Oral Poliovirus Vaccine Vaccination Research Articles

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

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

Response to back-to-back outbreaks of circulating vaccine-derived poliovirus type 2 in two nomadic pastoralist settlements in Oti Region, Ghana-2019

BackgroundThe global switch from trivalent oral poliovirus vaccine (OPV) to bivalent OPV in April 2016 without corresponding co-administration of inactivated poliovirus vaccine (IPV) until June 2018, created a cohort of poliovirus type 2 naïve children with risk of developing vaccine-derived poliovirus type 2 (VDPV2). In November and December 2019, two cases of circulating vaccine-derived poliovirus type 2 (cVDPV2) were confirmed in quick succession through Acute Flaccid Paralysis (AFP) surveillance in two nomadic pastoralist settlements in Oti Region. We investigated to determine the outbreak extent, identify risk factors and implement control and preventive measures.MethodsWe interviewed case-patients’ families, abstracted immunization records, assessed AFP surveillance and conducted rapid OPV and IPV vaccination coverage surveys. Using AFP case definition of any child less than 15 years in the community with sudden onset of paralysis from July to November 2019 (in case-patient 1’s district) and August to December 2019 (in case-patient 2’s district), we conducted active case search. Stool samples from apparently healthy children and close contacts of the case-patients were collected and tested for poliovirus. We conducted environmental assessment of the community to identify potential risk factors.ResultsCase-patient 1 was an eight-year-old female who had taken two doses of OPV while case-patient 2 was an eight-month-old male who had taken three out of required four OPV doses in addition to IPV at seven months. Families of both case-patients had either travelled to or received visitors from areas with confirmed cVDPV2. Of all children surveyed, eight (29.6%) of 27 and three (18.8%) of 16 eligible children in communities of case-patient 1 and 2 respectively had received required four doses of OPV. No AFP case was found in both communities and surrounding settlements. Both communities had no source of potable water and toilet facilities. A stool sample from a contact of case-patient 1 tested positive for cVDPV2.ConclusionOutbreaks of cVDPV2 occurred in insanitary, under-vaccinated nomadic pastoralist settlements in Oti Region. Three rounds of monovalent OPV vaccination campaigns for children under 5 years of age in the districts and region as well as countrywide IPV vaccination campaign for poliovirus type 2 naïve cohort were conducted.

One Full or Two Fractional Doses of Inactivated Poliovirus Vaccine for Catch-up Vaccination in Older Infants: A Randomized Clinical Trial in Bangladesh.

BackgroundThe polio eradication endgame called for the removal of trivalent oral poliovirus vaccine (OPV) and introduction of bivalent (types 1 and 3) OPV and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies.MethodsWe conducted an open-label randomized clinical trial assessing 2 interventions, full or fractional-dose IPV (fIPV, one-fifth of IPV), administered at age 9–13 months with a second dose given 2 months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment.ResultsA single fIPV dose at age 9–13 months yielded 75% (95% confidence interval [CI], 6%–82%) seroconversion against type 2, whereas 2 fIPV doses resulted in 100% seroconversion compared with 94% (95% CI, 89%–97%) after a single full dose (P < .001). Two doses of IPV resulted in 100% seroconversion.ConclusionsOur study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either 1 full dose of IPV or 2 doses of fIPV could be used to vaccinate missed cohorts, 2 fIPV doses being antigen sparing and more immunogenic.Clinical Trial RegistrationNCT03890497.

Impact of polio vaccines (oral polio vaccine - OPV or inactivated polio vaccine - IPV) on rotavirus vaccine-associated intussusception

ABSTRACT Although safe, rotavirus vaccines have been associated with increased intussusception risk. In Brazil, after the oral human rotavirus vaccine (OHRV) introduction in the childhood immunization, in 2006, increased intussusception risk was identified after the second OHRV dose, whereas in other countries, higher risk was associated to the first vaccine dose. It was hypothesized that the concomitant use of oral poliovirus vaccine (OPV) in Brazil might explain this difference. In 2012, the inactivated polio vaccine (IPV) was adopted in the first two doses of Brazilian childhood immunization schedule, creating an opportunity to study the subject. Our objective was analyzing the impact of polio vaccines on rotavirus-associated intussusception. We used surveillance data on intussusception in infants living in São Paulo State. Two periods were considered: an OPV-period (March 2006 to June 2012) and an IPV-period (October 2012 to December 2017). The period from June to September 2012 were considered as transition. Self-controlled case series analysis with event-dependent exposure was performed, considering two risk periods (7 and 21 days post-vaccination). We identified 325 intussusception cases in infants reported to the surveillance systems during the study period. The statistical analysis included 221 cases that occurred within 60 days after vaccination. Overall, a higher intussusception risk was observed in the first week after vaccination for both the first (Relative Incidence [RI] = 4.3, 95%CI 2.8–6.5, p < .001) and second vaccine doses (RI = 4.2, 95%CI 2.7–6.4; p < .001). There were no statistically significant differences in intussusception risk according to the rotavirus vaccine dose and the polio vaccine (OPV or IPV) administered concomitantly.

Immunization Against Poliomyelitis and the Challenges to Worldwide Poliomyelitis Eradication.

Both inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) have contributed to the rapid disappearance of paralytic poliomyelitis from developed countries despite possessing different vaccine properties. Due to cost, ease of use, and other properties, the Expanded Programme on Immunization added OPV to the routine infant immunization schedule for low-income countries in 1974, but variable vaccine uptake and impaired immune responses due to poor sanitation limited the impact. Following launch of the Global Polio Eradication Initiative in 1988, poliomyelitis incidence has been reduced by >99% and types 2 and 3 wild polioviruses are now eradicated, but progress against type 1 polioviruses which are now confined to Afghanistan and Pakistan has slowed due to insecurity, poor access, and other problems. A strategic, globally coordinated replacement of trivalent OPV with bivalent 1, 3 OPV in 2016 reduced the incidence of vaccine-associated paralytic poliomyelitis (VAPP) but allowed the escape of type 2 vaccine–derived polioviruses (VDPV2) in areas with low immunization rates and use of monovalent OPV2 in response seeded new VDPV2 outbreaks and reestablishment of type 2 endemicity. A novel, more genetically stable type 2 OPV vaccine is undergoing clinical evaluation and may soon be deployed prevent or reduce VDPV2 emergences.

Estimation of oral poliovirus vaccine effectiveness in Afghanistan, 2010–2020

BackgroundAfghanistan is one of two countries with endemic wild poliovirus type 1 (WPV1). The oral poliovirus vaccine (OPV) is the predominant vaccine used for polio eradication. Although OPV has been administered in routine childhood immunization and during frequent supplementary immunization activities, WPV1 continues to circulate in Afghanistan and case incidence has been increasing since 2017. We estimated the effectiveness of OPV in Afghanistan during 2010–2020. MethodsWe conducted a matched case-control analysis using acute flaccid paralysis (AFP) surveillance data from 29,370 children < 15 years with AFP onset between January 1, 2010 and December 31, 2020. We matched children with confirmed WPV1 (cases) with children with non-polio AFP (controls) by age at onset of paralysis (+/- 3 months), date of onset of paralysis (+/- 3 months), and province of residence, and compared their reported OPV vaccination history to estimate the effectiveness of OPV in preventing paralysis by WPV1 using conditional logistic regression. To account for changes in OPV formulations provided over the analysis period, we stratified the analysis based on dates of the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) in April 2016. ResultsBetween January 1, 2010 and December 31, 2020, there were 329 WPV1 cases in Afghanistan. The per-dose estimated effectiveness of OPV against WPV1 was 19% (95% CI: 15%–22%) and of ≥ 7 doses was 94% (95% CI: 90%-97%). Before the global switch from tOPV to bOPV, the per-dose estimated effectiveness of OPV was 14% (95% CI: 11%-18%) and of ≥ 7 doses was 92% (95% CI: 85%-96%). After the switch, the per-dose estimated effectiveness of OPV against WPV1 was 32% (24%-39%) and of ≥ 7 doses was 96% (95% CI: 90%-99%). DiscussionOPV is highly effective in preventing paralysis by WPV1; these results indicate that continued WPV1 transmission in Afghanistan is due to failure to vaccinate, not failure of the vaccine. Although difficult to implement in parts of country, improving the administration of OPV in routine immunization and supplementary immunization activities will be critical for achieving polio eradication in Afghanistan.

Hypothetical emergence of poliovirus in 2020: part 2. exploration of the potential role of vaccines in control and eradication

ABSTRACT Objectives The emergence of human pathogens with pandemic potential motivates rapid vaccine development. We explore the role of vaccines in control and eradication of a novel emerging pathogen. Methods We hypothetically simulate emergence of a novel wild poliovirus (nWPV) in 2020 assuming an immunologically naïve population. Assuming different nonpharmaceutical interventions (NPIs), we explore the impacts of vaccines resembling serotype-specific oral poliovirus vaccine (OPV), novel OPV (nOPV), or inactivated poliovirus vaccine (IPV). Results Vaccines most effectively change the trajectory of an emerging disease when disseminated early, rapidly, and widely in the background of ongoing strict NPIs, unless the NPIs successfully eradicate the emerging pathogen before it establishes endemic transmission. Without strict NPIs, vaccines primarily reduce the burden of disease in the remaining susceptible individuals and in new birth cohorts. Live virus vaccines that effectively compete with the nWPVs can reduce disease burdens more than other vaccines. When relaxation of existing NPIs occurs at the time of vaccine introduction, nWPV transmission can counterintuitively increase in the short term. Conclusions Vaccines can increase the probability of disease eradication in the context of strict NPIs. However, successful eradication will depend on specific immunization strategies used and a global commitment to eradication.

Metagenomic sequencing of stool samples in Bangladeshi infants: virome association with poliovirus shedding after oral poliovirus vaccination

The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log10 vs. 2.25 log10, p = 0.002), particularly from potential viral pathogens (2.78log10 vs. 0.83log10, p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus shedding. Following vaccination, 28.6% of 14 infants tested developed neutralizing antibodies to all three Sabin types and also exhibited higher rates of poliovirus shedding (p = 0.020). No vaccine-derived poliovirus variants were detected. These results reveal an inverse association between eukaryotic virome abundance and poliovirus shedding. Overall gut virome ecology and concurrent viral infections may impact oral vaccine responsiveness in Bangladeshi infants.

Case of Poliomyelitis Caused by Significantly Diverged Derivative of the Poliovirus Type 3 Vaccine Sabin Strain Circulating in the Orphanage.

Significantly divergent polioviruses (VDPV) derived from the oral poliovirus vaccine (OPV) from Sabin strains, like wild polioviruses, are capable of prolonged transmission and neuropathology. This is mainly shown for VDPV type 2. Here we describe a molecular-epidemiological investigation of a case of VDPV type 3 circulation leading to paralytic poliomyelitis in a child in an orphanage, where OPV has not been used. Samples of feces and blood serum from the patient and 52 contacts from the same orphanage were collected twice and investigated. The complete genome sequencing was performed for five polioviruses isolated from the patient and three contact children. The level of divergence of the genomes of the isolates corresponded to approximately 9–10 months of evolution. The presence of 61 common substitutions in all isolates indicated a common intermediate progenitor. The possibility of VDPV3 transmission from the excretor to susceptible recipients (unvaccinated against polio or vaccinated with inactivated poliovirus vaccine, IPV) with subsequent circulation in a closed children’s group was demonstrated. The study of the blood sera of orphanage residents at least twice vaccinated with IPV revealed the absence of neutralizing antibodies against at least two poliovirus serotypes in almost 20% of children. Therefore, a complete rejection of OPV vaccination can lead to a critical decrease in collective immunity level. The development of new poliovirus vaccines that create mucosal immunity for the adequate replacement of OPV from Sabin strains is necessary.

Socioeconomic Status, Health Inequalities, and Solidarity Trends in a Mass Vaccination Campaign

Abstract Background In July 2013, Israel was swept with fear of a polio outbreak. In response to the importation of wild polio virus, the Ministry decided to take preventive action by administering oral poliovirus vaccine (OPV) to all children born after 1 January 2004 who had received at least one dose of inactivated poliovirus vaccine (IPV) in the past. This study analyzes the vaccination uptake rates resulting from the mass polio vaccination campaign on the basis of health inequality parameters of socioeconomic status (SES), principles of solidarity, and the Gini inequality index. The research explores understanding the value of the Gini inequality index within the context of SES and solidarity. Methods The study is based on data gathered from the Israeli Ministry of Health’s administrative records from mother-and-child clinics across Israel. The research population is comprised of resident infants and children whom the Ministry of Health defined as eligible for the OPV between August and December 2013. Results The higher the SES level of the area where the mother-and-child clinic is located, the lower the OPV vaccination uptake is. The greater the income inequality is in the municipality where the mother-and-child clinic is situated, the lower the vaccination uptake. As time passed in the vaccination campaign, vaccination uptake increased regardless of the location of the mother-and-child clinics. The highest vaccination uptake rate was found among populations of low SES and low Gini inequality index. The lowest vaccination uptake rate was found among populations of high SES/high Gini inequality index. Conclusions Public health professionals promoting vaccine programs need to make specially-designed efforts both in localities with high average income and in localities with a high level of income diversity/inequality. Such practice will better utilize funds, resources, and manpower dedicated to increasing vaccination uptake across varying populations and communities. Key messages The higher the SES in municipalities with mother-and-child clinics, the less likely children were to be vaccinated. The lower the Gini inequality index, there is a higher polio vaccination uptake among of children.

Vaccination uptake and income inequalities within a mass vaccination campaign

BackgroundIn July 2013, Israel was swept with fear of a polio outbreak. In response to the importation of wild polio virus, the Ministry decided to take preventive action by administering oral poliovirus vaccine (OPV) to all children born after 1 January 2004 who had received at least one dose of inactivated poliovirus vaccine (IPV) in the past. This study analyzes the vaccination uptake rates resulting from the mass polio vaccination campaign on the basis of health inequality parameters of socioeconomic status (SES), principles of solidarity, and the Gini inequality index. The research explores understanding the value of the Gini inequality index within the context of SES and solidarity.MethodsThe study is based on data gathered from the Israeli Ministry of Health’s administrative records from mother-and-child clinics across Israel. The research population is comprised of resident infants and children whom the Ministry of Health defined as eligible for the OPV between August and December 2013 (the “campaign period”). The analysis was carried out at the municipality level as well as the statistical area level.ResultsThe higher the SES level of the municipality where the mother-and-child clinic is located, the lower the OPV vaccination uptake is. The greater the income inequality is in the municipality where the mother-and-child clinic is situated, the lower the vaccination uptake.ConclusionsPublic health professionals promoting vaccine programs need to make specially-designed efforts both in localities with high average income and in localities with a high level of income diversity/inequality. Such practice will better utilize funds, resources, and manpower dedicated to increasing vaccination uptake across varying populations and communities.

Pediatric HIV Infection and Decreased Prevalence of OPV Point Mutations Linked to Vaccine-associated Paralytic Poliomyelitis.

BackgroundMutations associated with prolonged replication of the attenuated polioviruses found in oral poliovirus vaccine (OPV) can lead to vaccine-derived poliovirus (VDPV) and cause paralysis indistinguishable from that caused by wild poliovirus. In response, the World Health Organization has initiated the transition to exclusive use of inactivated poliovirus vaccine (IPV), with OPV administration in cases of outbreak. However, it is currently unclear how IPV-only vaccination, well known to provide humoral but not mucosal immunity, will impact the development of paralysis causing OPV variants. Children infected with human immunodeficiency virus (HIV) have been documented to show decreased mucosal immunity following OPV vaccination. Thus, HIV-infected children vaccinated with OPV may serve as proxy for children with IPV-only vaccination.MethodsWe conducted a prospective study of Zimbabwean infants receiving OPV as part of their routine vaccination schedule. Stool samples collected from OPV-vaccinated children serially until age 24 months were tested for OPV serotypes using a real-time polymerase chain reaction protocol that quantifies the amount of mutant OPV variants found in each sample.ResultsOut of 2130 stool samples collected from 402 infants 365 stool samples were OPV positive: 313 from 212 HIV-noninfected (HIV−) infants and 52 from 34 HIV-infected (HIV+) infants. HIV− infants showed significantly higher proportions of OPV mutants when compared to HIV+ infants.ConclusionsHIV infection is associated with a reduced proportion of OPV vaccine associated paralytic polio mutants. These results suggest that OPV administered to individuals previously vaccinated only with IPV will show decreased propensity for OPV mutations.

OPV Vaccination and Shedding Patterns in Mexican and US Children.

BackgroundAs wild poliovirus is eradicated and countries switch from oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) per World Health Organization recommendations, preventing circulation of vaccine-derived poliovirus (cVDPV) is a top priority. Currently, the impact of prior poliovirus vaccination on OPV shedding is not fully understood.MethodsStool samples from 2 populations were tested for OPV to assess shedding patterns. 505 samples from 43 US children vaccinated with OPV were collected over 42 days post-vaccination. 1,379 samples from 148 Mexican children vaccinated with OPV were collected over 71 days post-vaccination. Prior vaccination history was recorded for both groups.ResultsSeventeen (40%) of the US children had never received poliovirus vaccination while the Mexican children had received at least 2 doses of IPV and 116 (78%) had OPV exposure. In total, 84% of US children and 78% of Mexican children shed OPV (P = .44, Fisher exact test), with a mean shedding duration of 17.4 days for US children and 9.3 days for Mexican children (P < .0001, Wilcoxon-Mann Whitney test).ConclusionsPrior vaccination did not affect the likelihood of shedding, as the US and Mexico cohorts had similar shedding proportions. However, prior vaccination affected shedding duration as the Mexican children, who were largely OPV exposed and all of whom had at least 2 IPV vaccinations, shed OPV for half as long as the US cohort. Since different countries maintain different poliovirus vaccination schedules, it is likely that duration of shedding of OPV varies in populations around the world.

Adverse Events Following Immunization in Brazil: Age of Child and Vaccine-Associated Risk Analysis Using Logistic Regression.

Objective: Vaccines are effective in controlling and eradicating infectious diseases. However, adverse events following immunization (AEFI) can occur in susceptible individuals. The objective of this study was to analyze the Brazilian AEFI database and compare eight vaccines in order to profile risks of AEFIs related to the mandated pediatric schedule of immunization, considering the age and sex of the child, type of vaccine, and reported adverse events. Methods: We analyzed the Brazilian AEFI database integrating reports between 2005 and 2010 for children less than 10-years old immunized with eight mandated vaccines: diphtheria, pertussis, tetanus, Haemophilus influenzae type b (TETRA); diphtheria, tetanus, and pertussis (DTP); Bacillus Calmette–Guerin (BCG); oral poliovirus vaccine (OPV); measles, mumps, and rubella (MMR); oral rotavirus vaccine (ORV); hepatitis B (HB); and yellow fever (YF). We compared the children’s age regarding types of AEFI, evaluated AEFI factors associated with the chance of hospitalization of the child, and estimated the chance of notification of an AEFI as a function of the type of vaccine. In total, 47,105 AEFIs were observed for the mandated vaccines. Results: The highest AEFI rate was for the TETRA vaccine and the lowest was for the OPV vaccine, with 60.1 and 2.3 events per 100,000 inoculations, respectively. The TETRA vaccine showed the highest rate of hypotonic hyporesponsive episode, followed by convulsion and fever. The MMR and YF vaccines were associated with generalized rash. BCG was associated with enlarged lymph glands but showed the largest negative (protective) association with hyporesponsive events and seizures. Compared with children aged 5–9-years old, young children (<1 year) showed significantly higher odds of hospitalization. Conclusions: The Brazilian AEFI registry is useful to compare the magnitude and certain characteristics of adverse events associated with mandated pediatric vaccines.

Coverage estimates and patterns of inactivated poliovirus vaccine (IPV) use prior to and during the polio eradication endgame, Jinan City, China, 2010–2015

ABSTRACTBackground: Use of inactivated poliovirus vaccine (IPV) in Jinan during the polio eradication endgame has not been previously documented. Two IPV-containing vaccines were made available as an option for Jinan parents in 2009. We describe coverage levels and patterns of use of IPV over time using data from the Jinan Childhood Immunization Information Management System (JNCIIMS).Methods: Children born between January 2010 and December 2014 who were registered in JNCIIMS were included in this study. Vaccination records were obtained from JNCIIMS on April 30, 2015. JNCIIMS distinguishes among available poliovirus vaccines; doses administered data were used to describe IPV usage over time. We identified the polio vaccination sequences used by children in the 2012 and 2013 birth cohorts. Coverage estimates were analyzed by birth cohort and migration status. We developed 3 categories for analysis: “resident child,” “migrant child” and “other child” according to migration status.Results: In total, 12,354 (11.7%) IPV, 5,893(5.6%) DTP-IPV-Hib vaccine and 87,054(82.7%) OPV doses were administered to children in the 2010 to 2014 birth cohorts. The proportion of children using an IPV-only schedule increased each year, consistent with the introduction of IPV that is called for by the Polio Eradication Endgame Strategic Plan 2013–2018. During this time, 4.7% children used a schedule containing both IPV and oral poliovirus vaccine (OPV). In the 2012 to 2013 birth cohorts, 14.4% children used an IPV-only schedule; 5.7% children used a sequential schedule, and 79.9% used OPV-only schedule. Use of IPV only schedules was higher among migrant children than among resident children. Among those sequential schedule using both IPV and OPV, 87.2% children used IPV for the first dose and 12.8% used OPV for the first dose.Conclusions: JNCIIMS provided a mechanism for tracking IPV and OPV vaccination patterns, and showed areas in need of improvement. Ensuring appropriately sequenced IPV and OPV supports reduction of risk of vaccine associated paralytic polio.

PCR assays for the identification of rare recombination types from VP1 to 3D genomic region of vaccine derived poliovirus strains

Poliomyelitis has been effectively controlled by the use of inactivated poliovirus vaccine (IPV) or trivalent live attenuated oral poliovirus vaccine (OPV). Since 1964, the use of OPV in mass vaccinations has resulted in drastic reductions of the number of poliomyelitis cases caused by wild-type polioviruses. However, the characterization of OPV derivatives with increased neurovirulence, constituted a real problem with respect to OPV safety. Mutations at attenuating sites of the genome and recombination events between Sabin strains of the trivalent OPV vaccine have been correlated with the loss of the attenuated phenotype of OPV strains and the acquisition of traits characteristic of wild polioviruses. In consequence, early detection and characterization of recombinant evolved derivatives of vaccine strains is highly important. In this report, ten PCR assays are described which allow for the identification of rare recombination events located in VP1, 2A, 2C, 3A, 3C and 3D genomic regions and predominant recombination events located in 2C and 3D genomic regions of OPV derivatives. These assays could be readily implemented in diagnostics laboratories lacking sequencing facilities as a first approach for the early detection and characterization of recombinant OPV derivatives.

Characterizing Poliovirus Transmission and Evolution: Insights from Modeling Experiences with Wild and Vaccine‐Related Polioviruses

With national and global health policymakers facing numerous complex decisions related to achieving and maintaining polio eradication, we expanded our previously developed dynamic poliovirus transmission model using information from an expert literature review process and including additional immunity states and the evolution of oral poliovirus vaccine (OPV). The model explicitly considers serotype differences and distinguishes fecal-oral and oropharyngeal transmission. We evaluated the model by simulating diverse historical experiences with polioviruses, including one country that eliminated wild poliovirus using both OPV and inactivated poliovirus vaccine (IPV) (USA), three importation outbreaks of wild poliovirus (Albania, the Netherlands, Tajikistan), one situation in which no circulating vaccine-derived polioviruses (cVDPVs) emerge despite annual OPV use and cessation (Cuba), three cVDPV outbreaks (Haiti, Madura Island in Indonesia, northern Nigeria), one area of current endemic circulation of all three serotypes (northern Nigeria), and one area with recent endemic circulation and subsequent elimination of multiple serotypes (northern India). We find that when sufficient information about the conditions exists, the model can reproduce the general behavior of poliovirus transmission and outbreaks while maintaining consistency in the generic model inputs. The assumption of spatially homogeneous mixing remains a significant limitation that affects the performance of the differential equation-based model when significant heterogeneities in immunity and mixing may exist. Further studies on OPV virus evolution and improved understanding of the mechanisms of mixing and transmission may help to better characterize poliovirus transmission in populations. Broad application of the model promises to offer insights in the context of global and national policy and economic models.

Waning Intestinal Immunity After Vaccination With Oral Poliovirus Vaccines in India

The eradication of wild-type polioviruses in areas with efficient fecal-oral transmission relies on intestinal mucosal immunity induced by oral poliovirus vaccine (OPV). Mucosal immunity is thought to wane over time but the rate of loss of protection has not been examined. We examined the degree and duration of intestinal mucosal immunity in India by measuring the prevalence of vaccine poliovirus in stool samples collected 4-28 days after a "challenge" dose of OPV among 47 574 children with acute flaccid paralysis reported during 2005-2009. Previous vaccination with OPV was protective against excretion of vaccine poliovirus after challenge, but the odds of excretion increased significantly with the time since the child was last exposed to an immunization activity (odds ratio, 1.39 [95% confidence interval .99-1.97], 2.04 [1.28-3.25], and 1.31 [1.00-1.70] comparing ≥6 months with 1 month ago for serotypes 1, 2, and 3, respectively). Vaccine administered during the high season for enterovirus infections (April-September) was significantly less likely to result in excretion, especially in northern states (odds ratio, 0.57 [95% confidence interval, .50-.65], 0.58 [.41-.81], and 0.48 [.40-.57] for serotypes 1, 2, and 3). Infection with OPV (vaccine "take") is highly seasonal in India and results in intestinal mucosal immunity that appears to wane significantly within a year of vaccination.

Eradication of Poliovirus: Fighting Fire With Fire

Endemic wild polioviruses have been eliminated from most of the world, and the number of human paralytic cases has been reduced by .99%, from an estimated annual incidence of .500,000 cases to ,2000 cases [1–3]. Circulating wild polioviruses remain endemic in only 2 major locations, Nigeria and a zone extending from northern India west to Pakistan and Afghanistan [1–3]. Furthermore, wild-type 2 poliovirus has been eliminated altogether, with the last documented case reported in northern India in 1999 [4]. These remarkable accomplishments represent a triumph for oral poliovirus vaccine (OPV), composed of attenuated variants of the 3 poliovirus serotypes [5]. OPV is administered by mouth, induces mucosal and humoral immunity, and is relatively inexpensive to produce—attributes that have contributed to its widespread use even in regions with rudimentary health systems. However, OPV has an Achilles heel. The attenuated variants in the vaccine are rapidly replaced by revertant mutants, even on a single passage through the human intestine [6]. The revertant genotype has been mapped to a limited number of point mutations [7, 8], and revertant viruses can be distinguished genetically from wild polioviruses [8]. OPV vaccinees excrete a mix of viruses, some of which are as paralytogenic as wild polioviruses. These excreted viruses, similar to wild polioviruses, are readily transmitted to contacts of vaccinated infants and children by the fecal-oral route. Therefore, after mass OPV vaccination campaigns, the environment is inundated with a mix of excreted viruses, some of which have the disease potential of wild polioviruses. Therefore, the use of OPV could be considered to be an example of fighting fire with fire. The dangers of OPV were recognized during early vaccine trials, and one epidemiologist coined the epigram ‘‘in like a lamb out like a lion’’ [9 p. 1214]. On the basis of meticulous surveillance in the United States, vaccine-associated paralytic poliomyelitis was documented both in vaccinees and their immediate contacts [10–14]. However, vaccine-associated paralytic poliomyelitis in contacts was rare and sporadic, occurring at a rate of 1–2 cases per 1,000,000 primary vaccinations. In retrospect, it is likely that vaccine-derived polioviruses (VDPV) did not spread widely in the United States because most susceptible children were vaccinated with OPV, rendering them resistant to virus shed by their vaccinated contacts. Since 2000, .15 outbreaks of paralytic poliomyelitis caused by circulating VDPV (cVDPV) have been recognized throughout the world [1]. Such outbreaks have shared one epidemiological characteristic. They have occurred in areas where OPV vaccination coverage has been incomplete; thus, .50% of children remained susceptible. Under these circumstances, cVDPV can circulate for many generations, infect large numbers of persons, and cause outbreaks of paralytic poliomyelitis. The article by Wassilak et al [15] in this issue of the Journal and a companion article [16] describe the most significant of these outbreaks of cVDPV. The Nigerian epidemic, in which type 2 VDPV has caused .300 paralytic cases, began in 2005 and has continued through 2010. Because wild-type 2 poliovirus causes only 1 paralytic case per 2000 infections [1], the Nigerian outbreak might represent .600,000 infections with virulent VDPV. Under what circumstances did this outbreak occur? First, similar to other outbreaks of cVDPV, the epidemic was concentrated in the northern region of Nigeria, where there were relatively low rates of OPV vaccination [15]. Second, during 2006–2010, most of the vaccination campaigns in Nigeria used either monovalent or, more recently, bivalent vaccine lacking type 2 OPV. The Received 15 November 2010; accepted 16 November 2010. Potential conflicts of interest: none reported. Reprints or correspondence: Neal Nathanson, MD, Global Health Programs, School of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6021 (nathansn@upenn.edu). The Journal of Infectious Diseases 2011;203:889–90 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com 1537-6613/2011/2037-0001$15.00 DOI: 10.1093/infdis/jiq148

Prevalence of vaccine-derived polioviruses in stools of immunodeficient children in South Africa

The aim of the study was to determine the prevalence of vaccine-derived polioviruses (VDPVs) in stool specimens of immunodeficient patients such as HIV-positive children (including those with an AIDS indicator condition, according to the Centres for Disease Control and Prevention classification) by applying various molecular techniques. A total of 164 stool samples from HIV-positive children and 23 stool samples from healthy immunocompetent children (the control group) were analysed during 2003 and 2004. By applying a reverse transcription polymerase chain reaction (RT-PCR) in combination with a nested PCR, a total of 54 enteroviruses were detected in the stool specimens of the immunodeficient children. The use of restriction enzymes and a Sabin specific RT-triplex PCR confirmed the presence of 13 polioviruses (PVs), such as seven Sabin PV type 1, four Sabin PV type 3 and two Sabin PV type 2 isolates. The 5'untranslated region and the VP1 capsid-encoding protein of the 13 PVs and the three PVs from the stools of the immunocompetent children were partially sequenced and their genetic relatedness was deduced from the constructed phylogenetic trees. The majority of the PVs isolated from the stools of the immunodeficient children (10 of 13 isolates) were classified as 'oral poliovirus vaccine (OPV)-like viruses', as these isolates had close sequence relationships (>99% in VP1 nucleotide sequences) to the original Sabin PV vaccine strains. Three PVs showed < or =99% VP1 sequence identity to the Sabin PV vaccine strains and were classified as 'suspected' immunodeficient VDPVs (iVDPVs). All of the OPV-like isolates and the 'suspected' iVDPVs carried mutations at specific positions in their partially sequenced regions, which have been associated with reversion of the attenuated Sabin PV vaccine strains to increased neurovirulence. Thus, this study adds further evidence to the observation that immunodeficient individuals may excrete OPV strains with potential neurovirulent phenotypes. Prolonged excretion of PVs by immunodeficient individuals is of major concern, because continued replication of PVs in the human gut could result in the reversion of these viruses to greater neurovirulence. When exposed to OPV, immunodeficient patients may become chronically infected, spreading potentially neurovirulent VDPVs for many months or years to close contacts and children who are no longer being vaccinated after termination of OPV vaccination in the near future.