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Methods in Molecular Biology (Clifton,... 2024Mycobacterium tuberculosis is the main causative agent of tuberculosis (TB)-an ancient yet widespread global infectious disease to which 1.6 million people lost their...
Mycobacterium tuberculosis is the main causative agent of tuberculosis (TB)-an ancient yet widespread global infectious disease to which 1.6 million people lost their lives in 2021. Antimicrobial resistance (AMR) has been an ongoing crisis for decades; 4.95 million deaths were associated with antibiotic resistance in 2019. While AMR is a multi-faceted problem, drug discovery is an urgent part of the solution and is at the forefront of modern research.The landscape of drug discovery for TB has undoubtedly been transformed by the development of high-throughput gene-silencing techniques that enable interrogation of every gene in the genome, and their relative contribution to fitness, virulence, and AMR. A recent advance in this area is CRISPR interference (CRISPRi). The application of this technique to antimicrobial susceptibility testing (AST) is the subject of ongoing research in basic science.CRISPRi technology can be used in conjunction with the high-throughput SPOT-culture growth inhibition assay (HT-SPOTi) to rapidly evaluate and assess gene essentiality including non-essential, conditionally essential (by using appropriate culture conditions), and essential genes. In addition, the HT-SPOTi method can develop drug susceptibility and drug resistance profiles.This technology is further useful for drug discovery groups who have designed target-based inhibitors rationally and wish to validate the primary mechanisms of their novel compounds' antibiotic action against the proposed target.
Topics: Microbial Sensitivity Tests; Mycobacterium tuberculosis; Drug Discovery; Gene Silencing; Humans; CRISPR-Cas Systems; Antitubercular Agents; Anti-Bacterial Agents; High-Throughput Screening Assays; Drug Resistance, Bacterial; Tuberculosis
PubMed: 38949697
DOI: 10.1007/978-1-0716-3981-8_3 -
Curationis Jun 2024In South Africa, screening for tuberculosis during pregnancy is a serious challenge. Tuberculosis is one of the leading indirect causes of mortality in pregnant women.
BACKGROUND
In South Africa, screening for tuberculosis during pregnancy is a serious challenge. Tuberculosis is one of the leading indirect causes of mortality in pregnant women.
OBJECTIVES
The objective of the study was to explore the challenges experienced by midwives regarding tuberculosis in pregnant women.
METHOD
A qualitative exploratory research method was used to conduct the study. The study population comprised midwives who worked at primary healthcare clinics in the selected local area, Capricorn District, Limpopo province. Purposive non-probability sampling was used to select 10 participants. Data from participants were acquired using in-depth individual semi-structured interviews. Data analysis was carried out using manual thematic analysis following Tesch's technique.
RESULTS
The outcomes of this study included midwives knowing their roles regarding tuberculosis screening among pregnant women. They further highlighted their challenges while screening tuberculosis in pregnant women, such as shortage of screening tools, withholding of tuberculosis information, and language barrier.
CONCLUSION
Midwives should have the necessary equipment and be trained in various languages used in the province to improve tuberculosis screening among all pregnant women.Contribution: Infected pregnant women and their unborn children's health can be improved by tuberculosis screening.
Topics: Humans; South Africa; Female; Pregnancy; Mass Screening; Midwifery; Qualitative Research; Tuberculosis; Adult; Interviews as Topic
PubMed: 38949423
DOI: 10.4102/curationis.v47i1.2533 -
Frontiers in Public Health 2024The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in...
Epidemiology and antimicrobial resistance of spp. in the United Arab Emirates: a retrospective analysis of 12 years of national antimicrobial resistance surveillance data.
INTRODUCTION
The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce.
METHODS
A retrospective 12-year analysis of = 8,086 non-duplicate diagnostic complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/).
RESULTS
A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021).
CONCLUSION
Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.
Topics: United Arab Emirates; Humans; Retrospective Studies; Tuberculosis, Multidrug-Resistant; Male; Mycobacterium tuberculosis; Female; Adult; Antitubercular Agents; Middle Aged; Drug Resistance, Bacterial; Adolescent; Microbial Sensitivity Tests; Young Adult; Population Surveillance
PubMed: 38947352
DOI: 10.3389/fpubh.2024.1244353 -
Frontiers in Immunology 2024Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of...
INTRODUCTION
Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease.
METHODS
To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa.
RESULTS
Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1.
DISCUSSION
Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis.
Topics: Humans; Neutrophils; Male; Adult; Female; HIV Infections; Immunophenotyping; Tuberculosis, Pulmonary; South Africa; Coinfection; Middle Aged; Phenotype; Flow Cytometry; Young Adult; Mycobacterium tuberculosis
PubMed: 38947330
DOI: 10.3389/fimmu.2024.1422836 -
The Pan African Medical Journal 2024Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our...
Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4 month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
Topics: Humans; Male; Young Adult; Antitubercular Agents; Magnetic Resonance Imaging; Epididymis; Tuberculosis, Male Genital; Immunocompetence; Orchiectomy; Seizures; Anticonvulsants; Tuberculoma, Intracranial
PubMed: 38946746
DOI: 10.11604/pamj.2024.48.2.42965 -
Lancet (London, England) Jun 2024
Topics: Humans; Armed Conflicts; Epidemics; Mass Screening; Mobile Health Units; Tuberculosis; Ukraine
PubMed: 38945133
DOI: 10.1016/S0140-6736(24)01342-4 -
BMC Infectious Diseases Jun 2024Nocardia species can affect both immunocompetent and immunocompromised people. (Comparative Study)
Comparative Study
BACKGROUND
Nocardia species can affect both immunocompetent and immunocompromised people.
METHOD
This retrospective study, from 2009 to 2022, aims to compare the survival analyses of pulmonary nocardiosis in AIDS and non-AIDS patients in northeastern Thailand.
RESULTS
A total of 215 culture-confirmed cases of pulmonary nocardiosis: 97 with AIDS and 118 without AIDS. The median CD4 count of AIDS patients was 11 cells/µL (range: 1-198), and 33% had concurrent opportunistic infections. 63.6% of 118 non-AIDS patients received immunosuppressive medications, 28.8% had comorbidities, and 7.6% had no coexisting conditions. Disseminated nocardiosis and pleural effusion were more prevalent among AIDS patients, whereas non-AIDS patients revealed more shock and respiratory failure. One hundred-fifty patients underwent brain imaging; 15 (10%) had brain abscesses. Patients with pulmonary nocardiosis have overall 30-day and 1-year mortality rates of 38.5% (95% CI: 32.3%, 45.4%) and 52.1% (95% CI: 45.6%, 58.9%), respectively. The Cox survival analysis showed that AIDS patients with disseminated nocardiosis had a 7.93-fold (95% CI: 2.61-24.02, p < 0.001) increased risk of death within 30 days compared to non-AIDS patients when considering variables such as age, Charlson comorbidity index, concurrent opportunistic infections, duration of illness, shock, respiratory failure, multi-lobar pneumonia, lung abscesses, and combination antibiotic therapy. While AIDS and pulmonary nocardiosis had a tendency to die within 30 days (2.09 (95% CI, 0.74-5.87, p = 0.162)).
CONCLUSION
AIDS with pulmonary nocardiosis, particularly disseminated disease, is a serious opportunistic infection. Early diagnosis and empiric treatment with a multidrug regimen may be the most appropriate approach in a resource-limited setting.
Topics: Humans; Nocardia Infections; Male; Female; Retrospective Studies; Adult; Middle Aged; Thailand; AIDS-Related Opportunistic Infections; Acquired Immunodeficiency Syndrome; Aged; Nocardia; Anti-Bacterial Agents; Young Adult; CD4 Lymphocyte Count; Immunocompromised Host
PubMed: 38943055
DOI: 10.1186/s12879-024-09519-2 -
Scientific Reports Jun 2024In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of...
In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of Google teachable machine, a deep neural network-based image classification tool, to develop algorithm for predicting TB probability of CXRs. The training dataset included 348 TB CXRs and 3806 normal CXRs for training TB detection. We also collected 1150 abnormal CXRs and 627 normal CXRs for training abnormality detection. For external validation, we collected 250 CXRs from our hospital. We also compared the accuracy of the algorithm to five pulmonologists and radiological reports. In external validation, the AI algorithm showed areas under the curve (AUC) of 0.951 and 0.975 in validation dataset 1 and 2. The accuracy of the pulmonologists on validation dataset 2 showed AUC range of 0.936-0.995. When abnormal CXRs other than TB were added, AUC decreased in both human readers (0.843-0.888) and AI algorithm (0.828). When combine human readers with AI algorithm, the AUC further increased to 0.862-0.885. The TB CXR AI algorithm developed by using Google teachable machine in this study is effective, with the accuracy close to experienced clinical physicians, and may be helpful for detecting tuberculosis by CXR.
Topics: Humans; Deep Learning; Tuberculosis, Pulmonary; Radiography, Thoracic; Algorithms; Female; Male; Middle Aged; Adult; Area Under Curve
PubMed: 38942819
DOI: 10.1038/s41598-024-65703-z -
Scientific Reports Jun 2024Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's Disease, a chronic granulomatous enteritis of ruminants. MAP establishes an...
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's Disease, a chronic granulomatous enteritis of ruminants. MAP establishes an infection in the host via the small intestine. This requires the bacterium to adhere to, and be internalised by, cells of the intestinal tract. The effector molecules expressed by MAP for this purpose remain to be fully identified and understood. Mammalian cell entry (mce) proteins have been shown to enable other Mycobacterial species to attach to and invade host epithelial cells. Here, we have expressed Mce1A, Mce1D, Mce3C and Mce4A proteins derived from MAP on the surface of a non-invasive Escherichia coli to characterise their role in the initial interaction between MAP and the host. To this end, expression of mce1A was found to significantly increase the ability of the E. coli to attach and survive intracellularly in human monocyte-like THP-1 cells, whereas expression of mce1D was found to significantly increase attachment and invasion of E. coli to bovine epithelial cell-like MDBK cells, implying cell-type specificity. Furthermore, expression of Mce1A and Mce1D on the surface of a previously non-invasive E. coli enhanced the ability of the bacterium to infect 3D bovine basal-out enteroids. Together, our data contributes to our understanding of the effector molecules utilised by MAP in the initial interaction with the host, and may provide potential targets for therapeutic intervention.
Topics: Mycobacterium avium subsp. paratuberculosis; Paratuberculosis; Animals; Humans; Cattle; Bacterial Proteins; Bacterial Adhesion; Epithelial Cells; Escherichia coli; Cell Line; THP-1 Cells
PubMed: 38942800
DOI: 10.1038/s41598-024-65592-2 -
Annals of Agricultural and... Jun 2024. Pets infected with zoonotic pathogens might become a source of infections for their owners, especially those who are immuno-compromised. The aim of this report is to...
. Pets infected with zoonotic pathogens might become a source of infections for their owners, especially those who are immuno-compromised. The aim of this report is to describe a case of chronic, untreatable pneumonia in a domestic ferret. The subject was a 5-year-old female ferret suffering from recurrent pneumonia. Ante-mortally, swabs from the nasal cavity, alveolus and throat were collected from the animal. Post-mortally, lesioned organ fragments were collected. Standard microbiological testing was performed. Additionally, mycobacterial diagnosis including culture and molecular tests was performed. . The co-infection of Mycobacterium avium and Klebsiella pneumoniae was microbiologically confirmed. This case demonstrates the need to pay attention to the possibility of zoonotic pathogens in ferrets. Veterinarians diagnosing ferrets are potentially exposed to Mycobacteria spp. infections and other pathogens.
Topics: Animals; Ferrets; Female; Klebsiella pneumoniae; Coinfection; Klebsiella Infections; Mycobacterium avium; Tuberculosis; Fatal Outcome
PubMed: 38940116
DOI: 10.26444/aaem/174216