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Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus used in the manufacturing process), perceived lack of ability to induce intestinal mucosal immunity, high cost and increased complexity to administer compared to oral polio vaccine (OPV), have limited its use in the global efforts to eradicate poliomyelitis. In order to harvest the full potential of IPV, a program of work has been carried out by the Global Polio Eradication Initiative (GPEI) over the past two decades that has focused on: (1) increasing the scientific knowledge base of IPV; (2) translating new insights and evidence into programmatic action; (3) expanding the IPV manufacturing infrastructure for global demand; and (4) continuing to pursue an ambitious research program to develop more immunogenic and safer-to-produce vaccines. While the knowledge base of IPV continues to expand, further research and product development are necessary to ensure that the program priorities are met (e.g., non-infectious production through virus-like particles, non-transmissible vaccine inducing humoral and intestinal mucosal immunity and new methods for house-to-house administration through micro-needle patches and jet injectors), the discussions have largely moved from whether to how to use this vaccine most effectively. In this review, we summarize recent developments on expanding the science base of IPV and provide insight into policy development and the expansion of IPV manufacturing and production, and finally we provide an update on the current priorities.
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The emergence of vaccine-derived polioviruses (VDPVs) in patients with Primary Immunodeficiency (PID) is a threat to the polio-eradication program. In a first of its kind pilot study for successful screening and identification of VDPV excretion among patients with PID in India, enteroviruses were assessed in stool specimens of 154 PID patients across India in a period of two years. A total of 21.42% of patients were tested positive for enteroviruses, 2.59% tested positive for polioviruses (PV), whereas 18.83% of patients were positive for non-polio enteroviruses (NPEV). A male child of 3 years and 6 months of age diagnosed with Hyper IgM syndrome was detected positive for type1 VDPV (iVDPV1) with 1.6% nucleotide divergence from the parent Sabin strain. E21 (19.4%), E14 (9%), E11 (9%), E16 (7.5%), and CVA2 (7.5%) were the five most frequently observed NPEV types in PID patients. Patients with combined immunodeficiency were at a higher risk for enterovirus infection as compared to antibody deficiency. The high susceptibility of PID patients to enterovirus infection emphasizes the need for enhanced surveillance of these patients until the use of OPV is stopped. The expansion of PID surveillance and integration with a national program will facilitate early detection and follow-up of iVDPV excretion to mitigate the risk for iVDPV spread.
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Introduction: The essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies drive catalytic improvements in vaccination coverage are not well established. To address this gap, we identified critical success factors that may have led to substantial improvements in routine childhood immunization coverage in Nepal from 2000 through 2019. Methods: We identified Nepal as an exemplar in the delivery of early childhood immunization through analysis of DTP1 and DTP3 coverage data. Through interviews and focus group discussions at the national, regional, district, health post, and community level, we investigated factors that contributed to high and sustained vaccine coverage. We conducted a thematic analysis through application of implementation science frameworks to determine critical success factors. We triangulated these findings with quantitative analyses using publicly available data. Results: The following success factors emerged: 1) Codification of health as a human right, - along with other vaccine-specific legislation - ensured the stability of vaccination programming; 2) National and multi-national partnerships supported information sharing, division of labor, and mutual capacity building; 3) Pro-vaccine messaging through various mediums, which was tailored to local needs, generated public awareness; 4) Female Community Health Volunteers educated community members as trusted and compassionate neighbors; and 5) Cultural values fostered collective responsibility and community ownership of vaccine coverage. Conclusion: This case study of Nepal suggests that the success of its national immunization program relied on the engagement and understanding of the beneficiaries. The immunization program was supported by consistent and reliable commitment, collaboration, awareness, and collective responsibility between the government, community, and partners. These networks are strengthened through a collective dedication to vaccination programming and a universal belief in health as a human right.
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Poliomyelitis is the leading infectious cause of acute flaccid paralysis among children under five years of age, caused by the Wild Poliovirus, with no medical cure other than prevention through vaccination. The advent of mass vaccination campaigns against polio disease worldwide has greatly decreased the number of global cases and limited the rate of transmission. However, the emergence of Vaccine-derived Poliovirus due to genetic reversions in the live attenuated oral polio vaccine has posed a significant impediment to global polio eradication efforts. Therefore, There is a need to modify the vaccination regimen by utilizing more doses of inactivated poliovirus vaccine or adopting the bivalent oral polio vaccine in order to eliminate the transmission of Vaccine-derived Poliovirus. In addition, collective efforts from governments, health policymakers, vaccination groups and health-related bodies are required to improve vaccine coverage and suppress the circulation of Vaccine-derived Poliovirus.
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BACKGROUND: Lessons from polio eradication efforts and the Global Polio Eradication Initiative (GPEI) are useful for improving health service delivery and outcomes globally. The Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) is a multi-phase project which aims to map, package and disseminate knowledge from polio eradication initiatives as academic and training programs. This paper discusses initial findings from the knowledge mapping around polio eradication activities across a multi-country context. METHODS: The knowledge mapping phase (January 2018 - December 2019) encompassed four research activities (scoping review, survey, key informant interviews (KIIs), health system analyses). This paper utilized a sequential mixed method design combining data from the survey and KIIs. The survey included individuals involved in polio eradication between 1988 and 2019, and described the contexts, implementation strategies, intended and unintended outcomes of polio eradication activities across levels. KIIs were conducted among a nested sample in seven countries (Afghanistan, Bangladesh, the Democratic Republic of Congo, Ethiopia, India, Indonesia, Nigeria) and at the global level to further explore these domains. RESULTS: The survey generated 3955 unique responses, mainly sub-national actors representing experience in over 74 countries; 194 KIIs were conducted. External factors including social, political, and economic factors were the most frequently cited barriers to eradication, followed by the process of implementing activities, including program execution, planning, monitoring, and stakeholder engagement. Key informants described common strategies for addressing these barriers, e.g. generating political will, engaging communities, capacity-building in planning and measurement, and adapting delivery strategies. The polio program positively affected health systems by investing in system structures and governance, however, long-term effects have been mixed as some countries have struggled to institutionalize program assets. CONCLUSION: Understanding the implementing context is critical for identifying threats and opportunities to global health programs. Common implementation strategies emerged across countries; however, these strategies were only effective where organizational and individual capacity were sufficient, and where strategies were appropriately tailored to the sociopolitical context. To maximize gains, readiness assessments at different levels should predate future global health programs and initiatives should consider system integration earlier to ensure program institutionalization and minimize system distortions.
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Difusión de Innovaciones , Erradicación de la Enfermedad , Salud Global , Poliomielitis/prevención & control , Investigación/organización & administración , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Complex global initiatives, like the Global Polio Eradication Initiative (GPEI), have prevented millions of paralyses and improved the health status of diverse populations. Despite the logistical challenges these initiatives must overcome at several levels, scant methods exist for systematically identifying and reaching a range of actors involved in their implementation. As a result, efforts to document the lessons learned from such initiatives are often incomplete. This paper describes the development and application of the Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) systematic approach for identifying a comprehensive sample of actors involved in the GPEI. RESULTS: The survey for collecting lessons learned from the GPEI was conducted at the global level and within seven countries that represented GPEI operational contexts. Standard organizational and operational levels, as well as goals of program activities, were defined across contexts. Each survey iteration followed similar methodologies to theorize a target population or "universe" of all polio-related actors in the study area, enumerate a source population of specific individuals within the target population, and administer the survey to individuals within the source population. Based on the systematic approach used to obtain a comprehensive sample for lessons learned in GPEI, steps for obtaining a comprehensive sample for studying complex initiatives can be summarized as follows: (i) State research goal(s); (ii) Describe the program of interest; (iii) Define a sampling universe to meet these criteria; (iv) Estimate the size of the sampling universe; (v) Enumerate a source population within the universe that can be feasibly reached for sampling; (vi) Sample from the source population; and (vii) Reflect on the process to determine strength of inferences drawn. CONCLUSIONS: The application of these methods can inform future evaluations of complex public health initiatives, resulting in better adoption of lessons learned, ultimately improving efficacy and efficiency, and resulting in significant health gains. Their use to administer the STRIPE lessons learned survey reflects experiences related to implementation challenges and strategies used to overcome barriers from actors across an extensive range of organizational, programming, and contextual settings.
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Erradicación de la Enfermedad/organización & administración , Salud Global , Relaciones Interinstitucionales , Poliomielitis/prevención & control , Humanos , Encuestas y CuestionariosRESUMEN
Today, acceptance of oral polio vaccine is the highest ever. Reaching this level of acceptance has depended on decades of engaging with communities, building trust amid extraordinary social contexts, and responding to the complex variables that trigger behavioral and social change. Drawing on both the successes and setbacks in the 28 years of the Global Polio Eradication Initiative (GPEI), this article articulates what happened when the GPEI began to pay more attention to the dynamics of human and social behavior change. Three particular lessons for other health and immunization programs can be drawn from the experience of GPEI: change begins from within (ie, success needs institutional recognition of the importance of human behavior), good data are not enough for good decision-making, and health workers are important agents of behavior change. These lessons should be harnessed and put into practice to build demand and trust for the last stages of polio eradication, as well as for other life-saving health interventions.
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Erradicación de la Enfermedad/métodos , Conocimientos, Actitudes y Práctica en Salud , Programas de Inmunización/métodos , Poliomielitis/prevención & control , Cambio Social , Salud Global , Humanos , Vacuna Antipolio Oral , Conducta SocialRESUMEN
In 2009, the international Stop Transmission of Polio (STOP) program began supporting the Global Polio Eradication Initiative in the Republic of South Sudan to address shortages of human resources and strengthen acute flaccid paralysis surveillance. Workforce capacity support is provided to the South Sudan Expanded Program on Immunization by STOP volunteers, implementing partners, and non-governmental organizations. In 2013, the Polio Technical Advisory Group recommended that South Sudan transition key technical support from external partners to national staff as part of the Polio Eradication and Endgame Strategic Plan, 2013-2018. To assist in this transition, the South Sudan Expanded Program on Immunization human resources development project was launched in 2015. This 3-year project aims to build national workforce capacity as a legacy of the STOP program by training 56 South Sudanese at national and state levels with the intent that participants would become Ministry of Health staff on their successful completion of the project.
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Erradicación de la Enfermedad/organización & administración , Programas de Inmunización/organización & administración , Poliomielitis/prevención & control , Creación de Capacidad , Salud Global , Personal de Salud , Humanos , Sudán del Sur , Recursos HumanosRESUMEN
Herein, we prepared PEI-immobilized core-shell particles possessing various types of polymer cores via a visible light-induced surfactant-free emulsion polymerization (SFEP) of three vinyl monomers: styrene (St), methyl methacrylate (MMA), and 2-hydroxyethyl methacrylate (HEMA). An effect of monomers on the polymerization and characteristics of resulting products was investigated. Monomers with high polarity can provide high monomer conversion, high percentage of grafted PEI, stable particles with uniform size distribution but less amino groups per particles. All prepared nanoparticles exhibited a core-shell nanostructure, containing PEI on the shell with hydrodynamic size around 140-230nm. For in-vitro study in Caco-2 cells, we found that the incorporation of PEI into these core-shell nanoparticles can significantly reduce its cytotoxic effect and also be able to internalized within the cells. Accordingly, these biocompatible particles would be useful for various biomedical applications, including gene transfection and intracellular drug delivery.
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Materiales Biocompatibles/química , Ensayo de Materiales/métodos , Nanopartículas/química , Polietileneimina/química , Polietileneimina/síntesis química , Células CACO-2 , Supervivencia Celular , Emulsiones , Humanos , Espacio Intracelular/metabolismo , Metacrilatos/química , Metilmetacrilatos/química , Nanopartículas/ultraestructura , Polimerizacion , Poliestirenos/química , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Propiedades de Superficie , Tensoactivos/químicaRESUMEN
Because induction of phase II detoxification enzyme is important for chemoprevention, we study the effects of Indigofera suffruticosa Mill, a medicinal herb, on the expression of π class of glutathione S-transferase (GSTP) and NAD(P)H: quinone oxidoreductase 1 (NQO1) in rat Clone 9 liver cells. Both water and ethanolic extracts of I. suffruticosa significantly increased the expression and enzyme activities of GSTP and NQO1. I. suffruticosa extracts up-regulated GSTP promoter activity and the binding affinity of nuclear factor erythroid 2-related factor 2 (Nrf2) with the GSTP enhancer I oligonucleotide. Moreover, I. suffruticosa extracts increased nuclear Nrf2 accumulation as well as ARE transcriptional activity. The level of phospho-ERK was augmented by I. suffruticosa extracts, and the ERK inhibitor PD98059 abolished the I. suffruticosa extract-induced ERK activation and GSTP and NQO-1 expression. Moreover, I. suffruticosa extracts, especially the ethanolic extract increased the glutathione level in mouse liver and red blood cells as well as Clone 9 liver cells. The efficacy of I. suffruticosa extracts in induction of phase II detoxification enzymes and glutathione content implies that I. suffruticosa could be considered as a potential chemopreventive agent.