Prevalence of non-tuberculous mycobacteria among people with acid-fast positive presumptive tuberculosis in Mali.

Background: Non-tuberculous mycobacteria (NTM) are environmental agents that can cause opportunistic pulmonary disease in humans and animals, often misdiagnosed as tuberculosis (TB). In this study, we describe the cases of NTM identified during the first national anti-TB drug resistance survey conducted in Mali and explore associated risk factors.

Methods: Sputum was collected from people presenting for pulmonary TB diagnosis from April to December 2019, regardless of age.

Successful Mycobacterium tuberculosis culture isolation from tongue swabs: Results from both experimentally infected and clinical swabs from pulmonary tuberculosis patients.

This study explored Mycobacterium tuberculosis (MTB) growth from tongue swabs, both experimentally infected after sampling from healthy controls, or sampled from patients with smear-microscopy confirmed pulmonary tuberculosis (PTB). For both, we evaluated the performance of NALC-NaOH/MGIT960 (MGIT), Kudoh-Ogawa (KO), and cetylpyridinium chloride-Löwenstein-Jensen (CPC/LJ) culture processing methods. Experimentally spiked swabs from 20 participants exhibited 94.

Acquired rifampicin resistance during first TB treatment: magnitude, relative importance, risk factors and keys to control in low-income settings.

Background: The incidence of acquired rifampicin resistance (RIF-ADR; RR) during first-line treatment varies.

Objectives: Compare clinically significant RIF-ADR versus primary and reinfection RR, between regimens (daily versus no rifampicin in the continuation phase; daily versus intermittent rifampicin in the continuation phase) and between rural Bangladesh and Kinshasa, Democratic Republic of Congo.

Methods: From patients with treatment failure, relapse, or lost to follow-up, both the outcome and baseline sputum sample were prospectively collected for sequencing to determine whether RR was present in both samples (primary RR) or only at outcome (RIF-ADR or reinfection RR).

Bedaquiline can act as core drug in a standardised treatment regimen for fluoroquinolone-resistant rifampicin-resistant tuberculosis.

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The simple direct slide method is comparable to indirect Lowenstein Jensen proportion culture for detecting rifampicin resistant tuberculosis.

Drug resistant tuberculosis remains a worldwide problem that requires prompt diagnosis. The WHO recommended direct, rapid Xpert MTB/RIF is prohibitively costly, therefore, there is a need to validate a rapid, affordable DST for use in low- and middle-income settings. The technical performance and time to results of a simple, direct microscopy-based slide DST (SDST) assay for diagnosis of rifampicin-resistant TB was evaluated in Uganda.

Injectables' key role in rifampicin-resistant tuberculosis shorter treatment regimen outcomes.

Background: Since a meta-analysis showed little or no effect of second-line injectables on treatment success, and using injectables may induce ototoxicity, injectable-free rifampicin-resistant tuberculosis (RR-TB) treatment regimens are recommended. However, acquired resistance preventing activity was overlooked. No previous study assessed the effect of shortening the duration of kanamycin administration to 2 months during the intensive phase of the RR-TB shorter treatment regimen (STR).

The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance.

Background: Meta-analyses on impact of isoniazid-resistant tuberculosis informed the World Health Organization recommendation of a levofloxacin-strengthened rifampicin-based regimen. We estimated the effect of initial rifampicin resistance (Rr) and/or isoniazid resistance (Hr) on treatment failure or relapse. We also determined the frequency of missed initial and acquired Rr to estimate the impact of true Hr.

First-line tuberculosis treatment with double-dose rifampicin is well tolerated.

To compare the occurrence of unfavourable treatment and safety outcomes of double-dose rifampicin (RMP; 20 mg/kg/d, intervention) with standard dose (10 mg/kg/d, control) in a first-line tuberculosis (TB) treatment regimen for smear-positive TB patients in Bangladesh. This was a randomised clinical trial. The primary efficacy and safety endpoints were the occurrence of an unfavourable treatment outcome (death, failure, relapse or loss to follow-up) and the occurrence of any serious drug-related adverse event (SAE).

Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: Nationwide programmatic achievements.

Background: In Niger, the Shorter Treatment Regimen (STR) has been implemented nationwide for rifampicin resistant tuberculosis (RR-TB), since 2008. No previous publication has shown the results from countrywide programmatic implementation using few exclusion criteria, nor exhaustively assessed the effect of initial resistance to companion drugs on outcomes.

Methods: The National Tuberculosis Programme and the Damien Foundation conducted a retrospective observational study to evaluate the management of RR-TB from 2008 to 2016.

Variable ability of rapid tests to detect Mycobacterium tuberculosis rpoB mutations conferring phenotypically occult rifampicin resistance.

We compared the ability of commercial and non-commercial, phenotypic and genotypic rapid drug susceptibility tests (DSTs) to detect rifampicin resistance (RR)-conferring 'disputed' mutations frequently missed by Mycobacterium Growth Indicator Tube (MGIT), namely L430P, D435Y, L452P, and I491F. Strains with mutation S450L served as positive control while wild-types were used as negative control. Of the 38 mutant strains, 5.

Twenty years of rifampicin resistance surveillance in Bangladesh: periodic vs. continuous monitoring.

Objective: To analyse 20 years of tuberculosis (TB) drug resistance surveillance, comparing conventional periodic random drug resistance surveys with continuous monitoring, in Damien Foundation-supported districts of Bangladesh.

Design: Retrospective study of data on TB drug resistance from five periodic surveys among newly registered patients vs. continuous monitoring of retreatment patients from 1996 to 2016.

Gatifloxacin Pharmacokinetics/Pharmacodynamics-based Optimal Dosing for Pulmonary and Meningeal Multidrug-resistant Tuberculosis.

Background: Gatifloxacin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB). The optimal dose is unknown.

Methods: We performed a 28-day gatifloxacin hollow-fiber system model of tuberculosis (HFS-TB) study in order to identify the target exposures associated with optimal kill rates and resistance suppression.

The majority of patients with multidrug-resistant tuberculosis in Sub-Saharan Africa present a concomitant resistance to pyrazinamide.

Objective/background: Pyrazinamide (PZA) is an antibacterial used in the first-line regimen against tuberculosis (TB) for its action against dormant bacilli. PZA is also included in the new short regimen to treat multidrug-resistant TB (MDR-TB). However, the prevalence and significance of PZA resistance is not known in Central and West Africa.

Specific gyrA gene mutations predict poor treatment outcome in MDR-TB.

Objectives: Mutations in the gyrase genes cause fluoroquinolone resistance in Mycobacterium tuberculosis. However, the predictive value of these markers for clinical outcomes in patients with MDR-TB is unknown to date. The objective of this study was to determine molecular markers and breakpoints predicting second-line treatment outcomes in M.

Disputed rpoB mutations can frequently cause important rifampicin resistance among new tuberculosis patients.

Setting: Greater Mymensingh area, Bangladesh.

Objectives: To document among new tuberculosis (TB) patients the proportions and treatment outcomes of silent, non-disputed and disputed (generally missed by rapid drug susceptibility testing [DST]) rpoB mutations, and their detection by commercial molecular assays.

Design: Retrospective analysis of rpoB sequences from randomly selected ethanol-preserved diagnostic sputum samples; comparison of sequencing with conventional DST results and standard first-line treatment outcome; retesting of samples with mutations using the Xpert MTB/RIF and GenoType MTBDRplus assays.

An operational study comparing microscopes and staining variations for tuberculosis LED FM.

Setting: Tuberculosis control projects, Damien Foundation Bangladesh.

Objectives: To compare transmitted fluorescence (Olympus CX21™/FRAEN FluoLED™) with epi-fluorescence (Zeiss Primostar iLED™) light-emitting diode microscopes (LED-FM) and various auramine staining and destaining/counterstaining techniques for the detection of acid-fast bacilli.

Design: Multicentre blinded reading of routine smears on both types of microscopes using different staining techniques in multiple phases.

Rifampin resistance missed in automated liquid culture system for Mycobacterium tuberculosis isolates with specific rpoB mutations.

WHO-endorsed phenotypic drug susceptibility testing (DST) methods for Mycobacterium tuberculosis are assumed to be the gold standard for identifying rifampin (RMP) resistance. However, previous results indicated that low-level, yet probably clinically relevant, RMP resistance linked to specific rpoB mutations is easily missed by some growth-based methods. We aimed to compare the level of resistance detected on Löwenstein-Jensen (LJ) medium with resistance detected by the Bactec MGIT 960 automated DST (MGIT-DST) system for various rpoB mutants.

Fluorescein diacetate vital staining allows earlier diagnosis of rifampicin-resistant tuberculosis.

Setting: Damien Foundation Project, Bangladesh.

Objective: To evaluate sputum smear fluorescein diacetate (FDA) vital staining to predict culture-defined failure and rifampicin (RMP) resistance.

Design: A retrospective, operational study.

Methylene blue is a good background stain for tuberculosis light-emitting diode fluorescence microscopy.

Setting: Damien Foundation Bangladesh tuberculosis (TB) control projects.

Objectives: To compare blue ink, potassium permanganate and methylene blue background staining for transmitted light-emitting diode (LED) TB fluorescence microscopy (FM).

Design: Auramine smears made in triplicate from Ziehl-Neelsen (ZN) acid-fast bacilli (AFB) positive or negative sputum and stained with one of the background variations were read blind by LED FM.

Performance and acceptability of the FluoLED Easy module for tuberculosis fluorescence microscopy.

Setting: Tuberculosis (TB) reference laboratory in Bangkok, Thailand, and two health centres in Dar es Salaam, Tanzania.

Objectives: To assess the performance and user-friendliness of a light-emitting diode (LED) module (FluoLED Easy) for TB fluorescence microscopy (FM).

Design: Equivalence study vs.

Ziehl-Neelsen staining: theory and practice.

The information provided in the guidelines of the World Health Organization and the International Union Against Tuberculosis and Lung Disease for Ziehl-Neelsen staining is not practical on a number of points. The advice given here is meant to supplement the guidelines. It is based on experiments on and field experience of basic fuchsin stain and staining solutions.