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Most hematological malignancies are associated with reduced expression of one or more components of the Endosomal Sorting Complex Required for Transport (ESCRT). However, the roles of ESCRT in stem cell and progenitor maintenance are not resolved. Parsing signaling pathways in relation to the canonical role of ESCRT poses a challenge. The Drosophila hematopoietic organ, the larval lymph gland, provides a path to dissect the roles of cellular trafficking pathways such as ESCRT in blood development and maintenance. Drosophila has 13 core ESCRT components. Knockdown of individual ESCRTs showed that only Vps28 and Vp36 were required in all lymph gland progenitors. Using the well-conserved ESCRT-II complex as an example of the range of phenotypes seen upon ESCRT depletion, we show that ESCRTs have cell-autonomous as well as non-autonomous roles in progenitor maintenance and differentiation. ESCRT depletion also sensitized posterior lobe progenitors to respond to immunogenic wasp infestation. We also identify key heterotypic roles for ESCRT in position-dependent control of Notch activation to suppress crystal cell differentiation. Our study shows that the cargo sorting machinery determines the identity of progenitors and their adaptability to the dynamic microenvironment. These mechanisms for control of cell fate may tailor developmental diversity in multiple contexts.
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Complexos Endossomais de Distribuição Requeridos para Transporte , Animais , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Linhagem da Célula , Diferenciação Celular/genética , Drosophila , Transdução de Sinais , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , ImunidadeRESUMO
Background: To reduce burden of pneumonia, India has introduced Pneumococcal Conjugate vaccine (PCV) in routine immunization programme. The state of West Bengal, India introduced PCV in 2021. Uptake of new vaccines depends a lot on knowledge of caregivers on the disease and vaccine. This study aimed to assess the knowledge of caregivers regarding pneumococcal diseases and PCV. The study will inform programme managers to develop a comprehensive demand generation strategy for improving uptake of PCV and other new vaccines. Methods: It is an observational, cross-sectional study using a predesigned, pretested and structured questionnaire conducted among 353 caregivers of children who has received at least one dose of PCV. The children were aged between 6 weeks to 20 months, residing in rural and urban areas of Howrah district of West Bengal. Sample size was calculated considering 95 % confidence interval and 5 % margin of error. Results: Results are analysed taking into consideration rural/urban divide, socioeconomic status and other factors influencing vaccine uptake. Study findings suggest lack of knowledge of caregivers regarding pneumococcal diseases and PCV. Most of respondents have no idea about any other pneumococcal diseases apart from pneumonia. More than 40 % does not know about what causes pneumonia and more than 47 % does not know how to prevent pneumonia. They also have poor knowledge about injection site, number of doses, schedule and when to start PCV. Conclusions: Limited knowledge among caregivers may cause negative impact on vaccine coverage and jeopardise the goal of government to reduce morbidity and mortality due to pneumonia.The study findings suggest that there is dearth of knowledge regarding pneumococcal diseases and PCV among caregivers. Therefore the policy makers need to develop a comprehensive plan for awareness generation for improving PCV uptake and strategy developed for this purpose can be implemented in future new vaccine introduction also.
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We conducted a field evaluation using qualitative and quantitative methods to assess freeze prevention of vaccines transported and stored in a recently developed, World Health Organization-prequalified freeze-preventive cold box (FPCB) as compared to currently used standard cold boxes (SCBs). The study assessed the FPCB's practical use, health worker acceptance, health system fit (including cost considerations), and challenges faced by health workers in variable conditions and geographical settings. The evaluation took place in five health facilities across hilly and plains districts of Nepal in two phases: Phase 1 involved FPCBs in simulated use alongside SCBs. In Phase 2, actual vaccines were used in the FPCBs. The study gathered quantitative data from logbooks and electronic temperature monitors placed inside and outside the cold boxes. Qualitative data were collected from health workers, cold chain personnel, and immunization program managers involved in the vaccine cold chain at multiple levels. No damage, durability issues, or freezing incidents were observed when using FPCBs, but two incidents of freezing occurred when using SCBs. FPCBs also took longer to cool down than SCBs. Participants mostly found the FPCB to be safe and user friendly for vaccine transportation and short-term storage. Advantages of the FPCB as compared to the SCB include its ability to minimize vaccine wastage, to keep freeze-sensitive vaccines safe (the average value of freeze-sensitive vaccines transported per shipment was $1,704), and to ease preparation through elimination of the need to condition ice packs. Procurement price ranges for FPCBs overlap those for SCBs. Disadvantages of the FPCB include its greater size and weight, which require more personnel and vehicles during transportation. This suggests that lighter and smaller FPCBs would be more effective and acceptable for the Nepal immunization program and other, similar immunization programs conducted globally.
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Background: Estimates suggest that 78,000 children died due to rotavirus gastroenteritis annually between 2011 and 2013 in India. The north eastern state of Assam reported 38.4% pediatric diarrheal admissions testing positive for rotavirus. Rotavirus vaccine (RVV) was introduced in Assam in 2017 following which the National Family Health Survey-5 (NFHS-5) (2019) revealed low RVV coverage in Assam with wide variation between the districts. the current study was conceptualized and undertaken to capture the enablers and barriers to RVV coverage in Assam. Methods: Qualitative study conducted in 5 randomly selected districts in Assam. Participants (key informants) were recruited by purposive sampling at each level of the health system including healthcare officials, service providers and caregivers based on availability. Thirty-five in-depth interviews (IDIs) and five focus group discussions (FGDs) were conducted. Interviews were tape recorded and transcribed. Data was coded and analyzed using the thematic framework approach. Results: Findings from the qualitative data collection were collated and analyzed under 7 identified themes. Difficult terrain, limited service provider availability and no catch-up training for new recruits were some of the barriers to RVV coverage. In contrast, Information, Education & Communication (IEC) in vernacular language, RVV safety profile, development partner support and adequate RVV supply were identified as some of the enablers of RVV coverage. Conclusion: Few broad recommendations to overcome identified barriers include comprehensive inter-sectoral coordination, regular monitoring and frequent refresher training sessions. There is a need for a future study utilizing existing coverage data and larger sample size to triangulate the findings of this study.
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Background and aims: The Rotavirus vaccine (RVV) introduction is a landmark event in the history of Indian public health as for the first time a novel, low-cost indigenous vaccine was introduced in a short timeline between 2016 and 2019. As per WHO mandate, post-introduction evaluation (PIE) be conducted within 6 to 12 months of vaccine introduction to provide an understanding of the operational aspects of the program. For RVV PIE, an innovative approach to developing and deploying a digitized tool was employed. The present study aims to document the processes followed for digitizing the data collection and analysis tools. Methods: The development of the RVV-PIE digital tool was undertaken in two phases. In the first phase, conceptualization and iteration of the modified WHO PIE tool were undertaken. Questions were organized sequentially to ensure natural progression in responses. The finalized questionnaire was converted to a digital version and extensive dummy data was entered to improve automated qualitative data analysis. Phase 2 involved updating the draft tool and incorporating changes to provide a field-tested version for deployment. Results: The digital version of the tool was successfully developed. The GPS functionality of the tool allowed live tracking of data collection making the process more accountable. The tool was prepopulated with reference materials and data points for easy reference and retrieval by the evaluators. The digitization of the tool also allowed easy visualization of data through maps, charts, and graphs on a real-time user-friendly dashboard. Conclusions: The digitization of the PIE tool for RVV in India has been a great learning experience where the dire situation of an ongoing pandemic catapulted us towards a more efficient and comprehensive process innovation. The RVV PIE tool could serve as a customizable digital PIE tool for other health programs heralding an era of a more effective and proficient process of PIE.
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Many children do not receive a full schedule of childhood vaccines, yet there is limited evidence on the cost-effectiveness of strategies for improving vaccination coverage. Evidence is even scarcer on the cost-effectiveness of strategies for reaching 'zero-dose children', who have not received any routine vaccines. We evaluated the cost-effectiveness of periodic intensification of routine immunization (PIRI), a widely applied strategy for increasing vaccination coverage. We focused on Intensified Mission Indradhanush (IMI), a large-scale PIRI intervention implemented in India in 2017-2018. In 40 sampled districts, we measured the incremental economic cost of IMI using primary data, and used controlled interrupted time-series regression to estimate the incremental vaccination doses delivered. We estimated deaths and disability-adjusted life years (DALYs) averted using the Lives Saved Tool and reported cost-effectiveness from immunization programme and societal perspectives. We found that, in sampled districts, IMI had an estimated incremental cost of 2021US$13.7 (95% uncertainty interval: 10.6 to 17.4) million from an immunization programme perspective and increased vaccine delivery by an estimated 2.2 (-0.5 to 4.8) million doses over a 12-month period, averting an estimated 1413 (-350 to 3129) deaths. The incremental cost from a programme perspective was $6.21 per dose ($2.80 to dominated), $82.99 per zero-dose child reached ($39.85 to dominated), $327.63 ($147.65 to dominated) per DALY averted, $360.72 ($162.56 to dominated) per life-year saved and $9701.35 ($4372.01 to dominated) per under-5 death averted. At a cost-effectiveness threshold of 1× per-capita GDP per DALY averted, IMI was estimated to be cost-effective with 90% probability. This evidence suggests IMI was both impactful and cost-effective for improving vaccination coverage, though there is a high degree of uncertainty in the results. As vaccination programmes expand coverage, unit costs may increase due to the higher costs of reaching currently unvaccinated children.
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Análise Custo-Benefício , Programas de Imunização , Cobertura Vacinal , Humanos , Índia , Programas de Imunização/economia , Cobertura Vacinal/economia , Cobertura Vacinal/estatística & dados numéricos , Lactente , Anos de Vida Ajustados por Deficiência , Pré-Escolar , Vacinação/economia , Vacinas/economia , Esquemas de ImunizaçãoRESUMO
Background: India became the first country in the WHO South-East Asia Region (SEAR) to introduce the rotavirus vaccine (RVV) in the Universal immunization programme (UIP) in 2016 with nationwide expansion by 2019. It was a landmark move to reduce the diarrheal disease burden in under-five children. To assess the implementation process of introduction of RVV, Post Introduction Evaluation (PIE) was conducted in March 2022. Methods: The evaluation was conducted across 14 states, 28 districts and 28 health facilities to obtain a nationwide geographical inclusion. Stakeholders involved in program decision-making, planning, training, vaccine delivery, logistics, and communication from all levels (National, state, district, health facility, health worker, caregiver) were interviewed using standardized data collection tool for PIE (adapted from the standard WHO PIE questionnaire) and scripted on a digital tool. Results: A total of 260 interviews were conducted. Political willingness, well-planned preparedness activities, securing vaccines timely, strong supply chain monitoring, availability of domestic RVV products, quality trainings and intense communication activities were the key factors identified for the successful RVV introduction. Key activities during the introduction included cold chain space assessment, trainings of healthcare workforce, dissemination of job aids, updation of recording & reporting formats and strengthening of AEFI surveillance. Lack of community awareness for immunization in a few areas, fear of AEFI amongst some caregivers and local issues with Alternate Vaccine Delivery (AVD) were some reported challenges in achieving high coverage for RVV. Conclusions: Overall, the nationwide roll-out of RVV was smooth and the vaccine has been well-accepted in the community. The assessment emphasizes on having a well-strategized operational and communication planning, which is very crucial for any new vaccine introduction.