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Frontiers in Cellular and Infection... 2024The rapid detection of Mycobacterium tuberculosis (MTB) is essential for controlling tuberculosis. We designed a portable thermocycler-based real-time fluorescence...
BACKGROUND
The rapid detection of Mycobacterium tuberculosis (MTB) is essential for controlling tuberculosis. We designed a portable thermocycler-based real-time fluorescence loop-mediated isothermal amplification assay (cyp141-RealAmp) using six oligonucleotide primers derived from cyp141 to detect MTB. A combined number of 213 sputum samples (169 obtained from clinically diagnosed cases of pulmonary TB and 44 from a control group without tuberculosis) underwent Acid-fast bacillus (AFB) smear, culture, Xpert MTB/RIF assays, and cyp141-RealAmp assay.
RESULTS
By targeting MTB cyp141, this technique could detect as low as 10 copies/reaction within 30 min, and it was successfully rejected by other mycobacteria and other bacterial species tested. Of the 169 patients, there was no statistical difference between the detection rate of cyp141-RealAmp (92.90%, 95% CI: 89.03-96.07) and that of Xpert MTB/RIF (94.67%, 95% CI: 91.28-98.06) ( > 0.05), but both were statistically higher than that of culture (65.68%, 95% CI: 58.52-72.84) (< 0.05) and AFB (57.40%, 95% CI: 49.94-64.86) (< 0.05). Both cyp141-RealAmp and Xpert MTB/RIF had a specificity of 100%. Furthermore, a high concordance between cyp141-RealAmp and Xpert MTB/RIF was found ( = 0.89).
CONCLUSION
The cyp141-RealAmp assay was shown to be effective, responsive, and accurate in this study. This method offers a prospective strategy for the speedy and precise detection of MTB.
Topics: Mycobacterium tuberculosis; Humans; Nucleic Acid Amplification Techniques; Sensitivity and Specificity; Molecular Diagnostic Techniques; Sputum; Tuberculosis, Pulmonary; DNA Primers; Female; Fluorescence; Adult; Male; Tuberculosis; Middle Aged
PubMed: 38938885
DOI: 10.3389/fcimb.2024.1349063 -
Assessing the quality of life in patients with drug-resistant tuberculosis: a cross-sectional study.BMC Pulmonary Medicine Jun 2024This study investigated the current status of the quality of life (QOL) of drug-resistant tuberculosis (DR-TB) patients in Nanjing, China, and analyzed the influencing...
BACKGROUND
This study investigated the current status of the quality of life (QOL) of drug-resistant tuberculosis (DR-TB) patients in Nanjing, China, and analyzed the influencing factors.
METHODS
The survey was conducted among patients with DR-TB who were hospitalized in the tuberculosis department of the Second Hospital of Nanjing (Nanjing Public Health Medical Center) from July 2022 to May 2023. The Chinese version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was used to investigate the QOL levels of patients with DR-TB, and a multiple linear regression model was used to analyze the QOL influencing factors.
RESULTS
A total of 135 patients participated in the study; 69.6% were male, the average age was 46.30 ± 17.98 years, 13.33% had an education level of elementary school or below, and 75.56% were married. The QOL scores were 51.35 ± 17.24, 47.04 ± 20.28, 43.89 ± 17.96, and 35.00 ± 11.57 in the physiological, psychological, social, and environmental domains, respectively. The differences between the four domain scores and the Chinese normative results were statistically significant (P < 0.05). The results of multiple linear regression analysis showed that the factors related to the physiological domain included residence, family per-capita monthly income, payment method, adverse drug reactions (ADRs), and comorbidities; psychological domain correlates included educational level, family per-capita monthly income, course of the disease, and caregivers; social domain correlates included age and comorbidities; and factors related to the environmental domain included age, education level, and comorbidities.
CONCLUSIONS
In Nanjing, China, patients with younger age, higher education level, living in urban areas, high family per-capita monthly income, no adverse drug reactions, no comorbidities, and having caregivers have better quality of life. Future interventions to improve the quality of life of patients with drug-resistant tuberculosis could be tailored to a specific factor.
Topics: Humans; Quality of Life; Male; Female; Tuberculosis, Multidrug-Resistant; Middle Aged; Cross-Sectional Studies; Adult; China; Surveys and Questionnaires; Linear Models; Aged
PubMed: 38937809
DOI: 10.1186/s12890-024-03119-1 -
BMC Infectious Diseases Jun 2024Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has...
BACKGROUND
Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has been deemed a risk condition to develop mycobacterial infection, as a result of the immunosuppressive treatments. TB, in turn, can be a predisposing factor for secondary infections.
CASE PRESENTATION
Here we present a case of a 28-year-old indigenous woman from Colombia, previously diagnosed with AIHA and pulmonary TB. Despite various treatments, therapies and medical interventions, the patient died after severe medullary aplasia of multiple causes, including secondary myelotoxicity by immunosuppressive therapy and secondary disseminated infections, underlining infection by Staphylococcus aureus, Klebsiella pneumoniae and Candida glabrata, which were identified as drug-resistant microorganisms. Together, this led to significant clinical complications. Invasive aspergillosis was diagnosed at autopsy.
CONCLUSIONS
This report presents a rarely finding of AIHA followed by TB, and highlights the great challenges of dealing with co-infections, particularly by drug resistant pathogens. It also aims to spur governments and public health authorities to focus attention in the prevention, screening and management of TB, especially among vulnerable communities, such as indigenous people.
Topics: Humans; Female; Adult; Coinfection; Fatal Outcome; Anemia, Hemolytic, Autoimmune; Colombia; Klebsiella pneumoniae; Staphylococcus aureus; Candida glabrata; Tuberculosis, Pulmonary; Staphylococcal Infections; Indigenous Peoples; Candidiasis
PubMed: 38937714
DOI: 10.1186/s12879-024-09557-w -
Nature Communications Jun 2024The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT...
The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT subfamily of TA systems have been functionally characterized. We demonstrate that ectopic expression of these toxins inhibits bacterial growth and this is rescued upon co-expression of their cognate antitoxins. Here, we show that simultaneous deletion of menT3 and menT4 results in enhanced susceptibility of M. tuberculosis upon exposure to oxidative stress and attenuated growth in guinea pigs and mice. We observed reduced expression of transcripts encoding for proteins that are essential or required for intracellular growth in mid-log phase cultures of ΔmenT4ΔT3 compared to parental strain. Further, the transcript levels of proteins involved in efficient bacterial clearance were increased in lung tissues of ΔmenT4ΔT3 infected mice relative to parental strain infected mice. We show that immunization of mice and guinea pigs with ΔmenT4ΔT3 confers significant protection against M. tuberculosis infection. Remarkably, immunization of mice with ΔmenT4ΔT3 results in increased antigen-specific T1 bias and activated memory T cell response. We conclude that MenT3 and MenT4 are important for M. tuberculosis pathogenicity and strains lacking menT3 and menT4 have the potential to be explored further as vaccine candidates.
Topics: Animals; Guinea Pigs; Mycobacterium tuberculosis; Mice; Bacterial Proteins; Tuberculosis; Female; Lung; Gene Deletion; Bacterial Toxins; Mice, Inbred C57BL; Tuberculosis Vaccines; Oxidative Stress; Virulence
PubMed: 38937463
DOI: 10.1038/s41467-024-49246-5 -
Nature Communications Jun 2024Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods...
Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose - 2-[F]fluoro-2-deoxytrehalose ([F]FDT) - is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [F]FDT from the most globally-abundant organic F-containing molecule, [F]FDG. The full, pre-clinical validation of both production method and [F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [F]FDT directly from the widely-available clinical reagent [F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.
Topics: Animals; Mycobacterium tuberculosis; Positron-Emission Tomography; Trehalose; Tuberculosis; Humans; Mice; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Radiopharmaceuticals; Disease Models, Animal; Female
PubMed: 38937448
DOI: 10.1038/s41467-024-48691-6 -
Global Health, Science and Practice Jun 2024Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy...
Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.
Topics: Humans; Vietnam; COVID-19; Tuberculosis, Pulmonary; Mass Screening; SARS-CoV-2; Middle Aged; Radiography, Thoracic; Tuberculosis; Female; Pandemics; Male; Vulnerable Populations
PubMed: 38936961
DOI: 10.9745/GHSP-D-24-00024 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic review aimed to evaluate the epidemiology and impact of eumycetoma. PubMed and Web of Science were searched to identify studies published between 1 January 2011 and 19 February 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 14 studies were eligible for inclusion. Morbidity was frequent with moderate to severe impairment of quality of life in 60.3%, amputation in up to 38.5%, and recurrent or long-term disease in 31.8%-73.5% of patients. Potential risk factors included male gender (56.6%-79.6%), younger age (11-30 years; 64%), and farming occupation (62.1%-69.7%). Mycetoma was predominantly reported in Sudan, particularly in central Sudan (37%-76.6% of cases). An annual incidence of 0.1/100 000 persons and 0.32/100 000 persons/decade was reported in the Philippines and Uganda, respectively. In Uganda, a decline in incidence from 3.37 to 0.32/100 000 persons between two consecutive 10-year periods (2000-2009 and 2010-2019) was detected. A community-based, multi-pronged prevention programme was associated with a reduction in amputation rates from 62.8% to 11.9%. With the pre-specified criteria, no studies of antifungal drug susceptibility, mortality, and hospital lengths of stay were identified. Future research should include larger cohort studies, greater drug susceptibility testing, and global surveillance to develop evidence-based treatment guidelines and to determine more accurately the incidence and trends over time.
Topics: Humans; Mycetoma; Incidence; Antifungal Agents; World Health Organization; Risk Factors; Male; Female; Quality of Life
PubMed: 38935904
DOI: 10.1093/mmy/myae044 -
PloS One 2024Tuberculosis is a serious life-threatening disease among the top global health challenges and rapid and effective diagnostic biomarkers are vital for early diagnosis...
BACKGROUND
Tuberculosis is a serious life-threatening disease among the top global health challenges and rapid and effective diagnostic biomarkers are vital for early diagnosis especially given the increasing prevalence of multidrug resistance.
METHODS
Two human whole blood microarray datasets, GSE42826 and GSE42830 were retrieved from publicly available gene expression omnibus (GEO) database. Deregulated genes (DEGs) were identified using GEO2R online tool and Gene Ontology (GO), protein-protein interaction (PPI) network analysis was performed using Metascape and STRING databases. Significant genes (n = 8) were identified using T-test/ANOVA and Molecular Complex Detection (MCODE) score ≥10, which was validated in GSE34608 dataset. The diagnostic potential of three biomarkers was assessed using Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) plot. The transcriptional levels of these genes were also examined in a separate dataset GSE31348, to monitor the patterns of variation during tuberculosis treatment.
RESULTS
A total of 62 common DEGs (57 upregulated, 7 downregulated genes) were identified in two discovery datasets. GO functions and pathway enrichment analysis shed light on the functional roles of these DEGs in immune response and type-II interferon signaling. The genes in Module-1 (n = 18) were linked to innate immune response, interferon-gamma signaling. The common genes (n = 8) were validated in GSE34608 dataset, that corroborates the results obtained from discovery sets. The gene expression levels demonstrated responsiveness to Mtb infection during anti-TB therapy in GSE31348 dataset. In GSE34608 dataset, the expression levels of three specific genes, GBP5, IFITM3, and EPSTI1, emerged as potential diagnostic makers. In combination, these genes scored remarkable diagnostic performance with 100% sensitivity and 89% specificity, resulting in an impressive Area Under Curve (AUC) of 0.958. However, GBP5 alone showed the highest AUC of 0.986 with 100% sensitivity and 89% specificity.
CONCLUSIONS
The study presents valuable insights into the critical gene network perturbed during tuberculosis. These genes are determinants for assessing the effectiveness of an anti-TB response and distinguishing between active TB and healthy individuals. GBP5, IFITM3 and EPSTI1 emerged as candidate core genes in TB and holds potential as novel molecular targets for the development of interventions in the treatment of TB.
Topics: Humans; Tuberculosis; Protein Interaction Maps; RNA-Seq; Computational Biology; Gene Expression Profiling; ROC Curve; Gene Regulatory Networks; Databases, Genetic; Biomarkers; Gene Ontology
PubMed: 38935691
DOI: 10.1371/journal.pone.0305582 -
Impact of COVID-19 Pandemic on Tuberculosis Care and Treatment in Puducherry - A Mixed Method Study.Indian Journal of Public Health Oct 2023The shift of focus toward pandemic control had an impact on public health issues that need to be addressed. As the impact may vary in the different areas based on...
BACKGROUND
The shift of focus toward pandemic control had an impact on public health issues that need to be addressed. As the impact may vary in the different areas based on COVID-19 cases and strictness of measures to control the disease, studying the local situation and related factors is essential to strengthening the TB program.
OBJECTIVES
The objective is to compare the TB care before and during the COVID-19 pandemic and to explore the challenges faced by stakeholders during the pandemic.
MATERIALS AND METHODS
A mixed method study was conducted in Puducherry with a quantitative phase involving data extraction from the National TB Elimination Programme (NTEP), followed by in-depth interviews to explore the challenges faced by stakeholders.
RESULTS
In 2020, there were 67% and 23% reductions in number of presumptive TB case and notified TB cases, respectively, while the decline was lesser in the year 2021 (reduction of 59% and 13%, respectively). The main challenges faced in providing and accessing TB care were social stigma, lockdown restrictions, fear of getting COVID-19, redeployment of staff to COVID-19-related activities and increased COVID-19 workload.
CONCLUSIONS
There is a need to strengthen active case finding for the missed TB cases through the mobile vans equipped with diagnostics, combined testing for COVID-19 and TB, greater inclusion of private sector and dispensaries as well as community awareness for stigma prevention.
Topics: Humans; COVID-19; India; Tuberculosis; SARS-CoV-2; Pandemics; Social Stigma; Health Services Accessibility
PubMed: 38934831
DOI: 10.4103/ijph.ijph_1406_22 -
Indian Journal of Public Health Oct 2023National Strategic Plan to End tuberculosis (TB) in India 2020-2025 aims to prevent the emergence of TB in susceptible populations. Airborne infection control (AIC)...
BACKGROUND
National Strategic Plan to End tuberculosis (TB) in India 2020-2025 aims to prevent the emergence of TB in susceptible populations. Airborne infection control (AIC) practices in high-risk settings like homes for the aged (HFA) will be essential to achieve this.
OBJECTIVE
The objective is to assess the AIC practices (AICPs) in HFA in the Kollam district in Kerala, India.
MATERIALS AND METHODS
A mixed method approach was used. the study was done in five HFA s in a southern district of Kerala to find AICPs. Using purposive sampling, in-depth interviews was conducted among inmates with recent respiratory infection and administrators. Environmental measures were assessed using an observation checklist.
RESULTS
Ventilation was inadequate in 25%-40% of HFA. Air change per hour and distance between beds were less. Very few inmates were aware of the need for proper ventilation and personal hygiene. Wearing masks and hand hygiene was not practiced. Administrators faced shortages of space, funds, and human resources for caring for hospitalized inmates, and psychiatric and terminally ill patients.
CONCLUSIONS
There is a need to train the staff and inmates on AIC. Infrastructural improvements, like the use of partition screens in the short term and the creation of model airborne infection control HFA in the long run, with a collaborative effort from health professionals and architects, are needed for TB elimination efforts to succeed.
Topics: Humans; India; Ventilation; Infection Control; Tuberculosis; Homes for the Aged; Interviews as Topic; Male
PubMed: 38934828
DOI: 10.4103/ijph.ijph_912_22