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1.
PLoS One ; 16(1): e0244785, 2021.
Article in English | MEDLINE | ID: mdl-33406153

ABSTRACT

BACKGROUND: As per national policy, all diagnosed tuberculosis patients in India are to be tested using Xpert® MTB/RIF assay at the district level to diagnose rifampicin resistance. Regardless of the result, samples are transported to the reference laboratories for further testing: first-line Line Probe Assay (FL-LPA) for rifampicin-sensitive samples and second-line LPA(SL-LPA) for rifampicin-resistant samples. Based on the results, samples undergo culture and phenotypic drug susceptibility testing. We assessed among patients diagnosed with tuberculosis at 13 selected Xpert laboratories of Karnataka state, India, i) the proportion whose samples reached the reference laboratories and among them, proportion who completed the diagnostic algorithm ii) factors associated with non-reaching and non-completion and iii) the delays involved. METHODS: This was a cohort study involving review of programme records. For each TB patient diagnosed between 1st July and 31st August 2018 at the Xpert laboratory, we tracked the laboratory register at the linked reference laboratory until 30th September (censor date) using Nikshay ID (a unique patient identifier), phone number, name, age and sex. RESULTS: Of 1660 TB patients, 1208(73%) samples reached the reference laboratories and among those reached, 1124(93%) completed the algorithm. Of 1590 rifampicin-sensitive samples, 1170(74%) reached and 1104(94%) completed the algorithm. Of 64 rifampicin-resistant samples, only 35(55%) reached and 17(49%) completed the algorithm. Samples from rifampicin-resistant TB, extra-pulmonary TB and two districts were less likely to reach the reference laboratory. Non-completion was more likely among rifampicin-resistant TB and sputum-negative samples. The median time for conducting and reporting results of Xpert® MTB/RIF was one day, of FL-LPA 5 days and of SL-LPA16 days. CONCLUSION: These findings are encouraging given the complexity of the algorithm. High non-reaching and non-completion rates in rifampicin-resistant patients is a major concern. Future research should focus on understanding the reasons for the gaps identified using qualitative research methods.


Subject(s)
Algorithms , Tuberculosis, Multidrug-Resistant/diagnosis , Adolescent , Adult , Child , Cohort Studies , Drug Resistance, Bacterial/drug effects , Female , Humans , India , Male , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Reagent Kits, Diagnostic , Rifampin/pharmacology , Rifampin/therapeutic use , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Young Adult
2.
Nucleic Acids Res ; 41(5): 3414-23, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23314154

ABSTRACT

The relative levels of different σ factors dictate the expression profile of a bacterium. Extracytoplasmic function σ factors synchronize the transcriptional profile with environmental conditions. The cellular concentration of free extracytoplasmic function σ factors is regulated by the localization of this protein in a σ/anti-σ complex. Anti-σ factors are multi-domain proteins with a receptor to sense environmental stimuli and a conserved anti-σ domain (ASD) that binds a σ factor. Here we describe the structure of Mycobacterium tuberculosis anti-σ(D) (RsdA) in complex with the -35 promoter binding domain of σ(D) (σ(D)4). We note distinct conformational features that enable the release of σ(D) by the selective proteolysis of the ASD in RsdA. The structural and biochemical features of the σ(D)/RsdA complex provide a basis to reconcile diverse regulatory mechanisms that govern σ/anti-σ interactions despite high overall structural similarity. Multiple regulatory mechanisms embedded in an ASD scaffold thus provide an elegant route to rapidly re-engineer the expression profile of a bacterium in response to an environmental stimulus.


Subject(s)
Bacterial Proteins/chemistry , Mycobacterium tuberculosis , Sigma Factor/chemistry , Amino Acid Sequence , Binding Sites , Crystallography, X-Ray , DNA, Bacterial/chemistry , Molecular Dynamics Simulation , Molecular Sequence Data , Promoter Regions, Genetic , Proteasome Endopeptidase Complex/chemistry , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary , Proteolysis
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