Impact of N-Acetyl Cysteine (NAC) on Tuberculosis (TB) Patients—A Systematic Review

This research article was published by MDPI in 2022Sustained TB infection overproduces reactive oxygen species (ROS) as a host defense mechanism. Research shows ROS is destructive to lung tissue. Glutathione (GSH) neutralizes ROS, although it is consumed. NAC is a precursor of GSH synthesis, and administering an appropriate dose of NAC to patients with respiratory conditions may enhance lung recovery and replenish GSH. The present review searched for articles reporting on the effects of NAC in TB treatment from 1960 to 31 May 2022. The PICO search strategy was used in Google Scholar, PubMed, SciFinder, and Wiley online library databases. The COVIDENCE tool was used to delete inappropriate content. We eventually discovered five clinical trials, one case report, seven reviews, in vitro research, and four experimental animal studies from the twenty-four accepted articles. The use of NAC resulted in increased GSH levels, decreased treatment time, and was safe with minimal adverse events. However, the evidence is currently insufficient to estimate the overall effects of NAC, thus the study warrants more NAC clinical trials to demonstrate its effects in TB treatment

Xpert MTB/RIF Ultra assay for the diagnosis of pulmonary tuberculosis in children: a multicentre comparative accuracy study

We evaluated the diagnostic performance of the novel next-generation Xpert MTB/RIF Ultra (Xpert Ultra) in comparison to Xpert MTB/RIF (Xpert) assay for the detection of paediatric pulmonary tuberculosis in high burden settings.; From May 2011 to September 2012, children with suspected pulmonary tuberculosis were enrolled at two Tanzanian sites and sputum samples were examined using sputum smear, Xpert and culture. Xpert Ultra was tested between January and June 2017 using sputum pellets, which had been stored at -80°C. The diagnostic accuracy of Ultra versus Xpert was determined using well-defined case definitions as reference standard.; In total, 215 children were included. The median age was 5.4 years, the HIV prevalence was 52% and 13% had culture-confirmed pulmonary tuberculosis. When only the first available sample of each patient was analysed, the sensitivity of Xpert Ultra was 64.3 % (95% CI: 44.1 to 81.4) while that of Xpert was 53.6% (95%CI: 33.9 to 72.5). The specificity of Xpert Ultra based on analysis of all available samples was 98.1% (95%CI: 93.4 to 99.7), that of Xpert was 100%.; Xpert Ultra was found to have a higher sensitivity, but slightly reduced specificity compared to Xpert in detecting pulmonary tuberculosis in children

N-acetylcysteine modulates markers of oxidation, inflammation and infection in tuberculosis

This research article was published by Journal, 2025Background Half the global tuberculosis health burden is due to post-tuberculosis lung disease. Host-directed therapies have been proposed to reduce this burden. N-acetylcysteine (NAC) provides the conditionally essential amino acid cysteine required for synthesis of glutathione, an antioxidant thiol. We recently reported clinical outcomes of a trial of adjunctive NAC in patients with pulmonary tuberculosis, finding that NAC improved the secondary endpoint of recovery of lung function. Here we report the effects of NAC on biomarkers of oxidation, inflammation, and infection in that trial. Methods 140 adults with moderate or far-advanced pulmonary tuberculosis were randomly assigned to standard tuberculosis treatment with or without NAC 1200 mg twice daily for months 1-4. Sputum and blood samples were obtained at specified intervals to measure total glutathione, MTB-induced cytokines, haemoglobin, whole blood mycobactericidal activity (WBA), and sputum MTB burden. Results NAC treatment rapidly increased total glutathione (P<.0001), but levels did not reach those of healthy volunteers (P<.001). NAC reduced MTB-induced TNF-α (P =.011) without affecting IL-10, and accelerated the recovery of hemoglobin in participants with low values on entry. NAC did not affect killing in ex vivo whole blood culture but did slow the clearance of MTB from sputum (P=0.003). Conclusion Adjunctive NAC showed antioxidant and anti-inflammatory effects consistent with the amelioration of immunopathology seen in preclinical models. Two biomarkers of antimicrobial activity showed discordant results; neither demonstrated the enhanced antimicrobial effects seen preclinically. The reduction of oxidative stress and inflammation by NAC may explain its effects on the recovery of lung function post-TB

Performance of Tuberculosis Molecular Bacterial Load Assay Compared to Alere TB-LAM in Urine of Pulmonary Tuberculosis Patients with HIV Co-Infections

This research article was published by MDPI in 2023Alternative tools are needed to improve the detection of M. tuberculosis (M. tb) in HIV co-infections. We evaluated the utility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to lipoarabinomannan (LAM) to detect M. tb in urine. Sputum Xpert MTB/RIF-positive patients were consented to provide urine at baseline, weeks 2, 8, 16, and 24 of treatment for TB-MBLA, culture, and LAM. Results were compared with sputum cultures and microscopy. Initial M. tb. H37Rv spiking experiments were performed to validate the tests. A total of 63 urine samples from 47 patients were analyzed. The median age (IQR) was 38 (30–41) years; 25 (53.2%) were male, 3 (6.5%) had urine for all visits, 45 (95.7%) were HIV positive, of whom 18 (40%) had CD4 cell counts below 200 cells/µL, and 33 (73.3%) were on ART at enrollment. Overall urine LAM positivity was 14.3% compared to 4.8% with TB-MBLA. Culture and microscopy of their sputum counterparts were positive in 20.6% and 12.7% of patients, respectively. Of the three patients with urine and sputum at baseline, one (33.33%) had urine TB-MBLA and LAM positive compared to 100% with sputum MGIT culture positive. Spearman’s rank correction coefficient (r) between TB-MBLA and MGIT was −0.85 and 0.89 with a solid culture, p > 0.05. TB-MBLA has the promising potential to improve M. tb detection in urine of HIV-co-infected patients and complement current TB diagnostics

INNOVATIONS AND FRAGMENTS OF TRADITION IN SLOVENIAN VILLAGES

In this paper the author reports on some results of an investigation of innovations in ten different types of village in Slovenia. The investigation was designed to establish (1) the rate of development of rural communities in Slovenia (measured according to the diffusion of innovations), and (2) the influence of tradition (from the degree of the distribution of »isoetes«, i.e. local customs). , Two groups of innovations were investigated: innovations in land cultivation methods on peasant farms, and innovations in the equipment of rural households. The data were collected using the method of interviews, which were held with both pure farmers and peasants-workers in 1968 and again in 1973. The obtained results regarding the spread of farm innovations are shown in Diagram 1; the results regarding the spread of innovations in household equipment are presented graphically in Diagram 2; while Diagram 3 indicates the »standing« of each village as regards the degree of innovation it has achieved with all the 25 controled innovations. As was expected, the highest degree of innovation is shown by villages with the largest proportion of inhabitants in temporary employment abroad and villages vhich contain a comparatively numerous category of peasants-workers

OC 8215 DIAGNOSTIC ACCURACY OF XPERT MTB/RIF ULTRA FOR PULMONARY TUBERCULOSIS IN CHILDREN: A MULTICENTRE COMPARATIVE STUDY

BackgroundXpert® MTB/RIF (Xpert) has suboptimal sensitivity for the diagnosis of pulmonary tuberculosis in children. The next-generation Xpert MTB/RIF Ultra assay (Xpert Ultra) is substantially more sensitive than Xpert and may allow improved detection of paediatric tuberculosis. We evaluated the diagnostic accuracy of Xpert Ultra versus Xpert in the detection of pulmonary tuberculosis in children.MethodsFrom May 2011 to September 2012, children with presumptive pulmonary tuberculosis were enrolled at two „Tanzanian research sites in the EDCTP-funded TB CHILD project. Sputum samples were collected and examined for tuberculosis using sputum smear, Xpert and culture. Xpert Ultra analysis was performed between January and June 2017 at both sites using decontaminated sputum pellets which had been stored at −80°C. The diagnostic accuracy of Xpert and Xpert Ultra was determined using well-defined case definitions as reference standard.ResultsIn total, 215 children were included in the analysis. The median age was 5.4 years (IQR, 1.5 to 9.9), the HIV prevalence was 52%, and 28 children (13%) had culture-confirmed pulmonary tuberculosis. When only the first available sample of each patient was considered, the sensitivity of Xpert Ultra was 64.3% (95% CI: 44.1 to 81.4) while that of Xpert was 53.6% (95% CI: 33.9 to 72.5). The specificity of Xpert Ultra based on the analysis of all available samples was 98.1% (95% CI: 93.4 to 99.7), whereas that of Xpert was 100%.ConclusionIn settings with a high burden of tuberculosis and HIV, Xpert Ultra had a better sensitivity than Xpert in children. However, the specificity was slightly lower than that of Xpert. Thus, Xpert Ultra has the potential to increase the reliability and the speed of tuberculosis diagnosis in children.</jats:sec

Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in children : a prospective, multi-centre evaluation

Following endorsement by the World Health Organisation, the Xpert MTB/RIF assay has been widely incorporated into algorithms for the diagnosis of adult tuberculosis (TB). However, data on its performance in children remain scarce. This prospective, multi-centre study evaluated the performance of Xpert MTB/RIF to diagnose pulmonary tuberculosis in children.; Children older than eight weeks and younger than 16 years with suspected pulmonary tuberculosis were enrolled at three TB endemic settings in Tanzania and Uganda, and assigned to five well-defined case definition categories: culture-confirmed TB, highly probable TB, probable TB, not TB, or indeterminate. The diagnostic accuracy of Xpert MTB/RIF was assessed using culture-confirmed TB cases as reference standard.; In total, 451 children were enrolled. 37 (8%) had culture-confirmed TB, 48 (11%) highly probably TB and 62 probable TB (13%). The Xpert MTB/RIF assay had a sensitivity of 68% (95% CI, 50%-82%) and specificity of 100% (95% CI, 97%-100%); detecting 1.7 times more culture-confirmed cases than smear microscopy with a similar time to detection. Xpert MTB/RIF was positive in 2% (1/48) of highly probable and in 3% (2/62) of probable TB cases.; Xpert MTB/RIF provided timely results with moderate sensitivity and excellent specificity compared to culture. Low yields in children with highly probable and probable TB remain problematic

Tuberculosis Molecular Bacterial Load Assay reveals early delayed bacterial killing in patients with relapse

Bacterial killing in patients with tuberculosis (TB) relapse was compared to that in patients achieving cure, measured by TB molecular bacterial load assay (TB-MBLA) or mycobacteria growth indicator tube (MGIT) time to positivity (TTP). TB-MBLA in 4 relapsed patients was significantly different compared to 132 cured patients after 2 weeks of treatment; MGIT TTP showed a significant difference from week 8

Limited value of whole blood Xpert(®) MTB/RIF for diagnosing tuberculosis in children

We evaluated the ability of the Xpert(®) MTB/RIF assay to detect Mycobacterium tuberculosis in whole blood of children with tuberculosis in tuberculosis endemic settings with high rates of HIV infection.; From June 2011 to September 2012 we prospectively enrolled children with symptoms or signs suggestive of tuberculosis at three research centres in Tanzania and Uganda. After clinical assessment, respiratory specimens were collected for microscopy and culture, as well as whole blood for Xpert(®) MTB/RIF. Children were classified according to standardised case definitions.; A total of 232 children were evaluated; 14 (6.0%) had culture-confirmed tuberculosis. The Xpert(®) MTB/RIF assay detected M. tuberculosis in 5/232 (2.2%) blood samples with 1 (0.4%) error reading and presumably 1 (0.4%) false-positive result. The sensitivity of the assay in children with culture-confirmed (1/14) versus no tuberculosis (1/117) was 7.1% (95% CI, 1.3-31.5). Three of the five Xpert(®) MTB/RIF positive patients had negative cultures, but were classified as probable tuberculosis cases. Assay sensitivity against a composite reference standard (culture-confirmed, highly probable or probable tuberculosis) was 5.4% (95% CI, 2.1-13.1).; Whole blood Xpert(®) MTB/RIF demonstrated very poor sensitivity, although it may enhance the diagnostic yield in select cases, with culture-negative tuberculosis