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This was a cross-sectional community-based serological survey of polio antibodies assessing the immunogenicity of inactivated poliovirus vaccine (IPV) focusing on poliovirus serotype 2. IPV was administered to 5-month-old children. Type 2 antibody seroprevalence when measured 1 month after IPV administration was >95%. One IPV dose successfully closed the immunity gap.

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.

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 In July 2016, Sri Lanka replaced 1 intramuscular dose of inactivated poliovirus vaccine (IPV) with 2 doses of intradermal fractional-dose IPV (fIPV) in its routine immunization schedule. We carried out a survey of seroprevalence of antipolio antibodies in children who received 2 fIPV doses and compared it with those who received 1 full IPV dose. Methods Children born between March and December 2016 were randomly selected from 3 Sri Lankan districts (Colombo, Badulla, and Anuradhapura). Serum samples were collected and tested for presence of neutralizing antibodies to poliovirus types 1, 2, and 3. Results Seroprevalence of antipolio antibodies was 100% in all districts for poliovirus type 1 and poliovirus type 3; it ranged between 90% and 93% for poliovirus type 2 (PV2) in children who received 1 full IPV dose and between 78% and 100% in those receiving 2 fIPV doses (P = .22). The median reciprocal titers of anti-PV2 antibodies were similar in children who received full-dose IPV and those who received fIPV (1:64 vs 1:45, respectively; P = .11). Conclusions Our study demonstrated not only that Sri Lanka succeeded in maintaining very high primary immunization coverage also but that it is feasible for a national immunization program to implement fIPV immunization and achieve high coverage with intradermal application. The seroprevalence of anti-PV2 antibodies did not decrease after the introduction of fIPV.

Background There is no uniform guideline for postchemotherapy vaccination of children with acute lymphoblastic leukemia (ALL). We evaluated waning immunity to 14 pneumococcal serotypes, pertussis toxin (PT), tetanus toxoid (TT) and varicella, and immunogenicity of postchemotherapy diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) and pneumococcal vaccination among previously vaccinated children treated for ALL. Methods This was a multicenter trial of children with ALL enrolled 4–12 months postchemotherapy completion. Exclusion criteria included: infant ALL, relapsed ALL, and stem cell transplant recipients. Immunocompetent children were recruited as controls. Postchemotherapy participants received DTaP-IPV-Hib and 13-valent pneumococcal conjugate vaccine (PCV13) concurrently, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later. Serology was measured at baseline, 2 and 12 months postvaccination. Adverse events were captured via surveys. Results At enrollment, postchemotherapy participants (n = 74) were less likely than controls (n = 78) to be age-appropriately immunized with DTaP (41% vs 89%, P, In this multicenter trial, previously vaccinated children treated for acute lymphoblastic leukemia had lower antibody levels than controls to Streptococcus pneumoniae, tetanus toxoid, pertussis toxin, and varicella. Booster vaccination was immunogenic and well tolerated, suggesting benefit of systematic revaccination postchemotherapy.

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 Inactivated poliovirus vaccine (IPV) boosts mucosal immunity in persons previously vaccinated with oral poliovirus vaccine (OPV). We assessed whether fractional-dose IPV (fIPV, 1/5th of full dose) administered intradermally also boosts mucosal immunity. Methods Children 10-12 years old were enrolled in Sri Lanka and randomized to receive one dose IPV, fIPV, or no IPV vaccine. One month later, they received OPV challenge. Blood was collected at enrolment and before challenge; stool was collected at 3, 7, and 14 days post-challenge. Sera were analysed for presence of poliovirus neutralizing antibodies; stool was analysed for poliovirus. Results We analysed 304/309 (98%) enrolled subjects. There were 16/97 (16%), 9/99 (9%), and 72/95 (76%) subjects excreting poliovirus after challenge in the IPV, fIPV and "No IPV Vaccine" study arms, respectively (P < .001 for comparison of IPV [or fIPV] vs "No IPV Vaccine"; P = .1 for comparisons of fIPV vs IPV). Relative decrease in excretion prevalence was 80% and 88% to IPV and fIPV, respectively, compared with the "No IPV Vaccine" control arm. Conclusions Single fIPV dose boosted mucosal immunity to a similar degree as single full dose of IPV. This finding provides further evidence in support of fIPV for poliovirus outbreak response at the time of IPV global supply shortage. Clinical trials registration Australia New Zealand Clinical Trial Registry ACTRN12616000124437p.

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.

Background. Kano State, Nigeria, introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in March 2015 and was the pilot site for an RI data module for the National Health Management Information System (NHMIS). We determined factors impacting IPV introduction and the value of the RI module on monitoring new vaccine introduction. Methods. Two assessment approaches were used: (1) analysis of IPV vaccinations reported in NHMIS, and (2) survey of 20 local government areas (LGAs) and 60 associated health facilities (HF). Results. By April 2015, 66% of LGAs had at least 20% of HFs administering IPV, by June all LGAs had HFs administering IPV and by July, 91% of the HFs in Kano reported administering IPV. Among surveyed staff, most rated training and implementation as successful. Among HFs, 97% had updated RI reporting tools, although only 50% had updated microplans. Challenges among HFs included: IPV shortages (20%), hesitancy to administer 2 injectable vaccines (28%), lack of knowledge on multi-dose vial policy (30%) and age of IPV administration (8%). Conclusion. The introduction of IPV was largely successful in Kano and the RI module was effective in monitoring progress, although certain gaps were noted, which should be used to inform plans for future vaccine introductions.

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.

Background. National Immunization Technical Advisory Groups (NITAGs) are established by national authorities to provide them with independent, bias-free, objective, and evidence-based advice on vaccines and immunization challenges. As of December 2015, 125 countries have reported having set up an NITAG. The Health Policy and Institutional Development Center at the Agence de Médecine Préventive, a World Health Organization (WHO) Collaborative Center for evidence-informed immunization, through its Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative project, provides assistance to low- and middle-income countries in the establishment and strengthening of their NITAGs. The Indonesian NITAG (ITAGI) was formed in December 2006 and Uganda’s (UNITAG) was formed in November 2014. Both Uganda and Indonesia have introduced inactivated polio vaccine (IPV) as part of the Global Polio Eradication and Endgame Strategic Plan (the Endgame plan). The authors reflect on the process and the role played by NITAGs in the introduction of IPV in the routine immunization program and the lessons learned. Methods. This commentary is a reflection of the authors’ experience on NITAG’s role as observed in 2 particular local settings and applied to a global public health issue, the polio eradication Endgame plan. The reflection is backed up by the relevant (policy and technical) documents on polio eradication, along with minutes and reports from countries’ ministries of health, immunization programs, WHO, and NITAGs. Results. NITAGs are valuable tools for ministries of health to ensure sustainable, evidence-informed immunization policies that are trusted and accepted by their communities. Early engagement with NITAGs also ensures that the adoption of strategies addressing global public health threats at the country level reinforces the national immunization programs. On the other end, when NITAGs are proactive and forward-thinking, they can contribute to a smooth and effective introduction of the above-mentioned strategies. Time and resources are key factors to ensure optimal performance of NITAGs.

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette–Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities.

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 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.

Background. Albania introduced inactivated polio vaccine (IPV) into its immunization system in May 2014, increasing the maximum recommended number of injectable vaccines given in a single visit from 2 to 3. Methods. Health-care providers and caregivers were interviewed at 42 health facilities in Albania to assess knowledge, attitudes, and practices regarding injectable vaccine administration. Immunization register data were abstracted from December 2014 to July 2015 at the same facilities to explore the number of injectable vaccines children received during their 2- and 4-month visits. Results. The majority of children (87%) identified in the record review at either their 2- or 4-month immunization visit received all 3 injectable vaccines in a single visit. Almost all children who did not receive the vaccines in a single visit were subsequently fully immunized, most within a 2-week period. Over half of caregivers whose children got 3 or more injectable vaccines in a single visit reported being only comfortable with 1 or 2 injectable vaccines in a single visit. Conclusions. Despite most caregivers expressing hesitation regarding children receiving multiple injectable vaccines in a single visit, most children received vaccines according to the recommended schedule. Almost all children eventually received all recommended vaccines.

BACKGROUND. Inactivated poliovirus vaccine (IPV) boosts mucosal immunity in persons previously vaccinated with oral poliovirus vaccine (OPV). We assessed whether fractional-dose IPV (fIPV, 1/5th of full dose) administered intradermally also boosts mucosal immunity. METHODS. Children 10–12 years old were enrolled in Sri Lanka and randomized to receive one dose IPV, fIPV, or no IPV vaccine. One month later, they received OPV challenge. Blood was collected at enrolment and before challenge; stool was collected at 3, 7, and 14 days post-challenge. Sera were analysed for presence of poliovirus neutralizing antibodies; stool was analysed for poliovirus. RESULTS. We analysed 304/309 (98%) enrolled subjects. There were 16/97 (16%), 9/99 (9%), and 72/95 (76%) subjects excreting poliovirus after challenge in the IPV, fIPV and “No IPV Vaccine” study arms, respectively (P < .001 for comparison of IPV [or fIPV] vs “No IPV Vaccine”; P = .1 for comparisons of fIPV vs IPV). Relative decrease in excretion prevalence was 80% and 88% to IPV and fIPV, respectively, compared with the “No IPV Vaccine” control arm. CONCLUSIONS. Single fIPV dose boosted mucosal immunity to a similar degree as single full dose of IPV. This finding provides further evidence in support of fIPV for poliovirus outbreak response at the time of IPV global supply shortage. CLINICAL TRIALS REGISTRATION. Australia New Zealand Clinical Trial Registry ACTRN12616000124437p.

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.

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.

To better understand underlying causes of lower rotavirus vaccine effectiveness in low-middle income countries (LMICs), we measured innate antiviral factors in Nicaraguan mothers' milk and immune response to the first dose of the pentavalent rotavirus vaccine in corresponding infants. No relationship was found between concentrations of innate factors and rotavirus vaccine response.

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).

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost.

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.

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.

BACKGROUND In Turkey, several changes have been made in the vaccination schedule. Vaccines against diphtheria, tetanus, pertussis and poliomyelitis were applied as DTwP and OPV until the end of 2006. Hib vaccine was added to the schedule and was administered as a separate injection in 2007 as DPT + OPV + Hib. DTaP-IPV/Hib combined vaccine replaced them in 2008. The aim of this study was to evaluate the alterations in the frequency of adverse reactions of these different schedules in the consecutive three years. METHODS A total of 2401 infants who were vaccinated in Gazi University Well Child Clinics during the first 3 months of each schedule were enrolled in the study. Local and systemic adverse events were recorded in diaries by the parents for the next three days. RESULTS No significant differences existed between infants vaccinated with DPT + OPV and DPT + OPV + Hib regarding all adverse events detected. Frequency of local and systemic reactions were lower in infants vaccinated with DTaP-IPV/Hib combined vaccine (p < 0.001). Frequency of adverse events in infants vaccinated with DPT + OPV or DPT+ OPV + Hib were highest at booster doses. CONCLUSIONS The original experience of the study is the demonstration of the adverse event profile for three different schedules which allowed us to draw the profile of the adverse events in a country with changing national schedules. Implementation of Schedule 3 reduced the adverse events of vaccination. Thus reduction in the number of injections and reactogenicity of pertussis vaccine contributed to an increase in the compliance to the vaccination program.

To address gaps in traditional postlicensure vaccine safety surveillance and to promote rapid signal identification, new prospective monitoring systems using large health-care database cohorts have been developed. We newly adapted clinical trial group sequential methods to this observational setting in an original safety study of a combination diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) conjugate vaccine (DTaP-IPV-Hib) among children within the Vaccine Safety Datalink population. For each prespecified outcome, we conducted 11 sequential Poisson-based likelihood ratio tests during September 2008-January 2011 to compare DTaP-IPV-Hib vaccinees with historical recipients of other DTaP-containing vaccines. No increased risk was detected among 149,337 DTaP-IPV-Hib vaccinees versus historical comparators for any outcome, including medically attended fever, seizure, meningitis/encephalitis/myelitis, nonanaphylactic serious allergic reaction, anaphylaxis, Guillain-Barré syndrome, or invasive Hib disease. In end-of-study prespecified subgroup analyses, risk of medically attended fever was elevated among 1- to 2-year-olds who received DTaP-IPV-Hib vaccine versus historical comparators (relative risk = 1.83, 95% confidence interval: 1.34, 2.50) but not among infants under 1 year old (relative risk = 0.83, 95% confidence interval: 0.73, 0.94). Findings were similar in analyses with concurrent comparators who received other DTaP-containing vaccines during the study period. Although lack of a controlled experiment presents numerous challenges, implementation of group sequential monitoring methods in observational safety surveillance studies is promising and warrants further investigation.

The population-level safety benefits of the acellular pertussis vaccine may have been underestimated because only specific adverse events were considered, not overall impact on health services utilization. Using the Vaccine and Immunization Surveillance in Ontario (VISION) system, the authors analyzed data on 567,378 children born between April 1994 and March 1996 (before introduction of acellular pertussis vaccine) and between April 1998 and March 2000 (after introduction of acellular pertussis vaccine) in Ontario, Canada. Using the self-controlled case series study design, they examined emergency room visits and hospital admissions occurring after routine pediatric vaccinations. The authors determined the relative incidence of events taking place before introduction of the acellular vaccine versus after introduction by calculating relative incidence ratios (RIRs). The observed RIRs demonstrated a highly statistically significant reduction in relative incidence after introduction of the acellular vaccine. RIRs for vaccine administered at ages 2, 4, 6, and 18 months were 1.82 (95% confidence interval (CI): 1.64, 2.01), 1.91 (95% CI: 1.71, 2.13), 1.54 (95% CI: 1.38, 1.72), and 1.51 (95% CI: 1.34, 1.69), respectively, comparing event rates before the introduction of acellular vaccine with those after introduction. The authors estimated that approximately 90 emergency room visits and 9 admissions per month were avoided by switching to the acellular vaccine, which is a 38-fold higher impact than when they considered only admissions for febrile and afebrile convulsions. Future analyses comparing vaccines for safety should examine specific endpoints and general health services utilization.

Background The teenage booster of tetanus/diphtheria/polio vaccine is the final dose in the routine UK childhood schedule. It has the lowest uptake of all childhood vaccines in Wales and no Health Board (HB) has achieved 95% uptake. We examined the services used to deliver this vaccine across Wales in order to determine how to improve the national uptake rate. Methods A cross-sectional survey of the systems used to deliver the vaccine in the 7 HBs in Wales and their 22 constituent local authorities. Routinely published quarterly and annual COVER report uptake data for each HB were used to compare system effectiveness. Results The vaccine was either offered in school, in general practice or in both settings. Higher uptake rates were achieved with greater consistency in schools (76‐81%) compared with general practice (5‐74%), and when coordinated by the HB. When an option was available, most parents chose for their child to be vaccinated in school. Conclusions Higher uptake rates of the teenage booster were observed when it was given in school compared with general practice. The findings suggest that offering the teenage booster in schools in all areas of Wales may improve vaccine uptake.

Twenty years of global polio eradication efforts may soon eliminate the transmission of wild-type poliovirus. However, new information that has been learned about poliovirus, as well as the political realities of a modern world, demand that universal immunity against poliomyelitis be maintained, even after wild-type poliovirus is eradicated. Although 2 excellent vaccines have proven to be highly effective in the past, neither the live-attenuated vaccine nor the currently used inactivated vaccine are optimal for use in the posteradication era. Therefore, concerted efforts are urgently needed to develop a new generation of vaccine that is risk-free and affordable and can be produced on a global scale. Here, we discuss the desired properties of a vaccine and methods to create a new polio vaccine.

Background: Travelers seeking protection from hepatitis A also often need protection against other infections, prevalent at their destinations. Methods: A total of 396 volunteers received not only a hepatitis A vaccine but also either a vaccine against polio, hepatitis B, diphtheria, tetanus, yellow fever, Japanese encephalitis, typhoid fever or rabies according to their individual needs. We investigated the potential influence of the hepatitis A vaccination on the immune response to the other travelers vaccines that were administered concurrently. Results: With seroprotection rates of 100%for yellow fever, Japanese encephalitis and rabies immunization and tetanus boosters our data demonstrate that the concurrent administration of hepatitis A vaccine does not compromise the immune response of these vaccines. Also for oral typhoid, hepatitis B and diphtheria vaccination we did not detect a negative influence of concurrent hepatitis A vaccine administration as compared with respective vaccinations when given alone. Prior to vaccination, more than one third of our subjects lacked protective antibody levels against diphtheria and only 44%of initially seronegative travelers seroconverted to an anti-diphtheria titer ≥ 0.01 mIU/mL, supporting a need for an additional dose. Furthermore, only two thirds of the vaccinees tested prior to vaccination were protected against polio type 3, and the seroconversion rate following the administration of oral polio vaccine, was lower for viral type 3 (80%), as has been previously demonstrated in settings without concurrent other vaccinations. Conclusion: No negative effect of concurrent travelers vaccinations on the immune response of a hepatitis A vaccine has been detected in a previous report, and, likewise our data suggest no impairment of the antibody response of these travelers vaccines by the concurrent administration of the hepatitis A vaccine.

BACKGROUND: Dutch people born between 1925 and 1945 were ineligible for vaccination with the inactivated poliovirus vaccine (IPV) introduced in 1957 and may have escaped natural infection because of reduced poliovirus circulation. We examined whether people with low or undetectable antibody levels are susceptible to infection and whether memory immunity provides protection against virus excretion. METHODS: A total of 429 elderly participants were challenged with monovalent oral poliovirus vaccine (type 1 or 3) and followed for 8 weeks. Immune responses and virus excretion were compared for 4 groups, defined on the basis of seronegativity for poliovirus type 1 or 3, natural immunity, and IPV-induced immunity. RESULTS: On the basis of the rapidity of the antibody response and the absence of immunoglobulin M, we saw clear evidence of memory immune responses in 33% of the participants without detectable antibodies against poliovirus type 1 and in 5% of the participants without detectable antibodies against poliovirus type 3. Fecal virus-excretion patterns were not significantly different for seronegative participants, regardless of whether they showed evidence of memory immunity. CONCLUSIONS: Rapid antibody responses after challenge with oral polio vaccine provide evidence for poliovirus-specific memory immunity in seronegative elderly people. However, in contrast to preexisting immunity, memory immunity does not protect against virus excretion. These results have important implications for the poliomyelitis-eradication initiative, in particular for future immunization policies after eradication has been achieved.

Antibody responses to poliovirus type 3 were studied in fecal samples of 66 children immunized with 3 doses of enhanced-potency inactivated poliovirus vaccine (E-IPV), followed by 1 dose of monovalent oral poliovirus vaccine (OPV, type 3 Sabin). One fecal sample taken before OPV vaccination and 9 collected thereafter were tested for neutralizing antibodies by a microneutralization assay and for class-specific responses by heavy chain-capture radioimmunoassays. Both neutralizing antibody and IgA responses usually occurred during the second week and coincided with ceasing of virus excretion or a decrease in the excreted virus titer. Half of the vaccinees had received a trypsin-modified E-IPV, but their responses did not differ from those of children immunized with the regular E-IPV. These results are in agreement with the view that an intestinal antibody response, mainly consisting of IgA, may be involved in the ceasing of a primary poliovirus excretion.

Between January and June 1999, 1,100 suspected cases of poliomyelitis were reported in Angola. Poliovirus types 3 and 1 were isolated. Patients' ages ranged from 2 months to 14 years. Of the 588 patients whose vaccine status was known, 58 (9.9%) received >4 doses, 216 (36.7%) received 3 or 4 doses, 178 (30.3%) received 1 or 2 doses, and 136 (23.1%) had no history of vaccination. Civil conflict, economic decline, and crowded areas with scarce sanitation and poor water supply are the most important factors implicated in declining rates of routine vaccination, low population immunity, and intense wild poliovirus transmission. The socioeconomic situation and poor roads have created major difficulties for vaccination and surveillance. The Angolan outbreak has serious implications for the global eradication of poliomyelitis. Surveillance of acute flaccid paralysis remains essential in the assessment of strategies for eradication and interventions to interrupt wild poliovirus transmission.

In view of the planned eradication of poliovirus, the suitability of transgenic mice bearing the human receptor for poliovirus (PVRtg mice) as a nonprimate animal model to study mucosal immunity against poliovirus was investigated. After intraperitoneal (ip) priming followed by ip or oral booster with live poliovirus, PVRtg mice had detectable IgA and IgG responses. The IgA response was restricted to PVRtg mice and could not be induced by oral immunization. After ip priming, PVRtg mice did shed virus in the stool, whereas control mice did not. Moreover, the amount of virus shed in the stools of PVRtg mice that had an IgA response after immunization was significantly lower than that of nonimmunized mice. A virusspecific mucosal IgA response is dependent on expression of the poliovirus receptor and is influenced by the route of immunization and the virus strain. PVRtg mice are a suitable model for the study of poliovirus-specific immunity and protection against poliovirus infection. Poliomyelitis is an acute paralytic disease caused by infection of the central nervous system by poliovirus, a member of the enterovirus genus of the family Picornaviridae. Poliovirus infection is initiated by oral ingestion of the virus, followed by binding to epithelial cells in the tonsils and M cells in the intestine. After local replication, the virus is transmitted into cervical and mesenteric lymph nodes and then into the circulation. When viremia is established, the virus invades the central nervous system, and paralytic poliomyelitis may occur as a result of destruction of motoneurons [1]. A dramatic reduction in the incidence of poliomyelitis was achieved by vaccination with either attenuated live oral poliovirus (OPV) or wild-type inactivated poliovirus (IPV) [2]. Although both vaccines protect persons from illness by induction of circulating neutralizing antibodies, OPV is a more potent inducer of mucosal antibodies than is IPV [3‐6]. Mucosal immunity is becoming increasingly important in the advancing steps of the World Health Organization’s polio eradication cam

SUMMARYEnterovirus-specific cellular immunity was studied in Estonian and in Finnish children at the age of 9 months. The aim was to evaluate the level of responsiveness in two neighbouring countries with different poliovirus immunization practices and striking differences in the incidence of insulin-dependent diabetes mellitus (IDDM), a disease in which early enterovirus infections are an aetiological risk factor. The Estonian children immunized with live attenuated polio vaccine had stronger T cell responses to coxsackievirus B4 and poliovirus type 1 when compared with Finnish children immunized with inactivated polio vaccine (median stimulation indices 10.4 and 6.3 in Estonian children and 1.9 and 2.9 in Finnish children, respectively; P

The modern era of vaccine evaluation began with the landmark field trial of inactivated poliomyelitis vaccine conducted during 1954-1955 under the overall direction of Thomas Francis, Jr. The trial set the standard for the future by establishing the need for double-blind controlled assessment of vaccine efficacy. Other characteristics of the trial, such as definition of clear primary and secondary endpoints as ways to assess specified outcomes, also began the process culminating in currently accepted procedures. However, the trial also had features more similar to the then current laboratory investigations than to modern clinical trials, including evaluation of relative immunogenicity of different lots of vaccine. The fact that the trial was not conducted in a vacuum but, rather, under extreme levels of public scrutiny, also places the trial squarely at the start of the modern era. In particular, the choice of designs is illustrative of the conflict between the scientific requirement for randomization and the need to involve as many voluntary participants as possible in the evaluation of the vaccine under circumstances that were then deemed currently acceptable to them and to society. Obviously, the statistical analysis reflected the time; if the trial were conducted today, it would be analyzed differently and almost certainly would not be so large. The involvement of close to a million voluntary participants makes it unique in size alone. The regulatory climate at the time of the trial was totally different from that under which we currently operate, but the beginning of strict government oversight was an indirect result of the aftermath of the evaluation.

Factors affecting immunogenicity of the first 2 doses of oral poliovirus vaccine (OPV) among unimmunized Mayan infants were prospectively evaluated. The relative impact of multiple variables, including mass or routine vaccination, concurrent enteric bacterial (salmonella, shigella, and campylobacter) and viral (adenovirus 40/41, astrovirus, nonpolio enteroviruses, and rotavirus) infections, interference among Sabin vaccine viruses, and preexisting poliovirus antibodies were studied. Sera were available from 181 infants after 2 OPV doses. Seroresponses were 86% to Sabin type 1, 97% to Sabin type 2, and 61% to Sabin type 3 vaccines. Mass versus routine vaccination and preexisting poliovirus antibodies did not affect immunogenicity. By multiple logistic regression analysis, fecal shedding of homologous Sabin strains was associated with increased seroresponses to all Sabin types, especially to Sabin type 3. Decreased OPV immunogenicity was primarily attributable to interference of Sabin type 3 by Sabin type 2. OPV formulations with higher doses of Sabin type 3 could improve immunogenicity among infants in developing countries.

To determine the feasibility of a vaccination strategy that would reduce the risk of vaccine-associated paralysis while retaining a barrier against the spread of wild poliovirus, a 2-year project was undertaken using enhanced-potency inactivated poliovirus vaccine (IPV) administered at 2 and 3 months of age followed by doses of both IPV and oral poliovirus vaccine (OPV) administered at 4 and 9 months of age. Vaccination coverage by 12 months of age with three or more doses of IPV and two doses of OPV among 16,566 infants eligible for vaccination was > 95% and > 80%, respectively. Among 51 children from whom blood samples were obtained 45 days after their third dose of IPV and first dose of OPV, 100% had serum neutralizing antibodies (reciprocal titer > or = 10) to all three poliovirus types. No cases of paralytic poliomyelitis due to either wild or vaccine-related strains were reported. The project demonstrated the feasibility, safety, and high immunogenicity of sequential use of IPV followed by OPV in Romania.

Timely investigation of children with acute flaccid paralysis, with collection of stool specimens for virus isolation, is the primary strategy used to detect wild poliovirus circulation. To determine the optimal timing of stool specimen collection, studies of wild and vaccine poliovirus excretion published between 1935 and 1995 were reviewed. Data were compiled from comparable studies, scatter plots of the data were created, and third-order regression lines were calculated. The data indicated that wild polioviruses were excreted by a majority of previously unvaccinated infants and young children for 3-4 weeks. The duration of viral shedding was reduced, however, among children who were previously vaccinated with inactivated poliovirus vaccine, who had preexisting antibodies to the infecting serotype, or who had previous intestinal infection with homologous poliovirus. These data suggest that the 14-day period after onset of paralysis is the interval with the highest probability of detecting wild poliovirus excretion in paralyzed children.

The African Region of the World Health Organization includes a diverse membership of 48 countries and territories that has made substantial progress toward controlling poliomyelitis. The coverage with three doses of oral poliovirus vaccine among 1-year-old children reached 58% in 1995, a substantial increase from 49% in 1993, and the incidence of poliomyelitis decreased from 5126 cases in 1980 to 1597 in 1995. To interrupt poliovirus circulation, 29 countries planned to conduct either national immunization days (25 countries) or subnational immunization days (4 countries) during 1996. To ensure the success of these efforts, high-level political commitment has been obtained in many countries, and the campaign to "Kick polio out of Africa" is supported by some of the most respected African politicians. Provided the necessary resources can be obtained from internal and external sources, the African Region may be able to achieve the eradication of poliomyelitis by the year 2000 or shortly thereafter.

To determine if inactivated poliovirus vaccine combined with diphtheria and tetanus toxoids and whole-cell pertussis vaccine interferes with the immunogenicity of pertussis vaccine, we performed a randomized trial of diphtheria and tetanus toxoids and pertussis vaccine combined with inactivated poliovirus vaccine given as a single injection or as two separate injections at the same visit to infants immunized at 2, 4, and 6 months of age. A total of 84 infants were enrolled in the study; 44 received the single injection, and 40 received separate injections. Before immunization, there were no differences in antibody values between the two groups. After two vaccine doses, infants immunized with the single injection had significantly lower values of antibody to filamentous hemagglutinin (8.3 vs. 23.7 ELISA units; P < .001), fimbriae (266.5 vs. 771.8 ELISA units; P < 0.01), and the 69-kD membrane protein (442.2 vs. 1,352 ELISA units; P < .001). After the third dose, these differences persisted, and differences were also detected for antibody to pertussis toxin (10.0 vs. 35.5 ELISA units; P < .001) and a whole-bacteria antigen preparation (2,667 vs. 3,829 ELISA units; P < .05). We conclude that there is a diminished antibody response to the pertussis vaccine when inactivated poliovirus vaccine is combined with the diphtheria and tetanus toxoids and pertussis vaccine.