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Introduction: The BetterBack model of care (MoC), a best practice physiotherapy MoC for low back pain (LBP), was implemented in Swedish primary care to improve management of patients with LBP and provide patients with support tools to better self-manage episodes of LBP., Purpose: The objective was to describe how physiotherapists in primary care experienced the implementation of the BetterBack MoC for LBP., Methods: Focus group interviews were conducted with physiotherapists in 2018-2019, 14-18 months after the introduction of the BetterBack MoC. Data were analyzed using qualitative content analysis., Results: Five focus group interviews with 23 (15 female and 8 male) physiotherapists, age range 24-61 years were analyzed. A supportive organization and adaptation to the local culture, combined with health care professionals' attitudes and collaboration between physiotherapists emerged as important factors for a successful implementation and for long-term sustainability of the MoC. Physiotherapists had differing opinions if the implementation led to change in clinical practice. Improved confidence in how to manage patients with LBP was expressed by physiotherapists., Conclusions: Several barriers and facilitators influence the implementation of a best practice physiotherapy MoC for LBP in primary care, which need to be considered in future implementation and sustainability processes.

Vaccines have contributed to substantial improvements in health and social development outcomes for millions in recent decades. However, equitable access to immunization remains a critical challenge that has stalled progress toward improving several health indicators around the world. The COVID-19 pandemic has also negatively impacted routine immunization services around the world further threatening universal access to the benefits of lifesaving vaccines. To overcome these challenges, the Immunization Agenda 2030 (IA2030) focuses on increasing both commitment and demand for vaccines. There are three broad barriers that will need to be addressed in order to achieve national and subnational immunization targets: (1) shifting leadership priorities and resource constraints, (2) visibility of disease burden, and (3) social and behavioral drivers. IA2030 proposes a set of interventions to address these barriers. First, efforts to ensure government engagement on immunization financing, regulatory, and legislative frameworks. Next, those in subnational leadership positions and local community members need to be further engaged to ensure local commitment and demand. Governance structures and health agencies must accept responsibility and be held accountable for delivering inclusive, quality, and accessible services and for achieving national targets. Further, the availability of quality immunization services and commitment to adequate financing and resourcing must go hand-in-hand with public health programs to increase access to and demand for vaccination. Last, strengthening trust in immunization systems and improving individual and program resilience can help mitigate the risk of vaccine confidence crises. These interventions together can help ensure a world where everyone, everywhere has access to and uses vaccines for lifesaving vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

(1) Introduction: The Democratic Republic of the Congo (DRC) has one of the largest cohorts of un- and under-vaccinated children worldwide. This study aimed to identify and compare the main reasons for there being zero-dose (ZD) or under-vaccinated children in the DRC. (2) Methods: This is a secondary analysis derived from a province-level vaccination coverage survey conducted between November 2021 and February 2022; this survey included questions about the reasons for not receiving one or more vaccines. A zero-dose child (ZD) was a person aged 12-23 months not having received any pentavalent vaccine (diphtheria-tetanus-pertussis- Hemophilus influenzae type b (Hib)-Hepatitis B) as per card or caregiver recall and an under-vaccinated child was one who had not received the third dose of the pentavalent vaccine. The proportions of the reasons for non-vaccination were first presented using the WHO-endorsed behavioral and social drivers for vaccination (BeSD) conceptual framework and then compared across the groups of ZD and under-vaccinated children using the Rao-Scott chi-square test; analyses were conducted at province and national level, and accounting for the sample approach. (3) Results: Of the 51,054 children aged 12-23 m in the survey sample, 19,676 ZD and under-vaccinated children were included in the study. For the ZD children, reasons related to people's thinking and feelings were cited as 64.03% and those related to social reasons as 31.13%; both proportions were higher than for under-vaccinated children (44.7% and 26.2%, respectively, p < 0.001). Regarding intentions to vaccinate their children, 82.15% of the parents/guardians of the ZD children said they wanted their children to receive "none" of the recommended vaccines, which was significantly higher than for the under-vaccinated children. In contrast, "practical issues" were cited for 35.60% of the ZD children, compared to 55.60% for the under-vaccinated children ( p < 0.001). The distribution of reasons varied between provinces, e.g., 12 of the 26 provinces had a proportion of reasons for the ZD children relating to practical issues that was higher than the national level. (4) Conclusions: reasons provided for non-vaccination among the ZD children in the DRC were largely related to lack of parental/guardian motivation to have their children vaccinated, while reasons among under-vaccinated children were mostly related to practical issues. These results can help inform decision-makers to direct vaccination interventions.

Background: COVID-19 vaccine coverage and experiences of structural and attitudinal barriers to vaccination vary across populations. Education-related inequality in COVID-19 vaccine coverage and barriers within and between countries can provide insight into the hypothesised role of education as a correlate of vaccine access and acceptability. We aimed to characterise patterns of within-country education-related inequality in COVID-19 vaccine indicators across 90 countries., Methods: This study used data from the University of Maryland Social Data Science Center Global COVID-19 Trends and Impact Survey. Data from 90 countries (more than 14 million participants aged 18 years and older) were included in our analyses. We assessed education-related inequalities globally, across country-income groupings, and nationally for four indicators (self-reported receipt of COVID-19 vaccine, structural barriers to vaccination, vaccine hesitancy, and vaccine refusal) for the study period June 1-Dec 31, 2021. We calculated an absolute summary measure of inequality to assess the latest situation of inequality and time trends and explored the association between government vaccine availability policies and education-related inequality., Findings: Nearly all countries had higher self-reported receipt of a COVID-19 vaccine among the most educated respondents than the least educated respondents. Education-related inequality in structural barriers, vaccine hesitancy, and vaccine refusal varied across countries, and was most pronounced in high-income countries, overall. Low-income and lower-middle-income countries reported widespread experiences of structural barriers and high levels of vaccine hesitancy alongside low levels of education-related inequality. Globally, vaccine hesitancy in unvaccinated people was higher among those with lower education and vaccine refusal was higher among those with higher education, especially in high-income countries. Over the study period, education-related inequalities in self-reported receipt of a COVID-19 vaccine declined, globally and across all country income groupings. Government policies expanding vaccine availability were associated with lower education-related inequality in self-reported receipt of vaccine., Interpretation: This study serves as a baseline for continued inequality monitoring and could help to inform targeted actions for the equitable uptake of vaccines., Funding: Gavi, the Vaccine Alliance., Competing Interests: Declaration of interests We declare no competing interests. The views expressed in this Article are those of the authors and do not necessarily represent the views or policies of WHO., (© 2023 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: The quality of interactions between health workers (HWs) and caregivers is key in vaccine acceptance. To optimize this, HWs need knowledge about best vaccine communication practices in person and on social media. Most pre-service curricula do not include such approaches. COVID-19 necessitated the International Pediatric Association (IPA) to shift from in-person train the trainer workshops to developing an online Vaccine Trust Course to address these gaps., Method: The seven-module, 8-hour Vaccine Trust Course was offered online in seven languages and promoted globally. Course outcomes for participants between September 1, 2020 and September 30, 2021 were assessed using enrollment, participation, and completion data; pre-and post-training surveys of attitudes, knowledge, and practice skills; and follow-up practice surveys 3 months post course completion., Results: Of the 4,926 participants across 137 countries who registered; 2,381 (48.3 %) started the course, with 1,217 (51.1 %) completing. The majority were 25 - 39 years (57 %), female (57 %), and in pediatrics (70 %); 31 % came from India. 62 % of completers rated course structure/design as excellent, 36 % as good. Over 80 % rated the content as the most valuable aspect. Three months post training, 61 % HWs reported increased empathy towards caregivers, confidence while counseling and increased vaccine acceptance amongst their patients. 21 % identified the course as the only factor in these positive changes., Conclusion: Shifting from face-to-face to online training due to the COVID-19 pandemic helped increase the global reach of HWs course engagement and uptake. Trained HWs reported increased empathy towards caregivers and confidence while counseling and increased patient vaccine acceptance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: [Walter A Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Tina D Purnat is staff of the World Health Organization, is alone responsible for the views expressed in this article, and does not represent the views of the organization.]., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The COVID-19 pandemic has disrupted vaccination services and raised the risk of a global resurgence of preventable diseases. We assessed the extent of and reasons for missed or delayed vaccinations (hereafter 'missed') in middle- and high-income countries in the early months of the pandemic., Methods: From May to June 2020, participants completed an online survey on missed vaccination. Analyses separated missed childhood and adult vaccination in middle-and high-income countries., Results: Respondents were 28,429 adults from 26 middle- and high-income countries. Overall, 9% of households had missed a vaccine, and 13% were unsure. More households in middle- than high-income countries reported missed childhood vaccination (7.6% vs. 3.0%) and missed adult vaccination (9.6% vs. 3.4%, both p < .05). Correlates of missed childhood vaccination in middle-income countries included COVID-19 risk factors (respiratory and cardiovascular diseases), younger age, male sex, employment, psychological distress, larger household size, and more children. In high-income countries, correlates of missed childhood vaccination also included immunosuppressive conditions, but did not include sex or household size. Fewer correlates were associated with missed adult vaccination other than COVID-19 risk factors and psychological distress. Common reasons for missed vaccinations were worry about getting COVID-19 at the vaccination clinic (15%) or when leaving the house (11%). Other reasons included no healthcare provider recommendation, clinic closure, and wanting to save services for others., Interpretation: Missed vaccination was common and more prevalent in middle- than high-income countries. Missed vaccination could be mitigated by emphasizing COVID-19 safety measures in vaccination clinics, ensuring free and accessible immunization, and clear healthcare provider recommendations., Competing Interests: Declaration of Competing Interest GKS, NG, JL, and KR report consulting fees from the World Health Organization during the conduct of the study. GKS is supported by a Canadian Institutes of Health Research 2019 Fellowship Award (CIHR MFE 171271) outside the submitted work. NB reports consulting fees for Merck, Novartis, Centers for Disease Control and Prevention, and World Health Organization. All other authors declare no conflict of interest. Pharmaceutical companies or other agencies were not involved in the funding of this article. The funders of this study played no role in the study design, data collection, data analysis, data interpretation, or writing of this manuscript., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The World Health Organization and global partners sought to identify existing measures of confidence in childhood vaccines, as part of a broader effort to measure the range of behavioural and social drivers of vaccination. We identified 14 confidence measures applicable to childhood vaccination in general, all published between 2010 and 2019. The measures examined 1-5 constructs and included a mean of 12 items. Validation studies commonly examined factor structure, internal consistency reliability, and criterion-related validity. Fewer studies examined convergent and discriminant validity, test-retest reliability, or used cognitive interviewing. Most measures were developed and validated only in high-income countries. These findings highlight the need for a childhood vaccine confidence measure validated for use in diverse global contexts., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In 2010, the World Health Assembly (WHA) set the following three milestones for measles control to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district, 2) reduce global annual measles incidence to <5 cases per 1 million population, and 3) reduce global measles mortality by 95% from the 2000 estimate* (1). In 2012, WHA endorsed the Global Vaccine Action Plan, † with the objective of eliminating measles § in five of the six World Health Organization (WHO) regions by 2020. This report describes progress toward WHA milestones and regional measles elimination during 2000-2019 and updates a previous report (2). During 2000-2010, estimated MCV1 coverage increased globally from 72% to 84% but has since plateaued at 84%-85%. All countries conducted measles surveillance; however, approximately half did not achieve the sensitivity indicator target of two or more discarded measles and rubella cases per 100,000 population. Annual reported measles incidence decreased 88%, from 145 to 18 cases per 1 million population during 2000-2016; the lowest incidence occurred in 2016, but by 2019 incidence had risen to 120 cases per 1 million population. During 2000-2019, the annual number of estimated measles deaths decreased 62%, from 539,000 to 207,500; an estimated 25.5 million measles deaths were averted. To drive progress toward the regional measles elimination targets, additional strategies are needed to help countries reach all children with 2 doses of measles-containing vaccine, identify and close immunity gaps, and improve surveillance., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Measles incidence and mortality rates have significantly decreased since vaccine introduction. Despite this progress, however, there has been a global resurgence of measles. To understand the current global epidemiology, we analyzed measles surveillance data., Methods: We analyzed data on measles cases from 2013-2018 reported to the World Health Organization. Univariate analysis was undertaken based on age, vaccination history, onset year, World Health Organization region, and World Bank income status for the country where the case was reported, and a surrogate indicator of the historical strength of the country's immunization program. Annual incidence and a 2013-2018 mean country incidence per million were calculated., Results: From 2013 through 2018, there were 899 800 reported measles cases, of which 57% occurred unvaccinated or undervaccinated persons, with an unknown vaccination history in another 30%. Lower-middle-income countries accounted for 66% of cases, 23% occurred in persons ≥15 years of age. In countries with stronger historical vaccination programs and higher country income, case patients had higher median ages., Conclusions: Although most measles case patients are <15 years of age, an age shift is seen in countries with a higher income or a stronger historical vaccination program. Countries must strengthen immunization programs to achieve high vaccination coverage; some must undertake strategies to reach persons ≥15 years of age and close immunity gaps., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Surveillance of AEFI is fundamental for improving safety and maintaining public support for vaccination. In SEAR, billions of doses of vaccine are given annually. The objective of the 2019 SEAR AEFI training workshop was to further strengthen in-country vaccine safety, assess capacity compared to 2014 and to better integrate communication into the AEFI causality assessment program., Methods: A 3 ½ day workshop with AEFI experts from all 11 SEAR countries. Participants outlined each county's AEFI data, critiqued their AEFI program, reviewed and critiqued causality assessment of 23 anonymized serious AEFI cases and proposed communication plans for each., Results: Between 2016 and 2018, over 2.9 billion doses of vaccine were given in SEAR. Compared to 2014, AEFI detection and causality assessment skills had improved. AEFI experts' communication planning skills markedly improved during the workshop. Good concordance was found between country causality assessment findings and the workshop critiques. A list of targeted recommendations (country, regional and global levels) arose from the workshop., Conclusions: SEAR countries have much improved their AEFI detection and causality assessment expertise since 2014. Given the high volume of doses administered and the AEFI technical expertise, SEAR countries can well monitor safety of regionally produced vaccines. Integration of AEFI communication into AEFI causality assessment can help mitigate potential negative impacts of serious AEFIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019.)

Introduction: WHO recommends influenza vaccination for pregnant women and health providers (HPs), yet global uptake for both is persistently low. Research suggests that HPs greatly influence uptake of influenza vaccine in pregnant women. Our review studies HPs' recommendation of influenza vaccine to pregnant women, determinants and barriers to recommendation, and the role that HPs may play in global influenza vaccine coverage., Methods: We undertook a comprehensive global review of literature relating to HPs' recommendation of seasonal influenza vaccines to pregnant women and the determinants and barriers to recommendation and how this may vary by country and context. We evaluated data from each study including frequency of HP recommendation, vaccine coverage, determinants and barriers to recommendation, and the odds of recommending. We tracked the frequency of determinants and barriers to recommendation in heat maps and organized data by world regions and income classifications., Results: From 32 studies in 15 countries, we identified 68 determinants or barriers to HPs' recommendation. Recommendation rates were highest (77%) in the Americas and lowest in South East Asia (18%). A HP's own influenza vaccine status was a main determinant of recommendation in multiple country contexts and from different provider types. Financial barriers to recommendation were present in higher-income countries and policy-related barriers were highlighted in lower-income countries. HP perceptions of safety, efficacy, and the utility of vaccine were the most frequently cited barriers, relevant in almost every context., Conclusions: HP recommendation is important to influenza vaccine implementation in pregnant women. A HP's own status is an important recommendation determinant in multiple contexts. Vaccine program implementation plans should consider the impact of HPs' knowledge, awareness and vaccine confidence on their own uptake and recommendation practices, as well as on the uptake among pregnant women. Addressing safety and efficacy concerns is relevant in all contexts for HPs and pregnant women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

The Council for the International Organizations of Medical Sciences (CIOMS) and WHO working group on pharmacovigilance defines five cause specific AEFI which includes an immunization anxiety-related reaction. Historically this term has been used to describe a range of symptoms and signs that may arise after immunization that are related to "anxiety" about the immunization. However, the term "anxiety" does not adequately capture all the elements of this cause specific AEFI. In 2015, the Global Advisory Committee for Vaccine Safety convened an expert working group with the purpose of redefining, preventing and managing this particular AEFI. The term "Immunization Stress-Related Response" is proposed to replace the former terminology. We present a manual that redefines this AEFI and present a framework for prevention, diagnosis and management in both an individual and also when such events occur as clusters and affect multiple individuals. Since such mass events can result in cessation of immunization programmes and/or a loss of public confidence, a communication response is essential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: As vaccine-preventable disease outbreaks increase, there is growing international interest in monitoring public attitudes towards vaccination and implementing and evaluating vaccine promotion interventions. Outcome selection and measurement are central to intervention evaluation. Measuring uptake rates alone cannot determine which elements in a multicomponent vaccine-promotion intervention are most effective, why specific populations are undervaccinated or when confidence in vaccines is wavering. To develop targeted and cost-effective interventions and policies, it is necessary to measure vaccination-related psychosocial factors such as knowledge, attitudes and aspects of decision-making. This scoping review aims to identify, compare and summarise the properties and validation of instruments for measuring vaccination-related psychosocial factors and identify gaps where no instruments exist., Methods and Analysis: We will search Medline OVID, Embase OVID, CINAHL and PsycINFO with no date restriction, using a pilot-tested search strategy of terms related to vaccination: knowledge, attitudes, trust, acceptance and decision-making and measurement, psychometric testing or validation. This search will be supplemented with manual search and expert consultation. We will include studies that describe instrument development, adaptation or testing and include evaluation of at least two measurement properties (eg, content, criterion, or construct validity; test-retest reliability; internal consistency; sensitivity; responsiveness). Instruments measuring a vaccination-related psychosocial factor in any population will be included. All studies will be screened by one reviewer, with a sample double-screened to confirm accuracy. Disagreements will be resolved with a third reviewer. Data will be synthesised narratively and through summary tables to chart and compare instrument characteristics such as factors measured, date and/or location of development or validation, measurement properties evaluated and population., Ethics and Dissemination: This scoping review aims to provide an overview of existing instruments and ascertain measurement gaps where no measurement instruments currently exist. The identified instruments will form the basis of an open-access online repository of instruments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The World Health Organization's Tailoring Immunization Programmes approach was used to develop a new strategy to increase child vaccination coverage in a disadvantaged community in New South Wales, Australia, including reminders, outreach and home visiting. After 18 months, the strategy hasn't been fully implemented. A process evaluation was conducted to identify barriers and facilitators for research translation. Participants included child health nurses, Population Health staff, managers and general practitioners. The Capability-Opportunity-Motivation model of behaviour change (COM-B) was used to develop questions. Twenty-four participants took part in three focus groups and four interviews. Five themes emerged: (i) designing and adopting new ways of working is time-consuming and requires new skills, new ways of thinking and changes in service delivery; (ii) genuine engagement and interaction across fields and institutions helps build capacity and strengthen motivation; (iii) implementation of a new strategy requires clarity; who's doing what, when and how?; (iv) it is important not to lose sight of research findings related to the needs of disadvantaged families; and (v) trust in the process and perseverance are fundamental. There was strong motivation and opportunity for change, but a need to enhance service capability. Areas requiring support and resources were identified.

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., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

In 2015, the Global Commission for the Certification of Polio Eradication certified the eradication of type 2 wild poliovirus, 1 of 3 wild poliovirus serotypes causing paralytic polio since the beginning of recorded history. This milestone was one of the key criteria prompting the Global Polio Eradication Initiative to begin withdrawal of oral polio vaccines (OPV), beginning with the type 2 component (OPV2), through a globally synchronized initiative in April and May 2016 that called for all OPV using countries and territories to simultaneously switch from use of trivalent OPV (tOPV; containing types 1, 2, and 3 poliovirus) to bivalent OPV (bOPV; containing types 1 and 3 poliovirus), thus withdrawing OPV2. Before the switch, immunization programs globally had been using approximately 2 billion tOPV doses per year to immunize hundreds of millions of children. Thus, the globally synchronized withdrawal of tOPV was an unprecedented achievement in immunization and was part of a crucial strategy for containment of polioviruses. Successful implementation of the switch called for intense global coordination during 2015-2016 on an unprecedented scale among global public health technical agencies and donors, vaccine manufacturers, regulatory agencies, World Health Organization (WHO) and United Nations Children's Fund (UNICEF) regional offices, and national governments. Priority activities included cessation of tOPV production and shipment, national inventories of tOPV, detailed forecasting of tOPV needs, bOPV licensing, scaling up of bOPV production and procurement, developing national operational switch plans, securing funding, establishing oversight and implementation committees and teams, training logisticians and health workers, fostering advocacy and communications, establishing monitoring and validation structures, and implementing waste management strategies. The WHO received confirmation that, by mid May 2016, all 155 countries and territories that had used OPV in 2015 had successfully withdrawn OPV2 by ceasing use of tOPV in their national immunization programs. This article provides an overview of the global efforts and challenges in successfully implementing this unprecedented global initiative, including (1) coordination and tracking of key global planning milestones, (2) guidance facilitating development of country specific plans, (3) challenges for planning and implementing the switch at the global level, and (4) best practices and lessons learned in meeting aggressive switch timelines. Lessons from this monumental public health achievement by countries and partners will likely be drawn upon when bOPV is withdrawn after polio eradication but also could be relevant for other global health initiatives with similarly complex mandates and accelerated timelines., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, transmission of the three types of wild poliovirus (WPV) has been sharply reduced (1). WPV type 2 (WPV2) has not been detected since 1999 and was declared eradicated in September 2015. Because WPV type 3 has not been detected since November 2012, WPV type 1 (WPV1) is likely the only WPV that remains in circulation (1). This marked progress has been achieved through widespread use of oral poliovirus vaccines (OPVs), most commonly trivalent OPV (tOPV), which contains types 1, 2, and 3 live, attenuated polioviruses and has been a mainstay of efforts to prevent polio since the early 1960s. However, attenuated polioviruses in OPV can undergo genetic changes during replication, and in communities with low vaccination coverage, can result in vaccine-derived polioviruses (VDPVs) that can cause paralytic polio indistinguishable from the disease caused by WPVs (2). Among the 721 polio cases caused by circulating VDPVs (cVDPVs*) detected during January 2006-May 2016, type 2 cVDPVs (cVDPV2s) accounted for >94% (2). Eliminating the risk for polio caused by VDPVs will require stopping all OPV use. The first stage of OPV withdrawal involved a global, synchronized replacement of tOPV with bivalent OPV (bOPV) containing only types 1 and 3 attenuated polioviruses, planned for April 18-May 1, 2016, thereby withdrawing OPV type 2 from all immunization activities (3). Complementing the switch from tOPV to bOPV, introduction of at least 1 dose of injectable, trivalent inactivated poliovirus vaccine (IPV) into childhood immunization schedules reduces risks from and facilitates responses to cVDPV2 outbreaks. All 155 countries and territories that were still using OPV in immunization schedules in 2015 have reported that they had ceased use of tOPV by mid-May 2016.(†) As of August 31, 2016, 173 (89%) of 194 World Health Organization (WHO) countries included IPV in their immunization schedules.(§) The cessation of tOPV use is a major milestone toward the global goal of eradicating polio; however, careful surveillance for polioviruses and prompt, aggressive responses to polio outbreaks are still needed to realize a polio-free world.

Since the launch of the Global Polio Eradication Initiative (GPEI) by the World Health Assembly (WHA) in 1988, the number of polio-endemic countries has decreased from 125 to 2 (Afghanistan and Pakistan). To secure the gains and to address the remaining challenges, the GPEI developed the Polio Eradication and Endgame Strategic Plan, 2013-2018 (the Plan), endorsed by all Member States at the WHA in May 2013. One of the major elements that distinguishes this Plan from previous GPEI strategies is the approach to ending all polioviruses, both wild and vaccine-derived. Overall, the Plan outlines four main objectives: (1) to stop all wild poliovirus (WPV) transmission; (2) to introduce inactivated polio vaccine (IPV), withdraw all oral polio vaccines (OPV), and strengthen immunization systems in countries with weak immunization systems and strong polio infrastructure; (3) to certify all regions as polio-free and safely contain all poliovirus stocks; (4) and to mainstream the investment in polio eradication to benefit other priority public health initiatives for years to come. Implementing the Plan and meeting the milestones in a timely manner will help to ensure that that the world remains permanently polio-free.

Aims: UGT1A1 and UGT2B7 are enzymes that commonly contribute to drug glucuronidation. Since genetic factors have been suggested to contribute to variability in activities and expression levels of these enzymes, a quantitative assessment of the influence of the major genotypes (UGT1A1*28 or UGT2B7*2) on enzyme activities was conducted., Methods: Using a bank of microsomal samples from 59 human livers, the effect of UGT1A1*28 or UGT2B7*2 polymorphisms were investigated on rates of estradiol 3-glucuronidation (a marker of UGT1A1 enzyme activity) or zidovudine glucuronidation (a marker of UGT2B7 enzyme activity) and levels of immunoreactive protein for each enzyme. Glucuronidation rates for both enzymes were measured at K(m)/S(50) and 10 times K(m)/S(50) concentrations., Results: UGT1A1 and UGT2B7 enzyme activities varied up to 16-fold and sixfold, respectively. Rates at K(m)/S(50) concentration closely correlated with rates at 10 times K(m)/S(50) concentration for both enzymes (but not at 1/10th K(m) for UGT2B7). Enzyme activities correlated with relative levels of immunoreactive protein for UGT1A1 and UGT2B7. Furthermore, rates of zidovudine glucuronidation correlated well with rates of glucuronidation of the UGT2B7 substrate gemcabene, but did not correlate with UGT1A1 enzyme activities. For the UGT1A1*28 polymorphism, consistent with levels of UGT1A1 immunoreactive protein, mean UGT1A1 activity was 2.5- and 3.2-fold lower for TA(6)/TA(7) (P < 0.05) and TA(7)/TA(7) (P < 0.001) genotypes in comparison with the TA(6)/TA(6) genotype., Conclusions: Relative to the observed 16-fold variability in UGT1A1 activity, these data indicate only a partial (approximately 40%) contribution of the UGT1A1*28 polymorphism to variability of interindividual differences in UGT1A1 enzyme activity. For the UGT2B7*2 polymorphism, genotype had no influence on immunoreactive UGT2B7 protein or the rate of 3'-azido-3'-deoxythymidine glucuronidation.