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Background The world is set on the eradication of measles. Continuation of the measles vaccine (MV) after eradication could still reduce morbidity because the MV has so-called beneficial nonspecific effects. We evaluated the effect of a “booster” dose of the MV on overall severe morbidity. Methods We conducted a randomized controlled trial among children aged 17.5 to 48 months in Guinea-Bissau, where the MV is recommended only at 9 months of age. At the time of this interim analysis, 3164 children had been allocated 1:1 to a second dose of measles vaccine (MV2) at 18 months of age or to no vaccine. Severe morbidity (a composite outcome of nonaccidental deaths and hospital admissions) rate ratios (SMRRs) were calculated by Cox regression analysis censored for national oral polio vaccine (OPV) campaigns. Results There were no measles cases during the trial period. There were 43 nonaccidental deaths or hospital admissions during follow-up. Severe morbidity was 2.6 per 100 person-years in the MV2 group and 3.6 per 100 person-years among controls; hence, the estimated effect of MV2 on severe morbidity was 28% (SMRR, 0.72; 95% confidence interval [CI], .38–1.38). At 12 months of follow-up, the number needed to treat to prevent 1 severe morbidity event was 137 children. After OPV campaigns, the estimated effect of MV2 was reduced to 9% (SMRR, 0.91; 95% CI, .46–1.81). Conclusions MV2 may reduce nonmeasles severe morbidity by 28% (−38% to 62%), although this did not achieve statistical significance in this study. If significant in higher powered studies, this has major implications for child health, even after measles eradication. Clinical Trials Registration NCT02943681.

Introduction Following the withdrawal of Sabin type 2 from trivalent oral poliovirus vaccine (tOPV) in 2016, the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV) in routine immunization was recommended, either as 1 full dose (0.5mL, intramuscular) or 2 fractional doses of IPV (fIPV—0.1mL, intradermal). India opted for fIPV. We conducted a comparative assessment of IPV and fIPV. Methods This was a 4-arm, open-label, multicenter, randomized controlled trial. Infants were enrolled and vaccines administered according to the study design, and the blood was drawn at age 6, 14, and 18 weeks for neutralization testing against all 3 poliovirus types. Results Study enrolled 799 infants. The seroconversion against type 2 poliovirus with 2 fIPV doses was 85.8% (95% confidence interval [CI]: 80.1%-90.0%) when administered at age 6 and 14 weeks, 77.0% (95% CI: 70.5-82.5) when given at age 10 and 14 weeks, compared to 67.9% (95% CI: 60.4-74.6) following 1 full-dose IPV at age 14 weeks. Conclusion The study demonstrated the superiority of 2 fIPV doses over 1 full-dose IPV in India. Doses of fIPV given at 6 and 14 weeks were more immunogenic than those given at 10 and 14 weeks. Clinical Trial Registry of India (CTRI). Clinical trial registration number was CTRI/2017/02/007793.

Background We conducted a trial in Nigeria to assess the immunogenicity of the new bivalent oral poliovirus vaccine + inactivated poliovirus vaccine (bOPV+IPV) immunization schedule and gains in type 2 immunity with addition of second dose of IPV. The trial was conducted in August 2016–March 2017, well past the trivalent OPV-bOPV switch in April 2016. Methods This was an open-label, 2-arm, noninferiority, multicenter, randomized, controlled trial. We enrolled 572 infants aged ≤14 days and randomized them into 2 arms. Arm A received bOPV at birth, 6, and 10 weeks, bOPV+IPV at week 14, and IPV at week 18. Arm B received IPV each at 6, 10, and 14 weeks and bOPV at 18 weeks of age. Results Seroconversion rates for poliovirus types 1 and 3, respectively, were 98.9% (95% confidence interval [CI], 96.7–99.8) and 98.1% (95% CI, 88.2–94.8) in Arm A and 89.6% (95% CI, 85.4–93.0) and 98.5% (95% CI, 96.3–99.6) in Arm B. Type 2 seroconversion with 1 dose IPV in Arm A was 72.0% (95% CI, 66.2–77.3), which increased significantly with addition of second dose to 95.9% (95% CI, 92.8–97.9). Conclusions This first trial on the new Expanded Program on Immunization (EPI) schedule in a sub-Saharan African country demonstrated excellent immunogenicity against poliovirus types 1 and 3 and substantial/enhanced immunogenicity against poliovirus type 2 after 1 to 2 doses of IPV, respectively.

Uganda officially introduced the inactivated polio vaccine (IPV) in May 2016 as part of the polio eradication strategy and integrated it into its routine immunization programme in addition to the oral polio vaccine. The current coverage stands at 60% as of July 2017. We therefore aimed to determine factors associated with the uptake of IPV among children in Kalungu District so as to inform the implementation of the vaccine policy. A community-based cross-sectional study was conducted among caregivers of 406 eligible children aged 12–23 months through multi-stage systematic sampling and a standardized semi-structured questionnaire. Nine key informant interviews were conducted through purposive selection of health care providers and members of Village Health Teams (VHTs) based on their expertize. Modified Poisson regression and thematic content analysis were used to determine factors significant to IPV uptake among children. 71% of sampled children aged 12–23 months had received IPV in Kalungu District. The survey found that being encouraged by health workers and VHTs was significant to children’s uptake of IPV (Adjusted PR 1.24, 95% CI; 1.22–3.47). Distance to the immunization point (Adjusted PR 0.32,95% CI; 0.16–0.62) and caregiver’s education level (Adjusted PR 1.16,95% CI; 1.05–2.22) were also associated with IPV uptake. Qualitative findings from health workers and VHT members further confirmed the perception that distance to the immunization post was important, and VHTs also stated that being encouraged by health workers was critical to IPV uptake. The current prevalence of IPV uptake among children aged 12–23 months in Kalungu is 71%, higher than the last reported national coverage (60%), though still below the recommended national coverage of 95%. Efforts should be focused on sensitization of caregivers through health workers and VHTs. Immunization outreach should be strengthened so as to bring services closer to patients.

Aims This study compared the bag‐mediated filtration system (BMFS) and standard WHO two‐phase separation methods for poliovirus (PV) environmental surveillance, examined factors impacting PV detection and monitored Sabin‐like (SL) PV type 2 presence with withdrawal of oral polio vaccine type 2 (OPV2) in April 2016. Methods and Results Environmental samples were collected in Nairobi, Kenya (Sept 2015–Feb 2017), concentrated via BMFS and two‐phase separation methods, then assayed using the WHO PV isolation algorithm and intratypic differentiation diagnostic screening kit. SL1, SL2 and SL3 were detected at higher rates in BMFS than two‐phase samples (P 0·05), while SL3 was detected less frequently with higher shipment temperatures (P = 0·027). SL2 was detected more frequently before OPV2 withdrawal in BMFS and two‐phase samples (P

Background Next-generation sequencing (NGS) analysis was compared to the current MAPREC (mutational analysis by polymerase chain reaction and restriction enzyme cleavage) assay for quality control of live-attenuated oral polio vaccine (OPV). Methods MAPREC measures reversion of the main OPV attenuating mutations such as uracil (U) to cytosine (C) at nucleotide 472 in the 5′ noncoding region of type 3 OPV. Eleven type 3 OPV samples were analyzed by 8 laboratories using their in-house NGS method. Results Intraassay, intralaboratory, and interlaboratory variability of NGS 472-C estimates across samples and laboratories were very low, leading to excellent agreement between laboratories. A high degree of correlation between %472-C results by MAPREC and NGS was observed in all laboratories (Pearson correlation coefficient r = 0.996). NGS estimates of sequences at nucleotide 2493 with known polymorphism among type 3 OPV lots also produced low assay variability and excellent between-laboratory agreement. Conclusions The high consistency of NGS data demonstrates that NGS analysis can be used as high-resolution test alternative to MAPREC, producing whole-genome profiles to evaluate OPV production consistency, possibly eliminating the need for tests in animals. This would be very beneficial for the quality assessment of next-generation polio vaccines and, eventually, for other live-attenuated viral vaccines.

Background Pakistan is among 3 countries endemic for wild poliovirus type 1 (WPV1) circulation that are still struggling for eradication of poliomyelitis. Active clinical and environmental surveillance with meticulous laboratory investigations provide insights into poliovirus transmission patterns and genomic diversity to inform decisions for strategic operations required to achieve eradication. Methods We analyzed epidemiological and virological data to comprehend the current epidemiological status of WPV1 in Pakistan during 2015–2017. Stool specimens of patients with acute flaccid paralysis (AFP) and sewage samples collected from 60 environmental sites were tested. Viral culturing, intratypic differentiation by real-time polymerase chain reaction, and nucleic acid sequencing of the VP1 region of the poliovirus genome to determine genetic relatedness among WPV1 strains were applied. Results Poliovirus isolates were grouped into 11 distinct clusters, which had ≥95% nucleotide homology in the VP1 coding region. Most of the poliovirus burden was shared by 3 major reservoirs: Karachi, Peshawar, and Quetta block (64.2% in 2015, 75.4% in 2016, and 76.7% in 2017). Conclusions Environmental surveillance reveals importations and pockets of unimmunized children that dictate intensive target mop-up campaigns to contain poliovirus transmission. A decrease in the number of orphan isolates reflects effective combination of AFP and environmental surveillance in Pakistan. The genetic data reflect sustained transmission within reservoir areas, further expanded by periodic importations to areas of high immunity reflected by immediate termination of imported viruses. Improved immunization coverage with high-quality surveillance is vital for global certification of polio eradication.

Background An outbreak of an imported Type 1 wild poliovirus from Pakistan occurred in the Xinjiang Uygur Autonomous Region of China in 2011, although the local immunity status of the oral polio vaccine (OPV) was relatively satisfied. Methods Neutralizing antibody titers against the Xinjiang strain and Sabin 1 strain were measured in 237 sera from 3 groups of fully OPV-vaccinated persons and 1 group of infants fully vaccinated with the inactive polio vaccine (IPV). Additionally, 17 sera collected from 1 Xinjiang poliomyelitis case and his 16 contacts were also tested. Genomic sequencing was conducted the Xinjiang strain. Results The antibody titers against the Xinjiang strain in each of 237 sera were significantly lower than those against the Sabin 1 strain. Notably, 40.0% of children in Group 1 were seronegative against the Xinjiang strain, which indicated that they might play an important role in wild poliovirus transmission, although their antibody titers against the Sabin 1 strain varied between 1:8 and 1:512. Meanwhile, serological results of the Xinjiang poliomyelitis case and his contacts also provided evidence that a proportion of OPV-vaccinated children had indeed been involved in the transmission chain of the Xinjiang outbreak. Genomic sequencing indicated that the Xinjiang strain was greatly distinguishable from the Sabin 1 strain in neutralizing antigenic sites. Conclusion The lack of neutralizing antibodies against the Xinjiang strain in persons vaccinated by OPV may be associated with the transmission of Type 1 wild poliovirus in Xinjiang. Using Salk IPV along with OPV might be considered in a wild poliovirus outbreak response, especially in the countries which continued to have persistent wild poliovirus circulation.

Background Due to global shortage of inactivated poliovirus vaccine and withdrawal of oral vaccine containing poliovirus type 2 (PV2), a PV2-containing vaccine was not used in Vietnam May 2016 to October 2018. We assessed the population immunity gap to PV2. Methods A cross-sectional survey in children aged 1–18 months was carried out in January 2018. One blood sample per child was analyzed for presence of poliovirus neutralizing antibodies. In children with detectable anti-PV2 antibodies, a second sample was analyzed 4 months later to distinguish between passive (maternally derived) and active (induced by secondary transmission or vaccination) immunity. Results Sera were obtained from 1106/1110 children. Seroprevalence of PV2 antibodies was 87/368 (23.6%) at age 1–7 months, 27/471 (5.7%) at 8–15 months, and 19/267 (7.1%) at 16–18 months. Seroprevalence declined with age in the 1–7 months group; in the 8–18 months group there was no significant change with age. Four months later, 11/87 (14%), 9/27 (32%), and 12/19 (37%) remained seropositive in 1–7, 8–15, and 16–18 months age groups, respectively. Conclusions We found declining immunity to PV2, suggesting Vietnam is at risk for an outbreak of type 2 vaccine-derived poliovirus following virus importation or new emergence.

Background Currently, the primary mechanism for poliovirus detection is acute flaccid paralysis (AFP) surveillance, with environmental sampling serving as a complement. However, as AFP cases drop, environmental surveillance will become increasingly critical for poliovirus detection. Mexico provides a natural environment to study oral polio vaccine (OPV) transmission, as it provides routine injected polio vaccine immunization and biannual OPV campaigns in February and May. Methods As part of a study of OPV transmission in which 155 children were vaccinated with OPV, monthly sewage samples were collected from rivers leading from 3 indigenous Mexican villages (Capoluca, Campo Grande, and Tuxpanguillo) from February to May 2015. Samples were also collected from October 2015 to October 2017, during which time there were standard OPV campaigns. Samples were analyzed for the presence of OPV serotypes, using a real-time qualitative polymerase chain reaction assay capable of detecting as few as 9, 12, and 10 copies/100 µL of viral ribonucleic acid for OPV serotypes 1, 2, and 3 (OPV-1, -2, and -3), respectively. Included here are 54 samples, taken up to November 2016. Results Of the 54 samples, 13 (24%) were positive for OPV. After the vaccination of 155 children in February 2015, OPV was found 2 months after vaccination. After unrestricted OPV administration in February 2016, OPV was detected in sewage up to 8 months after vaccination. OPV-3 was found in 11 of the 13 positive samples (85%), OPV-2 was found in 3 positive samples (23%), and OPV-1 was found in 1 sample (8%). Conclusions OPV can be detected even when small amounts of the vaccine are introduced into a community, as shown by OPV-positive sewage samples even when only 155 children were vaccinated. When OPV vaccination was unrestricted, sewage samples were positive up to 8 months after vaccination, implying community OPV circulation for at least 8 months. OPV-3 was the serotype most found in these samples, indicating prolonged transmission of OPV-3 when compared to the other serotypes. Future work could compare the phylogenetic variance of OPV isolates from sewage after OPV vaccinations.

Background Global polio eradication efforts rely in part on molecular methods of detecting polioviruses, both wild and vaccine strains, from human and environmental samples. Previous assays used for detection of Sabin oral polio vaccine (OPV) in fecal samples have been labor and time intensive and vary in their sensitivity and specificity. Methods We developed a high-throughput, multiplex reverse-transcription quantitative polymerase chain reaction assay able to detect all 3 OPV strains in fecal samples. The assay used a KingFisher Duo Prime system for viral RNA isolation and extraction. Positive samples were retested and Sanger sequenced for verification of Sabin serotype identity. Results The 95% lower limit of detection was determined to be 3 copies per reaction for Sabin 1 and 3 and 4 copies per reaction for Sabin 2, with no cross-reactivity between the 3 serotypes and their primers. A total of 554 samples (3.6%) were positive, with 304 positive samples (54.9%) containing >1 serotype. Of the positive samples, 476 (85.9%) contained enough RNA to be sequenced, and of these all sequences were Sabin serotypes. The previous assay we used could process 48 samples in a 10-hour period, whereas the new assay processed >100 samples in 6 hours. Conclusions The new high-throughput, multiplex reverse-transcription quantitative polymerase chain reaction assay allowed for sensitive and specific detection of OPV serotypes while greatly decreasing sample handling and processing time. We were able to sequence 72.4% of the 210 positive samples in the cycle threshold range of 35–37.

Background Kano state has been a protracted reservoir of poliovirus in Nigeria. Immunity trends have been monitored through seroprevalence surveys since 2011. The survey in 2015 was, in addition, intended to assess the impact of use of inactivated poliovirus vaccine (IPV). Methods It was a health facility based seroprevalence survey. Eligible children aged 6-9, 12-15 and 19-22 months of age brought to the paediatrics outpatient department of Murtala Mohammad Specialist Hospital between 19 October and 6 November 2015, were screened for eligibility. Eligible children were enrolled after parental consent, history taken, physical examination conducted, and a blood sample collected to test for neutralizing antibody titres against the three poliovirus serotypes. Results Overall, 365 results were available in the three age groups. In the 6-9-month-old age group, the seroprevalence was 73% (95% confidence interval [CI] 64-80%), 83% (95% CI 75-88%), and 66% (95% CI 57-73%) for serotypes 1, 2, and 3, respectively. In the 12-15- and 19-22-month-old age groups, seroprevalence was higher but still remained Conclusions Seroprevalence for serotypes 1 and 3 remains low (

Background An essential component of the “Polio Eradication and Endgame Strategic Plan 2013–2018” is the evaluation of population immunity. Mexico introduced the inactivated polio vaccine (IPV) into its routine immunization schedule in 2007 but continued to give trivalent oral polio vaccine OPV twice a year during National Health Weeks through 2016. Methods To describe the seroprevalence of poliomyelitis among children one to four years old in Mexico and analyze risk factors for susceptibility. We detected antibodies to poliovirus type 1 by microneutralization test in 966 serum samples randomly selected from the National Health and Nutrition Survey, 2012. We assessed variables associated with susceptibility using multivariable logistic regression. Results The overall weighted seroprevalence of the general population was 98.39% (95% confidence interval [CI] 96.76–99.21). We found significant differences of prevalence according to age (94.39%, 95% CI 87.56–97.58; 99.02%, 95% CI 95.68–99.79; 99.82%, 95% CI 98.77–99.98; and 100% among children 1, 2, 3, and 4 years old respectively) and number of IPV doses (96.91%, 95% CI 90.55–99.44; 100%; 97.85%, 95% CI 94.46–99.18; and 99.92%, 95% CI 99.45–99.98 for 1 2, 3, and 4 number of doses, respectively). Multivariate analyses showed that susceptibility was associated with younger age, fewer doses of IPV, and certain socioeconomic levels. Conclusions Overall seroprevalence was high. However, we found susceptible children among younger ages and children with fewer or unknown IPV doses belonging to certain socioeconomic strata. Results are relevant for countries transitioning from OPV to IPV and underline the importance of achieving high coverage with IPV.

Background We aimed to elucidate household and community-level shedding and transmission of trivalent oral polio vaccine (tOPV) in communities with inactivated polio vaccine (IPV) routine immunization after tOPV is administered during a national health week (NHW). Methods We conducted a 3-arm, randomized trial with data collected at baseline through 10 weeks post-NHW in households with at least 1 child

Background Inactivated poliovirus vaccine (IPV) alone does not induce mucosal immunity. However, it was hypothesized that administration of IPV together with bivalent (types 1+3) oral poliovirus vaccine (bOPV) may stimulate mucosal cross-immunity to poliovirus type 2 (PV2). Methods Cuban infants were randomized to receive either one dose of IPV (Arm A); one dose of IPV with bOPV (Arm B) at about 6 months of age or no vaccine (Arm C). Subjects were challenged with one dose of trivalent OPV (tOPV); they were about 7 months old in arms A and B, and about 3 months old in arm C at a time of the tOPV challenge. Sera were collected before vaccination and 30 days after tOPV challenge and tested for presence of poliovirus neutralizing antibodies; stool samples were collected at days 0, 7, 14, 21 and 49 post-challenge and tested for presence of poliovirus. Results We enrolled 333 children. Excretion of PV2 following tOPV challenge was highest on day 7 (75 [CI 95% = 65-82%], 68 [CI 95% = 58-75%] and 73 [CI 95% = 63-80%] for study arms A, B, and C respectively); excretion decreased with every subsequent stool sampling; no significant differences either in proportion of PV2 excretion or in its duration were observed between study arms. Conclusions There was no reduction in excretion of PV2 after tOPV challenge in children who had received IPV with bOPV when compared to those who had received IPV alone or no vaccine. Polio eradication program cannot assume any PV2 mucosal response with the current polio immunization schedule. Clinical Trials Registration The trial was registered with the Australian New Zealand Clinical Trials Registry and allocated trial number ACTRN12616000169448.

Background We assessed immunity against polioviruses induced with a new Pakistani poliovirus immunization schedule and compared it to alternative poliovirus immunization schedules. Methods Newborns were randomized to undergo vaccination based on 1 of 5 vaccination schedules, with doses administered at birth and at 6, 10, and 14 weeks of age. Arm A received inactivated poliovirus vaccine (IPV) at all time points. Arm B received bivalent oral poliovirus vaccine (bOPV) at all time points. Arms C and D received bOPV at the first 3 time points and bOPV plus IPV at the final time point (the current schedule). Arm E received trivalent OPV (tOPV) at all time points. At 22 weeks of age, all children received 1 challenge dose of tOPV, and children in arm D received 1 additional IPV dose. Sera were analyzed for the presence of poliovirus neutralizing antibodies at birth and 14 and 22 weeks of age. Results Seroconversion for poliovirus type 1 (PV1) at 22 weeks of age was observed in 80% of individuals in arm A, 97% in arm B, 94% in arm C, 96% in arm D, and 94% in arm E; for PV2, seroconversion frequencies were 84%, 19%, 53%, 49%, and 93%, respectively; and for PV3, seroconversion frequencies were 93%, 94%, 98%, 94%, and 85%, respectively. Conclusions The current immunization schedule in Pakistan induced high seroconversion rates for PV1 and PV3; however, it induced PV2 seroconversion in only half of study subjects. There is a growing cohort of young children in Pakistan who are unprotected against PV2; and this creates an increasing risk of a large-scale outbreak of poliomyelitis caused by circulating vaccine-derived PV2.

The Immunization Systems Management Group (IMG) was established to coordinate and oversee objective 2 of the Polio Eradication and Endgame Strategic Plan 2013–2018, namely, (1) introduction of ≥1 dose of inactivated poliovirus vaccine in all 126 countries using oral poliovirus vaccine (OPV) only as of 2012, (2) full withdrawal of OPV, starting with the withdrawal of its type 2 component, and (3) using polio assets to strengthen immunization systems in 10 priority countries. The IMG’s inclusive, transparent, and partnership-focused approach proved an effective means of leveraging the comparative and complementary strengths of each IMG member agency. This article outlines 10 key factors behind the IMG’s success, providing a potential set of guiding principles for the establishment and implementation of other interagency collaborations and initiatives beyond the polio sphere.

The requirements under objective 2 of the Polio Eradication and Endgame Strategic Plan 2013–2018—to introduce at least 1 dose of inactivated poliomyelitis vaccine (IPV); withdraw oral poliomyelitis vaccine (OPV), starting with the type 2 component; and strengthen routine immunization programs—set an ambitious series of targets for countries. Effective implementation of IPV introduction and the switch from trivalent OPV (containing types 1, 2, and 3 poliovirus) to bivalent OPV (containing types 1 and 3 poliovirus) called for intense global communications and coordination on an unprecedented scale from 2014 to 2016, involving global public health technical agencies and donors, vaccine manufacturers, World Health Organization and United Nations Children’s Fund regional offices, and national governments. At the outset, the new program requirements were perceived as challenging to communicate, difficult to understand, unrealistic in terms of timelines, and potentially infeasible for logistical implementation. In this context, a number of core areas of work for communications were established: (1) generating awareness and political commitment via global communications and advocacy; (2) informing national decision-making, planning, and implementation; and (3) in-country program communications and capacity building, to ensure acceptance of IPV and continued uptake of OPV. Central to the communications function in driving progress for objective 2 was its ability to generate a meaningful policy dialogue about polio vaccines and routine immunization at multiple levels. This included efforts to facilitate stakeholder engagement and ownership, strengthen coordination at all levels, and ensure an iterative process of feedback and learning. This article provides an overview of the global efforts and challenges in successfully implementing the communications activities to support objective 2. Lessons from the achievements by countries and partners will likely be drawn upon when all OPVs are completely withdrawn after polio eradication, but also may offer a useful model for other global health initiatives.

This analysis describes an innovative and successful approach to risk identification and mitigation in relation to the switch from trivalent to bivalent oral polio vaccine (OPV) in the 11 countries of the World Health Organization’s (WHO’s) South-East Asia Region (SEAR) in April 2016. The strong commitment of governments and immunization professionals to polio eradication and an exemplary partnership between the WHO, United Nations Children’s Fund (UNICEF), and other partners and stakeholders in the region and globally were significant contributors to the success of the OPV switch in the SEAR. Robust national switch plans were developed and country-specific innovations were planned and implemented by the country teams. Close monitoring and tracking of the activities and milestones through dashboards and review meetings were undertaken at the regional level to ensure that implementation time lines were met, barriers identified, and solutions for overcoming challenges were discussed and implemented. The SEAR was the first WHO Region globally to complete the switch and declare the successful withdrawal of trivalent OPV from all countries on 17 May 2016. A number of activities implemented during the switch process are likely to contribute positively to existing immunization practices and to similar initiatives in the future. These activities include better vaccine supply chain management, improved mechanisms for disposal of vaccination-related waste materials, and a closer collaboration with drug regulators, vaccine manufacturers, and the private sector for immunization-related initiatives.

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

Surveillance for acute flaccid paralysis (AFP) is a fundamental cornerstone of the global polio eradication initiative (GPEI). Active surveillance (with visits to health facilities) is a critical strategy of AFP surveillance systems for highly sensitive and timely detection of cases. Because of the extensive resources devoted to AFP surveillance, multiple opportunities exist for additional diseases to be added using GPEI assets, particularly because there is generally 1 district officer responsible for all disease surveillance. For this reason, integrated surveillance has become a standard practice in many countries, ranging from adding surveillance for measles and rubella to integrated disease surveillance for outbreak-prone diseases (integrated disease surveillance and response). This report outlines the current level of disease surveillance integration in 3 countries (Nepal, India, and Nigeria) and proposes that resources continue for long-term maintenance in resource-poor countries of AFP surveillance as a platform for surveillance of vaccine-preventable diseases and other outbreak-prone diseases.

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

Background. Recent detections of circulating serotype 2 vaccine-derived poliovirus in northern Nigeria (Borno and Sokoto states) and Pakistan (Balochistan Province) and serotype 1 wild poliovirus in Pakistan, Afghanistan, and Nigeria (Borno) represent public health emergencies that require aggressive response. Methods. We demonstrate the importance of undervaccinated subpopulations, using an existing dynamic poliovirus transmission and oral poliovirus vaccine evolution model. We review the lessons learned during the polio endgame about the role of subpopulations in sustaining transmission, and we explore the implications of subpopulations for other vaccine-preventable disease eradication efforts. Results. Relatively isolated subpopulations benefit little from high surrounding population immunity to transmission and will sustain transmission as long as they do not attain high vaccination coverage. Failing to reach such subpopulations with high coverage represents the root cause of polio eradication delays. Achieving and maintaining eradication requires addressing the weakest links, which includes immunizing populations in insecure areas and/or with disrupted or poor-performing health systems and managing the risks of individuals with primary immunodeficiencies who can excrete vaccine-derived poliovirus long-term. Conclusions. Eradication efforts for vaccine-preventable diseases need to create performance expectations for countries to immunize all people living within their borders and maintain high coverage with appropriate interventions.Keywords. Polio; eradication; transmission; heterogeneity.

The Polio Eradication and Endgame Strategic plan outlines the phased removal of oral polio vaccines (OPVs), starting with type 2 poliovirus–containing vaccine and introduction of inactivated polio vaccine in routine immunization to mitigate against risk of vaccine-associated paralytic polio and circulating vaccine-derived poliovirus. The objective includes strengthening routine immunization as the primary pillar to sustaining high population immunity. After 2 years without reporting any wild poliovirus (July 2014–2016), the region undertook the synchronized switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) as recommended by the Strategic Advisory Group of Experts on Immunization. Consequently the 47 countries of the World Health Organization (WHO) African Region switched from the use of tOPV to bOPV within the stipulated period of April 2016. Planning started early, routine immunization was strengthened, and technical and financial support was provided for vaccine registration, procurement, destruction, logistics, and management across countries by WHO in collaboration with the United Nations Children’s Fund (UNICEF) and partners. National commitment and ownership, as well as strong coordination and collaboration between UNICEF and WHO and with partners, ensured success of this major, historic public health undertaking.

The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever.

The phased withdrawal of oral polio vaccine (OPV) associated with the Polio Eradication and Endgame Strategic Plan 2013-2018 began with the synchronized global replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV) during April - May 2016, a transition referred to as the “switch.” The World Health Organization’s (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization recommended conducting this synchronized switch in all 155 OPV-using countries and territories (which collectively administered several hundred million doses of tOPV each year via several hundred thousand facilities) to reduce risks of re-emergence of vaccine-derived polioviruses. Safe execution of this switch required implementation of an associated independent monitoring strategy, the primary objective of which was verification that tOPV was no longer available for administration post-switch. This strategy had to be both practical and rigorous such that tOPV withdrawal could be reasonably employed and confirmed in all countries and territories within a discreet timeframe. Following these principles, WHO recommended that designated monitors in each of the 155 countries and territories visit all vaccine stores as well as a 10% sample of highest-risk health facilities within two weeks of the national switch date, removing any tOPV vials found. National governments were required to provide the WHO with formal validation of execution and monitoring of the switch. In practice, all countries reported cessation of tOPV by 12 May 2016 and 95% of countries and territories submitted detailed monitoring data to WHO. According to these data, 272 out of 276 (99%) national stores, 3,741 out of 3.968 (94%) regional stores, 16,144 out of 22,372 (72%) district level stores, and 143,050 out of 595,401 (24%) of health facilities were monitored. These data, along with field reports suggest that monitoring and validation of the switch was efficient and effective, and that the strategies used during the process could be adapted to future stages of OPV withdrawal.

Until recently, waste management for national immunization programs was limited to sharps waste, empty vaccine vials, or vaccines that had expired or were no longer usable. However, because wild-type 2 poliovirus has been eradicated, the World Health Organization’s (WHO’s) Strategic Advisory Group of Experts on Immunization deemed that all countries must simultaneously cease use of the type 2 oral polio vaccine and recommended that all countries and territories using oral polio vaccine (OPV) “switch” from trivalent OPV (tOPV; types 1, 2, and 3 polioviruses) to bivalent OPV (bOPV; types 1 and 3 polioviruses) during a 2-week period in April 2016. Use of tOPV after the switch would risk outbreaks of paralysis related to type 2–circulating vaccine-derived poliovirus (cVDPV2). To minimize risk of vaccine-derived polio countries using OPV were asked to dispose of all usable, unexpired tOPV after the switch to bOPV. In this paper, we review the rationale for tOPV disposal and describe the global guidelines provided to countries for the safe and appropriate disposal of tOPV. These guidelines gave countries flexibility in implementing this important task within the confines of their national regulations, capacities, and resources. Steps for appropriate disposal of tOPV included removal of all tOPV vials from the cold chain, placement in appropriate bags or containers, and disposal using a recommended approach (ie, autoclaving, boiling, chemical inactivation, incineration, or encapsulation) followed by burial or transportation to a designated waste facility. This experience with disposal of tOPV highlights the adaptability of national immunization programs to new procedures, and identifies gaps in waste management policies and strategies with regard to disposal of unused vaccines. The experience also provides a framework for future policies and for developing programmatic guidance for the ultimate disposal of all OPV after the eradication of polio.

The World Health Organization (WHO) Western Pacific Region (WPR) has maintained its polio-free status since 2000. The emergence of vaccine-derived polioviruses (VDPVs), however, remains a risk, as oral polio vaccine (OPV) is still used in many of the region’s countries, and pockets of unimmunized or underimmunized children exist in some countries. From 2014 to 2016, the region participated in the globally coordinated efforts to introduce inactivated polio vaccine (IPV) into all countries that did not yet include it in their national immunization schedules, and to “switch” from trivalent OPV (tOPV) to bivalent OPV (bOPV) in all countries still using OPV in 2016. As of September 2016, 15 of 17 countries and areas that did not use IPV by the end of 2014 had introduced IPV. Introduction in the remaining 2 countries has been delayed because of the global shortage of IPV, making it unavailable to select lower-risk countries until the fourth quarter of 2017. All 16 countries using OPV as of 2016 successfully withdrew tOPV during the globally synchronized switch from April to May 2016, and 15 of 16 countries introduced bOPV at the same time, with the remaining country introducing it within 30 days. While countries were primarily responsible for self-funding these activities, additional support was provided. The main challenges encountered in the Western Pacific Region with both IPV introduction and the tOPV-bOPV switch were related to overcoming regulatory policies and challenges with vaccine procurement. As a result, substantial lead time was needed to resolve procurement and regulatory issues before the introductions of IPV and bOPV. As the global community prepares for the full removal of all OPV from immunization programs, this need for lead time and consideration of the impact on national policies should be considered.

Despite increased efforts and spending toward polio eradication, it has yet to be eliminated worldwide. We aimed to project economic costs of polio eradication compared to permanent control. We used historical Financial Resource Requirements from the Global Polio Eradication Initiative, as well as vaccination and population data from publicly available sources, to project costs for routine immunization, immunization campaigns, surveillance and laboratory resources, technical assistance, social mobilization, treatment, and overhead. We found that cumulative spending for a control strategy would exceed that for an eradication strategy in 2032 (range, 2027–2051). Eradication of polio would likely be cost-saving compared to permanent control.

The secretion of histo-blood group antigens at mucosal surfaces is genetically determined (FUT2) and influences susceptibility to enteric viruses. However, based on a case–control study in India, we did not observe a significant association between FUT2 genotype and oral poliovirus vaccine response., FUT2 determines whether histo-blood group antigens are secreted at mucosal surfaces. Secretor status influences susceptibility to enteric viruses, potentially including oral poliovirus vaccine (OPV). We performed a nested case–control study to determine the association between FUT2 genotype (single-nucleotide polymorphisms G428A, C302T, and A385T) and seroconversion among Indian infants who received a single dose of monovalent type 3 OPV. Secretor prevalence was 75% (89 of 118) in infants who seroconverted and 80% (97 of 122) in infants who did not seroconvert (odds ratio, 0.79; 95% confidence interval, .43–1.45). Our findings suggest that FUT2 genotype is not a key determinant of variation in OPV immunogenicity.

Background Many studies have documented lower vaccine efficacy among children in low-income countries, compared with their counterparts in high-income countries. This disparity is especially apparent with respect to oral vaccines such as rotavirus and oral polio vaccines. One potential contributing factor is the presence of maternal antenatal helminth infections, which can modulate the infant's developing immune system. Methods Using a multiplex immunoassay, we tested plasma immunoglobulin A (IgA) or immunoglobulin G (IgG) levels specific for antigens in 9 routinely administered childhood vaccines among 1639 children aged approximately 13 months enrolled in the ECUAVIDA (Ecuador Life) birth cohort study in Ecuador. We compared vaccine responses in 712 children of mothers who tested positive for helminth infections in the last trimester of pregnancy to responses in 927 children of mothers without helminth infection. Results Plasma IgA levels specific for antigens in rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 and 3 were all significantly higher in children of helminth-infected mothers, compared with children of uninfected mothers. Plasma IgG levels specific for diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b vaccine antigens were comparable between the 2 groups. Conclusions Antenatal maternal helminth infections were not associated with reduced antibody responses to infant vaccines, but rather with modestly increased IgA responses to oral vaccines.

The 41st World Health Assembly in 1988 resolved to launch the Global Polio Eradication Initiative aimed at achieving a polio-free world by the year 2000 [1, 2]. Remarkable progress has been made, with a reduction from 350 000 cases in 125 countries in 1988 to 223 cases in 5 countries by the end of 2012 [3, 4]. In May 2012, the 65th World Health Assembly declared the completion of polio eradication a programmatic emergency for global public health [5–7]. At that time endemic wild poliovirus (WPV) transmission in 3 countries—Nigeria, Pakistan, and Afghanistan—constituted a risk factor for WPV reintroduction to polio-free countries and an obstacle to global polio eradication [8, 9]. Nigeria reported 122 cases of WPV in 2012, of which 28 (23%) were from Kano State in northern Nigeria [3, 10]. Kano State has traditionally been regarded as the epicenter of polio transmission in Nigeria and was the origin of the boycott of polio vaccination campaigns in 2003 [11]. Poliovirus of Nigerian and Kano State origin has been implicated as the source of reinfection to 25 polio-free countries since 2003 [6, 12]. The 2012 Nigeria National Polio Eradication Emergency Plan (NPEEP) included in its priorities the need to significantly reduce the numbers of chronically missed children by strengthening microplanning [13]. The Sixth Independent Monitoring Board of the Global Polio Eradication Initiative report in June 2012 identified poor microplanning as a major impediment to achieving the implementation of quality polio supplemental immunization activities (SIAs) [8]. Microplanning for polio SIAs is a process of estimation of the target populations and resource requirements for conduct of good-quality implementation in a specified location. The guidelines for microplanning for polio SIAs in Nigeria were revised to focus on the target number of households rather than the target number of children per vaccination team in August 2012. The revised guidelines were piloted in 87 very high-risk (VHR) local government areas (LGAs) in the 11 VHR states that were identified based on their risk categorization using the combined US Centers for Disease Control and Prevention–Global Goods Criteria [14]. The 24th Expert Review Committee on Polio Eradication in Nigeria in September 2012 recommended the expansion of implementation to all the LGAs in the 11 VHR states and the intensification of oversight of the 2012 NPEEP [13]. This resulted in the establishment of the National Emergency Operations Center (EOC) by the presidential task force and subsequent establishment of EOCs in 5 states. In August 2013, the Kano State EOC identified inflation of target population estimates with its consequent increase in requests for vaccines and high number of missed settlements as areas of serious concern in the available microplans; and with orientation, guidance and support from the country team organized a revised household-based microplanning exercise including microcensus (a process of estimating the numbers of households and eligible children in a given area by physical count, enumeration, and revalidation) was initiated. This process was aimed at collecting reliable demographic information on the target numbers of households and children in the communities. This article describes the process of implementing revised household-based microplanning intervention in Kano State between September 2013 and April 2014 and highlights the contributions of revised microplanning to improved outcomes of polio SIAs.

Background Identifying polio vaccine regimens that can elicit robust intestinal mucosal immunity and interrupt viral transmission is a key priority of the polio endgame. Methods In a 2013 Chilean clinical trial (NCT01841671) of trivalent inactivated polio vaccine (IPV) and bivalent oral polio vaccine (bOPV; targeting types 1 and 3), infants were randomized to receive IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV at 8, 16, and 24 weeks of age and challenged with monovalent oral polio vaccine type 2 (mOPV2) at 28 weeks. Using fecal samples collected from 152 participants, we investigated the extent to which IPV-bOPV and IPV-only immunization schedules induced intestinal neutralizing activity and immunoglobulin A against polio types 1 and 2. Results Overall, 37% of infants in the IPV-bOPV groups and 26% in the IPV-only arm had detectable type 2–specific stool neutralization after the primary vaccine series. In contrast, 1 challenge dose of mOPV2 induced brisk intestinal immune responses in all vaccine groups, and significant rises in type 2–specific stool neutralization titers (P < .0001) and immunoglobulin A concentrations (P < 0.0001) were measured 2 weeks after the challenge. In subsidiary analyses, duration of breastfeeding also appeared to be associated with the magnitude of polio-specific mucosal immune parameters measured in infant fecal samples. Conclusions Taken together, these results underscore the concept that mucosal and systemic immune responses to polio are separate in their induction, functionality, and potential impacts on transmission and, specifically, provide evidence that primary vaccine regimens lacking homologous live vaccine components are likely to induce only modest, type-specific intestinal immunity.

Background Within Pakistan, estimates of vaccination coverage with the pentavalent vaccine, oral polio vaccine (OPV) and measles vaccine (MV) in 2011 were reported to be 74%, 75% and 53%, respectively. These national estimates may mask regional variation. The reasons for this variation have not been explored. Methods Data from the Multiple Indicator Cluster Surveys (MICS) for Balochistan and Punjab (2010–2011) are analysed to examine factors associated with receiving three or more doses of the pentavalent vaccine and one or more MVs using regression modelling. Pentavalent and OPV estimates from the MICS were compared to vaccine dose histories from surveillance for acute flaccid paralysis (AFP; poliomyelitis) to ascertain agreement. Results Adjusted coverage of children 12–23 months of age were estimated to be 16.0%, 75.5% and 34.2% in Balochistan and 58.0%, 87.7% and 72.6% in Punjab for the pentavalent vaccine, OPV and MV, respectively. Maternal education, healthcare utilization and wealth were associated with receiving the pentavalent vaccine and the MV. There was a strong correlation of district estimates of vaccination coverage between AFP and MICS data, but AFP estimates of pentavalent coverage in Punjab were biased toward higher values. Conclusions National estimates mask variation and estimates from individual surveys should be considered alongside other estimates. The development of strategies targeted towards poorly educated parents within low-wealth quintiles that may not typically access healthcare could improve vaccination rates.

Tremendous progress to a poliomyelitis free world has been made since the World Health Assembly in 1988 inaugurated the Global Polio Eradication Initiative [1], with >99% reduction in confirmed cases of wild poliovirus (WPV) [2]. Since this drive to eradicate poliomyelitis, 3 countries—Nigeria, Afghanistan, and Pakistan—remain endemic reservoirs of WPV [3]. Poliomyelitis is one of the leading causes of acute flaccid paralysis among individuals aged

Background Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule. Methods Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored. Results Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar. Conclusions A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539).

BACKGROUND. Moradabad district in Uttar Pradesh reported the highest number of paralytic polio cases in India during 2001–2007. We conducted a study in Moradabad in 2007 to assess seroprevalence against poliovirus types 1, 2, and 3 in children 6–12 and 36–59 months of age to guide future strategies to interrupt wild poliovirus transmission in high-risk areas. METHODS. Children attending 10 health facilities for minor illnesses who met criteria for study inclusion were eligible for enrollment. We recorded vaccination history, weight, and length and tested sera for neutralizing antibodies to poliovirus types 1, 2, and 3. RESULTS. Poliovirus type 1, 2, and 3 seroprevalences were 88% (95% confidence interval [CI], 84%–91%), 70% (95% CI, 66%–75%), and 75% (95% CI, 71%–79%), respectively, among 467 in the younger age group (n = 467), compared with 100% (95% CI, 99%–100%), 97% (95% CI, 95%–98%), and 93% (91%–95%), respectively, among 447 children in the older age group (P < .001 for all serotypes). CONCLUSIONS. This seroprevalence study provided extremely useful information that was used by the program in India to guide immunization policies, such as optimizing the use of different OPV formulations in vaccination campaigns and strengthening routine immunization services. Similar surveys in populations at risk should be performed at regular intervals in countries where the risk of persistence or spread of indigenous or imported wild poliovirus is high.

In August 2012, the Brazilian Ministry of Health introduced inactivated polio vaccine (IPV) as part of sequential polio vaccination schedule for all infants beginning their primary vaccination series. The revised childhood immunization schedule included 2 doses of IPV at 2 and 4 months of age followed by 2 doses of oral polio vaccine (OPV) at 6 and 15 months of age. One annual national polio immunization day was maintained to provide OPV to all children aged 6 to 59 months. The decision to introduce IPV was based on preventing rare cases of vaccine-associated paralytic polio, financially sustaining IPV introduction, ensuring equitable access to IPV, and preparing for future OPV cessation following global eradication. Introducing IPV during a national multivaccination campaign led to rapid uptake, despite challenges with local vaccine supply due to high wastage rates. Continuous monitoring is required to achieve high coverage with the sequential polio vaccine schedule.

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.

Background After the last case of type 1 wild poliovirus (WPV1) was reported in 2007, Somalia experienced another outbreak of WPV1 (189 cases) in 2013. Methods We conducted a retrospective, matched case-control study to evaluate the vaccine effectiveness (VE) of oral polio vaccine (OPV). We retrieved information from the Somalia Surveillance Database. A case was defined as any case of acute flaccid paralysis (AFP) with virological confirmation of WPV1. We selected two groups of controls for each case: non-polio AFP cases ("NPAFP controls") matched to WPV1 cases by age, date of onset of paralysis and region; and asymptomatic "neighborhood controls," matched by age. Using conditional logistic regression, we estimated the VE of OPV as (1-odds ratio)×100. Result We matched 99 WPV cases with 99 NPAFP controls and 134 WPV1 cases with 268 neighborhood controls. Using NPAFP controls, the overall VE was 70% (95% confidence interval [CI], 37-86), 59% (2-83) among 1-3 dose recipients, 77% (95% CI, 46-91) among ≥4 dose recipients. In neighborhood controls, the overall VE was 95% (95% CI, 84-98), 92% (72-98) among 1-3 dose recipients, and 97% (89-99) among ≥4 dose recipients. When the analysis was limited to cases and controls ≤24 months old, the overall VE in NPAFP and neighborhood controls was 95% (95% CI, 65-99) and 97% (95% CI, 76-100), respectively. Conclusions Among individuals who were fully vaccinated with OPV, vaccination was effective at preventing WPV1 in Somalia.

BACKGROUND Protection against paralytic poliomyelitis is provided mainly by antibody mediated host defense. Despite intensive oral polio vaccine (OPV) immunization campaigns wild poliovirus transmission could not be stopped in Uttar Pradesh (UP) and Bihar states of India by the end of 2010. The objective of our study was to quantitate serum IgG and IgA in children of western UP, India, to determine the prevalence of antibody immunodeficiency. METHODS A cross-sectional survey for IgG and IgA concentrations in serum samples from healthy children and children with acute flaccid paralysis (AFP), up to the age of 5 years, was performed using sandwich ELISA. RESULTS The overall mean IgG concentration for 1882 children of western UP, India, was 10.57 ± 4.53 (SD) g/L and mean IgA concentration for 979 children was 1.2 ± 0.818 g/L. Two 7-month-old female children had IgG levels below 2 g/L and there was an absence of neutralizing polio antibodies. The mean serum IgG level of children with AFP (n=979) was lower than levels observed in healthy children (n=903). The proportion of children with IgG levels below 2 g/L and IgA levels below 0.07 g/L was 0.7% in both healthy children and AFP cases. CONCLUSIONS There was no abnormal prevalence of immunodeficiency in children in western UP which could have delayed achieving the eradication of polio in the state. The immunoglobulin levels reported here may be used as age-specific normal values for Indian children.

BACKGROUND Response to challenge with live, attenuated, oral polio vaccine (OPV) is a measure of immunity induced by prior immunization. METHODS Using stool samples from a study from Oman in which an initial schedule of inactivated polio vaccine (IPV) was followed by an OPV type 1 challenge, we quantitated virus shed, sequenced capsid proteins of recovered virus, and developed assays for neutralization of poliovirus and mucosal immunoglobulin A (IgA) detection. RESULTS Neutralizing activity correlated with detection of polio-specific IgA in stool suspensions collected 7 days after OPV type 1 challenge. Both neutralization and IgA in stool were associated with cessation of virus shedding by day 7. Rapid development of an IgA response with cessation of shedding suggests that IPV primed for the early response to challenge. Correlation of neutralization activity and IgA detection provides evidence that polio-specific IgA intestinal antibody is a determinant of mucosal shedding/transmission and that IgA functions through neutralization of virus. In contrast, neither presence nor quantity of serum or intestinal antibody induced by IPV prior to challenge correlated with cessation of shedding. CONCLUSIONS These assays provide an opportunity to study other immunization schedules to gain a broader understanding of the appearance and duration of a protective mucosal response to polio vaccination.

Background. With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV. Methods. We conducted a prospective study collecting stool and blood samples at multiple time points from Zimbabwean infants receiving OPV according to the national schedule. Nucleic acid extracted from stool was analyzed by real-time polymerase chain reaction for OPV serotypes. Results. We analyzed 825 stool samples: 285 samples from 92 HIV-infected children and 540 from 251 HIV-uninfected children. Poliovirus shedding was similar after 0–2 OPV doses but significantly higher in the HIVinfected versus uninfected children after ≥3 OPV doses, particularly within 42 days of an OPV dose, independent of seroconversion status. HIV infection was not associated with prolonged or persistent poliovirus shedding. HIV infection was associated with significantly lower polio seroconversion rates. Conclusions. HIV infection is associated with decreased mucosal and humoral immune responses to OPV but not the prolonged viral shedding required to form iVDPV.

Historical records of patients with vaccine-associated paralytic poliomyelitis (VAPP) in Hungary during 1961-1981 were reviewed to assess the risk of VAPP after oral polio vaccine (OPV) administration. A confirmed VAPP case was defined as a diagnosis of paralytic poliomyelitis and residual paralysis at 60 days in a patient with an epidemiologic link to the vaccine. Archived poliovirus isolates were retested using polymerase chain reaction and sequencing of the viral protein 1 capsid region. This review confirmed 46 of 47 cases previously reported as VAPP. Three cases originally linked to monovalent OPV (mOPV) 3 and one case linked to mOPV1 presented after administration of bivalent OPV 1 + 3 (bOPV). The adjusted VAPP risk per million doses administered was 0.18 for mOPV1 (2 cases/11.13 million doses), 2.96 for mOPV3 (32 cases/10.81 million doses), and 12.82 for bOPV (5 cases/390,000 doses). Absence of protection from immunization with inactivated poliovirus vaccine or exposure to OPV virus from routine immunization and recent injections could explain the higher relative risk of VAPP in Hungarian children. In polio-endemic areas in which mOPV3 and bOPV are needed to achieve eradication, the higher risk of VAPP would be offset by the high risk of paralysis due to wild poliovirus and higher per-dose efficacy of mOPV3 and bOPV compared with trivalent OPV.

In China, 5 patients with acute flaccid paralysis (AFP) associated with type 2 vaccine-derived poliovirus (VDPV) were identified by an AFP surveillance system from 1996 through 2009. A maximum-likelihood tree shows that all 5 Chinese VDPVs were independent. These 5 VDPVs were 100-216 d old according to the number of synonymous substitutions per synonymous site and 176-292 d old according to the number of substitutions per site. This result indicates limited virus replication since the administration of the initiating oral polio vaccine (OPV) dose, which is consistent with the rapid evolution rate of poliovirus genomes. The above-mentioned VDPVs have important implications in the global polio eradication initiative. Localized, limited, and transient circulation may be typical of OPVs; hence, independent VDPVs could be found because of the large population and excellent surveillance system, which permitted early detection and response, but sustained transmission was limited because of high population immunity.

Background. A phase II, randomized, double-blind, placebo-controlled study was conducted in South Africa during 2003-2004 to evaluate the safety, reactogenicity, and immunogenicity of 2 regimens of the live attenuated oral human rotavirus vaccine RIX4414 when coadministered with the Expanded Program on Immunization childhood vaccines, including oral polio vaccine. Methods. Healthy infants were randomized (2:2:1) to receive either 2 doses of RIX4414 (n = 190; at 10 and 14 weeks, with placebo at 6 weeks), 3 doses of RIX4414 (n = 189; at 6, 10, and 14 weeks), or 3 doses of placebo (n = 96), all with concomitant routine vaccinations. The antirotavirus IgA seroconversion rate was assessed using enzyme-linked immunosorbent assay at 2 months after the last dose of RIX4414 or placebo. Antipolio types 1, 2, and 3 antibodies were measured using a virus neutralization assay. Solicited symptoms were recorded for 15 days after each dose. Results. The antirotavirus IgA seroconversion rates were similar in the RIX4414 2- and 3-dose groups (44.3% and 44.4%, respectively; P = .544, by 1-sided Fisher exact test) and antirotavirus IgA geometric mean concentrations were also comparable. Seroprotection rates for antipolio types 1, 2, and 3 antibodies were high (93%-100%) and were not significantly different among groups. Solicited symptoms reported within 15 days after vaccination were similar in all groups. Conclusions. The immune seroconversion response to the RIX4414 vaccine with 3 doses was not superior to the 2-dose regimen. There was no interference by either regimen with antibody response to oral polio vaccine, and RIX4414 was well tolerated when given with routine vaccinations.

Hungarian children were immunized with monovalent oral poliovaccine (mOPV) delivered at 6-week intervals in the order Sabin 1, Sabin 3, Sabin 2, from 1959 until 1992. During that period, 90 cases of vaccine-associated paralytic poliomyelitis (VAPP) were reported, 52 of which were associated with Sabin 3-related virus (76% of VAPP cases with virologic data). Because of renewed interest in type 3 mOPV (mOPV3), molecular methods were used to reanalyze 18 of the Sabin 3-related isolates from 15 VAPP patients, confirming the original identification. All isolates had the U472C 5'-untranslated region (5'-UTR) substitution associated with reversion to neurovirulence, and from zero to seven nucleotide substitutions in the virus protein 1 (VP1) region. No evidence was found for prolonged mOPV3 replication in the VAPP patients or for spread of Sabin 3-related viruses beyond close vaccinee contacts. The VAPP diseases were prevented by a single dose of inactivated poliovirus vaccine from 1992 to 2006 in Hungary, as proved by continuous surveillance of acute flaccid paralysis.

Two new vaccines against severe rotavirus gastroenteritis that have high efficacy in middle- and high-income countries have recently been licensed in many countries worldwide. Clinical trials in low-income countries in Africa and Asia are ongoing. Experience gained through studies of natural rotavirus infection and the clinical trials for the current and previous rotavirus vaccines indicate that, as countries begin to introduce these newly approved vaccines into routine childhood immunization programs, monitoring their performance in real world settings should be a high priority. Key epidemiological considerations in the postlicensure period include (1) how the vaccine will perform against severe rotavirus disease under routine public health use; (2) how routine vaccination will impact the epidemiology of disease with regard to the burden of severe disease and death, age distribution of cases, seasonality, and serotype distribution; (3) whether vaccination will have a sufficient impact on transmission to reduce disease burden in unvaccinated age groups; and (4) whether vaccine will confer protection through the first 3 years of life, when most severe disease and mortality associated with rotavirus occur. Monitoring of impact with focus on these public health considerations will allow parents, health care providers, and decision makers to appreciate the health benefits of vaccination in reducing the burden of severe rotavirus disease. It will also allow assessment of the effectiveness of rotavirus vaccines in programmatic use and the need for modifying vaccination schedules or vaccine formulations to enhance the performance of immunization. In this article, we review data for the protective efficacy of the 2 new rotavirus vaccines, with emphasis on issues particularly important for consideration as these vaccines are introduced in routine infant immunization programs.