Pulmonary tuberculosis still remains a major communicable disease worldwide. In 2013, 9 million people developed TB and 1.5 million people died from the disease. India constitutes 24% of the total TB ...burden. Early detection of TB cases is the key to successful treatment and reduction of disease transmission. Xpert MTB/RIF, an automated cartridge-based molecular technique detects Mycobacterium tuberculosis and rifampicin resistance within two hours has been endorsed by WHO for rapid diagnosis of TB. Our study is the first study from India with a large sample size to evaluate the performance of Xpert MTB/RIF assay in PTB samples. The test showed an overall sensitivity and specificity of 95.7% (430/449) and 99.3% (984/990) respectively. In smear negative-culture positive cases, the test had a sensitivity of 77.7%. The sensitivity and specificity for detecting rifampicin resistance was 94.5% and 97.7% respectively with respect to culture as reference standard. However, after resolving the discrepant samples with gene sequencing, the sensitivity and specificity rose to 99.0% and 99.3% respectively. Hence, while solid culture still forms the foundation of TB diagnosis, Xpert MTB/RIF proposes to be a strong first line diagnostic tool for pulmonary TB cases.
•Gas turbine obstacles are solved concurrently by the proposed integration.•Suggested model led to improved thermal efficiency and reduced pollutants.•Predictive equations of the system performance ...are created by linear-regression.•Model’s optimum performances are determined by multi-parameter optimization.•Payback period is calculated using economic analysis.
Gas turbine (GT) power plants suffer from sensitivity to ambient-air temperature, high fuel consumption, and a high amount of waste heat dumped into the ambient. Various solutions were proposed to solve these drawbacks, which could simultaneously solve at most two problems, usually, at the expense of the third. In this work, however, a novel integration consisting of cascaded solar heat exchangers and a combined cycle power plant CCPP was used to simultaneously address the GTs shortcomings. Parabolic trough collectors PTCs were used to initially preheat the air at the combustion chamber inlet. The collectors were then used to drive an absorption inlet-air cooling cycle that will control the air temperature at the compressor’s inlet. Simple design point analysis of the proposed integration showed an increase in thermal efficiency by 7.2% and a 27.7 MW increase in power output. A linear-regression LR based optimization was then performed to generate highly accurate polynomial equations for predicting the system’s performance. These equations were then used in a Genetic Algorithm GA multi-objective optimization MOO with efficiency and capital cost as conflicting objectives. The optimum thermal efficiency was found to be in the range of 53.1 – 61.11% corresponding to a capital cost of the novel system in the range of 86.5–158.3 Mil$. A favorable optimum point for both objectives was found at an efficiency of 57.86% corresponding to a capital cost of 131.8 Mil$. Feasibility in terms of the payback period (PBP) was explored for the optimum range; resulting in a PBP equal to 2.8 years, an implication of a feasible novel cycle.
The objectives of the study were to compare the performance of line probe assay (GenoType MTBDRplus) with solid culture method for an early diagnosis of multidrug resistant tuberculosis (MDR-TB), and ...to study the mutation patterns associated with rpoB, katG and inhA genes at a tertiary care centre in north India.
In this cross-sectional study, 269 previously treated sputum-smear acid-fast bacilli (AFB) positive MDR-TB suspects were enrolled from January to September 2012 at the All India Institute of Medical Sciences hospital, New Delhi. Line probe assay (LPA) was performed directly on the sputum specimens and the results were compared with that of conventional drug susceptibility testing (DST) on solid media Lowenstein Jensen (LJ) method.
DST results by LPA and LJ methods were compared in 242 MDR-TB suspects. The LPA detected rifampicin (RIF) resistance in 70 of 71 cases, isoniazid (INH) resistance in 86 of 93 cases, and MDR-TB in 66 of 68 cases as compared to the conventional method. Overall (rifampicin, isoniazid and MDR-TB) concordance of the LPA with the conventional DST was 96%. Sensitivity and specificity were 98% and 99% respectively for detection of RIF resistance; 92% and 99% respectively for detection of INH resistance; 97% and 100% respectively for detection of MDR-TB. Frequencies of katG gene, inhA gene and combined katG and inhA gene mutations conferring all INH resistance were 72/87 (83%), 10/87 (11%) and 5/87 (6%) respectively. The turnaround time of the LPA test was 48 hours.
The LPA test provides an early diagnosis of monoresistance to isoniazid and rifampicin and is highly sensitive and specific for an early diagnosis of MDR-TB. Based on these findings, it is concluded that the LPA test can be useful in early diagnosis of drug resistant TB in high TB burden countries.
To evaluate the performance of Genotype MTBDRplus VER 2.0 in the diagnosis of Mycobacterium tuberculosis (MTB) in sputum smear-negative pulmonary TB cases.
A total of 572 Ziehl-Neelsen sputum ...smear-negative samples were selected and subjected to line probe assay (Genotype MTBDRplus VER 2.0), and culture in mycobacterial growth indicator tube (MGIT-960). Immunochromatographic test was used to confirm the MTB-complex (MTBC) in culture-positive samples and phenotypic drug-susceptibility testing was done using MGIT-960.
The line probe assay was able to diagnose MTBC in 38.2% (213/558) of specimens after excluding 14 nontuberculous mycobacteria. Sensitivity and specificity of the assay were 68.4% and 89.3% respectively, considering MGIT-960 culture as gold standard after excluding contaminated and invalid results. On comparing with composite reference standard, the assay had 71.5% sensitivity and 100% specificity in the diagnosis of tuberculosis. The sensitivity and specificity for detecting resistance to rifampicin (RMP) were 100% and 99.24% respectively and for resistance to isoniazid (INH) were 97.62% and 98.55%, respectively.
Genotype MTBDRplus VER 2.0 is a rapid and precise diagnostic tool for detection of MTB in sputum smear-negative samples. It also facilitates accurate diagnosis of RMP and INH resistance within turn around-time.
The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was ...conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse.
This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture.
A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups.
The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion.
CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).
Background & objectives: The burden of non-tuberculous mycobacterial (NTM) disease is increasing worldwide. The disease shares clinicoradiological features with tuberculosis (TB), Nocardia and ...several fungal diseases, and its diagnosis is frequently delayed. The present study was performed to determine the frequency of NTM disease among TB suspects in a tertiary care centre in north India.
Methods: In this prospective study, mycobacterial culture isolates from pulmonary and extrapulmonary specimens among TB suspects were tested with immunochromatographic assay (ICA). All ICA-negative isolates were considered as NTM suspects and further subjected to 16S-23S rRNA internal transcribed spacer gene sequencing for confirmation and species identification. Patients with active disease were treated with drug regimen as per the identified NTM species. Follow up of patients was done to determine clinical, radiological and microbiological outcomes.
Results: Of the 5409 TB suspects, 42 (0.77%) were diagnosed with NTM disease. Patients with active disease consenting for treatment were treated and followed up. Thirty four patients had NTM pulmonary disease (NTM-PD) and the remaining eight had extrapulmonary NTM (EP-NTM) disease. Mycobacterium intracellulare and M. abscessus, respectively, were most frequently isolated from NTM-PD and EP-NTM patients. Fifteen NTM-PD and seven EP-NTM patients successfully completed the treatment. Ten patients died due to unrelated causes, five were lost to follow up and another four declined the treatment.
Interpretation & conclusions: Our study showed that the frequency of NTM disease was low among TB suspects at a large tertiary care centre in north India and this finding was similar to other Indian studies. More studies need to be done in other parts of the country to know the geographical variation in NTM disease, if any.
Background & objectives: The fluoroquinolones (FQs) group of antibiotics is the backbone drugs for the management of drug-resistant tuberculosis (TB). In routine clinical practice, drug ...susceptibility testing (DST) for FQs is not performed, and the patients are empirically treated. A limited information exists regarding FQs resistance among pulmonary TB cases. The present study was conducted to determine the FQs resistance among drug sensitive and drug-resistant pulmonary TB patients in a tertiary care centre in north India.
Methods: A total of 1619 sputum/smear-positive specimens of pulmonary TB patients were subjected to DST for first-line drugs (FLDs) and second-line drugs. In addition, FQs DST was also performed using automated Mycobacterial Growth Indicator Tube-960 liquid culture technique. The immuno-chromatographic assay was performed to distinguish Mycobacterium tuberculosis complex (MTBC) from non-MTBC.
Results: Mycobacterium tuberculosis (Mtb) was isolated in 1499 sputum specimens; 1099 culture specimens were sensitive to FLDs, 249 grew as multidrug-resistant (MDR) Mtb and the remaining 151 isolates revealed any drug resistance to FLDs. While FQs monoresistance among the FLD sensitive isolates was 3.1 per cent (35/1099), 27.3 per cent (68/249) among MDR Mtb isolates had additional FQs resistance.
Interpretation & conclusions: FQs resistance among drug sensitive and MDR Mtb isolates was high in Delhi, India. Based on these findings, it is recommended that the DST for FQs should be routinely performed to avoid further amplification of drug resistance.
The emergence of drug resistant tuberculosis (TB), is a major menace to cast off TB worldwide. Line probe assay (GenoType MTBDRplus ver. 2) and Xpert® MTB/RIF assays are two rapid molecular TB ...detection/diagnostic tests.
To compare the performance of line probe assay (LPA) and Xpert® MTB/RIF assay for early diagnosis of rifampicin-resistant (RR) TB in acid-fast bacillus (AFB) smear-positive and negative sputum samples.
A total 576 presumptive multidrug-resistant TB (MDR-TB) patients were selected and subjected to AFB microscopy, Xpert® MTB/RIF assay and recent version of LPA (GenoType MTBDRplus assay ver.2) tests directly on sputum samples. Results were compared with phenotypic culture and drug susceptibility testing (DST). DNA sequencing was performed with rpoB gene for samples with discordant rifampicin susceptibility results.
Among culture-positive samples, Xpert® MTB/RIF assay detected Mtb in 97.3% (364/374) of AFB smear-positive samples and 76.5% (13/17) among smear-negative samples, and the corresponding values for LPA test (valid results with TUB band) were 97.9% (366/374) and 58.8% (10/17) respectively. For detection of RR among Mtb positive molecular results, the sensitivity of Xpert® MTB/RIF assay and LPA (after resolving discordant phenotypic DST results with DNA sequencing) were found to be 96% and 99% respectively. Whereas, specificity of both test for detecting RR were found to be 99%.
We conclude that although Xpert® MTB/RIF assay is comparatively superior to LPA in detecting Mtb among AFB smear-negative pulmonary TB. However, both tests are equally efficient in early diagnosis of AFB smear-positive presumptive RR-TB patients.
The management of neurological infections due to non-tubercular mycobacteria is extremely challenging because of scarce literature, issues with penetration, lack of easily available susceptibility ...platforms and adverse effects associated with long term therapy. We report a case of a young girl with neurological infection due to rapidly growing mycobacteria to discuss the factors that should be considered while choosing the therapy for such rare and persistent infections.
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