the population is constantly at risk of further cases of paralytic poliomyelitis. CONCLUSION: The appeal to vaccinate children against polio is crucial, as prevention through vaccination is the only defense against the disease. We think that an efficient vaccination campaign can positively influence the process of eliminating the virus. At the same time, however, it demonstrates that simply lowering one's guard can quickly lead to a resurgence of polio cases. Hence, until polio is eradicated, we can be sure that contagion by the wild virus and the risk of vaccine-derived poliovirus will remain possible.

Monovalent type 2 OPV (mOPV2) management in the field: Interventions and lessons learned.

The polio endgame strategy calls for ending the use of and removal of all Sabin vaccines globally given the risks of generation and spread of cVDPVs. With the successful eradication of wild poliovirus type 2 in 2015, the process of removing type 2 Sabin vaccines began with the switch from tOPV to bOPV across national vaccination programs. Following the tOPV to bOPV switch in April/May 2016, monovalent type 2 OPV (mOPV2) has been put into use in response to detected cVDPV2 polioviruses outbreaks. Between 31 May 2016 and 30 Jun 2020, 453 million doses of mOPV2 were provided to 21 countries to conduct 235 campaigns to respond to cVDPV2 outbreaks and high-risk events. However, the use of this vaccine paradoxically reintroduces live attenuated type 2 poliovirus into the populations and the environment, therefore, poses a risk for the emergence of new VDPV2s. Thus, it is critical to carefully and appropriately manage all in-country mOPV2 stocks utilized in outbreak response to minimize this risk. In this article, we examine the performance of mOPV2 vaccine management utilized for various outbreak responses after the switch.We present the major challenges faced and the lessons learned, to improve technical guidance and future response activities. Performance varied significantly across countries in terms of each of the activity areas evaluated. There were major gaps, especially in terms of vaccine accountability, and in many instances large numbers of vials went unaccounted presenting additional risk for further VDPV2 emergences. We have shown that especially at the beginning of implementation, insufficient attention has been given to mOPV2 vaccine management. Enhanced focus on mOPV2 vaccine management in line with the lessons learned presented in this paper should be a priority for public health programs and countries to consider and adapt in future VDPV2 responses as well as potential future activities associated with eventual complete withdrawal & cessation of OPV.These experiences can also be extended to other vaccines for which strict stock management and containment measures are required.

Use of oral polio vaccine and the incidence of COVID-19 in the world.

BACKGROUND: Several live attenuated vaccines were shown to provide temporary protection against a variety of infectious diseases through stimulation of the host innate immune system. OBJECTIVE: To test the hypothesis that countries using oral polio vaccine (OPV) have a lower cumulative number of cases diagnosed with COVID-19 per 100,000 population (CP100K) compared with those using only inactivated polio vaccine (IPV). METHODS: In an ecological study, the CP100K was compared between countries using OPV vs IPV. We used a random-effect meta-analysis technique to estimate the pooled mean for CP100K. We also used negative binomial regression with CP100K as the dependent variable and the human development index (HDI) and the type of vaccine used as independent variables. RESULTS: The pooled estimated mean CP100K was 4970 (95% CI 4030 to 5900) cases per 100,000 population for countries using IPV, significantly (p<0.001) higher than that for countries using OPV-1580 (1190 to 1960). Countries with higher HDI prefer to use IPV; those with lower HDI commonly use OPV. Both HDI and the type of vaccine were independent predictors of CP100K. Use of OPV compared to IPV could independently decrease the CP100K by an average of 30% at the mean HDI of 0.72. CONCLUSIONS: Countries using OPV have a lower incidence of COVID-19 compared to those using IPV. This might suggest that OPV may either prevent SARS-CoV-2 infection at individual level or slow down the transmission at the community level.

COVID-19 Infection Among Women in Iran Exposed vs Unexposed to Children Who Received Attenuated Poliovirus Used in Oral Polio Vaccine.

Importance: Live attenuated vaccines may provide short-term protection against infectious diseases through stimulation of the innate immune system. Objective: To evaluate whether passive exposure to live attenuated poliovirus is associated with diminished symptomatic infection with SARS-CoV-2. Design, Setting, and Participants: In a longitudinal cohort study involving 87 923 people conducted between March 20 and December 20, 2020, the incidence of COVID-19 was compared between 2 groups of aged-matched women with and without exposure to live attenuated poliovirus in the oral polio vaccine (OPV). Participants were people receiving health care services from the Petroleum Industry Health Organization and residing in 2 cities in Iran (ie, Ahwaz and Shiraz). Participants were women aged 18 to 48 years whose children were aged 18 months or younger and a group of age-matched women from the same residence who had had no potential exposure to OPV. Exposures: Indirect exposure to live attenuated poliovirus in OPV. Main Outcomes and Measures: Symptomatic COVID-19, diagnosed by reverse transcription-polymerase chain reaction. Results: After applying the inclusion and exclusion criteria, 419 mothers (mean [SD] age, 35.5 [4.9] years) indirectly exposed to the OPV and 3771 age-matched women (mean [SD] age, 35.7 [5.3] years) who had no exposure to OPV were available for analysis. COVID-19 was diagnosed in 1319 of the 87 923 individuals in the study population (151 per 10 000 population) during the study period. None of the mothers whose children received OPV developed COVID-19 after a median follow-up of 141 days (IQR, 92-188 days; range, 1-270 days); 28 women (0.74%; 95% CI, 0.47%-1.02%) in the unexposed group were diagnosed with COVID-19 during the 9 months of the study. Point-by-point comparison of the survival curves of the exposed and unexposed groups found that indirect exposure to OPV was significantly associated with decreased COVID-19 acquisition; probability of remaining without infection was 1.000 (95% CI, 1.000-1.000) in the exposed group vs 0.993 (95% CI, 0.990-0.995) in the unexposed group after 9 months (P < .001). Conclusions and Relevance: In this cohort study, indirect exposure to live attenuated poliovirus was associated with decreased symptomatic infection with COVID-19. Further study of the potential protective effect of OPV should be conducted, especially in nations where OPV is already in use for polio prevention and specific COVID-19 vaccines are delayed, less affordable, or fail to meet demand.

[Discovery of Foci of Type-2 Poliovirus Derived from Oral Polio Vaccine in Central African Republic in 2019]. / Découverte de Foyers de Poliovirus de Type-2 Dérivé du Vaccin Antipoliomyélitique Oral en République Centrafricaine en 2019.

Objective: In 2019, the Central African Republic identified foci of circulating vaccine-derived poliovirus 2 (PVDV2c). The objective of this work is to describe the vaccination status of children paralyzed by PVDV2c and their contacts and to assess the circulation of this strain in these contacts. Patients and method: The study population of this retrospective survey consists of children with acute flaccid paralysis (AFP) and their contacts. We included paralyzed children whose sequencing results showed the presence of PVDV2c. Results: A total of 21 children paralyzed by PVDVc and 64 contacts were enrolled in the survey. Fourteen out of 21 children who are paralyzed (66%) received at least one dose of bivalent oral polio vaccine (OPV) compared to 36 out of 64 contacts (57%, non-significant difference). Of the vaccinated patients, 7 had received less than three doses. For the injectable polio vaccine (IPV), vaccination coverage for both patients and contacts was 33%.The proportion of children who received both doses of OPV and IPV was 33% among patients and 25% in contacts. Contacts with VDPV2 were vaccinated with OPV and IPV, respectively 55 and 27%. VDPV2 and Sabin 2 were also found in contact stools, 34% and 9% respectively. Conclusion: The absence or inadequacy of IPV vaccination has a serious impact on children by the occurrence of virus derived from the vaccine responsible for life-old paralysis. Protecting children from poliomyelitis requires a combination of a good cold chain, multiple doses and adherence to the vaccine schedule.

Expected Implications of Globally Coordinated Cessation of Serotype 3 Oral Poliovirus Vaccine (OPV) Before Serotype 1 OPV.

Globally coordinated cessation of all three serotypes of oral poliovirus vaccine (OPV) represents a critical part of a successful polio endgame, which the Global Polio Eradication Initiative (GPEI) plans to conduct in phases, with serotype 2 OPV cessation completed in mid 2016. Although in 2016 the GPEI expected to globally coordinate cessation of the remaining OPV serotypes (1 and 3) by 2021, continuing transmission of serotype 1 wild polioviruses to date makes those plans obsolete. With increasing time since the last reported polio case caused by serotype 3 wild poliovirus (in November 2012) leading to high confidence about its successful global eradication, the Global Commission for the Certification of Poliomyelitis Eradication recently certified its eradication. Questions now arise about the optimal timing of serotype 3 OPV (OPV3) cessation. Using an integrated global model that characterizes the risks, costs, and benefits of global polio policy and risk management options, we explored the implications of different options for coordinated cessation of OPV3 prior to COVID-19. Globally coordinating cessation of OPV3 as soon as possible offers the opportunity to reduce cases of vaccine-associated paralytic polio globally. In addition, earlier cessation of OPV3 should reduce the risks of creating serotype 3 circulating vaccine-derived polioviruses after OPV3 cessation, which represents a significant threat to the polio endgame given current GPEI plans to reduce preventive OPV supplemental immunization activities starting in 2019.

Impact of COVID-19 on polio vaccination in Pakistan: a concise overview.

The pandemic of coronavirus disease 2019 (COVID-19) has disrupted immunization programs around the globe, potentially increasing life-threatening vaccine-preventable diseases. Pakistan and Afghanistan are the only countries, which are still struggling to eradicate wild poliovirus. All vaccination campaigns in Pakistan were suspended in April due to the COVID-19 outbreak, leading 40 million children to miss out on polio vaccination. Like the climate crisis, the COVID-19 pandemic could be regarded as a child-rights crisis because it could have life-threatening impact over children, who need immunization, now and in the long-term. Delays in polio vaccination programs might not have immediate impact but, in the long-term, the increase in polio cases in Pakistan could result in the global export of infections. Therefore, healthcare authorities must intensify their efforts to track and vaccinate unvaccinated children in countries like Pakistan and Afghanistan. Polio vaccination campaigns need to resume immediately, so we suggest applying social distancing measures along with standard operating procedure to flatten the transmission curve of COVID-19. Furthermore, the concurrent emergence of cVDPV2 means that tOPV should temporarily be used for primary immunization. In the current review, we have discussed delays in polio vaccination, surveillance of polio viruses, reported cases in Pakistan along with recommendations to overcome interrupted immunization.

Serostatus following polio-containing vaccination before and after liver transplantation.

BACKGROUND: The strategy to eradicate polio is based on preventing infection by immunizing all children until the world is polio-free. However, data regarding efficacy of polio-containing vaccination in immunocompromised patients such as LT recipients are limited. METHODS: We conducted an observational study at the largest pediatric transplant center in Japan from January 2011 to January 2015. LT recipients were enrolled after transplantation, and those who had completed the Japanese polio vaccination program were eligible for the study. Patients' demographics were collected from their medical records. Antibody titers against poliovirus serotypes 1-3 were measured using the neutralization test at the routine follow-up visits after enrollment. Factors associated with seropositivity against each type of poliovirus were evaluated. RESULTS: Sixty-four patients who had received the complete polio vaccination series were enrolled in the study. Of these, 37 patients had received all series of polio-containing vaccination before LT. Median age of the patients was 75 months. Their underlying diseases included the following: 40 (63%) with cholestatic liver diseases and 11 (17%) with metabolic disorders. After a median interval of 43 months after LT, seropositivity rates against poliovirus 1, 2, and 3 were 93.8% (60/64), 92.2% (59/64), and 54.7% (35/64), respectively. Among 32 patients who had received only oral polio vaccine (OPV), seropositivity against poliovirus 3 was particularly low (25.0%). No factors associated with seropositivity against each type of poliovirus were identified. CONCLUSIONS: In the LT recipients, seropositivity for poliovirus 3 was low, suggesting a need for additional inactivated polio-containing vaccination after LT, especially for patients who had received only OPV.

Prosocial polio vaccination in Israel.

Regions with insufficient vaccination have hindered worldwide poliomyelitis eradication, as they are vulnerable to sporadic outbreaks through reintroduction of the disease. Despite Israel's having been declared polio-free in 1988, a routine sewage surveillance program detected polio in 2013. To curtail transmission, the Israel Ministry of Health launched a vaccine campaign to vaccinate children-who had only received the inactivated polio vaccine-with the oral polio vaccine (OPV). Determining the degree of prosocial motivation in vaccination behavior is challenging because vaccination typically provides direct benefits to the individual as well as indirect benefits to the community by curtailing transmission. However, the Israel OPV campaign provides a unique and excellent opportunity to quantify and model prosocial vaccination as its primary objective was to avert transmission. Using primary survey data and a game-theoretical model, we examine and quantify prosocial behavior during the OPV campaign. We found that the observed vaccination behavior in the Israeli OPV campaign is attributable to prosocial behavior and heterogeneous perceived risk of paralysis based on the individual's comprehension of the prosocial nature of the campaign. We also found that the benefit of increasing comprehension of the prosocial nature of the campaign would be limited if even 24% of the population acts primarily from self-interest, as greater vaccination coverage provides no personal utility to them. Our results suggest that to improve coverage, communication efforts should also focus on alleviating perceived fears surrounding the vaccine.

Antirotavirus IgA seroconversion rates in children who receive concomitant oral poliovirus vaccine: A secondary, pooled analysis of Phase II and III trial data from 33 countries.

BACKGROUND: Despite the success of rotavirus vaccines over the last decade, rotavirus remains a leading cause of severe diarrheal disease among young children. Further progress in reducing the burden of disease is inhibited, in part, by vaccine underperformance in certain settings. Early trials suggested that oral poliovirus vaccine (OPV), when administered concomitantly with rotavirus vaccine, reduces rotavirus seroconversion rates after the first rotavirus dose with modest or nonsignificant interference after completion of the full rotavirus vaccine course. Our study aimed to identify a range of individual-level characteristics, including concomitant receipt of OPV, that affect rotavirus vaccine immunogenicity in high- and low-child-mortality settings, controlling for individual- and country-level factors. Our central hypothesis was that OPV administered concomitantly with rotavirus vaccine reduced rotavirus vaccine immunogenicity. METHODS AND FINDINGS: Pooled, individual-level data from GlaxoSmithKline's Phase II and III clinical trials of the monovalent rotavirus vaccine (RV1), Rotarix, were analyzed, including 7,280 vaccinated infants (5-17 weeks of age at first vaccine dose) from 22 trials and 33 countries/territories (5 countries/territories with high, 13 with moderately low, and 15 with very low child mortality). Two standard markers for immune response were examined including antirotavirus immunoglobulin A (IgA) seroconversion (defined as the appearance of serum antirotavirus IgA antibodies in subjects initially seronegative) and serum antirotavirus IgA titer, both collected approximately 4-12 weeks after administration of the last rotavirus vaccine dose. Mixed-effect logistic regression and mixed-effect linear regression of log-transformed data were used to identify individual- and country-level predictors of seroconversion (dichotomous) and antibody titer (continuous), respectively. Infants in high-child-mortality settings had lower odds of seroconverting compared with infants in low-child-mortality settings (odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.43-0.53, p < 0.001). Similarly, among those who seroconverted, infants in high-child-mortality settings had lower IgA titers compared with infants in low-child-mortality settings (mean difference [ß] = 0.83, 95% CI 0.77-0.90, p < 0.001). Infants who received OPV concomitantly with both their first and their second doses of rotavirus vaccine had 0.63 times the odds of seroconverting (OR = 0.63, 95% CI 0.47-0.84, p = 0.002) compared with infants who received OPV but not concomitantly with either dose. In contrast, among infants who seroconverted, OPV concomitantly administered with both the first and second rotavirus vaccine doses was found to be positively associated with antirotavirus IgA titer (ß = 1.28, 95% CI 1.07-1.53, p = 0.009). Our findings may have some limitations in terms of generalizability to routine use of rotavirus vaccine because the analysis was limited to healthy infants receiving RV1 in clinical trial settings. CONCLUSIONS: Our findings suggest that OPV given concomitantly with RV1 was a substantial contributor to reduced antirotavirus IgA seroconversion, and this interference was apparent after the second vaccine dose of RV1, as with the original clinical trials that our reanalysis is based on. However, our findings do suggest that the forthcoming withdrawal of OPV from the infant immunization schedule globally has the potential to improve RV1 performance.

Poliovirus neutralizing antibody levels among individuals in three regions of Ghana.

INTRODUCTION: Ghana was declared polio-free in 2015 after the last polio case in 2008. We determined the poliovirus neutralizing antibody levels among individuals to identify possible immunity gaps. METHODS: A cross-sectional, hospital-based study was undertaken in Northern, Ashanti and Greater Accra regions of Ghana. Individuals referred for haematology at the teaching hospitals' laboratories were invited to participate in our study. Neutralizing-antibody titers to poliovirus serotypes 1,2 & 3 were assayed by WHO-standards. Antibody titers of ≥8 were considered protective. Bivariate and multivariate analyses were conducted on subject characteristics to assess potential factors for failure to seroconvert. P-values < 0.05 were considered statistically significant. RESULTS: Poliovirus (PV) neutralizing-antibody serotypes 1, 2 and 3 were detected in 86.0% (264/307), 84% (258/307) and 75% (230/307) of samples respectively. 60.1% (185/307) were seropositive for the three poliovirus serotypes. Neutralizing poliovirus antibodies for PV1 and PV2 were higher than for PV3. Seroprevalence of poliovirus-neutralizing antibodies among males (PV1=51.9%, PV2= 51.6% and PV3= 52.6%) were higher than in females. Seroprevalence rates of poliovirus-neutralizing antibodies (PV1, PV2, and PV3) were highest in the Northern region (90%, 81%, and 77%). Poliovirus neutralizing-antibodies (PV1and PV2) decreased with age [p< 0.001]. Low seroprevalence of poliovirus-neutralizing antibodies was significantly associated with low school attendance of mothers (p<0.001). CONCLUSION: Our study population has some protection from polio. However, immunity appears to be lower with a higher age or low Mother's education. This may suggest the need for young-adult booster-dose to minimize the risk of wild poliovirus infection. FUNDING: WHO Country Office Ghana.

Vaccine schedules and the effect on humoral and intestinal immunity against poliovirus: a systematic review and network meta-analysis.

BACKGROUND: The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus vaccines (IPVs). The first phase of this effort was the withdrawal of the serotype 2 vaccine in April 2016, with a switch from trivalent OPVs to bivalent OPVs. The aim of our study was to produce comparative estimates of humoral and intestinal mucosal immunity associated with different routine immunisation schedules. METHODS: We did a random-effect meta-analysis with single proportions and a network meta-analysis in a Bayesian framework to synthesise direct and indirect data. We searched MEDLINE and the Cochrane Library Central Register of Controlled Trials for randomised controlled trials published from Jan 1, 1980, to Nov 1, 2018, comparing poliovirus immunisation schedules in a primary series. Only trials done outside western Europe or North America and without variation in age schedules (ie, age at administration of the vaccine) between study groups were included in the analyses, because trials in high-income settings differ in vaccine immunogenicity and schedules from other settings and to ensure consistency within the network of trials. Data were extracted directly from the published reports. We assessed seroconversion against poliovirus serotypes 1, 2, and 3, and intestinal immunity against serotype 2, measured by absence of shedding poliovirus after a challenge OPV dose. FINDINGS: We identified 437 unique studies; of them, 17 studies with a maximum of 8279 evaluable infants were eligible for assessment of humoral immunity, and eight studies with 4254 infants were eligible for intestinal immunity. For serotype 2, there was low between-trial heterogeneity in the data (τ=0·05, 95% credible interval [CrI] 0·009-0·15) and the risk ratio (RR) of seroconversion after three doses of bivalent OPVs was 0·14 (95% CrI 0·11-0·17) compared with three doses of trivalent OPVs. The addition of one or two full doses of an IPV after a bivalent OPV schedule increased the RR to 0·85 (0·75-1·0) and 1·1 (0·98-1·4). However, the addition of an IPV to bivalent OPV schedules did not significantly increase intestinal immunity (0·33, 0·18-0·61), compared with trivalent OPVs alone. For serotypes 1 and 3, there was susbstantial inconsistency and between-trial heterogeneity between direct and indirect effects, so we only present pooled estmates on seroconversion, which were at least 80% for serotype 1 and at least 88% for serotype 3 for all vaccine schedules. INTERPRETATION: For WHO's polio eradication programme, the addition of one IPV dose for all birth cohorts should be prioritised to protect against paralysis caused by type 2 poliovirus; however, this inclusion will not prevent transmission or circulation in areas with faecal-oral transmission. FUNDING: UK Medical Research Council.

Modeling Undetected Live Poliovirus Circulation After Apparent Interruption of Transmission: Pakistan and Afghanistan.

Since most poliovirus infections occur with no paralytic symptoms, the possibility of silent circulation complicates the confirmation of the end of poliovirus transmission. Based on empirical field experience and theoretical modeling results, the Global Polio Eradication Initiative identified three years without observing paralytic cases from wild polioviruses with good acute flaccid paralysis surveillance as an indication of sufficient confidence that poliovirus circulation stopped. The complexities of real populations and the imperfect nature of real surveillance systems subsequently demonstrated the importance of specific modeling for areas at high risk of undetected circulation, resulting in varying periods of time required to obtain the same level of confidence about no undetected circulation. Using a poliovirus transmission model that accounts for variability in transmissibility and neurovirulence for different poliovirus serotypes and characterizes country-specific factors (e.g., vaccination and surveillance activities, demographics) related to wild and vaccine-derived poliovirus transmission in Pakistan and Afghanistan, we consider the probability of undetected poliovirus circulation for those countries once apparent die-out occurs (i.e., in the absence of any epidemiological signals). We find that gaps in poliovirus surveillance or reaching elimination with borderline sufficient population immunity could significantly increase the time to reach high confidence about interruption of live poliovirus transmission, such that the path taken to achieve and maintain poliovirus elimination matters. Pakistan and Afghanistan will need to sustain high-quality surveillance for polioviruses after apparent interruption of transmission and recognize that as efforts to identify cases or circulating live polioviruses decrease, the risks of undetected circulation increase and significantly delay the global polio endgame.

Evaluation of Proactive and Reactive Strategies for Polio Eradication Activities in Pakistan and Afghanistan.

Only Pakistan and Afghanistan reported any polio cases caused by serotype 1 wild polioviruses (WPV1s) in 2017. With the dwindling cases in both countries and pressure to finish eradication with the least possible resources, a danger exists of inappropriate prioritization of efforts between the two countries and insufficient investment in the two countries to finish the job. We used an existing differential-equation-based poliovirus transmission and oral poliovirus (OPV) evolution model to simulate a proactive strategy to stop transmission, and different hypothetical reactive strategies that adapt the quality of supplemental immunization activities (SIAs) in response to observed polio cases in Pakistan and Afghanistan. To account for the delay in perception and adaptation, we related the coverage of the SIAs in high-risk, undervaccinated subpopulations to the perceived (i.e., smoothed) polio incidence. Continuation of the current frequency and quality of SIAs remains insufficient to eradicate WPV1 in Pakistan and Afghanistan. Proactive strategies that significantly improve and sustain SIA quality lead to WPV1 eradication and the prevention of circulating vaccine-derived poliovirus (cVDPV) outbreaks. Reactive vaccination efforts that adapt moderately quickly and independently to changes in polio incidence in each country may succeed in WPV1 interruption after several cycles of outbreaks, or may interrupt WPV1 transmission in one country but subsequently import WPV1 from the other country or enable the emergence of cVDPV outbreaks. Reactive vaccination efforts that adapt independently and either more rapidly or more slowly to changes in polio incidence in each country may similarly fail to interrupt WPV1 transmission and result in oscillations of the incidence. Reactive strategies that divert resources to the country of highest priority may lead to alternating large outbreaks. Achieving WPV1 eradication and subsequent successful OPV cessation in Pakistan and Afghanistan requires proactive and sustained efforts to improve vaccination intensity in under-vaccinated subpopulations while maintaining high population immunity elsewhere.

Neonatal vitamin A supplementation and immune responses to oral polio vaccine in Zimbabwean infants.

BACKGROUND: Micronutrient deficiencies may contribute to reduced oral vaccine immunogenicity in developing countries. We hypothesised that neonatal vitamin A supplementation (NVAS) would improve oral vaccine responses. METHODS: We performed a cross-sectional study of infants recruited at birth to the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial, a randomised controlled trial of single, high-dose NVAS vs placebo conducted in Zimbabwe between 1997-2001. We measured poliovirus-specific IgA to type 1-3 polio strains by semiquantitative capture ELISA in cryopreserved plasma samples collected at 6 months of age. RESULTS: A total of 181 infants fulfilled inclusion criteria, of whom 80 were randomised to NVAS and 101 to placebo. There were no significant differences in baseline characteristics between groups. At 6 months of age, median (IQR) vaccine titres for infants randomised to NVAS vs placebo were 932 (421-3001) vs 1774 (711-5431) for Sabin-1 (p=0.04); 1361 (705-3402) vs 2309 (1081-4283) for Sabin-2 (p=0.15); and 1584 (796-4216) vs 2260 (996-5723) for Sabin-3 (p=0.14), respectively. After adjusting for breast feeding status, birth weight, season and infant sex in a linear regression model, there was only weak evidence of difference in log mean titres between vitamin A and placebo groups for Sabin-1 (p=0.08) and no evidence of difference in log mean titres for Sabin-2 and Sabin-3. CONCLUSIONS: NVAS did not augment oral polio vaccine responses in Zimbabwean infants. Further research is required to understand the impact of NVAS on responses to other oral vaccines.The trial is registered with clinicaltrials.gov identifier: NCT00198718.