Key Learnings from the Development and Early Use of Global Guidance on the Integration of COVID-19 Vaccination into Broader Health Systems.

More than 13.5 billion COVID-19 vaccine doses were delivered between 2021 and 2023 through a mix of delivery platforms, with mass vaccination campaigns being the main approach. In 2022, with the continued circulation of SARS-CoV2 and the need for periodic boosters being most likely, countries were required to plan for more sustainable approaches to provide COVID-19 vaccinations. In this context of uncertainty, a global tool for integrating COVID-19 vaccines into immunization programs and as part of broader health systems was published jointly by the WHO and UNICEF to respond to country needs. This paper summarizes the approach to, and lessons learned during, the development of a global guidance document and describes some examples of its early use in low- and middle-income countries (LMICs). The guidance leveraged existing health system frameworks, proposed four steps for planning and implementing the COVID-19 vaccination integration journey, and identified investment areas. The development process maximized robust global stakeholder and country engagement, and the timeframe was aligned with donor funding windows to support countries with the integration of COVID-19 vaccination. The rapid dissemination of the guidance document allowed countries to ascertain their readiness for integrating COVID-19 vaccination and inform the development of national plans and funding applications. While progress has been made in specific areas (e.g., optimizing cold chain and logistics leveraging COVID-19 vaccination), in the context of decreasing demand for COVID-19 vaccines, reaching adult COVID-19 vaccine high-priority-use groups and engaging and coordinating with other health programs (beyond immunization) remain challenges, particularly in LMICs. We share the learning that despite the uncertainties of a pandemic, guidance documents can be developed and used within a short timeframe. Working in partnership with stakeholders within and beyond immunization towards a common objective is powerful and can allow progress to be made in terms of integrating health services and better preparing for future pandemics.

Within-Country Inequality in COVID-19 Vaccination Coverage: A Scoping Review of Academic Literature.

Since December 2020, COVID-19 vaccines have become increasingly available to populations around the globe. A growing body of research has characterised inequalities in COVID-19 vaccination coverage. This scoping review aims to locate, select and assess research articles that report on within-country inequalities in COVID-19 vaccination coverage, and to provide a preliminary overview of inequality trends for selected dimensions of inequality. We applied a systematic search strategy across electronic databases with no language or date restrictions. Our inclusion criteria specified research articles or reports that analysed inequality in COVID-19 vaccination coverage according to one or more socioeconomic, demographic or geographic dimension of inequality. We developed a data extraction template to compile findings. The scoping review was carried out using the PRISMA-ScR checklist. A total of 167 articles met our inclusion criteria, of which half (n = 83) were conducted in the United States. Articles focused on vaccine initiation, full vaccination and/or receipt of booster. Diverse dimensions of inequality were explored, most frequently relating to age (n = 127 articles), race/ethnicity (n = 117 articles) and sex/gender (n = 103 articles). Preliminary assessments of inequality trends showed higher coverage among older population groups, with mixed findings for sex/gender. Global research efforts should be expanded across settings to understand patterns of inequality and strengthen equity in vaccine policies, planning and implementation.

Progress and barriers towards maternal and neonatal tetanus elimination in the remaining 12 countries: a systematic review.

This systematic review assessed the progress and barriers towards maternal and neonatal tetanus elimination in the 12 countries that are yet to achieve elimination, globally. Coverage of at least 80% (the coverage level required for elimination) was assessed among women of reproductive age for five factors: (1) at least two doses of tetanus toxoid-containing vaccine, (2) protection at birth, (3) skilled birth attendance, (4) antenatal care visits, and (5) health facility delivery. A scoping review of the literature and data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys provided insights into the barriers to attaining maternal and neonatal tetanus elimination. Findings showed that none of the 12 countries attained at least 80% coverage for women of reproductive age receiving at least two doses of tetanus toxoid-containing vaccine or protection at birth according to the data from Demographic and Health Surveys or Multiple Indicator Cluster Surveys. Barriers to maternal and neonatal tetanus elimination were mostly related to health systems and socioeconomic factors. Modification to existing maternal and neonatal tetanus elimination strategies, including innovations, will be required to accelerate maternal and neonatal tetanus elimination in these countries.

The World of Immunization: Achievements, Challenges, and Strategic Vision for the Next Decade.

Immunization is among the most cost-effective public health interventions available and is estimated to have averted at least 37 million deaths between 2000 and 2019. Since the establishment of the Expanded Programme on Immunization in 1974, global vaccination coverage increased and the coverage gap between rich and poor countries decreased. Creation of Gavi, the Vaccine Alliance, in 2000 allowed the poorest countries in the world to benefit from new, life-saving vaccines and expand the breadth of protection against an increasing number of vaccine-preventable diseases. Despite this progress, inequities in access to and uptake of vaccines persist. Opportunities to realize the full potential of vaccines are within reach but require focused, tailored and committed action by Governments and immunization stakeholders. The Immunization Agenda 2030 provides a framework for action during the next decade to attain a world where everyone, everywhere, at every age fully benefits from vaccines for good health and well-being.

The binomial nature of immunization session size distributions and the implications for vaccine wastage.

In this paper we demonstrate that immunization session size distributions are governed by binomial statistics and determined by just two readily available programmatic parameters, the birth cohort of the catchment area and the session frequency. Given this new knowledge, the unavoidable component of an immunization facility's opened vial wastage rate can be determined algebraically for each vial size and discard time. This has significant positive programmatic implications for immunization session planning, vaccine needs forecasting, vaccine wastage monitoring, and vaccine product specification and choice. Further operational research is required to field test the different applications of the model and to inform the development of tools and guidance.

Monitoring and Validation of the Global Replacement of tOPV with bOPV, April-May 2016.

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.

Disposing of Excess Vaccines After the Withdrawal of Oral Polio Vaccine.

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

Implementing the Synchronized Global Switch from Trivalent to Bivalent Oral Polio Vaccines-Lessons Learned From the Global Perspective.

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.

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

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.

Cessation of Trivalent Oral Poliovirus Vaccine and Introduction of Inactivated Poliovirus Vaccine - Worldwide, 2016.

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.

Polio endgame: the global switch from tOPV to bOPV.

Globally, polio cases have reached an all-time low, and type 2 poliovirus (one of three) is eradicated. Oral polio vaccine (OPV) has been the primary tool, however, in rare cases, OPV induces paralysis. In 2013, the World Health Assembly endorsed the phased withdrawal of OPV and introduction of inactivated poliovirus vaccine (IPV) into childhood routine immunization schedules. Type 2 OPV will be withdrawn through a globally synchronized "switch" from trivalent OPV (all three types) to bivalent OPV (types 1 and 3). The switch will happen in 155 OPV-using countries between April 17(th) and May 1(st), 2016. Planned activities to reduce type 2 outbreak risks post-switch include the following: tOPV campaigns to increase type 2 immunity prior to the switch, monovalent OPV2 stockpiling to respond to outbreaks should they occur, containment of both wild and vaccine type 2 viruses, enhanced acute flaccid paralysis (AFP) and environmental surveillance, outbreak response protocols, and ensured access to IPV and bivalent OPV.