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The Cavity as a Lasting Abode for Tuberculous Bacilli: An Observational Study.

ABSTRACT: The aim of this study was to determine the factors associated with persistent sputum positivity at the end of 2 months of treatment in patients presenting with (drug-susceptible) pulmonary tuberculosis at a tertiary care hospital in Karachi. A cross-sectional study was conducted at the Department of Chest Medicine (Ward 12), Jinnah Postgraduate Medical Center (JPMC), Karachi, over 6 months. A sample of 73 consenting, newly diagnosed, smear-positive drug-susceptible pulmonary tuberculosis patients was studied. Demographic (age, gender, height, weight and duration of tuberculosis, BMI, socioeconomic, occupational, marital, educational and residential statuses) and clinical factors (chest X-ray extent and cavities, initial smear results, diabetic and smoking statuses) which may be associated with sputum non-conversion were entered in a proforma. Patients were followed up at 2 months of treatment with a sputum smear. Data analysis was done on SPSS (Statistical Package for Social Sciences-version 20.0). Rate of sputum positivity after 2 months of anti-tubercular drug treatment was 17.8%. None of the above-mentioned demographic and clinical factors was associated with persistence of sputum positivity except for the presence of CXR cavities, which made it 5.5 times more likely that the patient would remain smear-positive at 2 months (p = 0.035). The finding of chest radiograph cavities makes it highly likely that a pulmonary tuberculosis patient may remain infectious or have an unfavorable outcome despite taking treatment for 2 months. Clinicians and national policy-makers should thus bear in mind the implications this can have with regard to disease control and therefore pay particular attention to such patients in terms of stringent monitoring and directly observed treatment short-course (DOTS) provision.

Supplementary information

The online version contains supplementary material available at 10.1007/s42399-021-01098-6.

SUBMITTER: Jawad N

PROVIDER: S-EPMC8762190 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTuberculous sputum provides a sample of bacilli that must be eliminated by chemotherapy and that may go on to transmit infection. A preliminary observation that Mycobacterium tuberculosis cells contain triacylglycerol lipid bodies in sputum, but not when growing in vitro, led us to investigate the extent of this phenomenon and its physiological basis.Methods and findingsMicroscopy-positive sputum samples from the UK and The Gambia were investigated for their content of lipid body-positive mycobacteria by combined Nile red and auramine staining. All samples contained a lipid body-positive population varying from 3% to 86% of the acid-fast bacilli present. The recent finding that triacylglycerol synthase is expressed by mycobacteria when they enter in vitro nonreplicating persistence led us to investigate whether this state was also associated with lipid body formation. We found that, when placed in laboratory conditions inducing nonreplicating persistence, two M. tuberculosis strains had lipid body levels comparable to those found in sputum. We investigated these physiological findings further by comparing the M. tuberculosis transcriptome of growing and nonreplicating persistence cultures with that obtained directly from sputum samples. Although sputum has traditionally been thought to contain actively growing tubercle bacilli, our transcript analyses refute the hypothesis that these cells predominate. Rather, they reinforce the results of the lipid body analyses by revealing transcriptional signatures that can be clearly attributed to slowly replicating or nonreplicating mycobacteria. Finally, the lipid body count was highly correlated (R(2) = 0.64, p < 0.03) with time to positivity in diagnostic liquid cultures, thereby establishing a direct link between this cytological feature and the size of a potential nonreplicating population.ConclusionAs nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis.

Project description:BackgroundScale-up of insecticide-based interventions has averted more than 500 million malaria cases since 2000. Increasing insecticide resistance could herald a rebound in disease and mortality. We aimed to investigate whether insecticide resistance was associated with loss of effectiveness of long-lasting insecticidal nets and increased malaria disease burden.MethodsThis WHO-coordinated, prospective, observational cohort study was done at 279 clusters (villages or groups of villages in which phenotypic resistance was measurable) in Benin, Cameroon, India, Kenya, and Sudan. Pyrethroid long-lasting insecticidal nets were the principal form of malaria vector control in all study areas; in Sudan this approach was supplemented by indoor residual spraying. Cohorts of children from randomly selected households in each cluster were recruited and followed up by community health workers to measure incidence of clinical malaria and prevalence of infection. Mosquitoes were assessed for susceptibility to pyrethroids using the standard WHO bioassay test. Country-specific results were combined using meta-analysis.FindingsBetween June 2, 2012, and Nov 4, 2016, 40 000 children were enrolled and assessed for clinical incidence during 1·4 million follow-up visits. 80 000 mosquitoes were assessed for insecticide resistance. Long-lasting insecticidal net users had lower infection prevalence (adjusted odds ratio [OR] 0·63, 95% CI 0·51-0·78) and disease incidence (adjusted rate ratio [RR] 0·62, 0·41-0·94) than did non-users across a range of resistance levels. We found no evidence of an association between insecticide resistance and infection prevalence (adjusted OR 0·86, 0·70-1·06) or incidence (adjusted RR 0·89, 0·72-1·10). Users of nets, although significantly better protected than non-users, were nevertheless subject to high malaria infection risk (ranging from an average incidence in net users of 0·023, [95% CI 0·016-0·033] per person-year in India, to 0·80 [0·65-0·97] per person year in Kenya; and an average infection prevalence in net users of 0·8% [0·5-1·3] in India to an average infection prevalence of 50·8% [43·4-58·2] in Benin).InterpretationIrrespective of resistance, populations in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. As nets provide only partial protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden.FundingBill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

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The Cavity as a Lasting Abode for Tuberculous Bacilli: An Observational Study.

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