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.
The transmission of malaria through population inflows from highly endemic areas with limited control efforts poses major challenges for national malaria control programmes. Several multilateral ...programmes have been launched in recent years to address cross-border transmission. This study assesses the potential impact of such a programme at the Angolan-Namibian border.
Community-based malaria prevention programmes involving bed net distribution and behaviour change home visits were rolled-out using a controlled, staggered (stepped wedge) design between May 2014 and July 2016 in a 100 × 40 km corridor along the Angolan-Namibian border. Three rounds of survey data were collected. The primary outcome studied was fever among children under five in the 2 weeks prior to the survey. Multivariable linear and logistic regression models were used to assess overall programme impact and the relative impact of unilateral versus coordinated bilateral intervention programmes.
A total of 3844 child records were analysed. On average, programme rollout reduced the odds of child fever by 54% (aOR: 0.46, 95% CI 0.29 to 0.73) over the intervention period. In Namibia, the programme reduced the odds of fever by 30% in areas without simultaneous Angolan efforts (aOR: 0.70, 95% CI 0.34 to 1.44), and by an additional 62% in areas with simultaneous Angolan programmes. In Angola, the programme was highly effective in areas within 5 km of Namibian programmes (OR: 0.37, 95% CI 0.22 to 0.62), but mostly ineffective in areas closer to inland Angolan areas without concurrent anti-malarial efforts.
The impact of malaria programmes depends on programme efforts in surrounding areas with differential control efforts. Coordinated malaria programming within and across countries will be critical for achieving the vision of a malaria free world.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
This analysis describes specific gaps in the quality of health care in Central Africa and assesses the association between quality of clinical care and mortality at age 2–59 months. ...Regionally representative facility and household surveys for the Democratic Republic of the Congo, Cameroon and Central African Republic were collected between 2012 and 2016. These data are novel in linking facilities with households in their catchment area. Compliance with diagnostic and danger sign protocols during sick-child visits was observed by trained assessors. We computed facility- and district-level compliance indicators for patients aged 2–59 months and used multivariate multi-level logistic regression models to estimate the association between clinical assessment quality and mortality at age 2–59 months in the catchment areas of the observed facilities. A total of 13 618 live births were analysed and 1818 sick-child visits were directly observed and used to rate 643 facilities. Eight percent of observed visits complied with 80% of basic diagnostic protocols, and 13% of visits fully adhered to select general danger sign protocols. A 10% greater compliance with diagnostic protocols was associated with a 14.1% (adjusted odds ratio (aOR) 95% CI: 0.025–0.244) reduction in the odds of mortality at age 2–59 months; a 10% greater compliance with select general danger sign protocols was associated with a 15.3% (aOR 95% CI: 0.058–0.237) reduction in the same odds. The results of this article suggest that compliance with recommended clinical protocols remains poor in many settings and improvements in mortality at age 2–59 months could be possible if compliance were improved.
While school-aged children in low- and middle-income countries remain highly exposed to acute infections, programs targeting this age group remain limited in scale and scope. In this paper, we ...evaluate the impact of a new and comprehensive primary school-based health intervention program on student-reported morbidity and anthropometric outcomes in Lusaka, Zambia.
A prospective matched control study identified 12 classes in 7 schools for the intervention and 12 classes in 7 matched schools as controls. Teachers in intervention schools were trained to deliver health lessons and to refer sick students to care. In addition, vitamin A and deworming medication were biannually administered to intervention students. The primary study outcome was student-reported morbidity. Secondary outcomes were weight, height, health knowledge, and absenteeism. Multivariable linear and logistic regression models were used to estimate program impact.
380 students ages 4-16 were enrolled in the study in 2015, and 97% were followed up at endline in 2016. The intervention decreased the adjusted odds of self-reported acute illnesses by 38% (95% CI: 0.48, 0.77) and the adjusted odds of stunting by 52% (95% CI: 0.26, 0.87). It also increased health knowledge by 0.53 standard deviations (95% CI: 0.24, 0.81). No impact was found on weight (adjusted mean difference β = 0.17, 95% CI: - 1.11, 1.44) and student absenteeism (adjusted odds ratio (aOR) = 0.89, 95% CI: 0.60, 1.33).
The results presented in this paper suggest that comprehensive school-based health programs may offer a highly effective way to improve students' health knowledge as well as their health status. Given their low cost, a more general adoption and implementation of such programs seems recommendable.
ClinicalTrials.gov Identifier: NCT03607084.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Glucose oxidase is one of the most conspicuous commercial enzymes due to its many different applications in diverse industries such as food, chemical, energy and textile. Among these applications, ...the most remarkable is the manufacture of glucose biosensors and in particular sensor strips used to measure glucose levels in serum. The generation of ameliorated versions of glucose oxidase is therefore a significant biotechnological objective. We have used a strategy that combined random and rational approaches to isolate uncharacterized mutations of Aspergillus niger glucose oxidase with improved properties. As a result, we have identified two changes that increase significantly the enzyme's thermal stability. One (T554M) generates a sulfur-pi interaction and the other (Q90R/Y509E) introduces a new salt bridge near the interphase of the dimeric protein structure. An additional double substitution (Q124R/L569E) has no significant effect on stability but causes a twofold increase of the enzyme's specific activity. Our results disclose structural motifs of the protein which are critical for its stability. The combination of mutations in the Q90R/Y509E/T554M triple mutant yielded a version of A. niger glucose oxidase with higher stability than those previously described.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Microbial diversity is associated with improved outcomes in recipients of allogeneic hematopoietic cell transplantation (allo-HCT), but the mechanism underlying this observation is unclear. In a ...cohort of 174 patients who underwent allo-HCT, we demonstrate that a diverse intestinal microbiome early after allo-HCT is associated with an increased number of innate-like mucosal-associated invariant T (MAIT) cells, which are in turn associated with improved overall survival and less acute graft-versus-host disease (aGVHD). Immune profiling of conventional and unconventional immune cell subsets revealed that the prevalence of Vδ2 cells, the major circulating subpopulation of γδ T cells, closely correlated with the frequency of MAIT cells and was associated with less aGVHD. Analysis of these populations using both single-cell transcriptomics and flow cytometry suggested a shift toward activated phenotypes and a gain of cytotoxic and effector functions after transplantation. A diverse intestinal microbiome with the capacity to produce activating ligands for MAIT and Vδ2 cells appeared to be necessary for the maintenance of these populations after allo-HCT. These data suggest an immunological link between intestinal microbial diversity, microbe-derived ligands, and maintenance of unconventional T cells.
T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the ...site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.
•It is safe and feasible to deliver autologous hematopoietic cell transplantation care in a homebound setting.•Less than one-half of patients required inpatient admission.•Patients and caregivers ...report high satisfaction with care.
For eligible patients with multiple myeloma (MM) and amyloid light chain (AL) amyloidosis, high-dose chemotherapy and autologous hematopoietic cell transplantation (HCT) is a standard and widely used consolidation therapy. Autologous HCT requires specialized care at a transplantation center and investment from patients and caregivers. We studied the safety and feasibility of delivering transplantation care in a homebound setting to decrease the burden of therapy and increase access to autologous HCT. Patients with MM and AL amyloidosis undergoing autologous HCT were eligible if they resided in designated ZIP codes and had a full-time caregiver, Wi-Fi connection, HCT Comorbidity Index ≤3, and Karnofsky Performance Status score ≥80. High-dose melphalan (on day -2) and hematopoietic cell reinfusion (day 0) were administered in the outpatient clinic. Protocol-specific home care was provided from day +1 through engraftment. Patients were assessed and blood was drawn daily by advanced practice providers. Interventions were delivered by registered nurses. Attending physicians communicated daily through telemedicine. Quality of life, patient and caregiver satisfaction, and fecal microbiota profiling data were collected. Fifteen patients were enrolled and received transplantation care at home starting on day +1 following hematopoietic cell infusion. Patients remained in the program for an average of 12 days and required an average of 2 outpatient visits while receiving home care. Seven of 15 patients were admitted for a median of 4 days (range, 3 to 10 days); admission occurred on day +7 in 5 patients, on day +8 in 1 patient, and on day +12 in 1 patient for neutropenic fever in 2 patients, fever attributed to engraftment syndrome in 2 patients, diarrhea in 2 patients, and dehydration in 1 patient. Only 1 patient had a documented infection (Clostridioides difficile). One patient admitted with neutropenic fever required intensive care unit admission for a gastrointestinal bleed. Forty-seven percent of the patients experienced a grade ≥3 nonhematologic toxicity. There were no deaths on the study. Patients and caregivers reported high satisfaction with care. Microbiota diversity patterns were similar to those of autologous HCT recipients who did not receive post-HCT care at home, although a subset of the cohort maintained microbiota diversity throughout. Homebound HCT in an urban setting is safe and feasible, with less than one-half of patients requiring inpatient admission. Despite increased patient and caregiver responsibility in the homebound setting compared with an inpatient setting, patient and caregiver satisfaction was high. These results support expansion of homebound transplantation care programs.
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Since its launch in 2010, the Tanzania National Voluntary Medical Male Circumcision (VMMC) Program has focused efforts on males ages 10-34 in 11 priority regions. Implementers have noted that over ...70% of VMMC clients are between the ages of 10 and 19, raising questions about whether additional efforts would be required to recruit men age 20 and above. This analysis uses mathematical modeling to examine the economic and epidemiological consequences of scaling up VMMC among specific age groups and priority regions in Tanzania.
Analyses were conducted using the Decision Makers' Program Planning Tool Version 2.0 (DMPPT 2.0), a compartmental model implemented in Microsoft Excel 2010. The model was populated with population, mortality, and HIV incidence and prevalence projections from external sources, including outputs from Spectrum/AIDS Impact Module (AIM). A separate DMPPT 2.0 model was created for each of the 11 priority regions. Tanzania can achieve the most immediate impact on HIV incidence by circumcising males ages 20-34. This strategy would also require the fewest VMMCs for each HIV infection averted. Circumcising men ages 10-24 will have the greatest impact on HIV incidence over a 15-year period. The most cost-effective approach (lowest cost per HIV infection averted) targets men ages 15-34. The model shows the VMMC program is cost saving in all 11 priority regions. VMMC program cost-effectiveness varies across regions due to differences in projected HIV incidence, with the most cost-effective programs in Njombe and Iringa.
The DMPPT 2.0 results reinforce Tanzania's current VMMC strategy, providing newfound confidence in investing in circumcising adolescents. Tanzanian policy makers and program implementers will continue to focus scale-up of VMMC on men ages 10-34 years, seeking to maximize program impact and cost-effectiveness while acknowledging trends in demand among the younger and older age groups.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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