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Global Public Health Jan 2024The emergent threat of antimicrobial resistance (AMR) has resulted in debates around the use and preservation of effective antimicrobials. Concerns around AMR reflect a... (Review)
Review
Cycles of antibiotic use and emergent antimicrobial resistance in the South African tuberculosis programme (1950-2021): A scoping review and critical reflections on stewardship.
The emergent threat of antimicrobial resistance (AMR) has resulted in debates around the use and preservation of effective antimicrobials. Concerns around AMR reflect a history of increasing dependence on antibiotics to address disease epidemics rooted in profound structural and systemic challenges. In the context of global health, this process, often referred to as pharmaceuticalisation, has commonly occurred within disease programmes, of which lessons are vital for adding nuance to conversations around antimicrobial stewardship. Tuberculosis (TB) is a notable example. A disease which accounts for one-third of AMR globally and remains the leading cause of death from a single infectious agent in many low - and middle-income countries, including South Africa. In this scoping review, we chart TB science in South Africa over 70 years of programming. We reviewed published manuscripts about the programme and critically reflected on the implications of our findings for stewardship. We identified cycles of programmatic responses to new drug availability and the emergence of drug resistance, which intersected with cycles of pharmaceuticalisation. These cycles reflect the political, economic, and social factors influencing programmatic decision-making. Our analysis offers a starting point for research exploring these cycles and drawing out implications for stewardship across the TB and AMR communities.
Topics: Humans; South Africa; Antimicrobial Stewardship; Tuberculosis; Anti-Bacterial Agents; Drug Resistance, Microbial; Antitubercular Agents; History, 20th Century; Drug Resistance, Bacterial
PubMed: 38771831
DOI: 10.1080/17441692.2024.2356623 -
PloS One 2024Tuberculosis (TB) is a global public health problem. Evaluation of TB treatment outcome enables health institutions to measure and improve the effectiveness of TB...
BACKGROUND
Tuberculosis (TB) is a global public health problem. Evaluation of TB treatment outcome enables health institutions to measure and improve the effectiveness of TB control programs. This study aimed to assess treatment outcomes of tuberculosis and identify associated factors among TB patients registered at Alemgena Health Center, Oromia, Ethiopia.
METHOD
A retrospective study was conducted; Secondary data were collected from medical records of 1010 TB patients treated at Alemgena Health Center between September 2012 and August 2018, inclusively. Logistic regression was used to identify factors associated with TB treatment outcomes. P-value less than 0.05 was considered statistically significant.
RESULTS
The proportion of males and females was almost equal. Among the patients 64.7% were in the age group 15-34, 98% were new cases, 31.2% were smear positive, 13% were HIV positive and 40.3% had extra-pulmonary tuberculosis. 94.2% of the patients had successful treatment outcome, with 26.9% cured and 67.3% treatment completed, whereas 5.8% had unsuccessful treatment outcomes, of whom 4.2% died and 1.5% defaulted. Death rate was higher among patients older than 44 years (10.4%) than among children (0%). In bivariate logistic regression analysis, treatment success rate was 3.582 (95% CI 1.958-6.554, p-value = .000) times higher in the age group 44 and below compared to the age group 45 and above.
CONCLUSION
Treatment success rate exceeded the one targeted by WHO. Age was found to be associated with treatment outcome. Success rate has to be improved for TB patients in the age group greater than 45 years of age.
Topics: Humans; Ethiopia; Female; Male; Adult; Adolescent; Retrospective Studies; Middle Aged; Child; Young Adult; Tuberculosis; Treatment Outcome; Antitubercular Agents; Child, Preschool; Infant; Logistic Models
PubMed: 38771813
DOI: 10.1371/journal.pone.0303797 -
International Journal of... Jan 2024Disseminated tuberculosis (dTB) disease is associated with a significant burden of morbidity and mortality and it requires improved awareness among clinicians. Case...
BACKGROUND
Disseminated tuberculosis (dTB) disease is associated with a significant burden of morbidity and mortality and it requires improved awareness among clinicians. Case reports revealing the clinical and microbiological characteristics of dTB patients will help us to extend our knowledge of dTB. In our study, we have documented dTB cases followed for 6 years and revealed patients' clinical characteristics.
METHODS
Patients followed between 2017 and 2023 who were diagnosed with dTB in a tertiary referral hospital in Istanbul have been evaluated. Data regarding patients' characteristics, methods used in establishing the definitive diagnosis, radiological patterns in chest X-rays, extrapulmonary sites involved, antituberculosis (TB) treatment regimens received, medication side effects, and drug resistance have been examined. Descriptive statistics were performed.
RESULTS
Clinical characteristics of 55 patients with a median age of 41 (range 20-85, 52.7% male) were examined. The most common extrapulmonary involvements in our study were the skeletal system (n = 24), central nervous system (n = 7), and genitourinary tract (n = 7). Isoniazid (INH) resistance was detected in four patients. Mono resistance was reported for pyrazinamide in one patient. Multidrug resistance was detected in two patients and one of them was also resistant to ethambutol. Preextensively, drug resistance was reported in three patients. Another three patients were evaluated as resistant to both INH and streptomycin.
CONCLUSION
Migrating from a high TB burden country and comorbidities such as diabetes mellitus, human immunodeficiency virus, and rheumatoid arthritis that are related to immunocompromisation are thought to be risk factors for dTB.
Topics: Humans; Male; Tertiary Care Centers; Female; Adult; Middle Aged; Antitubercular Agents; Aged; Young Adult; Aged, 80 and over; Mycobacterium tuberculosis; Turkey; Tuberculosis, Multidrug-Resistant; Tuberculosis; Isoniazid; Retrospective Studies; Tuberculosis, Miliary
PubMed: 38771287
DOI: 10.4103/ijmy.ijmy_12_24 -
International Journal of... Jan 2024Rapid detection of tuberculosis (TB) and its resistance are essential for the prompt initiation of correct drug therapy and for stopping the spread of drug-resistant TB....
BACKGROUND
Rapid detection of tuberculosis (TB) and its resistance are essential for the prompt initiation of correct drug therapy and for stopping the spread of drug-resistant TB. There is an urgent need for increased use of rapid diagnostic tests to control the threat of increased TB and multidrug-resistant TB (MDR-TB).
METHODS
EMPE Diagnostics has developed a multiplex molecular diagnostic platform called mfloDx™ by combining nucleotide-specific padlock probe-dependent rolling circle amplification with sensitive lateral flow biosensors, providing visual signals, similar to a COVID-19 test. The first test kit of this platform, mfloDx™ MDR-TB can identify Mycobacterium tuberculosis (MTB) complex and its clinically significant mutations in the rpoB and katG genes and in the inhA promotor contributing resistance to rifampicin (RIF) and isoniazid (INH), causing MDR-TB.
RESULTS
We have evaluated the performance of the mfloDx™ MDR-TB test on 210 sputum samples (110 from suspected TB cases and 100 from TB-negative controls) received from a tertiary care center in India. The clinical sensitivity for detecting MTB compared to acid-fast microscopy and mycobacteria growth indicator tube (MGIT) cultures was 86.4% and 84.9%, respectively. All the 100 control samples were negative indicating excellent specificity. In smear-positive sputum samples, the mfloDx™ MDR-TB test showed a sensitivity of 92.5% and 86.4% against MGIT culture and Xpert MTB/RIF, respectively. The clinical sensitivity for the detection of RIF and INH resistance in comparison with MGIT drug susceptibility testing was 100% and 84.6%, respectively, while the clinical specificity was 100%.
CONCLUSION
From the above evaluation, we find mfloDx™ MDR-TB to be a rapid and efficient test to detect TB and its multidrug resistance in 3 h at a low cost making it suitable for resource-limited laboratories.
Topics: Rifampin; Humans; Isoniazid; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Sensitivity and Specificity; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; Sputum; Bacterial Proteins; India; Molecular Diagnostic Techniques; Catalase; Oxidoreductases
PubMed: 38771285
DOI: 10.4103/ijmy.ijmy_21_24 -
International Journal of... Jan 2024Tuberculosis (TB) remains a prominent global health challenge, distinguished by substantial occurrences of infection and death. The upsurge of drug-resistant TB strains...
In silico Screening of Food and Drug Administration-approved Compounds against Trehalose 2-sulfotransferase (Rv0295c) in Mycobacterium tuberculosis: Insights from Molecular Docking and Dynamics Simulations.
BACKGROUND
Tuberculosis (TB) remains a prominent global health challenge, distinguished by substantial occurrences of infection and death. The upsurge of drug-resistant TB strains underscores the urgency to identify novel therapeutic targets and repurpose existing compounds. Rv0295c is a potentially druggable enzyme involved in cell wall biosynthesis and virulence. We evaluated the inhibitory activity of Food and Drug Administration (FDA)-approved compounds against Rv0295c of Mycobacterium tuberculosis, employing molecular docking, ADME evaluation, and dynamics simulations.
METHODS
The study screened 1800 FDA-approved compounds and selected the top five compounds with the highest docking scores. Following this, we subjected the initially screened ligands to ADME analysis based on their dock scores. In addition, the compound exhibited the highest binding affinity chosen for molecular dynamics (MD) simulation to investigate the dynamic behavior of the ligand-receptor complex.
RESULTS
Dihydroergotamine (CHEMBL1732) exhibited the highest binding affinity (-12.8 kcal/mol) for Rv0295c within this set of compounds. We evaluated the stability and binding modes of the complex over extended simulation trajectories.
CONCLUSION
Our in silico analysis demonstrates that FDA-approved drugs can serve as potential Rv0295c inhibitors through repurposing. The combination of molecular docking and MD simulation offers a comprehensive understanding of the interactions between ligands and the protein target, providing valuable guidance for further experimental validation. Identifying Rv0295c inhibitors may contribute to new anti-TB drugs.
Topics: Mycobacterium tuberculosis; Molecular Docking Simulation; Molecular Dynamics Simulation; Antitubercular Agents; United States Food and Drug Administration; United States; Sulfotransferases; Bacterial Proteins; Drug Approval; Humans; Ligands; Tuberculosis
PubMed: 38771283
DOI: 10.4103/ijmy.ijmy_20_24 -
International Journal of... Jan 2024Tuberculosis (TB) remains a global public health issue, impacting millions of people worldwide. This study determined the outcomes of TB treatment managed within a 10...
BACKGROUND
Tuberculosis (TB) remains a global public health issue, impacting millions of people worldwide. This study determined the outcomes of TB treatment managed within a 10 year period at the Bamenda Regional Hospital in Cameroon.
METHODS
A retrospective study was carried out among 2428 patients diagnosed and treated for active TB infection from 2013 to 2022, at the Bamenda Regional Hospital. Data collection was done from March to April 2023 using a data extraction form. Bivariate and multivariate logistic regression models were used to identify factors associated with successful TB treatment outcomes. Data was analyzed using SPSS software version 26.
RESULTS
Of the 2428 patients with TB, 1380 (56.8%) were cured, 739 (30.4%) completed treatment, treatment failures were recorded in 10 (0.4%) patients, and 200 (8.2%) died during or after receiving treatment. Treatment default was the outcome in 99 (4.1%). Successful treatment outcomes were reported in 2119 (87.3%). Patients within age groups 41-50 (P = 0.010), 51-60 (P = 0.041), and >60 years (P = 0.006), male (P = 0.004), and human immunodeficiency virus-positive patients (P < 0.001) had decreased odds of successful treatment outcomes.
CONCLUSION
The outcomes of treatment within a 10 year period showed that the treatment success was 2.7% below the World Health Organizations target. Prioritizing vulnerable patient groups in TB management and implementing public health interventions such as financial assistance and nutritional support will go a long way in improving treatment outcomes.
Topics: Humans; Retrospective Studies; Male; Female; Adult; Middle Aged; Antitubercular Agents; Cameroon; Treatment Outcome; Young Adult; Adolescent; Tuberculosis; Aged; Child; Child, Preschool; Infant; Logistic Models; HIV Infections; Hospitals
PubMed: 38771282
DOI: 10.4103/ijmy.ijmy_219_23 -
International Journal of... Jan 2024Smear microscopy for acid-fast bacilli visualization is important to assess the infectivity rate in patients with pulmonary tuberculosis (PTB), but it has limited... (Comparative Study)
Comparative Study
Correlation of Cyclic Threshold Values Generated by GeneXpert Ultra MTB/RIF and Fluorescence Microscopy to Predict Mycobacterial Burden in Suspected Cases of Pulmonary Tuberculosis.
BACKGROUND
Smear microscopy for acid-fast bacilli visualization is important to assess the infectivity rate in patients with pulmonary tuberculosis (PTB), but it has limited sensitivity; hence, it is important to find an alternative strategy. The aim of our study was to compare the fluorescence microscopy grading by Auramine O phenol staining technique of respiratory samples with the cyclic threshold (Ct) values of GeneXpert Ultra (Mycobacterium tuberculosis/rifampicin [MTB/RIF]) and assess the diagnostic efficacy of GeneXpert Ultra (MTB/RIF) compared to microscopy in suspected cases of PTB.
METHODS
The study was conducted in the Mycobacteriology Laboratory, Department of Microbiology, in Kasturba Hospital, Manipal. The study was a prospective, single-centered, cross-sectional study. Four hundred and fifty-two respiratory samples were included in the study. An optimal Ct cutoff value for ruling smear-positivity and smear-negativity and the mean Ct cutoff value were calculated. Clinical and radiological data from the requisition forms were assessed. IBM SPSS statistics software version 22 was used. The correlation between GeneXpert Ultra (MTB/RIF) Ct values and smear status was calculated by polychoric correlation. The extended McNemar's test was used to find the association between the variables.
RESULTS
GeneXpert Ultra (MTB/RIF) yielded a higher positivity rate of 22.2% compared to smear microscopy 17.2%. Ct value and smear grading yielded a positive correlation (P = 0.8681; P < 0.05). GeneXpert Ultra (MTB/RIF) yielded nontuberculous mycobacteria in five undetected cases and speciated as Mycobacterium abscessus complex.
CONCLUSIONS
Our study confirms the GeneXpert Ultra (MTB/RIF) Ct value levels as a predictor of smear positivity.
Topics: Humans; Tuberculosis, Pulmonary; Mycobacterium tuberculosis; Cross-Sectional Studies; Prospective Studies; Microscopy, Fluorescence; Male; Female; Adult; Middle Aged; Sputum; Young Adult; Rifampin; Aged; Sensitivity and Specificity; Adolescent; Bacterial Load
PubMed: 38771279
DOI: 10.4103/ijmy.ijmy_199_23 -
International Journal of... Jan 2024The coinfection of Mycobacterium tuberculosis and SARS-CoV-2 is called tuberculosis and COVID-19 coinfection (TB-COVID-19). We aimed to share the clinical, radiological,...
BACKGROUND
The coinfection of Mycobacterium tuberculosis and SARS-CoV-2 is called tuberculosis and COVID-19 coinfection (TB-COVID-19). We aimed to share the clinical, radiological, and laboratory findings and treatment processes of our patients with TB-COVID-19 coinfection in our tertiary reference hospital.
METHODS
Patients aged 18 years and over and hospitalized in the tuberculosis service between March 2020 and September 2022 were included. All coinfected patients whose COVID-19 polymerase chain reaction results were positive while receiving tuberculosis treatment or who were diagnosed with tuberculosis while receiving treatment for COVID-19 were included.
RESULTS
The number of patients was 39; 61.6% of males; the mean age was 52 ± 17.1 years; 20% were foreign nationals; 92.5% were Asian; 69.5% had a bacteriological diagnosis; 84.6% had pulmonary tuberculosis; 10% had received antituberculosis treatment before; and 87.5% were sensitive to the first-line antituberculosis drugs. The most common comorbidities were diabetes and hypertension. 87.5% of the patients were diagnosed with tuberculosis and were superinfected with COVID-19 while receiving tuberculosis treatment. 49.5% of patients had received at least one dose of COVID-19 vaccine. The most common presenting symptom was cough and sputum; the prominent laboratory parameter was C-reactive protein increase, and thorax computed tomography finding was consolidation, tree-in-bud, and cavitation. While 45.9% of the patients were still under treatment, 1 (2.5%) patient also resulted in mortality.
CONCLUSION
In this study, attention was drawn to two infectious diseases seen with respiratory tract symptoms. The mortality rate was found to be low. Neither disease was found to be a factor aggravating the course of each other.
Topics: Humans; Male; COVID-19; Middle Aged; Female; Coinfection; Adult; Aged; SARS-CoV-2; Tuberculosis; Antitubercular Agents; Tuberculosis, Pulmonary; Comorbidity; Mycobacterium tuberculosis; Pandemics
PubMed: 38771276
DOI: 10.4103/ijmy.ijmy_189_23 -
International Journal of... Jan 2024Although Zimbabwe has transitioned out of the 30 high-burden countries, it still remained in the 30 high multidrug-resistant (MDR)/rifampicin-resistant tuberculosis (TB)...
Diagnostic Performance of STANDARD™ M10 Multidrug-resistant Tuberculosis Assay for Detection of Mycobacterium tuberculosis and Rifampicin and Isoniazid Resistance in Zimbabwe.
BACKGROUND
Although Zimbabwe has transitioned out of the 30 high-burden countries, it still remained in the 30 high multidrug-resistant (MDR)/rifampicin-resistant tuberculosis (TB) burden. Rapid detection of rifampicin (RIF) and isoniazid (INH) is essential for the diagnosis of MDR-TB. The World Health Organization has recommended the use of molecular WHO-recommended rapid diagnostic (mWRD) for TB and DR-TB. STANDARD™ M10 MDR-TB assay is a new molecular rapid diagnostic assay developed by SD Biosensor for the detection of Mycobacterium tuberculosis (MTB) and RIF and INF resistance. This study aims to determine the diagnostic accuracy of STANDARD™ M10 MDR-TB assay.
METHODS
The study was conducted on 214 samples with different MTB and RIF and INH resistance status. The STANDARD™ M10 MDR-TB assay was performed according to the manufacturer's instructions. Xpert MTB/RIF Ultra, MGIT culture, and phenotypic drug susceptibility testing are used as comparative methods.
RESULTS
The sensitivity and specificity of STANDARD™ M10 MDR-TB assay for the detection of MTB are 99% and 97.9%, respectively. The sensitivity and specificity of the assay for detection of MDR-TB were 97.8% and 100%, respectively.
CONCLUSION
The STANDARD™ M10 MDR-TB assay demonstrated high diagnostic accuracy in the detection of MTB and RIF and INH resistance. This molecular assay can also be used as an alternative to other mWRD assays.
Topics: Mycobacterium tuberculosis; Rifampin; Zimbabwe; Humans; Isoniazid; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Sensitivity and Specificity; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; Molecular Diagnostic Techniques
PubMed: 38771275
DOI: 10.4103/ijmy.ijmy_194_23 -
International Journal of... Jan 2024The overexpression of efflux pumps (Eps) was reported to contribute to multidrug resistant tuberculosis (MDR-TB). Increases in Eps that expel structurally unrelated...
BACKGROUND
The overexpression of efflux pumps (Eps) was reported to contribute to multidrug resistant tuberculosis (MDR-TB). Increases in Eps that expel structurally unrelated drugs contribute to reduced susceptibility by decreasing the intracellular concentration of antibiotics. In the present study, an association of mycobacterial membrane protein (MmpS5-MmpL5) Ep and its gene regulator (Rv0678) was investigated in MDR-tuberculosis isolates.
METHODS
MTB strains were isolated from patients at two different intervals, i.e., once when they had persistent symptoms despite 3-15 ≥ months of treatment and once when they had started new combination therapy ≥2-3 months. Sputum specimens were subjected to Xpert MTB/rifampicin test and then further susceptibility testing using proportional method and multiplex polymerase chain reaction (PCR) were performed on them. The isolates were characterized using both 16S-23S RNA and hsp65 genes spacer (PCR-restriction fragment length polymorphism). Whole-genome sequencing (WGS) was investigated on two isolates from culture-positive specimen per patient. The protein structure was simulated using the SWISS-MODEL. The input format used for this web server was FASTA (amino acid sequence). Protein structure was also analysis using Ramachandran plot.
RESULTS
WGS documented deletion, insertion, and substitution in transmembrane transport protein MmpL5 (Rv0676) of Eps. Majority of the studied isolates (n = 12; 92.3%) showed a unique deletion mutation at three positions: (a) from amino acid number 771 (isoleucine) to 776 (valine), (b) from amino acid number 785 (valine) to 793 (histidine), and (c) from amino acid number 798 (leucine) to 806 (glycine)." One isolate (7.6%) had no deletion mutation. In all isolates (n = 13; 100%), a large insertion mutation consisting of 94 amino acid was observed "from amino acid number 846 (isoleucine) to amino acid number 939 (leucine)". Thirty-eight substitutions in Rv0676 were detected, of which 92.3% were identical in the studied isolates. WGS of mycobacterial membrane proteins (MmpS5; Rv0677) and its gene regulator (Rv0678) documented no deletion, insertion, and substitution. No differences were observed between MmpS5-MmpL5 and its gene regulator in isolates that were collected at different intervals.
CONCLUSIONS
Significant genetic mutation like insertion, deletion, and substitution within transmembrane transport protein MmpL5 (Rv0676) can change the functional balance of Eps and cause a reduction in drug susceptibility. This is the first report documenting a unique amino acid mutation (insertion and deletion ≥4-94) in Rv0676 among drug-resistant MTB. We suggest the changes in Mmpl5 (Rv0676) might occurred due to in-vivo sub-therapeutic drug stress within the host cell. Changes in MmpL5 are stable and detected through subsequent culture-positive specimens.
Topics: Humans; Tuberculosis, Multidrug-Resistant; Mycobacterium tuberculosis; Bacterial Proteins; Microbial Sensitivity Tests; Membrane Transport Proteins; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Whole Genome Sequencing; Sputum
PubMed: 38771273
DOI: 10.4103/ijmy.ijmy_37_24