Performance of LED-Based Fluorescence Microscopy to Diagnose Tuberculosis in a Peripheral Health Centre in Nairobi.

Sputum microscopy is the only tuberculosis (TB) diagnostic available at peripheral levels of care in resource limited countries. Its sensitivity is low, particularly in high HIV prevalence settings. Fluorescence microscopy (FM) can improve performance of microscopy and with the new light emitting diode (LED) technologies could be appropriate for peripheral settings. The study aimed to compare the performance of LED-FM versus Ziehl-Neelsen (ZN) microscopy and to assess feasibility of LED-FM at a low level of care in a high HIV prevalence country

Predicting Coulomb explosion fragment angular distributions using molecular ground-state vibrational motion

Laser-induced Coulomb explosions can be used to identify gas-phase molecular structures through correlations betweenfragment ion trajectories. This report presents a model for predicting these outcomes, which first establishes the neutralequilibrium geometry of a target molecule using electronic structure calculations, and then samples a probability distributionof potential ground-state configurations by allowing for zero-point vibrational motion. Candidate structuresare assumed to explode instantaneously into charged fragments, and the simulated ion trajectories are correlated usingrecoil-frame covariance analysis. The effects of detection efficiency and fluctuating experimental conditions are alsoconsidered. The results were found to match experimental data, indicating that Coulomb explosion fragment angulardistributions produced from highly-charged ions depend largely on the internal motion of the target molecule

Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosisMycobacterium\ tuberculosis

International audienceTo characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 $Mycobacterium\ tuberculosis$ clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps ($drrA$ and $Rv2688c$) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms