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Background: Despite the successes of the Global Polio Eradication Initiative, substantial challenges remain in eradicating the poliovirus. The Sabin-strain (live-attenuated) virus in oral poliovirus vaccine (OPV) can revert to circulating vaccine-derived poliovirus (cVDPV) in under-vaccinated communities, regain neurovirulence and transmissibility, and cause paralysis outbreaks. Since the cessation of type 2-containing OPV (OPV2) in 2016, there have been cVDPV type 2 (cVDPV2) outbreaks in four out of six geographical World Health Organization regions, making these outbreaks a significant public health threat. Preparing for and responding to cVDPV2 outbreaks requires an updated understanding of how different factors, such as outbreak responses with the novel type of OPV2 (nOPV2) and the existence of under-vaccinated areas, affect the disease spread., Methods: We built a differential-equation-based model to simulate the transmission of cVDPV2 following reversion of the Sabin-strain virus in prolonged circulation. The model incorporates vaccinations by essential (routine) immunization and supplementary immunization activities (SIAs), the immunity induced by different poliovirus vaccines, and the reversion process from Sabin-strain virus to cVDPV. The model's outcomes include weekly cVDPV2 paralytic case counts and the die-out date when cVDPV2 transmission stops. In a case study of Northwest and Northeast Nigeria, we fit the model to data on the weekly cVDPV2 case counts with onset in 2018-2021. We then used the model to test the impact of different outbreak response scenarios during a prediction period of 2022-2023. The response scenarios included no response, the planned response (based on Nigeria's SIA calendar), and a set of hypothetical responses that vary in the dates at which SIAs started. The planned response scenario included two rounds of SIAs that covered almost all areas of Northwest and Northeast Nigeria except some under-vaccinated areas (e.g., Sokoto). The hypothetical response scenarios involved two, three, and four rounds of SIAs that covered the whole Northwest and Northeast Nigeria. All SIAs in tested outbreak response scenarios used nOPV2. We compared the outcomes of tested outbreak response scenarios in the prediction period., Results: Modeled cVDPV2 weekly case counts aligned spatiotemporally with the data. The prediction results indicated that implementing the planned response reduced total case counts by 79% compared to no response, but did not stop the transmission, especially in under-vaccinated areas. Implementing the hypothetical response scenarios involving two rounds of nOPV2 SIAs that covered all areas further reduced cVDPV2 case counts in under-vaccinated areas by 91-95% compared to the planned response, with greater impact from completing the two rounds at an earlier time, but it did not stop the transmission. When the first two rounds were completed in early April 2022, implementing two additional rounds stopped the transmission in late January 2023. When the first two rounds were completed six weeks earlier (i.e., in late February 2022), implementing one (two) additional round stopped the transmission in early February 2023 (late November 2022). The die out was always achieved last in the under-vaccinated areas of Northwest and Northeast Nigeria., Conclusions: A differential-equation-based model of poliovirus transmission was developed and validated in a case study of Northwest and Northeast Nigeria. The results highlighted (i) the effectiveness of nOPV2 in reducing outbreak case counts; (ii) the need for more rounds of outbreak response SIAs that covered all of Northwest and Northeast Nigeria in 2022 to stop the cVDPV2 outbreaks; (iii) that persistent transmission in under-vaccinated areas delayed the progress towards stopping outbreaks; and (iv) that a quicker outbreak response would avert more paralytic cases and require fewer SIA rounds to stop the outbreaks., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pinar Keskinocak reports financial support was provided by Centers for Disease Control and Prevention. Lauren N. Steimle reports financial support was provided by Centers for Disease Control and Prevention. Yuming Sun reports financial support was provided by Centers for Disease Control and Prevention. Pinar Keskinocak reports a relationship with Merck & Co Inc that includes: funding grants., (© 2024 The Authors.)

Background: The polio eradication endgame continues to increase in complexity.  With polio cases caused by wild poliovirus type 1 and circulating vaccine-derived polioviruses of all three types (1, 2 and 3) reported in 2022, the number, formulation, and use of poliovirus vaccines poses challenges for national immunization programs and vaccine suppliers.  Prior poliovirus transmission modeling of globally-coordinated type-specific cessation of oral poliovirus vaccine (OPV) assumed creation of Sabin monovalent OPV (mOPV) stockpiles for emergencies and explored the potential need to restart OPV if the world reached a specified cumulative threshold number of cases after OPV cessation. Methods:   We document the actual experience of type 2 OPV (OPV2) cessation and reconsider prior modeling assumptions related to OPV restart.  We develop updated decision trees of national immunization options for poliovirus vaccines considering different possibilities for OPV restart. Results:   While OPV restart represented a hypothetical situation for risk management and contingency planning to support the 2013-2018 Global Polio Eradication Initiative (GPEI) Strategic Plan, the actual epidemiological experience since OPV2 cessation raises questions about what, if any, trigger(s) could lead to restarting the use of OPV2 in routine immunization and/or plans for potential future restart of type 1 and 3 OPV after their respective cessation.  The emergency use listing of a genetically stabilized novel type 2 OPV (nOPV2) and continued evaluation of nOPV for types 1 and/or 3 add further complexity by increasing the combinations of possible OPV formulations for OPV restart.  Conclusions: Expanding on a 2019 discussion of the logistical challenges and implications of restarting OPV, we find a complex structure of the many options and many issues related to OPV restart decisions and policies as of early 2023.  We anticipate many challenges for forecasting prospective vaccine supply needs during the polio endgame due to increasing potential combinations of poliovirus vaccine choices., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Kalkowska DA et al.)

Background: Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response., Methods: We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0·5 mL), and fIPV was administered intradermally (0·1 mL of the IPV formulation was administered using the 0·1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12·5%. This trial is registered with ClinicalTrials.gov, number NCT02847026., Findings: Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0·0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73-83]) versus 305 (57% [53-61]) participants, the type 2 response comprised 173 (64% [58-70]) versus 249 (46% [42-51]) participants, and the type 3 response comprised 196 (73% [67-78]) versus 196 (36% [33-41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vs group A) for serotype 1 (-1·12% [90% CI -2·18 to -0·06]), serotype 2 (0·40%, [-2·22 to 1·42]), and serotype 3 (1·51% [-3·23 to -0·21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV., Interpretation: fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses., Funding: US Centers for Disease Control and Prevention., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2., Methods: We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 10 5 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual., Findings: Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune responses after two mOPV2 doses were observed in 161 (93%) of 173 infants with testable serum samples in the 1 week group, 169 (96%) of 177 in the 2 week group, and 176 (97%) of 181 in the 4 week group. 1 week and 2 week intervals between two mOPV2 doses were non-inferior to 4 week intervals because the lower bound of the absolute differences in the percentage of immune responses were greater than -10% (-4·2% [90% CI -7·9 to -0·4] in the 1 week group and -1·8% [-5·0 to 1·5] in the 2 week group vs the 4 week group). The immune response elicited by two mOPV2 doses 4 weeks apart was not different when IPV was added to the first dose (176 [97%] of 182 infants with IPV vs 176 [97%] of 181 without IPV; p=1·0). During the trial, two serious adverse events (pneumonia; one [1%] of 186 patients in the 1 week group and one [1%] of 182 in the 4 week group) and no deaths were reported; the adverse events were not attributed to the vaccines., Interpretation: Administration of mOPV2 at short intervals does not interfere with its immunogenicity. The addition of IPV to the first mOPV2 dose did not improve poliovirus type 2 immune response., Funding: US Centers for Disease Control and Prevention., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: We assessed programmatic adaptations and infants' uptake of inactivated poliovirus vaccine (IPV) after its introduction into the routine immunization schedule in Bangladesh., Methods: Using convenience and probability sampling, we selected 23 health facilities, 36 vaccinators, and 336 caregivers, within 5 districts and 3 city corporations. We collected data during August-October 2015 by conducting interviews, reviewing vaccination records, and observing activities., Results: Knowledge about IPV was high among vaccinators (94%). No problems with IPV storage, transport, or waste disposal were detected, but shortages were reported in 20 health facilities (87%). Wastage per 5-dose vaccine vial was above the recommended 30% in 20 health facilities (87%); all were related to providing <5 doses per open vial. Among eligible infants, 87% and 86% received the third dose of pentavalent and oral poliovirus vaccine, respectively, but only 65% received IPV at the same visit. Among 73 infants not vaccinated with IPV, 58% of caregivers reported that vaccine was unavailable., Conclusions: Bangladesh successfully introduced IPV, but shortages related to insufficient global supply and high vaccine wastage in small outreach immunization sessions might reduce its impact on population immunity. Minimizing wastage and use of a 2-dose fractional-IPV schedule could extend IPV immunization to more children., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Global measures to eradicate polio began in 1988; as of 2014, four of six World Health Organization (WHO) regions have been certified polio-free. Within the two endemic regions (African and Eastern Mediterranean), Nigeria, Afghanistan, and Pakistan have never interrupted transmission of wild poliovirus (WPV) (1). The primary means of detecting poliovirus transmission is surveillance for acute flaccid paralysis (AFP) among children aged <15 years, combined with collection and testing of stool specimens from persons with AFP for detection of WPV and vaccine-derived polioviruses (VDPVs) (viruses that differ genetically from vaccine viruses and can emerge in areas with low vaccination coverage and cause paralysis) in WHO-accredited laboratories within the Global Polio Laboratory Network (2,3). AFP surveillance is supplemented by environmental surveillance for polioviruses in sewage from selected locations (4). Genomic sequencing of the VP1-coding region of isolated polioviruses enables mapping transmission by time and place, assessment of potential gaps in surveillance, and identification of the emergence of VDPVs. This report presents poliovirus surveillance data from 2015 and 2016, with particular focus on 20 countries in the African Region and six in the Eastern Mediterranean Region that reported WPV or circulating VDPVs (cVDPVs) during 2011-2016, as well as the three countries most affected by the 2014-2015 Ebola virus disease (Ebola) outbreak (Guinea, Liberia, and Sierra Leone). During 2016, 12 (60%) of the 20 African Region countries and all six of the Eastern Mediterranean Region countries met both surveillance quality indicators (nonpolio AFP rates of ≥2 per 100,000 persons aged <15 years per year and ≥80% of AFP cases with adequate stool specimens [stool adequacy]) at the national level; however, provincial-level variation was seen. To complete and certify polio eradication, surveillance gaps must be identified and surveillance activities, including supervision, monitoring, and specimen collection and handling, further strengthened.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide (1). One of the main tools used in polio eradication efforts has been the live, attenuated, oral poliovirus vaccine (OPV) (2), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but provides long-term protection against paralytic disease. Through effective use of OPV, the Global Polio Eradication Initiative (GPEI) has brought wild polioviruses to the threshold of eradication (1). However, OPV use, particularly in areas with low routine vaccination coverage, is associated with the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (3). VDPVs can emerge among immunologically normal vaccine recipients and their contacts as well as among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) (3) can emerge in areas with low OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (4).

In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Wild poliovirus (WPV) transmission persists in only two countries (Afghanistan and Pakistan) after the removal of Nigeria from the list of countries with endemic polio in September 2015.* Indigenous WPV type 2 has not been detected since 1999 and was declared eradicated by the Global Commission for the Certification of Poliomyelitis Eradication in September 2015.(†) Since November 2012, when the last case of WPV type 3 was detected in Nigeria, WPV type 1 has been the sole circulating type of WPV (1). This report summarizes global progress toward polio eradication during 2015-2016 and updates previous reports (2). In 2015, 74 WPV cases were reported in two countries (Afghanistan and Pakistan), a decrease of 79% from the 359 WPV cases reported in 2014 in nine countries; 12 WPV cases have been reported in 2016 (to date), compared with 23 during the same period in 2015 (3). Paralytic polio caused by circulating vaccine-derived poliovirus (cVDPV) remains a risk in areas with low oral poliovirus vaccine (OPV) coverage. Seven countries, including Pakistan, reported 32 cVDPV cases in 2015 (4). In four of these countries, ≥6 months have passed since the most recent case or isolate. One country (Laos) with VDPV transmission in 2015 has reported three additional cVDPV cases in 2016 to date. Encouraging progress toward polio eradication has been made over the last year; however, interruption of WPV transmission will require focus on reaching and vaccinating every missed child through high quality supplementary immunization activities (SIAs) and cross-border coordination between Afghanistan and Pakistan (5,6).

Global efforts to eradicate polio began in 1988, and polio-free certification has been achieved in four of the six World Health Organization (WHO) regions. Nigeria was removed from WHO's list of countries with endemic polio in September 2015, achieving an important milestone toward interruption of wild poliovirus (WPV) transmission in the African Region (1). Afghanistan and Pakistan, both in the Eastern Mediterranean Region, were the only countries to report WPV cases in 2015. Previously reported outbreaks caused by WPV importation during 2013-2014 have ended (2,3). The primary means for detecting poliovirus transmission is surveillance for acute flaccid paralysis (AFP) among children aged <15 years (4,5). Stool specimens collected from children with AFP are tested for both WPV and vaccine-derived poliovirus (VDPV) in WHO-accredited laboratories within the Global Polio Laboratory Network (GPLN). In selected locations, AFP surveillance is supplemented with environmental surveillance (testing sewage for poliovirus) (6). Testing of stool and sewage samples includes genomic sequencing to characterize poliovirus isolates; results are used to map poliovirus transmission and identify gaps in AFP surveillance. This report presents poliovirus surveillance data from 2014 and 2015, focusing on the 20 countries in the African Region and six in the Eastern Mediterranean Region that reported a WPV or circulating VDPV (cVDPV) case during 2011-2015, including Guinea, Liberia, and Sierra Leone, which were most affected by the 2014-2015 Ebola virus disease (Ebola) outbreak.

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

In 2015, wild poliovirus (WPV) transmission was identified in only Afghanistan and Pakistan (1). The widespread use of live, attenuated oral poliovirus vaccine (OPV) has been key in polio eradication efforts. However, OPV use, particularly in areas with low vaccination coverage, is associated with the low risk for emergence of vaccine-derived polioviruses (VDPV), which can cause paralysis (2). VDPVs vary genetically from vaccine viruses and can cause outbreaks in areas with low vaccination coverage. Circulating VDPVs (cVDPVs) are VDPVs in confirmed outbreaks. Single VDPVs for which the origin cannot be determined are classified as ambiguous (aVDPVs), which can also cause paralysis. Among the three types of WPV, type 2 has been declared to be eradicated. More than 90% of cVDPV cases have been caused by type 2 cVDPVs (cVDPV2). Therefore, in April 2016, all OPV-using countries of the world are discontinuing use of type 2 Sabin vaccine by simultaneously switching from trivalent OPV (types 1, 2, and 3) to bivalent OPV (types 1 and 3) for routine and supplementary immunization. The World Health Organization recently broadened the definition of cVDPVs to include any VDPV with genetic evidence of prolonged transmission (i.e., >1.5 years) and indicated that any single VDPV2 event (a case of paralysis caused by a VDPV or isolation of a VDPV from an environmental specimen) should elicit a detailed outbreak investigation and local immunization response. A confirmed cVDPV2 detection should elicit a full poliovirus outbreak response that includes multiple supplemental immunization activities (SIAs); an aVDPV designation should be made only after investigation and response (3). Since 2005, there have been 1-8 cVDPV outbreaks and 3-12 aVDPV events per year. There are currently five active cVDPV outbreaks in Guinea, Laos, Madagascar, Myanmar, and Ukraine, and four other active VDPV events.

Introduction: Inactivated poliovirus vaccine (IPV) introduction and phased oral poliovirus vaccine (OPV) cessation are essential for eradication of polio., Methods: Healthy 6-week old infants in Bangladesh were randomized to one of five study arms: receipt of trivalent OPV (tOPV) or bivalent OPV (bOPV) at ages 6, 10 and 14 weeks, intramuscular IPV or intradermal one-fifth fractional dose IPV (f-IPV) at ages 6 and 14 weeks, or f-IPV at ages 6 and 14 weeks with bOPV at age 10 weeks (f-IPV/bOPV). All participants received tOPV at age 18 weeks., Results: Of 975 infants randomized, 95% (922) completed follow-up. Type 1 seroconversion after 3 doses at 6, 10 and 14 weeks was higher with bOPV compared with tOPV (99% vs 94%, p=0.019). Seroconversions to types 1 and 3 after 2 IPV doses at ages 6 and 14 weeks were no different than after 3 doses of tOPV or bOPV at ages 6, 10 and 14 weeks. A priming response, seroconversion 1 week after IPV at 14 weeks among those who did not seroconvert after IPV at 6 weeks, was observed against poliovirus types 1, 2 and 3 in 91%, 84% and 97%, respectively. Compared with IPV, f-IPV failed non-inferiority tests for seroconversion with 1 or 2 doses and priming after 1 dose., Discussion: The findings demonstrate considerable priming with IPV at age 6 weeks, comparable immunogenicity of tOPV and bOPV, and inferior immunogenicity of one-fifth f-IPV compared with IPV. If IPV induced priming at age 6 weeks is similar to that at age 14 weeks, IPV could be administered at a younger age and possibly with a higher coverage., (Published by Elsevier Ltd.)

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

Since the 1988 launch of global poliomyelitis eradication efforts, four of the six World Health Organization (WHO) regions have been certified polio-free. Nigeria is one of only three countries, along with Afghanistan and Pakistan, where transmission of wild poliovirus (WPV) has never been interrupted. During 2003-2013, northern Nigeria served as a reservoir for WPV reintroduction into 26 previously polio-free countries. In 2012, the Nigerian government launched a national polio eradication emergency plan to intensify efforts to interrupt WPV transmission. This report describes polio eradication activities and progress in Nigeria during January 2014-July 2015 and updates previous reports. No WPV cases have been reported to date in 2015, compared with a total of six cases reported during 2014. Onset of paralysis in the latest reported WPV type 1 (WPV1) case was July 24, 2014. Only one case of circulating vaccine-derived poliovirus type 2 (cVDPV2) has been reported to date in 2015, compared with 20 cVDPV2 cases during the same period in 2014. Pending final laboratory testing of 218 remaining specimens of 16,617 specimens collected since January 2015, Nigeria could be removed from the WHO list of polio-endemic countries in September 2015. Major remaining challenges to the national polio eradication program include sustaining political support and program funding in the absence of active WPV transmission, maintaining high levels of population immunity in hard-to-reach areas, and accessing children in security-compromised areas of the northeastern states.

Background: The provision of several doses of monovalent type 1 oral poliovirus vaccine (mOPV1) and bivalent OPV1 and 3 (bOPV) vaccines through campaigns is essential to stop the circulation of remaining wild polioviruses. Our study aimed to assess the shortening of intervals between campaigns with bOPV and mOPV1 and to assess the immunogenicity of bOPV in routine immunisation schedules., Methods: We did an open-label, non-inferiority, five-arm, randomised controlled trial in Bangladesh. We recruited healthy infants aged 6 weeks at 42 immunisation clinics and randomly assigned them (with blocks of 15, three per group) to receive a short three-dose schedule of bOPV (bOPV short) or mOPV1 (mOPV1 short) with the first dose given at age 6 weeks, the second at age 8 weeks, and the third at age 10 weeks; or to a standard three-dose schedule of bOPV (bOPV standard) or mOPV1 (mOPV1 standard) or trivalent OPV (tOPV standard) with the first dose given at age 6 weeks, the second at 10 weeks, and the third at age 14 weeks. The primary outcome was the proportion of infants with antibody seroconversion for type 1, type 2, and type 3 polioviruses. The primary, modified intention-to-treat analysis included all patients who had testable serum samples before and after receiving at least one OPV dose. We used a 10% margin to establish non-inferiority for bOPV groups versus mOPV1 groups in seroconversion for type 1 poliovirus, and for bOPV1 short versus bOPV1 standard for types 1 and 3. This trial is registered at ClinicalTrials.gov, number NCT01633216, and is closed to new participants., Findings: Between May 13, 2012, and Jan 21, 2013, we randomly assigned 1000 infants to our study groups. 927 completed all study visits and were included in the primary analysis. Seroconversion for type-1 poliovirus was recorded in 183 (98%, 95% CI 95-100) of 186 infants given bOPV short, 179 (97%, 94-99) of 184 given bOPV standard, 180 (96%, 92-98) of 188 given mOPV short, 178 (99%, 97-100) of 179 given mOPV1 standard, and 175 (92%, 87-96) of 190 given tOPV standard. Seroconversion for type 2 was noted in 16 infants (9%, 5-14) on bOPV short, 29 (16%, 11-22) on bOPV standard, 19 (10%, 7-15) on mOPV short, 33 (18%, 13-25) on mOPV1 standard, and 182 (96%, 92-98) on tOPV standard. Seroconversion for type 3 was noted in 175 infants (94%, 90-97) on bOPV short, 176 (96%, 92-98) on bOPV standard, 18 (10%, 6-15) on mOPV short, 25 (14%, 10-20) on mOPV1 standard, and 167 (88%, 83-92) on tOPV standard. The short schedules for mOPV1 and bOPV elicited a non-inferior antibody response compared with the bOPV standard schedule. 104 adverse events were reported in 100 infants during follow up. 36 of these events needed admission to hospital (32 were pneumonia, two were vomiting or feeding disorders, one was septicaemia, and one was diarrhoea with severe malnutrition). One of the infants admitted to hospital for pneumonia died 5 days after admission. No adverse event was attributed to the vaccines., Interpretation: Our trial showed that three doses of mOPV1 or bOPV with a short schedule of 2 week intervals between doses induces an immune response similar to that obtained with the standard schedule of giving doses at 4 week intervals. These findings support the use of these vaccines in campaigns done at short intervals to rapidly increase population immunity against polioviruses to control outbreaks or prevent transmission in high-risk areas., Funding: Centers for Disease Control and Prevention and UNICEF., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The effect of transport temperature on the viability of poliovirus in stool specimens from paralyzed cases has not been tested. Quality assurance of programmatic indicators will be necessary in the final phase of polio eradication., Objective: To estimate the effect of time at elevated temperatures on wild poliovirus titers in stool specimens., Methods: We exposed aliquots of pooled wild poliovirus type 1 specimens to elevated temperatures (27 °C, 31 °C, and 35 °C) for varying time periods up to 14 days. We determined the virus titer of these aliquots and created decay curves at each temperature to estimate the relationship between time at temperature and virus titer., Results: We found significantly different slopes of decay at each temperature. The negative slopes increased as the temperature increased., Conclusions: While poliovirus in stool remains relatively stable at moderately elevated temperature, transport at higher temperatures could impact sample integrity and virus isolation results., (Published by Elsevier Inc.)

Since the World Health Assembly's 1988 resolution to eradicate poliomyelitis, one of the main tools of the World Health Organization (WHO) Global Polio Eradication Initiative (GPEI) has been the live, attenuated oral poliovirus vaccine (OPV). OPV might require several doses to induce immunity but provides long-term protection against paralytic disease. Through effective use of OPV, GPEI has brought polio to the threshold of eradication. Wild poliovirus type 2 (WPV2) was eliminated in 1999, WPV3 has not been detected since November 2012, and WPV1 circulation appears to be restricted to parts of Pakistan and Afghanistan. However, continued use of OPV carries two key risks. The first, vaccine-associated paralytic poliomyelitis (VAPP) has been recognized since the early 1960s. VAPP is a very rare event that occurs sporadically when an administered dose of OPV reverts to neurovirulence and causes paralysis in the vaccine recipient or a nonimmune contact. VAPP can occur among immunologically normal vaccine recipients and their contacts as well as among persons who have primary immunodeficiencies (PIDs) manifested by defects in antibody production; it is not associated with outbreaks. The second, the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs) was recognized more recently. Circulating VDPVs (cVDPVs) resemble WPVs and, in areas with low OPV coverage, can cause polio outbreaks. Immunodeficiency-associated VDPVs (iVDPVs) can replicate and be excreted for years in some persons with PIDs; GPEI maintains a registry of iVDPV cases. Ambiguous VDPVs (aVDPVs) are isolates that cannot be classified definitively. This report updates previous surveillance summaries and describes VDPVs detected worldwide during January 2014-March 2015. Those include new cVDPV outbreaks in Madagascar and South Sudan, and sharply reduced type 2 cVDPV (cVDPV2) circulation in Nigeria and Pakistan during the latter half of 2014. Eight newly identified persons in six countries were found to excrete iVDPVs, and a patient in the United Kingdom was still excreting iVDPV2 in 2014 after more than 28 years. Ambiguous VDPVs were found among immunocompetent persons and environmental samples in 16 countries. Because the large majority of VDPV case-isolates are type 2, WHO has developed a plan for coordinated worldwide withdrawal of trivalent (types 1, 2, and 3) OPV (tOPV) and replacement with bivalent (types 1 and 3) OPV (bOPV) in April 2016, preceded by introduction of at least 1 dose of injectable inactivated poliovirus vaccine (IPV) into routine immunization schedules worldwide to maintain immunity to type 2 viruses.

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

Background: After 25 years without poliomyelitis cases caused by circulating wild poliovirus (WPV) in Israel, sewage sampling detected WPV type 1 (WPV1) in April 2013, despite high vaccination coverage with only inactivated poliovirus vaccine (IPV) since 2005., Methods: We used a differential equation-based model to simulate the dynamics of poliovirus transmission and population immunity in Israel due to past exposure to WPV and use of oral poliovirus vaccine (OPV) in addition to IPV. We explored the influences of various immunization options to stop imported WPV1 circulation in Israel., Results: We successfully modeled the potential for WPVs to circulate without detected cases in Israel. Maintaining a sequential IPV/OPV schedule instead of switching to an IPV-only schedule in 2005 would have kept population immunity high enough in Israel to prevent WPV1 circulation. The Israeli response to WPV1 detection prevented paralytic cases; a more rapid response might have interrupted transmission more quickly., Conclusions: IPV-based protection alone might not provide sufficient population immunity to prevent poliovirus transmission after an importation. As countries transition to IPV in immunization schedules, they may need to actively manage population immunity and consider continued use of OPV, to avoid the potential circulation of imported live polioviruses before globally coordinated cessation of OPV use., (© The Author 2014. 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.)

In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to eradicate polio worldwide. Wild poliovirus (WPV) transmission has been interrupted in all but three countries (Afghanistan, Nigeria, and Pakistan). No WPV type 2 cases have been detected worldwide since 1999, and the last WPV type 3 case was detected in Nigeria in November 2012; since 2012, only WPV type 1 has been detected. Circulating vaccine-derived poliovirus (cVDPV), usually type 2, continues to cause cases of paralytic polio in communities with low population immunity. In 2012, the World Health Assembly declared global polio eradication "a programmatic emergency for global public health", and in 2014, WHO declared the international spread of WPV to previously polio-free countries to be "a public health emergency of international concern". This report summarizes global progress toward polio eradication during 2014-2015 and updates previous reports. In 2014, a total of 359 WPV cases were reported in nine countries worldwide. Although reported WPV cases increased in Pakistan and Afghanistan, cases in Nigeria decreased substantially in 2014, and encouraging progress toward global WPV transmission interruption has occurred. Overcoming ongoing challenges to interruption of WPV transmission globally will require sustained programmatic enhancements, including improving the quality of supplementary immunization activities (SIAs) to interrupt transmission in Afghanistan and Pakistan and to prevent WPV exportation to polio-free countries.

Global efforts to eradicate polio began in 1988 and have been successful in all but two of the six World Health Organization (WHO) regions. Within these two regions (African and Eastern Mediterranean), three countries (Afghanistan, Nigeria, and Pakistan) have never interrupted transmission of wild poliovirus (WPV). Outbreaks following importation of WPV from these countries occurred in the Horn of Africa, Central Africa, and in the Middle East during 2013-2014. The primary means of tracking polio is surveillance for cases of acute flaccid paralysis (AFP), the main symptom of polio, followed by testing of AFP patients' stool specimens for both WPV and vaccine-derived poliovirus (VDPV) in WHO-accredited laboratories within the Global Polio Laboratory Network (GPLN). This is supplemented with environmental surveillance (testing sewage for WPV and VDPV) (4). Both types of surveillance use genomic sequencing for characterization of poliovirus isolates to map poliovirus transmission and for identifying gaps in AFP surveillance by measuring genetic divergence between isolates. This report presents 2013 and 2014 poliovirus surveillance data, focusing primarily on the two WHO regions with endemic WPV transmission, and the 29 countries (African Region = 23; Eastern Mediterranean Region = six) with at least one case of WPV or circulating VDPV (cVDPV) reported during 2010-2014. In 2013, 20 of these 23 African region countries met both primary surveillance quality indicators; in 2014, the number decreased to 15. In 2013, five of the six Eastern Mediterranean Region countries met the primary indicators, and in 2014, all six did. To complete and certify polio eradication, surveillance gaps must be identified and surveillance activities, including supervision, monitoring, and specimen collection, further strengthened.

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

In 1988, the World Health Assembly resolved to eradicate polio worldwide. Since then, four of the six World Health Organization (WHO) regions have been certified as polio-free: the Americas in 1994, the Western Pacific Region in 2000, the European Region in 2002, and the South-East Asia Region in 2014. Currently, nearly 80% of the world's population lives in areas certified as polio-free. Certification may be considered when ≥3 years have passed since the last isolation of wild poliovirus (WPV) in the presence of sensitive, certification-standard surveillance. Although regional eradication has been validated in the European Region and the Western Pacific Region, outbreaks resulting from WPV type 1 (WPV1) imported from known endemic areas were detected and controlled in these regions in 2010 and 2011, respectively. The last reported case associated with WPV type 2 (WPV2) was in India in 1999, marking global interruption of WPV2 transmission. The completion of polio eradication was declared a programmatic emergency for public health in 2012, and the international spread of WPV1 was declared a public health emergency of international concern in May 2014. The efforts needed to interrupt all indigenous WPV1 transmission are now being focused on the remaining endemic countries: Nigeria, Afghanistan, and Pakistan. WPV type 3 (WPV3) has not been detected in circulation since November 11, 2012. This report summarizes the evidence of possible global interruption of transmission of WPV3, based on surveillance for acute flaccid paralysis (AFP) and environmental surveillance.

Background: The Strategic Advisory Group of Experts on Immunization (SAGE) has recommended introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) at ≥14 weeks of age through the routine immunization program in countries currently not using IPV., Methods: We analyzed all available unrestricted data obtained from the Demographic and Health Surveys since 2005 in sub-Saharan Africa (31 countries) and in South and Southeast Asia (9 countries) to determine coverage of the following injectable vaccines delivered through the routine immunization schedule: diphtheria-tetanus-pertussis vaccine dose 1 (DTP1), DTP2, DTP3, and measles vaccine. Coverage with these vaccines was used as a proxy measure of likely 1- and 2-dose IPV coverage., Results: Coverage with 1 dose of IPV is expected to be lowest when offered with DTP3 (median coverage, 73%) and highest when offered with DTP1 (median coverage, 90%). The median DTP1-DTP3 drop-out rate was 14%, which equates to an additional 12 million children not receiving IPV if IPV is offered with DTP3, rather than with DTP1. An increased geographical clustering of children who have not received IPV is expected in sub-Saharan Africa and Asia if IPV is offered with DTP3, rather than with DTP1. Coverage with 2 doses of IPV is expected to be lowest if IPV is administered with DTP3 and measles vaccine (69%) and highest if administered with DTP1 and DTP2 (84%)., Conclusions: Coverage with 1 dose of IPV is expected to be lowest if it is administered at the DTP3 visit. At present, there is insufficient evidence to determine whether the SAGE-recommended IPV schedule for the polio endgame would maximize population immunity to type 2 poliovirus., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

A renewed commitment at the regional and the global levels led to substantial progress in the fight for polio eradication in the African Region (AFR) of the World Health Organization (WHO) during 2008-2012. In 2008, there were 912 reported cases of wild poliovirus (WPV) infection in 12 countries in the region. This number had been reduced to 128 cases in 3 countries in 2012, of which 122 were in Nigeria, the only remaining country with endemic circulation of WPV in AFR. During 2008-2012, circulation apparently ceased in the 3 AFR countries with reestablished WPV transmission-Angola, the Democratic Republic of the Congo, and Chad. Outbreaks in West Africa continued to occur in 2008-2010 but were more rapidly contained, with fewer cases than during earlier years. This progress has been attributed to better implementation of core strategies, increased accountability, and implementation of innovative approaches. During this period, routine coverage with 3 doses of oral polio vaccine in AFR, as measured by WHO-United Nations Children's Fund estimates, increased slightly, from 72% to 74%. Despite this progress, challenges persist in AFR, and 2013 was marked by new setbacks and importations. High population immunity and strong surveillance are essential to sustain progress and assure that AFR reaches its goal of eradicating WPV., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Pockets of undervaccinated individuals continue to raise concerns about their potential to sustain epidemic transmission of vaccine-preventable diseases. Prior importations of live polioviruses (LPVs) into Amish communities in North America led to their recognition as a potential and identifiable linked network of undervaccinated individuals., Methods: We developed an individual-based model to explore the potential transmission of a LPV throughout the North American Amish population., Results: Our model demonstrates the expected limited impact associated with the historical importations, which occurred in isolated communities during the low season for poliovirus transmission. We show that some conditions could potentially lead to wider circulation of LPVs and cases of paralytic polio in Amish communities if an importation occurred during or after 2013. The impact will depend on the uncertain historical immunity to poliovirus infection among members of the community., Conclusions: Heterogeneity in immunization coverage represents a risk factor for potential outbreaks of polio if introduction of a LPV occurs, although overall high population immunity in North America suggests that transmission would remain relatively limited. Efforts to prevent spread between Amish church districts with any feasible measures may offer the best opportunity to contain an outbreak and limit its size., (© The Author 2014. 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.)

Background: Early detection and control of vaccine-derived poliovirus (VDPV) emergences are essential to secure the gains of polio eradication., Methods: Serial sewage samples were collected in 4 towns of Mexico before, throughout, and after the May 2010 oral poliovirus vaccine (OPV) mass immunization campaign. Isolation and molecular analysis of polioviruses from sewage specimens monitored the duration of vaccine-related strains in the environment and emergence of vaccine-derived polioviruses in a population partially immunized with inactivated poliovirus vaccine (IPV)., Results: Sabin strains were identified up to 5-8 weeks after the campaign in all towns; in Aguascalientes, 1 Sabin 3 was isolated 16 weeks after the campaign, following 7 weeks with no Sabin strains detected. In Tuxtla Gutiérrez, type 2 VDPV was isolated from 4 samples collected before and during the campaign, and type 1 VDPV from 1 sample collected 19 weeks afterward. During 2009-2010, coverage in 4 OPV campaigns conducted averaged only 57% and surveillance for acute flaccid paralysis (AFP) was suboptimal (AFP rate<1 per 100,000 population<15 years of age) in Tuxtla Gutierrez., Conclusions: VDPVs may emerge and spread in settings with inadequate coverage with IPV/OPV vaccination. Environmental surveillance can facilitate early detection in these settings., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Despite substantial progress, global polio eradication has remained elusive. Indigenous wild poliovirus (WPV) transmission in 4 endemic countries (Afghanistan, India, Nigeria, and Pakistan) persisted into 2010 and outbreaks from imported WPV continued. By 2013, most outbreaks in the interim were promptly controlled. The number of polio-affected districts globally has declined by 74% (from 481 in 2009 to 126 in 2013), including a 79% decrease in the number of affected districts in endemic countries (from 304 to 63). India is now polio-free. The challenges to success in the remaining polio-endemic countries include (1) threats to the security of vaccinators in each country and a ban on polio vaccination in areas of Afghanistan and Pakistan; (2) a risk of decreased government commitment; and (3) remaining surveillance gaps. Coordinated efforts under the International Health Regulations and efforts to mitigate the challenges provide a clear opportunity to soon secure global eradication., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Despite substantial progress toward eradication of poliomyelitis, the risk of poliomyelitis outbreaks resulting from virus importations into polio-free areas persists. We reviewed the changing epidemiology of outbreaks in the final stages of the eradication initiative., Methods: Available literature on outbreaks of poliomyelitis caused by wild polioviruses between 1996 and 2012 was reviewed., Results: During this period, there were 22 outbreaks involving 39 countries. Outbreaks ranged in size from 1 to 1335 cases. These outbreaks caused 4571 cases, representing 21% of all cases reported during this period. Five outbreaks involved multiple countries. In 76% of outbreaks (16/21) with a known age distribution, cases concentrated among children aged <5 years; in 19% (4/21), most cases were among adolescents and adults. The outbreaks among adolescents and adults were associated with higher case-fatality ratios, ranging from 12% in Albania in 1994 to 41% in the Republic of Congo in 2010. The majority of outbreaks were controlled within 6 months with oral poliovirus vaccine., Conclusions: Importations resulting in epidemic transmission of wild poliovirus caused thousands of cases of paralysis often in countries where poliomyelitis had not occurred for many years. The changing epidemiology, with cases and higher case-fatality ratios among adults, increased the severity of these outbreaks., (© The Author 2014. 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.)

Background: To assess the quality of supplementary immunization activities (SIAs), the Global Polio Eradication Initiative (GPEI) has used cluster lot quality assurance sampling (C-LQAS) methods since 2009. However, since the inception of C-LQAS, questions have been raised about the optimal balance between operational feasibility and precision of classification of lots to identify areas with low SIA quality that require corrective programmatic action., Methods: To determine if an increased precision in classification would result in differential programmatic decision making, we conducted a pilot evaluation in 4 local government areas (LGAs) in Nigeria with an expanded LQAS sample size of 16 clusters (instead of the standard 6 clusters) of 10 subjects each., Results: The results showed greater heterogeneity between clusters than the assumed standard deviation of 10%, ranging from 12% to 23%. Comparing the distribution of 4-outcome classifications obtained from all possible combinations of 6-cluster subsamples to the observed classification of the 16-cluster sample, we obtained an exact match in classification in 56% to 85% of instances., Conclusions: We concluded that the 6-cluster C-LQAS provides acceptable classification precision for programmatic action. Considering the greater resources required to implement an expanded C-LQAS, the improvement in precision was deemed insufficient to warrant the effort., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

In 1988, the World Health Assembly resolved to interrupt wild poliovirus (WPV) transmission worldwide. By 2006, the annual number of WPV cases had decreased by more than 99%, and only four remaining countries had never interrupted WPV transmission: Afghanistan, India, Nigeria, and Pakistan. The last confirmed WPV case in India occurred in January 2011, leading the World Health Organization (WHO) South-East Asia Regional Commission for the Certification of Polio Eradication (SEA-RCC) in March 2014 to declare the 11-country South-East Asia Region (SEAR), which includes India, to be free from circulating indigenous WPV. SEAR became the fourth region among WHO's six regions to be certified as having interrupted all indigenous WPV circulation; the Region of the Americas was declared polio-free in 1994, the Western Pacific Region in 2000, and the European Region in 2002. Approximately 80% of the world's population now lives in countries of WHO regions that have been certified polio-free. This report summarizes steps taken to certify polio eradication in SEAR and outlines eradication activities and lessons learned in India, the largest member state in the region and the one for which eradication was the most difficult.

Since 1988, when the Global Polio Eradication Initiative (GPEI) began, the annual number of polio cases has decreased by >99%. Only three countries remain that have never interrupted wild poliovirus (WPV) transmission: Afghanistan, Nigeria, and Pakistan. Since 2001, outbreaks have occurred in 31 formerly polio-free counties in Africa, with outbreaks in 25 countries caused by WPV originating in Nigeria (2-4). After the declaration of the World Health Assembly of polio eradication as a programmatic emergency in 2012, efforts to identify areas at high risk for importation-associated outbreaks and to reduce that risk have been intensified. This report updates the 2013 assessment of the risk for outbreaks attributable to importation of poliovirus in 33 countries in Africa, using indicators of childhood susceptibility to poliovirus and proximity to countries currently affected by polio . From January 2013 to August 12, 2014, outbreaks occurred in five African countries. Four of the five (Cameroon, Equatorial Guinea, Ethiopia, and Somalia) have had recent transmission (cases within the previous 12 months). Based on the current risk assessment, 15 countries are considered to be at high risk for WPV outbreaks, five at moderate-to-high risk, seven at moderate risk, and six at low risk. In 15 of the 33 countries, less than half of the population resides in areas where surveillance performance indicators have met minimum targets. Enhanced, coordinated activities to raise childhood immunity are underway in 2014 to prevent additional WPV spread. Although substantial progress toward polio eradication has occurred in Nigeria, all African countries remain at risk for outbreaks as long as WPV continues to circulate anywhere on the continent.

In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to interrupt wild poliovirus (WPV) transmission worldwide, and in 2012, the World Health Assembly declared the completion of global polio eradication a programmatic emergency for public health. By 2013, the annual number of WPV cases had decreased by >99% since 1988, and only three countries remained that had never interrupted WPV transmission: Afghanistan, Nigeria, and Pakistan. This report summarizes global progress toward polio eradication during 2013-2014 and updates previous reports. In 2013, a total of 416 WPV cases were reported globally from eight countries, an 86% increase from the 223 WPV cases reported from five countries in 2012. This upsurge in 2013 was caused by a 60% increase in WPV cases detected in Pakistan, and by outbreaks in five previously polio-free countries resulting from international spread of WPV. In 2014, as of May 20, a total of 82 WPV cases had been reported worldwide, compared with 34 cases during the same period in 2013. Polio cases caused by circulating vaccine-derived poliovirus (cVDPV) were detected in eight countries in 2013 and in two countries so far in 2014. To achieve polio eradication in the near future, further efforts are needed to 1) address health worker safety concerns in areas of armed conflict in priority countries, 2) to prevent further spread of WPV and new outbreaks after importation into polio-free countries, and 3) to strengthen surveillance globally. Based on the international spread of WPV to date in 2014, the WHO Director General has issued temporary recommendations to reduce further international exportation of WPV through vaccination of persons traveling from currently polio-affected countries.

In 2012, the World Health Assembly of the World Health Organization (WHO) declared completion of polio eradication a programmatic emergency. Polio cases are detected through surveillance of acute flaccid paralysis (AFP) cases and subsequent testing of stool specimens for polioviruses (PVs) at WHO-accredited laboratories within the Global Polio Laboratory Network (GPLN). AFP surveillance is supplemented by environmental surveillance, testing sewage samples from selected sites for PVs. Virologic surveillance, including genomic sequencing to identify isolates by genotype and measure divergence between isolates, guides Global Polio Eradication Initiative (GPEI) activities by confirming the presence of PV, tracking chains of PV transmission, and highlighting gaps in AFP surveillance quality. This report provides AFP surveillance quality indicators at national and subnational levels during 2012-2013 for countries that experienced PV cases during 2009-2013 in the WHO African Region (AFR) and Eastern Mediterranean Region (EMR), the remaining polio-endemic regions. It also summarizes the results of environmental surveillance and reviews indicators assessing the timeliness of reporting of PV isolation and of virus strain characterization globally. Regional-level performance indicators for timely reporting of PV isolation were met in five of six WHO regions in 2012 and 2013. Of 30 AFR and EMR countries that experienced cases of PV (wild poliovirus [WPV], circulating vaccine-derived poliovirus [cVDPV], or both) during 2009-2013, national performance indicator targets for AFP surveillance and collection of adequate specimens were met in 27 (90%) countries in 2012 and 22 (73%) in 2013. In 17 (57%) countries, ≥80% of the population lived in subnational areas meeting both AFP performance indicators in 2012, decreasing to 13 (43%) in 2013. To achieve polio eradication and certify interruption of PV transmission, intensive efforts to strengthen and maintain AFP surveillance are needed at subnational levels, including in field investigation and prompt collection of specimens, particularly in countries with current or recent active PV transmission.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide. One of the main tools used in polio eradication efforts has been live, attenuated oral poliovirus vaccine (OPV), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but then it provides long-term protection against paralytic disease through durable humoral immunity. Rare cases of vaccine-associated paralytic poliomyelitis can occur among immunologically normal OPV recipients, their contacts, and persons who are immunodeficient. In addition, vaccine-derived polioviruses (VDPVs) can emerge in areas with low OPV coverage to cause polio outbreaks and can replicate for years in persons who have primary, B-cell immunodeficiencies. This report updates previous surveillance summaries and describes VDPVs detected worldwide during July 2012-December 2013. Those include a new circulating VDPV (cVDPV) outbreak identified in Pakistan in 2012, with spread to Afghanistan; an outbreak in Afghanistan previously identified in 2009 that continued into 2013; a new outbreak in Chad that spread to Cameroon, Niger, and northeastern Nigeria; and an outbreak that began in Somalia in 2008 that continued and spread to Kenya in 2013. A large outbreak in Nigeria that was identified in 2005 was nearly stopped by the end of 2013. Additionally, 10 newly identified persons in eight countries were found to excrete immunodeficiency-associated VDPVs (iVDPVs), and VDPVs were found among immunocompetent persons and environmental samples in 13 countries. Because the majority of VDPV isolates are type 2, the World Health Organization has developed a plan for coordinated worldwide replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV; types 1 and 3) by 2016, preceded by introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) containing all three poliovirus serotypes into routine immunization schedules worldwide to ensure high population immunity to all polioviruses.

Background: Global efforts to eradicate wild polioviruses (WPVs) continue to face challenges due to uninterrupted endemic WPV transmission in three countries and importation-related outbreaks into previously polio-free countries. We explore the potential role of including older children and adults in supplemental immunization activities (SIAs) to more rapidly increase population immunity and prevent or stop transmission., Methods: We use a differential equation-based dynamic poliovirus transmission model to analyze the epidemiological impact and vaccine resource implications of expanding target age groups in SIAs. We explore the use of older age groups in SIAs for three situations: alternative responses to the 2010 outbreak in Tajikistan, retrospective examination of elimination in two high-risk states in northern India, and prospective and retrospective strategies to accelerate elimination in endemic northwestern Nigeria. Our model recognizes the ability of individuals with waned mucosal immunity (i.e., immunity from a historical live poliovirus infection) to become re-infected and contribute to transmission to a limited extent., Results: SIAs involving expanded age groups reduce overall caseloads, decrease transmission, and generally lead to a small reduction in the time to achieve WPV elimination. Analysis of preventive expanded age group SIAs in Tajikistan or prior to type-specific surges in incidence in high-risk areas of India and Nigeria showed the greatest potential benefits of expanded age groups. Analysis of expanded age group SIAs in outbreak situations or to accelerate the interruption of endemic transmission showed relatively less benefit, largely due to the circulation of WPV reaching individuals sooner or more effectively than the SIAs. The India and Nigeria results depend strongly on how well SIAs involving expanded age groups reach relatively isolated subpopulations that sustain clusters of susceptible children, which we assume play a key role in persistent endemic WPV transmission in these areas., Conclusions: This study suggests the need to carefully consider the epidemiological situation in the context of decisions to use expanded age group SIAs. Subpopulations of susceptible individuals may independently sustain transmission, which will reduce the overall benefits associated with using expanded age group SIAs to increase population immunity to a sufficiently high level to stop transmission and reduce the incidence of paralytic cases.

In 1988, the World Health Assembly resolved to globally eradicate poliomyelitis. As part of a four-pronged strategy with establishment of enhanced surveillance, institution of national immunization days, strengthening routine immunization, and carrying-out mopping-up activities, oral poliovirus vaccine (OPV) was selected as the vaccine-of-choice for eradication. Massive OPV use decreased the number of polio-endemic countries from >125 countries in 1988 to only 3 in 2012 and led to a >99.9% decrease in polio incidence in the corresponding period. In this communication, we will discuss polio vaccination options to accelerate eradication, to mitigate the risks during the planned withdrawal of type 2 OPV, and to secure eradication for future generations., (Published by Elsevier B.V.)

Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A481 in the 5'-untranslated region [5'-UTR] and VP1-Ile143) had been replaced in all VDPV2 isolates; most A481 5'-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries.

With the intensifying global efforts to eradicate wild polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated poliovirus vaccine (IPV) trigger renewed interest in poliovirus immunity, particularly the role of mucosal immunity in the transmission of polioviruses. Sustained high population immunity to poliovirus transmission represents a key prerequisite to eradication, but poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on poliovirus immunology and virology to review the literature relevant for modeling poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of poliovirus excretion, (3) the relationship between the concentration of poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps., (© 2013 Society for Risk Analysis.)

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., (© 2013 Society for Risk Analysis.)

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data., (© 2012 Society for Risk Analysis.)

The live, attenuated oral poliovirus vaccine (OPV) provides a powerful tool for controlling and stopping the transmission of wild polioviruses (WPVs), although the risks of vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived poliovirus (cVDPV) outbreaks exist as long as OPV remains in use. Understanding the dynamics of cVDPV emergence and outbreaks as a function of population immunity and other risk factors may help to improve risk management and the development of strategies to respond to possible outbreaks. We performed a comprehensive review of the literature related to the process of OPV evolution and information available from actual experiences with cVDPV outbreaks. Only a relatively small fraction of poliovirus infections cause symptoms, which makes direct observation of the trajectory of OPV evolution within a population impractical and leads to significant uncertainty. Despite a large global surveillance system, the existing genetic sequence data largely provide information about transmitted virulent polioviruses that caused acute flaccid paralysis, and essentially no data track the changes that occur in OPV sequences as the viruses transmit largely asymptomatically through real populations with suboptimal immunity. We updated estimates of cVDPV risks based on actual experiences and identified the many limitations in the existing data on poliovirus transmission and immunity and OPV virus evolution that complicate modeling. Modelers should explore the space of potential model formulations and inputs consistent with the available evidence and future studies should seek to improve our understanding of the OPV virus evolution process to provide better information for policymakers working to manage cVDPV risks., (© 2013 Society for Risk Analysis.)

Eradication of wild poliovirus (WPV) types 1 and 3, prevention and cessation of circulating vaccine-derived polioviruses, and achievement and maintenance of a world free of paralytic polio cases requires active risk management by focusing on population immunity and coordinated cessation of oral poliovirus vaccine (OPV). We suggest the need for a complementary and different conceptual approach to achieve eradication compared to the current case-based approach using surveillance for acute flaccid paralysis (AFP) to identify symptomatic poliovirus infections. Specifically, we describe a modeling approach to characterize overall population immunity to poliovirus transmission. The approach deals with the realities that exposure to live polioviruses (e.g., WPV, OPV) and/or vaccination with inactivated poliovirus vaccine provides protection from paralytic polio (i.e., disease), but does not eliminate the potential for reinfection or asymptomatic participation in poliovirus transmission, which may increase with time because of waning immunity. The AFP surveillance system provides evidence of symptomatic poliovirus infections detected, which indicate immunity gaps after outbreaks occur, and this system represents an appropriate focus for controlling disease outbreaks. We describe a conceptual dynamic model to characterize population immunity to poliovirus transmission that helps identify risks created by immunity gaps before outbreaks occur, which provides an opportunity for national and global policymakers to manage the risk of poliovirus and prevent outbreaks before they occur. We suggest that dynamically modeling risk represents an essential tool as the number of cases approaches zero., (© 2012 Society for Risk Analysis.)

With the circulation of wild poliovirus (WPV) types 1 and 3 continuing more than a decade after the original goal of eradicating all three types of WPVs by 2000, policymakers consider many immunization options as they strive to stop transmission in the remaining endemic and outbreak areas and prevent reintroductions of live polioviruses into nonendemic areas. While polio vaccination choices may appear simple, our analysis of current options shows remarkable complexity. We offer important context for current and future polio vaccine decisions and policy analyses by developing decision trees that clearly identify potential options currently used by countries as they evaluate national polio vaccine choices. Based on a comprehensive review of the literature we (1) identify the current vaccination options that national health leaders consider for polio vaccination, (2) characterize current practices and factors that appear to influence national and international choices, and (3) assess the evidence of vaccine effectiveness considering sources of variability between countries and uncertainties associated with limitations of the data. With low numbers of cases occurring globally, the management of polio risks might seem like a relatively low priority, but stopping live poliovirus circulation requires making proactive and intentional choices to manage population immunity in the remaining endemic areas and to prevent reestablishment in nonendemic areas. Our analysis shows remarkable variability in the current national polio vaccine product choices and schedules, with combination vaccine options containing inactivated poliovirus vaccine and different formulations of oral poliovirus vaccine making choices increasingly difficult for national health leaders., (© 2013 Society for Risk Analysis.)

Objectives: The United States eliminated indigenous wild polioviruses (WPVs) in 1979 and switched to inactivated poliovirus vaccine in 2000, which quickly ended all indigenous live poliovirus transmission. Continued WPV circulation and use of oral poliovirus vaccine globally allow for the possibility of reintroduction of these viruses. We evaluated the risk of a U.S. polio outbreak and explored potential vaccine needs for outbreak response., Methods: We synthesized information available on vaccine coverage, exemptor populations, and population immunity. We used an infection transmission model to explore the potential dynamics of a U.S. polio outbreak and potential vaccine needs for outbreak response, and assessed the impacts of heterogeneity in population immunity for two different subpopulations with potentially low coverage., Results: Although the risk of poliovirus introduction remains real, widespread transmission of polioviruses appears unlikely in the U.S., given high routine coverage. However, clusters of un- or underimmunized children might create pockets of susceptibility that could potentially lead to one or more paralytic polio cases. We found that the shift toward combination vaccine utilization, with limited age indications for use, and other current trends (e.g., decreasing proportion of the population with immunity induced by live polioviruses and aging of vaccine exemptor populations) might increase the vulnerability to poliovirus reintroduction at the same time that the ability to respond may decrease., Conclusions: The U.S. poliovirus vaccine stockpile remains an important resource that may potentially be needed in the future to respond to an outbreak if a live poliovirus gets imported into a subpopulation with low vaccination coverage.

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

Objective: To characterize the circumstances in which poliomyelitis occurred among three children in Bulgaria during 2001 and to describe the public health response., Methods: Bulgarian authorities investigated the three cases of polio and their contacts, conducted faecal and serological screening of children from high-risk groups, implemented enhanced surveillance for acute flaccid paralysis, and conducted supplemental immunization activities., Findings: The three cases of polio studied had not been vaccinated and lived in socioeconomically deprived areas of two cities. Four Roma children from the Bourgas district had antibody titres to serotype 1 poliovirus only, and wild type 1 virus was isolated from the faeces of two asymptomatic Roma children in the Bourgas and Sofia districts. Poliovirus isolates were related genetically and represented a single evolutionary lineage; genomic sequences were less than 90% identical to poliovirus strains isolated previously in Europe, but 98.3% similar to a strain isolated in India in 2000. No cases or wild virus isolates were found after supplemental immunization activities were launched in May 2001., Conclusions: In Bulgaria, an imported poliovirus was able to circulate for two to five months among minority populations. Surveillance data strongly suggest that wild poliovirus circulation ceased shortly after supplemental immunization activities with oral poliovirus vaccine were conducted.