The Replacement Principle of Tuberculosis. Why Prevention Matters.
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ABSTRACT:
SUBMITTER: Whalen CC
PROVIDER: S-EPMC5003332 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC10910596 | biostudies-literature
Project description:Colorectal cancer is a common and deadly disease in the United States accounting for over 50,000 deaths in 2020. This progressive disease is highly preventable with early detection and treatment, but many people do not comply with the recommended screening guidelines. The gut microbiome has emerged as a promising target for noninvasive detection of colorectal cancer. Most microbiome-based classification efforts utilize taxonomic abundance data from operational taxonomic units (OTUs) or amplicon sequence variants (ASVs) with the goal of increasing taxonomic resolution. However, it is unknown which taxonomic resolution is optimal for microbiome-based classification of colorectal cancer. To address this question, we used a reproducible machine learning framework to quantify classification performance of models based on data annotated to phylum, class, order, family, genus, OTU, and ASV levels. We found that model performance increased with increasing taxonomic resolution, up to the family level where performance was equal (P > 0.05) among family (mean area under the receiver operating characteristic curve [AUROC], 0.689), genus (mean AUROC, 0.690), and OTU (mean AUROC, 0.693) levels before decreasing at the ASV level (P < 0.05; mean AUROC, 0.676). These results demonstrate a trade-off between taxonomic resolution and prediction performance, where coarse taxonomic resolution (e.g., phylum) is not distinct enough, but fine resolution (e.g., ASV) is too individualized to accurately classify samples. Similar to the story of Goldilocks and the three bears (L. B. Cauley, Goldilocks and the Three Bears, 1981), mid-range resolution (i.e., family, genus, and OTU) is "just right" for optimal prediction of colorectal cancer from microbiome data. IMPORTANCE Despite being highly preventable, colorectal cancer remains a leading cause of cancer-related death in the United States. Low-cost, noninvasive detection methods could greatly improve our ability to identify and treat early stages of disease. The microbiome has shown promise as a resource for detection of colorectal cancer. Research on the gut microbiome tends to focus on improving our ability to profile species and strain level taxonomic resolution. However, we found that finer resolution impedes the ability to predict colorectal cancer based on the gut microbiome. These results highlight the need for consideration of the appropriate taxonomic resolution for microbiome analyses and that finer resolution is not always more informative.
| S-EPMC8749421 | biostudies-literature
Project description:BACKGROUND:Tuberculosis (TB) affects, and claims the lives of, millions every year. Despite efforts to find and treat TB, about four million cases were missed globally in 2017. Barriers to accessing health care, inadequate health-seeking behavior of the community, poor socioeconomic conditions, and stigma are major determinants of this gap. Unfortunately, TB-related stigma remains unexplored in Ethiopia. METHODS:This mixed methods survey was conducted using multistage cluster sampling to identify 32 districts and 8 sub-cities, from which 40 health centers were randomly selected. Twenty-one TB patients and 21 family members were enrolled from each health center, and 11 household members from each community in the catchment population. RESULTS:A total of 3463 participants (844 TB patients, 836 from their families, and 1783 from the general population) were enrolled for the study. The mean age and standard deviation were 34.3 ± 12.9 years for both sexes (34.9 ± 13.2 for men and 33.8 ± 12.5 for women). Fifty percent of the study participants were women; 32.1% were illiterate; and 19.8% came from the lowest wealth quintile. The mean stigma score was 18.6 for the general population, 20.5 for families, and 21.3 for TB patients. The general population of Addis Ababa (AOR: 0.1 [95% CI: 0.06-0.17]), those educated above secondary school (AOR: 0.58 [95% CI: 0.39-0.87]), and those with a high score for knowledge about TB (AOR: 0.62 [95% CI: 0.49-0.78]) had low stigma scores. Families of TB patients who attended above secondary school (AOR: 0.37 [95% CI: 0.23-0.61]) had low stigma scores. TB patients educated above secondary school (AOR: 0.61 [95% CI: 0.38-0.97]) had lower stigma scores, while those in the first (AOR: 1.93: 95% CI 1.05-3.57) and third quintiles (AOR: 1.81: 95% CI: 1.08-3.05) had stigma scores twice as high as those in the highest quintile. Fear of job loss (32.5%), isolation (15.3%), and feeling avoided (9.3%) affected disclosure about TB. CONCLUSIONS:More than a third of Ethiopians have high scores for TB-related stigma, which were associated with educational status, poverty, and lack of awareness about TB. Stigma matters in TB prevention, care, and treatment and warrants stigma reduction interventions.
| S-EPMC7006204 | biostudies-literature
Project description:BackgroundSouth Africa has one of the highest per capita rates of tuberculosis (TB) incidence in the world. In 2012, the South African government produced a National Strategic Plan (NSP) to control the spread of TB with the ambitious aim of zero new TB infections and deaths by 2032, and a halving of the 2012 rates by 2016.MethodsWe used a transmission model to investigate whether the NSP targets could be reached if immediate scale up of control methods had happened in 2014. We explored the potential impact of four intervention portfolios; 1) "NSP" represents the NSP strategy, 2) "WHO" investigates increasing antiretroviral therapy eligibility, 3) "Novel Strategies" considers new isoniazid preventive therapy strategies and HIV "Universal Test and Treat" and 4) "Optimised" contains the most effective interventions.FindingsWe find that even with this scale-up, the NSP targets are unlikely to be achieved. The portfolio that achieved the greatest impact was "Optimised", followed closely by "NSP". The "WHO" and "Novel Strategies" had little impact on TB incidence by 2050. Of the individual interventions explored, the most effective were active case finding and reductions in pre-treatment loss to follow up which would have a large impact on TB burden.ConclusionUse of existing control strategies has the potential to have a large impact on TB disease burden in South Africa. However, our results suggest that the South African TB targets are unlikely to be reached without new technologies. Despite this, TB incidence could be dramatically reduced by finding and starting more TB cases on treatment.
| S-EPMC4388715 | biostudies-literature
Project description:ObjectiveTo determine if severity of osteoarthritis-related knee pain is associated with a willingness to undergo total knee replacement (TKR) and whether this association is confounded or modified by components of socioeconomic status and health care coverage.MethodsCross-sectional analysis was conducted among 3,530 Osteoarthritis Initiative study participants. Logistic regression models were used to assess the effect of knee pain severity (where 0 = none, 1-3 = mild, 4-7 = moderate, and 8-10 = severe) on willingness to undergo TKR. Stratified analyses were conducted to evaluate whether socioeconomic status and health care coverage modify the effect of knee pain severity on willingness.ResultsParticipants with severe knee pain, compared to participants without pain, were less willing to undergo TKR (odds ratio [OR] 0.73, 95% confidence interval [95% CI] 0.57-0.93). This association was attenuated when adjusted for age, sex, comorbidity, depression, health insurance coverage, prescription medicine coverage, health care source, education, income, employment, race, and marital status (adjusted OR 0.92, 95% CI 0.68-1.24). The odds of willingness to undergo TKR were significantly lower in those with the highest level of pain, compared to those without pain, among participants without health insurance (adjusted OR 0.08, 95% CI 0.01-0.56), but not among those with health insurance (adjusted OR 1.03, 95% CI 0.73-1.38), when adjusted for demographic, clinical, health care access, and socioeconomic factors (P = 0.015). However, <5% of participants were without health insurance.ConclusionAmong participants without health insurance, severe knee pain was paradoxically associated with less willingness to undergo TKR. Policies that improve access to quality health care may affect patient preferences and increase utilization of TKR surgery among vulnerable populations.
| S-EPMC5525549 | biostudies-literature
Project description:The prevention of non-communicable diseases like cancer contributes to healthy aging. Dietary supplements might support such prevention; their effect likely depends on the personal characteristics of the individuals receiving them. To evaluate the influence of sex on reducing cancer incidence with multivitamin-multimineral (MVM) supplementation, sex-specific results of the efficacy of MVM supplementation for cancer prevention were collected and meta-analyzed (using fixed effect (FE) and random effect (RE) models). Three trials included in the "US Preventive Services Task Force Recommendation Statement Report regarding Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer" were used, namely, COSMOS, SU.VI.MAX, and PHS2. A total of 28,558 men and 20,542 women were included. Multivitamin-multimineral supplementation significantly reduced cancer incidence in the entire population (HR 0.93 [95% CI, 0.88-0.99], FE and RE); sex-specific meta-analysis showed beneficial effects of supplementation in men (HR 0.91 [95% CI, 0.85-0.97] (FE)/0.88 [95% CI, 0.77-1.01] (RE)); however, there was no effect in women (HR 1.00 [95% CI, 0.88-1.14], FR and RE); (Pdifference = 0.17). Sex could influence the effect of MVM supplementation in reducing cancer incidence, with supplementation being effective only in male individuals. These results might be informative for future research and public health policy makers.
| S-EPMC10828342 | biostudies-literature
Project description:Mycobacterium tuberculosis (Mt) produces complex virulence-enhancing lipids with scaffolds consisting of phthiocerol and phthiodiolone dimycocerosate esters (PDIMs). Sequence analysis suggested that PapA5, a so-called polyketide-associated protein (Pap) encoded in the PDIM synthesis gene cluster, as well as PapA5 homologs found in Mt and other species, are a subfamily of acyltransferases. Studies with recombinant protein confirmed that PapA5 is an acyltransferase [corrected]. Deletion analysis in Mt demonstrated that papA5 is required for PDIM synthesis. We propose that PapA5 catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosate. These studies present the functional characterization of a Pap and permit inferences regarding roles of other Paps in the synthesis of complex lipids, including the antibiotic rifamycin.
| S-EPMC384794 | biostudies-literature
Project description:RhCMV-based TB vaccines are able to elicit and maintain immune effector responses that can control Mtb at the earliest stages of infection, and the protection afforded by this vaccine can be complete, if not sterilizing. To our knowledge, this is the first demonstration of complete prevention of TB disease in Rhesus Macaques (RM) by a long-acting vaccine after highly pathogenic (Erdman strain) Mtb challenge.
2017-12-26 | GSE102440 | GEO
Project description:Timing matters: Impacts of host selection and social environment on gut microbiota vary over host ontogeny in estrildid finches
| PRJEB53212 | ENA
Project description:Tuberculosis is one of the most threatening infectious diseases and represents an important and significant reason for mortality in high-burden regions. The only licensed vaccine, BCG, is hardly capable of establishing long-term tuberculosis protection and is highly variable in its effectiveness. Even after 100 years of BCG use and research, we still cannot unequivocally answer the question of which immune correlates of protection are crucial to prevent Mycobacterium tuberculosis (Mtb) infection or the progression of the disease. The development of a new vaccine against tuberculosis arises a nontrivial scientific challenge caused by several specific features of the intracellular lifestyle of Mtb and the ability of the pathogen to manipulate host immunity. The purpose of this review is to discuss promising strategies and the possibilities of creating a new vaccine that could replace BCG and provide greater protection. The considered approaches include supplementing mycobacterial strains with immunodominant antigens and genetic engineering aimed at altering the interaction between the bacterium and the host cell, such as the exit from the phagosome. Improved new vaccine strains based on BCG and Mtb undergoing clinical evaluation are also overviewed.
| S-EPMC9863999 | biostudies-literature