National Immunization Program Decision Making Using the CAPACITI Decision-Support Tool: User Feedback from Indonesia and Ethiopia.

To ensure that limited domestic resources are invested in the most effective interventions, immunization programs in low- and middle-income countries (LMICs) must prioritize a growing number of new vaccines while considering opportunities to optimize the vaccine portfolio, as well as other components of the health system. There is a strong impetus for immunization decision-making to engage and coordinate various stakeholders across the health system in prioritization. To address this, national immunization program decision-makers in LMICs collaborated with WHO to structure deliberation among stakeholders and document an evidence-based, context-specific, and transparent process for prioritization or selection among multiple vaccination products, services, or strategies. The output of this effort is the Country-led Assessment for Prioritization on Immunization (CAPACITI) decision-support tool, which supports using multiple criteria and stakeholder perspectives to evaluate trade-offs affecting health interventions, taking into account variable data quality. Here, we describe the user feedback from Indonesia and Ethiopia, two initial countries that piloted the CAPACITI decision-support tool, highlighting enabling and constraining factors. Potential immunization program benefits and lessons learned are also summarized for consideration in other settings.

COVID-19 vaccine policy development in a sample of 44 countries - Key findings from a December 2021 survey of National Immunization Technical Advisory Groups (NITAGs).

National Immunization Technical Advisory Committees (NITAGs) are tasked with the responsibility of guiding ministries of health and national immunization programmes in their policy development processes. Many NITAGs rely on evidence reviewed by the World Health Organization's (WHO) Strategic Group of Experts(SAGE) on immunization and aim to adapt WHO's recommendations to their respective contexts. This relationship took on exceptional importance since the onset of the COVID-19 pandemic, during which NITAGs have expressed a notable struggle to craft appropriate policies on population prioritization and vaccine utilization in the face of supply constraints and complex programmatic and delivery logistics. This online survey was conducted to assess the usefulness of the SAGE guidance documents for COVID-19 vaccine policies and to examine the persisting needs and challenges facing NITAGs. Results confirmed that SAGE recommendations concerning COVID-19 vaccines are easy to access, understand, and adapt. They have been found to be comprehensive and timely under the data and time constrained circumstances confronting SAGE. The Global NITAG Network (GNN) appears to be the most popular vehicle for addressing questions among high income countries, in contrast to lower income countries who favour WHO Country or Regional Offices. NITAGs place much value on interaction with other NITAGs, which requires facilitation and could benefit from increased opportunities, especially within regions. It is further noted that some NITAGs have had to tackle issues during the pandemic not typically considered by SAGE, such as supply chain logistics and vaccine demand. Learning from the COVID-19 experience offers opportunities to strengthen NITAGs and the pandemic recovery effort through the development of more concrete procedures and consideration of more varied types of data, including implementation effectiveness and uptake data. There is also an opportunity for an increasing involvement of Country Office WHO personnel to support NITAGs, while ensuring information and evidence needs of countries are adequately reflected in SAGE deliberations.

Controlled temperature chain for vaccination in low- and middle-income countries: a realist evidence synthesis.

Objective: To evaluate the evidence describing how the controlled temperature chain approach for vaccination could lead to improved equitable immunization coverage in low- and middle-income countries. Methods: We created a theory of change construct from the Controlled temperature chain: strategic roadmap for priority vaccines 2017-2020, containing four domains: (i) uptake and demand for the approach; (ii) compliance and safe use of the approach; (iii) programmatic efficiency gains from the approach; and (iv) improved equitable immunization coverage. To verify and improve the theory of change, we applied a realist review method to analyse published descriptions of controlled temperature chain or closely related experiences. Findings: We evaluated 34 articles, describing 22 unique controlled temperature chain or closely related experiences across four World Health Organization regions. We identified a strong demand for this approach among service delivery providers; however, generating an equal level of demand among policy-makers requires greater evidence on economic benefits and on vaccination coverage gains, and use case definitions. Consistent evidence supported safety of the approach when integrated into special vaccination programmes. Feasible training and supervision supported providers in complying with protocols. Time-savings were the main evidence for efficiency gains, while cost-saving data were minimal. Improved equitable coverage was reported where vaccine storage beyond the cold chain enabled access to hard-to-reach populations. No evidence indicated an inferior vaccine effectiveness nor increased adverse event rates for vaccines delivered under the approach. Conclusion: Synthesized evidence broadly supported the initial theory of change. Addressing evidence gaps on economic benefits and coverage gains may increase future uptake.

Strategies for vaccine-product innovation: Creating an enabling environment for product development to uptake in low- and middle-income countries.

Vaccine-product innovations that address barriers to immunization are urgently needed to achieve equitable vaccine coverage, as articulated in the new Immunization Agenda 2030 and the Gavi 5.0 strategy. In 2020, the Vaccine Innovation Prioritisation Strategy (VIPS) prioritized three innovations, namely microarray patches (MAPs), heat-stable and controlled-temperature chain (CTC) enabled liquid vaccine formulations and barcodes on primary packaging. These innovations were prioritized based on the priority immunization barriers that they may help overcome in resource constrained contexts, as well as by considering their potential impact on health, coverage and equity, safety, economic costs and their technical readiness and commercial feasibility. VIPS is now working to accelerate the development and lay the foundation for future uptake of the three priority vaccine-product innovations, with the long term-goal to ensure equitable vaccine coverage and increased impact of vaccines in low- and middle- income countries. To inform our strategic planning, we analyzed four commercially available vaccine product-innovations and conducted interviews with individuals from 17 immunization organizations, and/or independent immunization experts. The findings are synthesized into an 'innovation conundrum' that describes the challenges encountered in developing vaccine-product innovations and a vaccine-product innovation 'theory of change', which highlights actions that should be undertaken in parallel to product development to incentivize sustainable investment and prepare the pathway for uptake and impact.

Vaccine innovation prioritisation strategy: Findings from three country-stakeholder consultations on vaccine product innovations.

As part of the Vaccine Innovation Prioritisation Strategy (VIPS), three immunization-stakeholder consultations were conducted between September 2018 and February 2020 to ensure that countries' needs drove the prioritization of vaccine product innovations. All consultations targeted respondents with immunization program experience. They included: (1) an online survey to identify immunization implementation barriers and desired vaccine attributes in three use settings, (2) an online survey to identify and evaluate the most important immunization challenges for ten exemplar vaccines, and (3) in-depth interviews to better understand the perceived programmatic benefits and challenges that could be addressed by nine innovations and to rank the innovations that could best address current challenges. The first consultation included responses from 442 participants in 61 countries, representing 89% of the 496 respondents who correctly completed at least one section of the online survey. For facility-based settings, missed opportunities for vaccination due to reluctance to open multidose vaccine vials was the barrier most frequently selected by respondents. In community-based (outreach) and campaign settings, limited access to immunization services due to geographic barriers was most frequently selected. Multidose presentations with preservative or single-dose presentations were most frequently selected as desired vaccine attributes for facility-based settings while improved thermostability was most frequently selected for outreach and campaign settings. The second online survey was completed by 220 respondents in 54 countries. For the exemplar vaccines, vaccine ineffectiveness or wastage due to heat or freeze exposure and missed opportunities due to multidose vial presentations were identified as the greatest vaccine-specific challenges. In-depth interviews with 84 respondents in six countries ranked microarray patches, dual-chamber delivery devices, and heat-stable/controlled temperature chain qualified liquid vaccines as the three innovations that could have the greatest impact in helping address current immunization program challenges. These findings informed the VIPS prioritization and provided broader application to designing immunization interventions to better meet country needs.

The CAPACITI Decision-Support Tool for National Immunization Programs.

OBJECTIVES: Immunization programs in low-income and middle-income countries (LMICs) are faced with an ever-growing number of vaccines of public health importance recommended by the World Health Organization, while also financing a greater proportion of the program through domestic resources. More than ever, national immunization programs must be equipped to contextualize global guidance and make choices that are best suited to their setting. The CAPACITI decision-support tool has been developed in collaboration with national immunization program decision makers in LMICs to structure and document an evidence-based, context-specific process for prioritizing or selecting among multiple vaccination products, services, or strategies. METHODS: The CAPACITI decision-support tool is based on multi-criteria decision analysis, as a structured way to incorporate multiple sources of evidence and stakeholder perspectives. The tool has been developed iteratively in consultation with 12 countries across Africa, Asia, and the Americas. RESULTS: The tool is flexible to existing country processes and can follow any type of multi-criteria decision analysis or a hybrid approach. It is structured into 5 sections: decision question, criteria for decision making, evidence assessment, appraisal, and recommendation. The Excel-based tool guides the user through the steps and document discussions in a transparent manner, with an emphasis on stakeholder engagement and country ownership. CONCLUSIONS: Pilot countries valued the CAPACITI decision-support tool as a means to consider multiple criteria and stakeholder perspectives and to evaluate trade-offs and the impact of data quality. With use, it is expected that LMICs will tailor steps to their context and streamline the tool for decision making.

How can we evaluate the potential of innovative vaccine products and technologies in resource constrained settings? A total systems effectiveness (TSE) approach to decision-making.

Innovations in vaccine product attributes could play an important role in addressing coverage and equity (C&E) gaps, but there is currently a poor understanding of the full system impact and trade-offs associated with investing in such technologies, both from the perspective of national immunisation programmes (NIPs) and vaccine developers. Total Systems Effectiveness (TSE) was developed as an approach to evaluate vaccines with different product attributes from a systems perspective, in order to analyse and compare the value of innovative vaccine products in different settings. The TSE approach has been advanced over the years by various stakeholders including the Bill and Melinda Gates Foundation (BMGF), Gavi, PATH, UNICEF and WHO. WHO further developed the TSE approach to incorporate the country perspective into immunisation decision-making, in order for countries to evaluate innovative products for introduction and product switch decisions, and for vaccine development stakeholders to conduct their assessments of product value in line with country preferences. This paper describes the original TSE approach, development of the tool and processes for NIPs to apply the WHO TSE approach, and results from piloting in 12 countries across Africa, Asia and the Americas. The WHO TSE framework emerged from this piloting effort. The WHO TSE approach has been welcomed by NIP and vaccine development stakeholders as a useful tool to evaluate trade-offs between different products. It was emphasised that the concept of "total systems effectiveness" is likely to be context-specific and that TSE is valuable in facilitating a deliberative process to articulate NIP priorities, for decisions around product choice, and for prioritising the development of future vaccine innovations.

Countries' interest in a hepatitis B vaccine licensed for the controlled temperature chain; survey results from African and Western Pacific regions.

Chronic hepatitis B infection can be prevented by hepatitis B vaccine birth dose (hepB-BD) given within 24 h after birth, followed by two hepatitis B vaccinations within the first year of life. Yet nearly half of World Health Organization (WHO) Member States do not provide a hepB-BD. Barriers are primarily attributed to vaccine storage and transportation, as well as high rates of home births. Delivering the vaccine outside the cold chain could potentially increase coverage. To do this, WHO recommends vaccines be licensed for use in a "controlled temperature chain" (CTC), which requires a given product to tolerate temperature excursions up to at least 40 °C for a minimum of three days. To date, no hepB vaccine is labelled for CTC. To inform dialogue with manufacturers, WHO conducted a survey among countries in the African and Western Pacific Regions (AFR and WPR) to assess demand for a hepatitis B product licensed for use in a CTC. Twenty-five (44%) countries responded, with 8 of 11 (73%) from the WPR and 17 of 46 (37%) from the AFR. Of these responding countries, 5 in AFR and all 8 in WPR have introduced universal hepB-BD. Seventy-two percent indicated that CTC would facilitate the provision of hepB-BD. While no overall difference in responses was detected between countries either providing or not providing hepB-BD, countries that already introduced hepB-BD but had low hepB-BD coverage were particularly interested in CTC. Irrespective of hepB-BD policy, responding countries suggested that a CTC-licenced product would be beneficial, though the price of such a vaccine would influence procurement decisions. This survey was beneficial to inform the CTC agenda. However, countries' lack of experience with HepB-BD as well as with CTC and the fact that countries were commenting on a product that is not yet on the market should be acknowledged.

[Impact of Controlled Temperature Chain (CTC) approach on immunization coverage achieved during the preventive vaccination campaign against meningitis A using MenAfriVac in Togo in 2014]. / L'utilisation de l'approche CTC: quel impact sur la couverture vaccinale lors de la campagne préventive de vaccination contre la méningite A avec le MenAfriVac au Togo en 2014?

METHOD: We conducted a survey from 9 to 14 March 2015 (for approximately 3 months) after the end of the vaccination campaign in these four regions. Interviewees were selected using two stages cluster sampling stratified according to the regions. MenAfriVac vaccine in Controlled Temperature Chain (CTC) was used in 10 districts, in Togo. RESULTS: A total of 2707 households were surveyed and 9082 people aged 1-29 years were interviewed. The average age of the individuals surveyed was 11.8±7.7 years and sex-ratio (H/F) was 1.01. The average number of individuals per household was 5.7 and that of persons aged 1-29 years targeted in the campaign was 3.4. Out of 9082 people surveyed 8889 (98%) were vaccinated. Multivariate analysis showed that the factors associated with immunization coverage using MenAfrivac vaccine were: habitual residence in the area at the time of the campaign (AOR = 4.52; 95%CI = [4.07 - 4.97]) and level of information about the campaign before it starts (AOR=2.42; 95%CI = [2.05 - 2.80]). By contrast, there were no differences in vaccination coverage between the areas based on whether the CTC approach was used or not (AOR=0.09; 95%CI = [-0.27 - 0.45]). Two hundred and seven respondents (2.3%) reported that they had Adverse Event Following Immunisation (AEFI) after the administration of the vaccine. These were usually minor AEFI involving fever, abscesses and swelling at the injection site. CONCLUSION: Survey results show that the use of CTC in a country with limited resources such as Togo doesn't have a negative impact on immunization coverage. Indeed, there was no difference between immunization coverage in CTC and non-CTC areas. It is important to capitalize on the experience gained in order to use vaccines by Expanded Program of Immunization in CTC approach especially in countries with limited resources in terms of cold chain availability.

Challenges of vaccine presentation and delivery: How can we design vaccines to have optimal programmatic impact?

Immunization program delivery strategies that enable high vaccine coverage, particularly in inaccessible and remote areas, are critical to achieving optimal vaccine impact. In addition to demonstration of safety and efficacy, there are many factors that influence whether a newly licensed vaccine will be introduced into a country's national immunization program, particularly in resource-constrained environments. This paper describes three case studies of novel approaches that represent the potential for improved programmatic impact by increasing vaccine accessibility in different ways. However, the pathway to regulatory approval, policy recommendation, and program introduction in low- and middle-income countries is complex, requiring engagement with multiple, diverse stakeholders. Consideration of aspects that affect uptake in low- and middle-income countries, during the product development stage, will help better position new or second-generation vaccine products for successful implementation to achieve public health impact.

An economic evaluation of the controlled temperature chain approach for vaccine logistics: evidence from a study conducted during a meningitis A vaccine campaign in Togo.

INTRODUCTION: A recent innovation in support of the final segment of the immunization supply chain is licensing certain vaccines for use in a controlled temperature chain (CTC), which allows excursions into ambient temperatures up to 40°C for a specific number of days immediately prior to administration. However, limited evidence exists on CTC economics to inform investments for labeling other eligible vaccines for CTC use. Using data collected during a MenAfriVac™ campaign in Togo, we estimated economic costs for vaccine logistics when using the CTC approach compared to full cold chain logistics (CCL) approach. METHODS: We conducted the study in Togo's Central Region, where two districts were using the CTC approach and two relied on a fullCCL approach during the MenAfriVac™ campaign. Data to estimate vaccine logistics costs were obtained from primary data collected using costing questionnaires and from financial cost data from campaign microplans. Costs are presented in 2014 US dollars. RESULTS: Average logistics costs per dose were estimated at $0.026±0.032 for facilities using a CTC and $0.029±0.054 for facilities using the fullCCL approach, but the two estimates were not statistically different. However, if the facilities without refrigerators had not used a CTC but had received daily deliveries of vaccines, the average cost per dose would have increased to $0.063 (range $0.007 to $0.33), with larger logistics cost increases occurring for facilities that were far from the district. CONCLUSION: Using the CTC approach can reduce logistics costs for remote facilities without cold chain infrastructure, which is where CTC is designed to reduce logistical challenges of vaccine distribution.

Predictors of incomplete immunization coverage among one to five years old children in Togo.

BACKGROUND: Incompleteness of vaccination coverage among children is a major public health concern because itcontinues to sustain a high prevalence of vaccine-preventable diseases in some countries. In Togo, very few data on the factors associated with incomplete vaccination coverage among children have been published. We determined the prevalence of incomplete immunization coverage in children aged one to five years in Togo and associated factors. METHODS: This was a cross-sectional study using secondary data from the 2010 Multiple Indicator Cluster Surveys (MICS4) conducted in 2010 among children aged 1 to 5 years in Togo. This survey was conducted over a period of two months from September to November, 2010. RESULTS: During Togo'sMICS4 survey, 2067 children met the inclusion criteria for our study. Female children accounted for 50.9 % (1051/2067) of the sample and 1372 (66.4 %) lived in rural areas. The majority of children (92.2 %; 1905/2067) lived with both parents and 30 % of the head of households interviewed were not schooled (620/2067). At the time of the survey, 36.2 % (750/2067) of the children had not received all vaccines recommended by Expanded Program on Immunization (EPI). In multivariate analysis, factors associated with incompleteness of immunization at 1 year were: health region of residences (Maritime aOR = 0.650; p = 0.043; Savanes: aOR = 0.324; p <0.001), non-schooled mother (aOR = 1.725; p = 0.002),standard of living (poor: aOR = 1.668; p = 0.013; medium: aOR = 1.393; p = 0.090) and the following characteristics of the household heads: sex (aOR = 1.465; p = 0.034), marital status (aOR = 1.591; p = 0.032), education level(non-educated: aOR = 1.435; p = 0.027. CONCLUSION: The incomplete immunization coverage among children in Togo remains high. It is necessary to strengthen health promotion among the population in order to improve the use of immunization services that are essential to reduce morbidity and mortality among under five years old children.

Polio vaccine hesitancy in the networks and neighborhoods of Malegaon, India.

OBJECTIVES: Eradication and control of childhood diseases through immunization can only work if parents allow their children to be vaccinated. To learn about social network factors associated with polio vaccine hesitancy, we investigated social and spatial clustering of households by their vaccine acceptance status in Malegaon, India, an area known for vaccine refusal and repeated detection of polio cases. METHODS: We interviewed family heads from 2462 households in 25 neighborhoods in July 2012 and constructed social networks based on advice seeking from other households. We restricted our main analyses to surveyed households for which we also had data on whether they accepted the polio vaccine for their eligible children or not. RESULTS: Data from 2452 households was retained and these households made 2012 nominations to 830 households. Vaccine-refusing households had fewer outgoing ties than vaccine-accepting households. After excluding 24 isolated households, vaccine-refusing households had 189% more nominations to other vaccine-refusing households (93% more in the largest component of the network) compared to vaccine-accepting households, revealing that vaccine-refusing households cluster in the social network. Since roughly half of all ties connect households within neighborhoods, vaccine-refusing clusters lie in spatially localized "pockets". CONCLUSIONS: The social (and spatial) clustering of vaccine-refusing households could be leveraged to tailor communication strategies to improve vaccine acceptance and community perceptions of immunization programs for polio and other vaccine-preventable diseases.

Switch from oral to inactivated poliovirus vaccine in Yogyakarta Province, Indonesia: summary of coverage, immunity, and environmental surveillance.

BACKGROUND: Inactivated poliovirus vaccine (IPV) is rarely used in tropical developing countries. To generate additional scientific information, especially on the possible emergence of vaccine-derived polioviruses (VDPVs) in an IPV-only environment, we initiated an IPV introduction project in Yogyakarta, an Indonesian province. In this report, we present the coverage, immunity, and VDPV surveillance results. METHODS: In Yogyakarta, we established environmental surveillance starting in 2004; and conducted routine immunization coverage and seroprevalence surveys before and after a September 2007 switch from oral poliovirus vaccine (OPV) to IPV, using standard coverage and serosurvey methods. Rates and types of polioviruses found in sewage samples were analyzed, and all poliovirus isolates after the switch were sequenced. RESULTS: Vaccination coverage (>95%) and immunity (approximately 100%) did not change substantially before and after the IPV switch. No VDPVs were detected. Before the switch, 58% of environmental samples contained Sabin poliovirus; starting 6 weeks after the switch, Sabin polioviruses were rarely isolated, and if they were, genetic sequencing suggested recent introductions. CONCLUSIONS: This project demonstrated that under almost ideal conditions (good hygiene, maintenance of universally high IPV coverage, and corresponding high immunity against polioviruses), no emergence and circulation of VDPV could be detected in a tropical developing country setting.

Poliovirus excretion among persons with primary immune deficiency disorders: summary of a seven-country study series.

BACKGROUND: Persons with primary immune deficiency disorders (PID), especially those disorders affecting the B-cell system, are at substantially increased risk of paralytic poliomyelitis and can excrete poliovirus chronically. However, the risk of prolonged or chronic excretion is not well characterized in developing countries. We present a summary of a country study series on poliovirus excretion among PID cases. METHODS: Cases with PID from participating institutions were enrolled during the first year and after obtaining informed consent were tested for polioviruses in stool samples. Those cases excreting poliovirus were followed on a monthly basis during the second year until 2 negative stool samples were obtained. RESULTS: A total of 562 cases were enrolled in Bangladesh, China, Iran, Philippines, Russia, Sri Lanka, and Tunisia during 2008-2013. Of these, 17 (3%) shed poliovirus, including 2 cases with immunodeficient vaccine-derived poliovirus. Poliovirus was detected in a single sample from 5/17 (29%) cases. One case excreted for more than 6 months. None of the cases developed paralysis during the study period. CONCLUSIONS: Chronic polioviruses excretion remains a rare event even among individuals with PID. Nevertheless, because these individuals were not paralyzed they would have been missed by current surveillance; therefore, surveillance for polioviruses among PID should be established.

Screening for long-term poliovirus excretion among children with primary immunodeficiency disorders: preparation for the polio posteradication era in Bangladesh.

BACKGROUND: Persons with primary immune deficiency disorders (PIDD) who receive oral poliovirus vaccine (OPV) may transmit immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) and cause paralytic polio. The objective of this study was to identify children with PIDD in Bangladesh, and estimate the proportion with chronic poliovirus excretion. METHODS: Patients admitted at 5 teaching hospitals were screened for PIDD according to standardized clinical case definitions. PIDD was confirmed by age-specific quantitative immunoglobulin levels. Stool specimens were collected from patients with confirmed PIDD. RESULTS: From February 2011 through January 2013, approximately 96 000 children were screened, and 53 patients were identified who met the clinical case definition for PIDD. Thirteen patients (24%) had age-specific quantitative immunoglobulins results that confirmed PIDD. Of these, 9 (69%) received OPV 3-106 months before stool specimen collection. Among 11 patients, stool specimens from 1 patient tested positive for polioviruses 34 months after OPV ingestion. However, the poliovirus isolate was not available for genetic sequencing, and a subsequent stool specimen 45 days later was negative. CONCLUSIONS: The risk of chronic poliovirus excretion among children with PIDD in Bangladesh seems to be low. The national polio eradication program should incorporate strategies for screening for poliovirus excretion among patients with PIDD.