Examining decentralization and managerial decision making for child immunization program performance in India

Despite widespread adoption of decentralization reforms, the impact of decentralization on health system attributes, such as access to health services, responsiveness to population health needs, and effectiveness in affecting health outcomes, remains unclear. This study examines how decision space, institutional capacities, and accountability mechanisms of the Intensified Mission Indradhanush (IMI) in India relate to measurable performance of the immunization program. Data on decision space and its related dimensions of institutional capacity and accountability were collected by conducting structured interviews with managers based in 24 districts, 61 blocks, and 279 subcenters. Two measures by which to assess performance were selected: (1) proportion reduction in the DTP3 coverage gap (i.e., effectiveness), and (2) total IMI doses delivered per incremental USD spent on program implementation (i.e., efficiency). Descriptive statistics on decision space, institutional capacity, and accountability for IMI managers were generated. Structural equation models (SEM) were specified to detect any potential associations between decision space dimensions and performance measures. The majority of districts and blocks indicated low levels of decision space. Institutional capacity and accountability were similar across areas. Increases in decision space were associated with less progress towards closing the immunization coverage gap in the IMI context. Initiatives to support health workers and managers based on their specific contextual challenges could further improve outcomes of the program. Similar to previous studies, results revealed strong associations between each of the three decentralization dimensions. Health systems should consider the impact that management structures have on the efficiency and effectiveness of health services delivery. Future research could provide greater evidence for directionality of direct and indirect effects, interaction effects, and/or mediators of relationships

Estimating the distribution of morbidity and mortality of childhood diarrhea, measles, and pneumonia by wealth group in low- and middle-income countries

__Background:__ Equitable access to vaccines has been suggested as a priority for low- and middle-income countries (LMICs). However, it is unclear whether providing equitable access is enough to ensure health equity. Furthermore, disaggregated data on health outcomes and benefits gained across population subgroups are often unavailable. This paper develops a model to estimate the distribution of childhood disease cases and deaths across socioeconomic groups, and the potential benefits of three vaccine programs in LMICs. __Methods:__ For each country and for three diseases (diarrhea, measles, pneumonia), we estimated the distributions of cases and deaths that would occur across wealth quintiles in the absence of any immunization or treatment programs, using both the prevalence and relative risk of a set of risk and prognostic factors. Building on these baseline estimates, we examined what might be the impact of three vaccines (first dose of measles, pneumococcal conjugate, and rotavirus vaccines), under five scenarios based on different sets of quintile-specific immunization coverage and disease treatment utilization rates. __Results:__ Due to higher prevalence of risk factors among the poor, disproportionately more disease cases and deaths would occur among the two lowest wealth quintiles for all three diseases when vaccines or treatment are unavailable. Country-specific context, including how the baseline risks, immunization coverage, and treatment utilization are currently distributed across quintiles, affects how different policies translate into changes in cases and deaths distribution. __Conclusions:__ Our study highlights several factors that would substantially contribute to the unequal distribution of childhood diseases, and finds that merely ensuring equal access to vaccines will not reduce the health outcomes gap across wealth quintiles. Such information can inform policies and planning of programs that aim to improve equitable delivery of healthcare services

Efficient Small Extracellular Vesicles (EV) Isolation Method and Evaluation of EV-Associated DNA Role in Cell-Cell Communication in Cancer

SIMPLE SUMMARY: Small extracellular vesicles (sEVs) released by all cell types function as a mediator in intercellular communication that can promote cell division and survival to remodel the tumor microenvironment to develop tumor invasion and metastasis. Even though dsDNA baggage is associated with all small EV populations, the functional role of EV-DNA in cancer remains poorly understood. This is due to a lack of methods allowing the efficient separation of small EVs (sEVs) from other non-sEV components. The main aim of our study was to develop an efficient sEV isolation method along with EV-associated DNA (EV-DNA) monitoring tool to evaluate the role of EV-DNA as a mediator of cell–cell communication in cancer. Our detailed small EV-DNA characterization confirmed that isolated sEVs using the TSU method (Tangential flow filtration + Size exclusion chromatography + Ultrafiltration) are free from contaminants such as cell-free and apoptotic bodies DNA, making TSU ideal for performing EV-DNA functional studies. Next, we revealed the exact EV-DNA distribution in the recipient cells using 3D image analysis and the association of EV-DNA with key cellular proteins, which may have an essential role in cancer. In the leukemia model, EV-DNA isolated from leukemia cell lines associated with mesenchymal stromal cells (MSCs), a crucial factor in the bone marrow (BM) microenvironment. ABSTRACT: Small extracellular vesicles (sEVs) play essential roles in intercellular signaling both in normal and pathophysiological conditions. Comprehensive studies of dsDNA associated with sEVs are hampered by a lack of methods, allowing efficient separation of sEVs from free-circulating DNA and apoptotic bodies. In this work, using controlled culture conditions, we enriched the reproducible separation of sEVs from free-circulated components by combining tangential flow filtration, size-exclusion chromatography, and ultrafiltration (TSU). EV-enriched fractions (F2 and F3) obtained using TSU also contained more dsDNA derived from the host genome and mitochondria, predominantly localized inside the vesicles. Three-dimensional reconstruction of high-resolution imaging showed that the recipient cell membrane barrier restricts a portion of EV-DNA. Simultaneously, the remaining EV-DNA overcomes it and enters the cytoplasm and nucleus. In the cytoplasm, EV-DNA associates with dsDNA-inflammatory sensors (cGAS/STING) and endosomal proteins (Rab5/Rab7). Relevant to cancer, we found that EV-DNA isolated from leukemia cell lines communicates with mesenchymal stromal cells (MSCs), a critical component in the BM microenvironment. Furthermore, we illustrated the arrangement of sEVs and EV-DNA at a single vesicle level using super-resolution microscopy. Altogether, employing TSU isolation, we demonstrated EV-DNA distribution and a tool to evaluate the exact EV-DNA role of cell–cell communication in cancer

Evaluation of cost-effective strategies for rabies post-exposure vaccination in low-income countries

<b>Background:</b> Prompt post-exposure prophylaxis (PEP) is essential in preventing the fatal onset of disease in persons exposed to rabies. Unfortunately, life-saving rabies vaccines and biologicals are often neither accessible nor affordable, particularly to the poorest sectors of society who are most at risk and upon whom the largest burden of rabies falls. Increasing accessibility, reducing costs and preventing delays in delivery of PEP should therefore be prioritized.<p></p> <b>Methodology/Principal Findings:</b> We analyzed different PEP vaccination regimens and evaluated their relative costs and benefits to bite victims and healthcare providers. We found PEP vaccination to be an extremely cost-effective intervention (from $200 to less than$60/death averted). Switching from intramuscular (IM) administration of PEP to equally efficacious intradermal (ID) regimens was shown to result in significant savings in the volume of vaccine required to treat the same number of patients, which could mitigate vaccine shortages, and would dramatically reduce the costs of implementing PEP. We present financing mechanisms that would make PEP more affordable and accessible, could help subsidize the cost for those most in need, and could even support new and existing rabies control and prevention programs.<p></p> <b>Conclusions/Significance:</b> We conclude that a universal switch to ID delivery would improve the affordability and accessibility of PEP for bite victims, leading to a likely reduction in human rabies deaths, as well as being economical for healthcare providers.<p></p&gt

The equity impact vaccines may have on averting deaths and medical impoverishment in developing countries

With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs’ total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preventable diseases and the health benefits associated with their prevention

'Communicate to vaccinate' (COMMVAC). building evidence for improving communication about childhood vaccinations in low- and middle-income countries: protocol for a programme of research

ABSTRACT: BACKGROUND: Effective provider-parent communication can improve childhood vaccination uptake and strengthen immunisation services in low- and middle-income countries (LMICs). Building capacity to improve communication strategies has been neglected. Rigorous research exists but is not readily found or applicable to LMICs, making it difficult for policy makers to use it to inform vaccination policies and practice. The aim of this project is to build research knowledge and capacity to use evidence-based strategies for improving communication about childhood vaccinations with parents and communities in LMICs. Methods and design This project is a mixed methods study with six sub-studies. In sub-study one, we will develop a systematic map of provider-parent communication interventions for childhood vaccinations by screening and extracting data from relevant literature. This map will inform sub-study two, in which we will develop a taxonomy of interventions to improve provider-parent communication around childhood vaccination. In sub-study three, the taxonomy will be populated with trial citations to create an evidence map, which will also identify how evidence is linked to communication barriers regarding vaccination. In the project's fourth sub-study, we will present the interventions map, taxonomy, and evidence map to international stakeholders to identify high-priority topics for systematic reviews of interventions to improve parent-provider communication for childhood vaccination. We will produce systematic reviews of the effects of high-priority interventions in the fifth sub-study. In the sixth and final sub-study of the project, evidence from the systematic reviews will be translated into accessible formats and messages for dissemination to LMICs. DISCUSSION: This project combines evidence mapping, conceptual and taxonomy development, priority setting, systematic reviews, and knowledge transfer. It will build and share concepts, terms, evidence, and resources to aid the development of communication strategies for effective vaccination programmes in LMIC

Inequitable childhood immunization uptake in Nigeria: a multilevel analysis of individual and contextual determinants

Background: Immunization coverage in many parts of Nigeria is far from optimal, and far from equitable. Nigeria accounts for half of the deaths from Measles in Africa, the highest prevalence of circulating wild poliovirus in the world, and the country is among the ten countries in the world with vaccine coverage below 50 percent. Studies focusing on community-level determinants therefore have serious policy implications Methods: Multilevel multivariable regression analysis was used on a nationally-representative sample of women aged 15-49 years from the 2003 Nigeria Demographic and Health Survey. Multilevel regression analysis was performed with children (level 1) nested within mothers (level 2), who were in turn nested within communities (level 3). Results: Results show that the pattern of full immunization clusters within families and communities, and that socio-economic characteristics are important in explaining the differentials in full immunization among the children in the study. At the individual level, ethnicity, mothers' occupation, and mothers' household wealth were characteristics of the mothers associated with full immunization of the children. At the community level, the proportion of mothers that had hospital delivery was a determinant of full immunization status. Conclusion: Significant community-level variation remaining after having controlled for child- and mother-level characteristics is indicative of a need for further research on community-levels factors, which would enable extensive tailoring of community-level interventions aimed at improving full immunization and other child health outcomes