Use Of Oral Polio Vaccine Research Articles

Antigenic diversity of type 1 polioviruses and its implications for the efficacy of polio vaccines.

Inactivated Polio Vaccines (IPV) and live Oral Polio Vaccine (OPV) were introduced in the mid-20th century, and their coordinated worldwide use led to almost complete elimination of the disease, with only one serotype of poliovirus remaining endemic in just two countries. Polio eradication will lead to discontinuation of OPV use and its replacement with IPV or other vaccines that are currently under development that will need to be tested in clinical trials. Despite decades of research, questions remain about the serological correlates of polio vaccine efficacy, specifically whether the vaccines are equally protective against immunologically different strains of the same serotype. The absence of significant morbidity does not allow use of a protection endpoint in clinical trials, so the answer could be obtained only by using surrogate markers such as immunogenicity. In this study, a panel of wild and vaccine-derived polioviruses of serotype 1 were tested in neutralization assays with sera from vaccine-immunized individuals. The results demonstrated that there was a significant difference in titers of neutralizing antibodies in human sera when measured against different strains. When measured with a homologous strain used for vaccine manufacture all subjects had detectable levels of antibodies, while neutralization tests with some heterologous strains failed to detect neutralizing antibodies in a number of subjects. Administration of a booster dose of IPV led to a significant increase in neutralizing titers against all strains. Results of the experiments using animal sera, performed to obtain more information on protectivity of neutralizing antibodies against heterologous strains, were consistent with the results obtained in the assays using human sera. These results are discussed in the context of serological biomarkers of protection against poliomyelitis, suggesting that potency of vaccines made from serologically different strains should be determined against both homologous and heterologous challenge viruses.

Emergence of vaccine-derived poliovirus in high-income settings in the absence of oral polio vaccine use

On June 22, 2022, the UK Health Security Agency announced that vaccine-derived poliovirus type 2 (VDPV2) had been repeatedly detected in sewage in London, UK.1 Several weeks later, the New York State Department of Health reported a case of acute flaccid paralysis caused by VDPV2 in an unvaccinated individual; the first case of poliomyelitis in almost a decade in the USA.2 A similar virus has also been detected in sewage from Jerusalem, Israel.3

Use of Oral Polio Vaccine and the Global Incidence of Mother-to-Child Human Immunodeficiency Virus Transmission.

BackgroundMother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is an important global health issue. We hypothesized that the live attenuated poliovirus existing in oral polio vaccine (OPV) may protect uninfected neonates born to HIV-positive mothers through the stimulation of innate immune system.ObjectiveTo test the hypothesis that countries using OPV have a lower MTCT rate (due to postnatal protection provided by the vaccine) compared with those using only inactivated polio vaccine (IPV).MethodsIn an ecological study, the incidence of HIV/AIDS in children aged <1 year (IncHIV1), considered a surrogate index for MTCT rate, was compared between countries using OPV vs. IPV. The aggregated population data were retrieved for 204 countries from the Global Burden of Disease (GBD 2019) Collaborative Network website, “Our World in Data” website, the World Bank website, and the WHO Global Polio Eradication Initiative (GPEI). We used a negative binomial regression model with IncHIV1 as the dependent variable and the prevalence of HIV/AIDS in women aged 15–49 years (PrevHIV), antiretroviral therapy (ART) coverage, human development index (HDI), and the type of vaccine used in each country as independent variables. Multivariate imputation by chained equations was used to treat missing values. Analyses were performed for both the original dataset (with missing values) and the five imputed datasets.ResultsIncHIV1 and PrevHIV were available for all 204 countries; vaccine type, 194 countries; HDI, 182 countries; and ART coverage, 133 countries. One-hundred and twenty-nine countries in the original dataset had complete data for all the above-mentioned variables; the imputed datasets had complete data for all 204 countries. The results obtained from the analysis of the original dataset had no overall difference with the pooled results obtained from the analysis of the five imputed datasets. Countries with higher HDI mainly use IPV; those with lower HDI commonly use OPV. PrevHIV, HDI, and the type of vaccine were independent predictors of IncHIV1. Use of OPV compared to IPV, was independently associated with an average decrease of 17% in IncHIV1 at the median HDI of 0.75. The protection provided by OPV increased in countries with lower HDI.ConclusionsUse of OPV compared with IPV, was independently associated with lower MTCT rate.

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

Several live attenuated vaccines were shown to provide temporary protection against a variety of infectious diseases through stimulation of the host innate immune system. 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). 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. 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. 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.

Polio vaccination coverage among children aged 12-23 months in a health block in North Kerala

Background: Polio (poliomyelitis) is a highly infectious viral disease which affects the nervous system and can result in irreversible paralysis within hours. There is no cure for polio, hence it becomes necessary to prevent the disease through vaccination. Thus, the objective of this study was to evaluate the polio vaccination coverage among children aged 12-23 months in a health block in Kannur, North Kerala.Methods: A community based cross sectional study was conducted among the children in the age group of 12-23 months residing in Pappinisseri block of Kannur district. Stratified random sampling was used. The details of 321 children were obtained using a pre-tested semi-structured questionnaire. The data was entered into Microsoft Excel 2007 spread sheet and analyzed using SPSS version 16.0 software.Results: Of the 321 children, males constituted 173 (54%) and females constituting 148 (46%). The total coverage of oral polio vaccines (OPV) (considering OPV-0, 1st, 2nd and 3rd doses) was found to be 92.8% and the inactivated poliomyelitis vaccine (IPV) coverage (IPV 1st and 2nd doses) to be 90.7%. Also, majority of the respondents were unaware of the use of OPV and IPV vaccines in the UIP.Conclusions: In spite of the efforts taken by the Government and the health officials, the OPV and IPV coverage has not reached 100% and also, the knowledge of mothers regarding the diseases prevented by the vaccines were very low. The reasons for this needs to be further evaluated.

Poliomyelitis eradication in four stages.

This article's objective is to review the "state of the art" in the progress, obstacles, and strategies for achieving global polio eradication. Poliomyelitis control measures began in the 1960s with the advent of two vaccines, the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV). From 1985 to 2020, strategies were implemented to reach the goal of eradication of wild poliovirus (WPV). Following the success with the interruption of indigenous WPV transmission in the Americas, the goal of global eradication was launched. We describe the process of eradication in four historical stages: (1) The advent of the inactivated and oral polio vaccines launched the age of poliomyelitis control; (2) The massive and simultaneous use of OPV had a significant impact on WPV transmission in the late 1970s in Brazil; (3) Domestic and international public policies set the goal of eradication of indigenous WPV transmission in the Americas and defined the epidemiological strategies to interrupt transmission; and (4) The implementation of eradication strategies interrupted indigenous WPV transmission in nearly all regions of the world except Pakistan and Afghanistan, where in 2020 the WPV1 transmission chains have challenged the strategies for containment of the virus. Meanwhile, the persistence and dissemination of circulation of OPV-derived poliovirus in countries with low vaccination coverage, plus the difficulties in replacing OPV with IPV, are currently the obstacles to eradication in the short term. Finally, we discuss the strategies for overcoming the obstacles and challenges in the post-eradication era.

The moral dilemma of the polio eradication programme.

During the last five years, globally, cases of polio caused by vaccine viruses have outnumbered those of polio caused by natural (wild) polioviruses, posing a moral dilemma. Public health ethics should ensure the best interests of the community, with equity in sharing benefits and risks irrespective of socioeconomic disparities. Vaccine viruses in oral polio vaccine (OPV) cause vaccine-associated paralytic polio (VAPP), while paralytic polio is also caused by vaccine-derived polioviruses (VDPVs). By its policy of the use of OPV in low and middle-income countries, while rich countries use the safe inactivated polio vaccine (IPV), the Global Polio Eradication Programme has been responsible for social injustice. In 2017 and 2018, there were outbreaks of polio in Syria and Papua New Guinea due to circulating VDPVs, after many years of these countries remaining free of polio due to wild polioviruses. The only ethical way forward for global polio eradication is to replace OPV with IPV in all countries.

Progress of polio eradication and containment requirements after eradication.

Wild poliovirus (WPV) is nearing eradication, and only three countries have never interrupted WPV transmission (Pakistan, Afghanistan, and Nigeria). WPV2 was last detected in 1999, and it was declared eradicated in 2015. WPV3 has not been detected since 2012. Since 2016, WPV1 has been detected in only two countries (Afghanistan and Pakistan), with only 22 cases reported in 2017 and 12 cases reported in 2018 (as of July 10). Because of WPV2 eradication and the risk of emergence of type 2 vaccine-derived polioviruses from continued use of trivalent oral polio vaccine (OPV), trivalent OPV was replaced by bivalent OPV (types 1 and 3) in a globally coordinated effort in 2016. WPV2 eradication and trivalent OPV cessation also mean that breach of containment in a facility working with type 2 poliovirus is now a major risk to reseed type 2 circulation in the community. As a result, the World Health Organization has developed a "Global Action Plan to minimize poliovirus facility-associated risk after type-specific eradication of wild polioviruses and sequential cessation of oral polio vaccine use." Because poliovirus has long been used as a standard for qualification of intravenous immunoglobulin, disinfectant products, and sanitation methods, poliovirus containment has implications far beyond poliovirus laboratories.

Vaccine-associated paralytic poliomyelitis in the Russian Federation in 1998–2014

ObjectivesDifferent polio vaccination schemes have been used in Russia: oral polio vaccine (OPV) was used in 1998–2007 and inactivated polio vaccine (IPV) followed by OPV in 2008–2014. This article presents the characteristics of vaccine-associated paralytic poliomyelitis (VAPP) cases in Russia during this period. MethodsVAPP cases were identified through the acute flaccid paralysis surveillance system, classified by the National Expert Classification Committee. Criteria for a ‘recipient VAPP’ (rVAPP) case were poliomyelitis symptoms 6–30days after OPV administration, isolation of the vaccine virus, and residual paralysis 60days after disease onset. Unvaccinated cases with a similar picture 6–60days after contact with an OPV recipient were classified as ‘contact VAPP’ (cVAPP) cases. ResultsDuring 1998–2014, 127 VAPP cases were registered: 82 rVAPP and 45 cVAPP. During the period in which only OPV was used, rVAPP cases prevailed (73.8%); cases of rVAPP were reduced during the sequential scheme period (15%). Poliovirus type 3 (39.5%) and type 2 (23.7%) were isolated more often. Vaccine-derived poliovirus types 1, 2, and 3 were isolated from three cases of cVAPP. The incidence of VAPP cases was higher during the period of OPV use (1 case/1.59 million OPV doses) than during the sequential scheme period (1 case/4.18 million doses). ConclusionThe risk of VAPP exists if OPV remains in the vaccination schedule.

Assessing the stability of polio eradication after the withdrawal of oral polio vaccine.

The oral polio vaccine (OPV) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV) to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV) is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore population immunity will be required to ensure the stability of polio eradication.

National introduction of fractional-dose inactivated polio vaccine in Sri Lanka following the global "switch".

As part of the Polio eradication and endgame strategic plan 2013-2018 to achieve and sustain a polio-free world, the use of oral polio vaccine (OPV) must eventually be stopped. This process started in April 2016, with the worldwide, planned synchronized "switch", whereby use of OPV containing poliovirus type 2 ceased. Prior to the switch, in line with international guidance on risk mitigation, Sri Lanka had introduced a single full dose (0.5 mL intramuscularly) of inactivated polio vaccine (IPV) into routine immunization. However, the two global suppliers of World Health Organization (WHO)-prequalified IPV had significant challenges in scaling up production to meet the new demand, resulting in a global shortage in April 2016. The WHO Strategic Advisory Group of Experts on Immunization recommended that countries should consider a two-dose schedule of intradermal fractional IPV (fIPV). After rapid consideration of the programmatic cost and logistic implications, Sri Lanka was the first country to roll out this dose-sparing schedule nationwide. The country ensured smooth implementation of fIPV use, reaching out to all eligible infants, maintaining equity and sustaining the IPV vaccination. With expedited refresher training in intradermal vaccination, confident, well-trained and dedicated health-care staff, from the field up to provincial levels, worked together as a dedicated team. Health authorities at all levels reported that public acceptance of the additional injections of the new schedule was high. A post-introduction evaluation and an assessment of population-level immunity are under way.

The risk of type 2 oral polio vaccine use in post-cessation outbreak response

BackgroundWild type 2 poliovirus was last observed in 1999. The Sabin-strain oral polio vaccine type 2 (OPV2) was critical to eradication, but it is known to revert to a neurovirulent phenotype, causing vaccine-associated paralytic poliomyelitis. OPV2 is also transmissible and can establish circulating lineages, called circulating vaccine-derived polioviruses (cVDPVs), which can also cause paralytic outbreaks. Thus, in April 2016, OPV2 was removed from immunization activities worldwide. Interrupting transmission of cVDPV2 lineages that survive cessation will require OPV2 in outbreak response, which risks seeding new cVDPVs. This potential cascade of outbreak responses seeding VDPVs, necessitating further outbreak responses, presents a critical risk to the OPV2 cessation effort.MethodsThe EMOD individual-based disease transmission model was used to investigate OPV2 use in outbreak response post-cessation in West African populations. A hypothetical outbreak response in northwest Nigeria is modeled, and a cVDPV2 lineage is considered established if the Sabin strain escapes the response region and continues circulating 9 months post-response. The probability of this event was investigated in a variety of possible scenarios.ResultsUnder a broad range of scenarios, the probability that widespread OPV2 use in outbreak response (~2 million doses) establishes new cVDPV2 lineages in this model may exceed 50% as soon as 18 months or as late as 4 years post-cessation.ConclusionsThe risk of a cycle in which outbreak responses seed new cVDPV2 lineages suggests that OPV2 use should be managed carefully as time from cessation increases. It is unclear whether this risk can be mitigated in the long term, as mucosal immunity against type 2 poliovirus declines globally. Therefore, current programmatic strategies should aim to minimize the possibility that continued OPV2 use will be necessary in future years: conducting rapid and aggressive outbreak responses where cVDPV2 lineages are discovered, maintaining high-quality surveillance in all high-risk settings, strengthening the use of the inactivated polio vaccine as a booster in the OPV2-exposed and in routine immunization, and gaining access to currently inaccessible areas of the world to conduct surveillance.

Silent Polio Transmission: A Spatial Analysis

BackgroundAs wild poliovirus is eradicated and countries switch from Oral Polio Vaccine (OPV) to Inactivated Polio Vaccine (IPV) per WHO recommendations, preventing circulation of vaccine-derived poliovirus is a top priority. However, spatial dynamics of OPV transmission are not well understood. Understanding these trends will improve resource targeting in the event of OPV reintroduction in undervaccinated communities. Mexico provides a natural environment to study OPV as it provides IPV routinely and bi-annual OPV campaigns.MethodsChildren in three villages near Orizaba, Mexico were randomized to three levels (10%, 30%, 70%) to receive OPV. We measured distance to nearest OPV shedding, and the amount of shedding close to unvaccinated individuals. We used maps to show the proximity and amount of shedding. Distance and density of shedding was analyzed separately using mixed effects logistic regression with random effects for household and time, adjusted for age, gender, area, and running water.ResultsThe median distance to nearest OPV shedding was 85 meters (IQR 46, 145). The median number of shedding individuals within 200m was 3 (2, 6). Shedding and between household transmission occurred rapidly with unvaccinated individuals shedding on day one of the study (Figure 1). There was little evidence (Odds Ratio [OR] 1.04 (95% Highest Posterior Density [HPD] 0.92, 1.16)) of an association between distance (per 100 m) from OPV shedding and odds of shedding. There was some suggestion that the number of OPV shedding within 200 m may have some effect on unvaccinated shedding with OR 0.93 (HPD 0.·84, 1·01) but not at 100 or 500m. Results were consistent across the three villages.ConclusionHousehold structure appears to have limited value in predicting transmission of poliovirus shedding. The use of OPV results in rapid but low levels of transmission throughout the community and this would usually go undetected. The only way to avoid this is to not use OPV or to have strong controls such as quarantine, or strict hygiene protocols. After withdrawal of OPV worldwide the decision to reintroduce due to an outbreak should not be taken lightly as it appears a small amount of OPV is needed to result in transmission.Figure 1.Contour Plot: Shedding Over Time.Disclosures All authors: No reported disclosures.

Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India.

Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014–April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped.

Considerations for the Full Global Withdrawal of Oral Polio Vaccine After Eradication of Polio.

Eliminating the risk of polio from vaccine-derived polioviruses is essential for creating a polio-free world, and eliminating that risk will require stopping use of all oral polio vaccines (OPVs) once all types of wild polioviruses have been eradicated. In many ways, the experience with the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) can inform the eventual full global withdrawal of OPV. Significant preparation will be needed for a thorough, synchronized, and full withdrawal of OPV, and such preparation would be aided by setting a reasonably firm date for OPV withdrawal as far in advance as possible, ideally at least 24 months. A shorter lead time would provide valuable flexibility for decisions about when to stop use of OPV in the context of uncertainty about whether or not all types of wild polioviruses had been eradicated, but it might increase the cost of OPV withdrawal.

Implementing the Synchronized Global Switch from Trivalent to Bivalent Oral Polio Vaccines-Lessons Learned From the Global Perspective.

In 2015, the Global Commission for the Certification of Polio Eradication certified the eradication of type 2 wild poliovirus, 1 of 3 wild poliovirus serotypes causing paralytic polio since the beginning of recorded history. This milestone was one of the key criteria prompting the Global Polio Eradication Initiative to begin withdrawal of oral polio vaccines (OPV), beginning with the type 2 component (OPV2), through a globally synchronized initiative in April and May 2016 that called for all OPV using countries and territories to simultaneously switch from use of trivalent OPV (tOPV; containing types 1, 2, and 3 poliovirus) to bivalent OPV (bOPV; containing types 1 and 3 poliovirus), thus withdrawing OPV2. Before the switch, immunization programs globally had been using approximately 2 billion tOPV doses per year to immunize hundreds of millions of children. Thus, the globally synchronized withdrawal of tOPV was an unprecedented achievement in immunization and was part of a crucial strategy for containment of polioviruses. Successful implementation of the switch called for intense global coordination during 2015–2016 on an unprecedented scale among global public health technical agencies and donors, vaccine manufacturers, regulatory agencies, World Health Organization (WHO) and United Nations Children’s Fund (UNICEF) regional offices, and national governments. Priority activities included cessation of tOPV production and shipment, national inventories of tOPV, detailed forecasting of tOPV needs, bOPV licensing, scaling up of bOPV production and procurement, developing national operational switch plans, securing funding, establishing oversight and implementation committees and teams, training logisticians and health workers, fostering advocacy and communications, establishing monitoring and validation structures, and implementing waste management strategies. The WHO received confirmation that, by mid May 2016, all 155 countries and territories that had used OPV in 2015 had successfully withdrawn OPV2 by ceasing use of tOPV in their national immunization programs. This article provides an overview of the global efforts and challenges in successfully implementing this unprecedented global initiative, including (1) coordination and tracking of key global planning milestones, (2) guidance facilitating development of country specific plans, (3) challenges for planning and implementing the switch at the global level, and (4) best practices and lessons learned in meeting aggressive switch timelines. Lessons from this monumental public health achievement by countries and partners will likely be drawn upon when bOPV is withdrawn after polio eradication but also could be relevant for other global health initiatives with similarly complex mandates and accelerated timelines.

Nonspecific Effects of Oral Polio Vaccine on Diarrheal Burden and Etiology Among Bangladeshi Infants

As the global polio eradication initiative prepares to cease use of oral polio vaccine (OPV) in 2020, there is increasing interest in understanding if oral vaccination provides non-specific immunity to other infections so that the consequences of this transition can be effectively planned for and mitigated. Data were collected from infants in an urban slum in Bangladesh (Mirpur, Dhaka) as part of the performance of rotavirus and oral polio vaccines in developing countries (PROVIDE) study. Following vaccination with trivalent oral polio vaccine (tOPV) at 6, 10, and 14 weeks, infants were randomly assigned to receive tOPV (n = 315) or inactivated polio vaccine (IPV) (n = 299) at 39 weeks. Episodes of diarrhea were documented through clinic visits and twice-weekly house visits through 52 weeks. In sum, 14 pathogens associated with diarrhea were analyzed with TaqMan Array Cards. Although the proportion of children experiencing diarrhea was not different between the tOPV and IPV groups (P = .18), the number of days with diarrhea (P = .0037) and the number of separate diarrheal episodes (P = .054) trended lower in the OPV arm. Etiological analysis revealed that male tOPV recipients were less likely to have diarrhea of bacterial etiology (P = .0099) compared to male IPV recipients but equally likely to experience diarrhea due to viruses (P = .57) or protozoa (P = .14). Among the 6 bacterial enteric pathogens tested, only Campylobacter jejuni/coli detection was significantly reduced in the OPV arm (P = .0048). Our results suggest that OPV may cause nonspecific reductions in mortality, as has been studied elsewhere, by reducing etiology-specific diarrheal burden. This is likely driven by reductions in bacterial diarrhea. Further study of nonspecific OPV effects before global cessation is supported. NCT01375647.

Wild and vaccine-derived poliovirus circulation, and implications for polio eradication.

Polio cases due to wild virus are reported by only three countries in the world. Poliovirus type 2 has been globally eradicated and the last detection of poliovirus type 3 dates to November 2012. Poliovirus type 1 remains the only circulating wild strain; between January and September 2016 it caused 26 cases (nine in Afghanistan, 14 in Pakistan, three in Nigeria). The use of oral polio vaccine (OPV) has been the key to success in the eradication effort. However, paradoxically, moving towards global polio eradication, the burden caused by vaccine-derived polioviruses (VDPVs) becomes increasingly important. In this paper circulation of both wild virus and VDPVs is reviewed and implications for the polio eradication endgame are discussed. Between April and May 2016 OPV2 cessation has been implemented globally, in a coordinated switch from trivalent OPV to bivalent OPV. In order to decrease the risk for cVDPV2 re-emergence inactivated polio vaccine (IPV) has been introduced in the routine vaccine schedule of all countries. The likelihood of re-emergence of cVDPVs should markedly decrease with time after OPV cessation, but silent circulation of polioviruses cannot be ruled out even a long time after cessation. For this reason, immunity levels against polioviruses should be kept as high as possible in the population by the use of IPV, and both clinical and environmental surveillance should be maintained at a high level.

Circulating vaccine-derived poliovirus type 2 outbreak in Democratic Republic of Congo 2011-2012

According to the WHO records of 2013, the incidence of poliomyelitis was reduced by more than 99%, the number of endemic countries decreased from 125 in 1988 to 3 in 2013 and over 10 million cases were prevented from poliomyelitis thanks to the intensive use of Oral polio vaccine (OPV). However, the emergence of circulating vaccine-derived poliovirus strains (cVDPV), causing serious epidemics like the wild poliovirus, is a major challenge on the final straight towards the goal of eradication and OPV cessation. This paper describes the cVDPVoutbreak that occurred in the Democratic Republic of Congo (DRC) from November 2011 to April 2012. All children under 15 years of age with acute flaccid paralysis (AFP) and confirmed presence of cVDPV in the stool samples were included. Thirty (30) children, all from the administrative territories of Bukama and Malemba Nkulu in the Katanga Province (south-east DRC), were reported. The virus responsible was the cVDPV type 2 (0.7% -3.5% divergent from the reference Sabin 2 strain) in 29 children (97%) and the ambiguous vaccine-derived poliovirus strain (0.7% divergent) was confirmed in one case (3%), a boy seventeen months old and already vaccinated four times with OPV. Twentyfive children (83%) were protected by any of the routine EPI vaccines and 3 children (10%) had never received any dose of OPV. In reaction, DRC has conducted five local campaigns over a period of 10 months (from January to October 2012) and the epidemic was stopped after the second round performed in March 2012. As elsewhere in similar conditions, low immunization coverage, poor sanitation conditions and the stop of the use of OPV2 have favoured the emergence of the third cVDPV epidemic in DRC. The implementation of the Strategic Plan for Polio eradication and endgame strategic plan 2013-2018 will prevent the emergence of cVDPV and set up the conditions for a coordinated OPV phase out.

Immunogenicity of inactivated polio vaccine, given with or without mucosal adjuvants dmLT and TCTA1T in rat model (VAC9P.1102)

Abstract To eradicate polio, the use of oral polio vaccine (OPV) should be stopped to avoid circulation of vaccine-derived polioviruses (VDPVs). After OPV cessation, transition to inactivated polio vaccine (IPV) is recommended. This can only be accomplished when IPV induce better mucosal protection. This can be achieved by adding mucosal adjuvant to the IPV formulation. In the present study we used wistar rats to elucidate the adjuvant effect of double mutant heat-labile toxin (dmLT) of E. coli and recombinant cholera toxin (TCTA1T) on IPV. Rats were administered by intramuscular injection of 1.0-0.6-1.0 D-antigen units (DU) of Inactivated Polio type 1, 2 and 3 /rat. The E. coli dmLT and TCTA1T was used as adjuvant and was administered subcutaneously along with IPV. The control groups received IPV alone or PBS. Rats were immunized on days 0, 14 and 28 days. After last vaccination mice were sacrificed and spleen cells and blood were collected. IgA secreting cells specific for Polio Type1, 2 and 3 were measured by ELISPOT. Intramuscular immunization results in robust mucosal response in inactivated polio antigens + dmLT group compared to other groups. Further measurement of antibodies in serum doesn’t show significant difference among IPV and adjuvanted IPV groups. Thus the present data suggest that vaccination with IPV and dmLT results in specific induction of mucosal immunity, which will provide barrier to infection from oral fecal route.