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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.We created a theory of change construct from theWe 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.Synthesized evidence broadly supported the initial theory of change. Addressing evidence gaps on economic benefits and coverage gains may increase future uptake.Évaluer les preuves exposant la manière dont la chaîne de température contrôlée pourrait constituer l'approche idéale pour garantir une couverture vaccinale plus équitable dans les pays à revenu faible et intermédiaire.Nous avons élaboré un concept basé sur la théorie du changement figurant dansNous avons examiné 34 articles décrivant 22 chaînes de température contrôlée ou d'autres expériences similaires dans quatre régions de l'Organisation mondiale de la Santé. Nous avons identifié une forte demande pour cette approche chez les fournisseurs de services; cependant, pour déclencher une demande identique chez les législateurs, il faut plus d'arguments axés sur les retombées économiques et l'amélioration de la couverture vaccinale, ainsi que des définitions de cas d'utilisation. De nombreux éléments probants ont confirmé que l'approche était sûre lorsqu'elle est intégrée dans des programmes de vaccination spéciaux. Assurer un niveau de formation et de supervision acceptable a permis aux fournisseurs de se conformer aux protocoles. Le gain de temps est le principal atout en termes d'efficacité, tandis que les données sur la réduction des coûts sont limitées. Stocker les vaccins au-delà de la chaîne du froid a rendu la couverture vaccinale plus équitable car les populations difficiles à atteindre ont ainsi pu y avoir accès. Rien n'a permis d'indiquer une diminution de l'efficacité des vaccins ou un taux d'effets indésirables plus élevé pour les vaccins fournis dans le cadre de cette approche.La synthèse des preuves a largement corroboré la théorie du changement. Apporter des arguments supplémentaires pour démontrer ses bienfaits en matière d'économie et de couverture vaccinale pourrait favoriser l'adhésion.Evaluar las pruebas que describen cómo el enfoque de la cadena de temperatura controlada para la vacunación podría suponer una mejora de la cobertura de inmunización equitativa en los países de ingresos bajos y medios.Se creó un constructo de teoría del cambio a partir de laSe evaluaron 34 artículos, que describían 22 experiencias específicas de cadena de temperatura controlada o muy relacionadas en cuatro regiones de la Organización Mundial de la Salud. Se identificó una fuerte demanda de este enfoque entre los prestadores de servicios; sin embargo, para generar un nivel igual de demanda entre los responsables de formular políticas se requieren mayores pruebas sobre los beneficios económicos y de la cobertura de vacunación, así como definiciones de casos de uso. Las pruebas consistentes apoyan la seguridad del enfoque cuando se integra en programas especiales de vacunación. La formación y la supervisión factibles ayudaron a los prestadores a cumplir los protocolos. El ahorro de tiempo fue la principal prueba de los beneficios de eficiencia, mientras que los datos de ahorro de costes fueron mínimos. Se informó de una mayor cobertura equitativa cuando el almacenamiento de vacunas más allá de la cadena de frío permitió el acceso a poblaciones de difícil acceso. No hay pruebas que indiquen una menor eficacia de las vacunas ni un aumento de las tasas de efectos adversos de las vacunas suministradas mediante este enfoque.La síntesis de las pruebas apoyaron ampliamente la teoría inicial del cambio. Resolver las deficiencias de las pruebas sobre los beneficios económicos y de cobertura podría aumentar su adopción en el futuro.تقييم الأدلة التي تصف كيف يمكن لأسلوب التطعيم بسلسلة درجات الحرارة الخاضعة للتحكم، أن يؤدي إلى تحسين تغطية التحصين المتكافئة في الدول ذات الدخل المنخفض والدخل المتوسط.لقد وضعنا نظرية لبناء التغيير من سلسلة درجات الحرارة الخاضعة للتحكم: خارطة طريق استراتيجية للقاحات ذات الأولوية 2017 إلى 2020، وتحتوي على أربعة قطاعات: (1) استيعاب الأسلوب والطلب عليه؛ و(2) الامتثال والاستخدام الآمن للأسلوب؛ و(3) مكاسب الكفاءة البرنامجية من هذا الأسلوب؛ و(4) تغطية التحصين المُحسّنة والمتكافئة. للتحقق من نظرية التغيير وتحسينها، قمنا بتطبيق طريقة مراجعة واقعية لتحليل التوصيفات المنشورة لسلسلة درجات الحرارة الخاضعة للتحكم، أو التجارب وثيقة الصلة.قمنا بتقييم 34 مقالاً، تصف 22 سلسلة فريدة لدرجات الحرارة الخاضعة للتحكم، أو تجارب وثيقة الصلة عبر أربع مناطق تابعة لمنظمة الصحة العالمية. لقد حددنا طلبًا قويًا على مثل هذا الأسلوب بين جهات تقديم الخدمات؛ إلا أن توليد مستوى مكافئ من الطلب بين واضعي السياسات يتطلب أدلة أكبر على الفوائد الاقتصادية، ومكاسب تغطية التحصين، وتعريفات حالة الاستخدام. دعمت الأدلة المتسقة سلامة الأسلوب عند دمجها في برامج التحصين الخاصة. ساعد كل من التدريب العملي والإشراف جهات تقديم الخدمات في الامتثال للبروتوكولات. كان التوفير في الوقت هو الدليل الرئيسي على مكاسب الكفاءة، بينما كانت بيانات توفير التكاليف عند حدها الأدنى. تم الإبلاغ عن تغطية مُحسّنة ومتكافئة حينما أتاح تخزين اللقاح خارج سلسلة التبريد، الوصول إلى السكان الذين يصعب الوصول إليهم. لا يوجد دليل يشير إلى فعالية أقل للقاح، ولا زيادة معدلات الأحداث السلبية للقاحات التي يتم تقديمها بموجب هذا الأسلوب.دعمت الأدلة المجمعة بشكل واضح النظرية الأولية للتغيير. إن التعامل مع فجوات الأدلة على الفوائد الاقتصادية ومكاسب التغطية، قد يؤدي إلى زيادة الاستيعاب في المستقبل.旨在评估有关疫苗受控温度链方法如何促使中低收入国家提高公平免疫接种率的证据。.我们根据我们评估了 34 篇文章，了解了世界卫生组织四个地区的 22 种独特的受控温度链或密切相关经验。我们发现服务提供商强烈要求采用这种方法；但是，如要促使同样多的政策制定者认同此类需求，则需要有更多的证据来证明经济效益以及疫苗接种率提高和用例定义。证据一致性表明将该方法纳入特殊疫苗接种计划时能够确保安全性。切实可行的培训和监督支持提供商遵守协议。节省时间是表明效率提高的主要依据，但成本节约相关数据很少。据报道，如果非冷链存储疫苗能够供难以触及的人群使用，则可提高公平接种率。并无任何证据表明采用该方法提供的疫苗效果较差或不良事件发生率升高。.综合证据广泛支持初始变革理论。解决经济效益和接种率升高方面的证据差距可能会导致未来采用率提高。.Оценить фактические данные, описывающие, как подход к вакцинации в рамках системы с регулируемой температурой может привести к обеспечению справедливого охвата иммунизацией в странах с низким и средним уровнем дохода.Авторы создали теорию преобразований на основеАвторы проанализировали 34 статьи, описывающие 22 уникальные системы с регулируемой температурой или подобный опыт в четырех регионах Всемирной организации здравоохранения. Авторы выявили высокий спрос на такой подход среди поставщиков услуг, однако для создания равного уровня спроса со стороны лиц, ответственных за разработку политики, требуется больше фактических данных об экономической пользе и увеличении охвата вакцинацией, а также определении сценариев. Убедительные данные подтверждают безопасность этого подхода при его включении в специальные программы по вакцинации. Поставщикам услуг предоставлялось возможное обучение и контроль при соблюдении протоколов. Данные об экономии времени были основными данными повышения эффективности, в то время как данные об экономии расходов были минимальными. Сообщалось об улучшении справедливого охвата там, где хранение вакцин за пределами холодовой цепи обеспечивало доступ к труднодоступным группам населения. Нет данных, указывающих на более низкую эффективность вакцины или повышенную частоту нежелательных явлений для вакцин, вводимых в рамках данного подхода.Объединенные данные в целом поддерживают первоначальную теорию преобразований. Устранение пробелов в фактических данных об экономической пользе и расширении охвата может увеличить вероятность использования подхода в будущем.

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.

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.

Highlights • A compelling public health need based on evidence is the foundation for product innovation. • Reaching the unreached with product innovations will require substantial investment. • Aligned partnership and sustained resources accelerates innovation development. • Strategies that de-risk investment by developers incentivizes development and uptake. • Overcoming barriers to innovation needs integrated, strategic stakeholder collaboration., 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.

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.

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.

Background: MenAfriVacTM is the first of the World Health Organization (WHO)’s pre-qualified vaccines to be allowed to mass vaccination campaign at a temperature below or equal to 40°C during 4 days. This new vaccination practice has already been used in some African countries. This article described the opinion and use of this new technique by actors on the field, during a mass vaccination campaign in Cote d’Ivoire, in December 2014. Methods: We conducted a crosssectional study on the practice of CTC by actors on the field and their perception on the new practice, during a mass vaccination campaign in 2 of 25 health districts in Cote d’Ivoire, in December 2014. Findings: As results, in Seguela 98.25% of respondents expressed a favourable opinion of CTC, citing advantages such as vaccine carriers requiring no ice packs (29.2%), financial benefit (12.28%) and lighter vaccine carriers (5.26%). In Bouna, respondents gave the same advantages in, respectively, 34%, 2% and 8% of cases. The peak of the total of vials used for immunization sessions reached 376 vials at day one, then dropped to 235 vials at day three and 220 vials at day six. Discussion: Vaccinators found some benefits related to CTC practice, but on the field, they were cautious in using CTC technique.

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.

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.

Highlights • There is a demand from countries for a hepatitis B vaccine product licensed for Controlled Temperature Chain (CTC). • CTC is considered to be a cost efficient approach to improve coverage and equity. • CTC was viewed as potential relief for facilities without continuous cold chain. • Vaccination of babies born at home would be greatly facilitated by the CTC approach. • This study highlights that countries still require comprehensive orientation to CTC., 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.

INTRODUCTION: une campagne de vaccination contre la meningite A avec le vaccin MenAfriVac a ete organisee dans les quatre regions septentrionales du Togo du 28 novembre au 07 decembre 2014. L’approche CTC a ete utilisee pour la premiere fois a une grande echelle pour la campagne de vaccination dans dix districts sanitaires du Togo. L’objectif de cette etude etait d’estimer la couverture vaccinale et, de determiner l’effet de l’utilisation de la Chaine a Temperature Controlee (CTC) sur ces couvertures vaccinales. METHODES: l’enquete s’est deroulee du 9 au 14 mars 2015, soit environ 3 mois apres la fin de la campagne de vaccination dans ces quatre regions. Le sondage en grappe a deux degres stratifies selon les regions a ete utilise. Dans 10 districts, le Togo a fait le choix d’utiliser le vaccin MenAfriVac en CTC. Resultats: au total, 2707 menages ont ete enquetes et 9082 personnes âgees de 1 a 29 ans ont ete interviewees. L’âge moyen des personnes enquetees etait de 11,8±7,7 ans et le sex-ratio (H/F) de 1,01. Le nombre moyen de personnes par menage etait de 5,7 et celui des personnes de 1 a 29 ans ciblees par la campagne etait de 3,4.Sur les 9082 personnes enquetees, 8889 (98%) etaient vaccinees. En analyse multivariee, les facteurs associes a la couverture vaccinale avec le MenAfrivac etaient la residence dans la zone au moment de la campagne (aOR = 4,52 ; 95%IC = [4.07 - 4.97]) et le fait d’etre informe de la campagne avant son demarrage (aOR=2,42 ; 95%IC = [2.05 - 2.80]). Par contre, la couverture vaccinale n’etait pas differente selon la zone ayant utilise l’approche CTC ou non (aOR=0,09 ; 95%IC = [-0,27 – 0,45]). Deux cent sept personnes interrogees (2,3%) ont declare avoir eu une Manifestation Adverse Post Immunisation (MAPI) apres l’administration du vaccin. Il s’agissait surtout de MAPI mineures a type de fievre, d’abces et de gonflement au point d’injection. CONCLUSION: les resultats de cette enquete montrent que l’utilisation de la CTC dans un pays a ressources limitees comme le Togo n’a pas eu un effet negatif sur les couvertures vaccinales. En effet, il n’y avait pas de difference entre la couverture vaccinale dans les zones CTC et celles non CTC. Il importe de capitaliser l’experience acquise pour l’utilisation des vaccins du Programme Elargi de Vaccination avec l’approche CTC surtout dans les pays a ressources limitees confrontes a la disponibilite de la chaine de froid.

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.

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.

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.

To reduce the costs of maintaining a poliovirus immunization base in low-income areas, we assessed the extent of priming immune responses after the administration of inactivated poliovirus vaccine (IPV).We compared the immunogenicity and reactogenicity of a fractional dose of IPV (one fifth of a full dose) administered intradermally with a full dose administered intramuscularly in Cuban infants at the ages of 4 and 8 months. Blood was collected from infants at the ages of 4 months, 8 months, 8 months 7 days, and 8 months 30 days to assess single-dose seroconversion, single-dose priming of immune responses, and two-dose seroconversion. Specimens were tested with a neutralization assay.A total of 320 infants underwent randomization, and 310 infants (96.9%) fulfilled the study requirements. In the group receiving the first fractional dose of IPV, seroconversion to poliovirus types 1, 2, and 3 occurred in 16.6%, 47.1%, and 14.7% of participants, respectively, as compared with 46.6%, 62.8%, and 32.0% in the group receiving the first full dose of IPV (P0.008 for all comparisons). A priming immune response to poliovirus types 1, 2, and 3 occurred in 90.8%, 94.0%, and 89.6% of participants, respectively, in the group receiving the fractional dose as compared with 97.6%, 98.3%, and 98.1% in the group receiving the full dose (P=0.01 for the comparison with type 3). After the administration of the second dose of IPV in the group receiving fractional doses, cumulative two-dose seroconversion to poliovirus types 1, 2, and 3 occurred in 93.6%, 98.1%, and 93.0% of participants, respectively, as compared with 100.0%, 100.0%, and 99.4% in the group receiving the full dose (P0.006 for the comparisons of types 1 and 3). The group receiving intradermal injections had the greatest number of adverse events, most of which were minor in intensity and none of which had serious consequences.This evaluation shows that vaccinating infants with a single fractional dose of IPV can induce priming and seroconversion in more than 90% of immunized infants. (Funded by the World Health Organization and the Pan American Health Organization; Australian New Zealand Clinical Trials Registry number, ACTRN12610001046099.).

Background The Global Polio Eradication Initiative, established in 1988, has made substantial progress toward achieving this target, with only 3 countries never having eliminated wild poliovirus. Persons with primary immune deficiency disorders (PIDD) exposed to OPV are at increased risk of vaccine-associated paralytic poliomyelitis (VAPP) and of prolonged excretion of Sabin polioviruses. However, the risk for prolonged excretion is not known. Therefore, we studied the prevalence of PIDD with long-term poliovirus excretion in Sri Lanka, a middle income country currently using OPV. Methods We stimulated the referral of patients under the age of 35 years, with clinical features suggestive of immune deficiency to the single immunology clinic in the country, where these patients were investigated for the presence of PIDD. Stool samples from patients with PIDD were cultured for the presence of poliovirus (PV). Poliovirus isolates were tested for intratypic differentiation (ITD). The VP1 region of all poliovirus isolates was sequenced. Results Of 942 patients investigated, 51 (5.4%) were diagnosed with PIDD. Five (10.2%) patients excreted poliovirus. A patient with X linked agammaglobulinemia (XLA) excreted a mixture of all three Sabin like (SL) poliovirus serotypes. One patient with severe combined immune deficiency (SCID) excreted SL type 2, and another with SCID excreted SL type 3. One patient with SCID excreted a P2 vaccine-derived poliovirus (VDPV 2), and another with common variable immune deficiency (CVID) excreted a VDPV 3. The 3 patients with SCID died before scheduled collection of subsequent samples one month later, while the patient with XLA had cleared the virus in stool sample collected after 3 and 11 months. The CVID patient with VDPV 3 excreted for 7 months, and has developed a 23 nucleotide divergence in VP1 (∼900 nucleotides) from the parental Sabin virus. Conclusions In our study, several patients with SCID, XLA and CVID excreted poliovirus. With improving health care quality patients with CVID and XLA may survive longer especially with provision of intravenous immune globulin. Regular screening of patients with PIDD for excretion of poliovirus is necessary to identify chronic excretors and make available specific therapies.

Background. The Global Polio Eradication Initiative aims to eradicate wild poliovirus by the end of 2012. Therefore, more-immunogenic polio vaccines, including monovalent oral poliovirus vaccines (mOPVs), are needed for supplemental immunization activities. This trial assessed the immunogenicity of monovalent types 1 and 3, compared with that of trivalent oral poliovirus vaccine (tOPV), in South Africa. Methods. We conducted a blinded, randomized, 4-arm controlled trial comparing the immunogenicity of a single dose of mOPV1 (from 2 manufacturers) and mOPV3 (from 1 manufacturer), given at birth, with the immunogenicity of tOPV. Results. Eight hundred newborns were enrolled; 762 (95%) were included in the analysis. At 30 days after vaccine administration, seroconversion to poliovirus type 1 was 73.4% and 76.4% in the 2 mOPV1 arms, compared with 39.1% in the tOPV arm (P , .0000001), and seroconversion to poliovirus type 3 was 58.0% in the mOPV3 arm, compared with 21.2% in the tOPV arm (P , .0000001). The vaccines were well tolerated, and no adverse events were attributed to trial interventions. Conclusion. A dose of mOPV1 or mOPV3 at birth was superior to that of tOPV in inducing type-specific seroconversion in this sub-Saharan African population. Our results support continued use of mOPVs in supplemental immunization activities in countries where poliovirus types 1 or 3 circulate. Clinical Trials Registration. ISRCTN18107202.