Dataset Information

SEVERITY OF TB CLASSIFIED BY MODIFIED BANDIM TB SCORING ASSOCIATES WITH THE SPECIFIC SEQUENCE OF ESXA GENES IN MDR-TB PATIENTS.

ABSTRACT: Background:The severity of pulmonary TB and detection of multidrug-resistant (MDR-TB) TB strains as potential causative agents could be crucial for the determination of treatment success. This study aimed to analyze the association between the specific sequences of the full esxA gene from MDR-TB sputum isolates and the severity class of MDR-TB patients. Material and Methods:A total of 98 sputum samples that were suspected to be MDR-TB were collected from Dr. Soetomo, Surabaya, Indonesia, from September to December 2016. A total of 24 isolates from the 98 patients were confirmed to have positive MDR-TB based on the GeneXpert test. MDR-TB isolates were tested using PCR targeting 580 bp encompassing the full esxA gene, and the resulting amplicon was sequenced. The severity class of the pulmonary TB patients was assessed using modified Bandim TB scoring. Results:The patient severity classification resulted in a moderate and severe degree of TB in 38% and a mild degree of TB in 63% of patients. Visualization of the PCR results showed that all MDR-TB samples were positive for the 580 bp band, and the sequence results showed 100% homology with that of the virulent wild-type M. tuberculosis H37Rv (NC_000962.3). Conclusions:In the current study, an association between the characteristics of the full esxA gene and the severity class of MDR-TB patients is yet to be found. However, the homologous sequence of all samples, associated with various degrees of disease severity, possess 100% identity with that of wild-type M. tuberculosis H37Rv.

SUBMITTER: Dewi DNSS

PROVIDER: S-EPMC7011159 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SEVERITY OF TB CLASSIFIED BY MODIFIED BANDIM TB SCORING ASSOCIATES WITH THE SPECIFIC SEQUENCE OF ESXA GENES IN MDR-TB PATIENTS.

Dewi Desak Nyoman Surya Suameitria DNSS Mertaniasih Ni Made NM Soedarsono

African journal of infectious diseases 20200108 1

<h4>Background</h4>The severity of pulmonary TB and detection of multidrug-resistant (MDR-TB) TB strains as potential causative agents could be crucial for the determination of treatment success. This study aimed to analyze the association between the specific sequences of the full esxA gene from MDR-TB sputum isolates and the severity class of MDR-TB patients.<h4>Material and methods</h4>A total of 98 sputum samples that were suspected to be MDR-TB were collected from Dr. Soetomo, Surabaya, Ind ...[more]

PMID: 32064451

Similar Datasets

Project description:The Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support.To assess whether CBMDR-TBC project's support improved treatment initiation.In this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as "receiving support" if date of project initiation in patient's township was before the date of diagnosis and "not receiving support", if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation.Of 456 patients, 57% initiated treatment: 64% and 56% among patients "receiving support (n = 208)" and "not receiving support (n = 228)" respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients "receiving support" and 50 (26,101) among patients "not receiving support". After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients "receiving support" had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients "not receiving support". In addition, age 15-54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation.Receiving support under CBMDR-TBC project improved treatment initiation: it not only improved the proportion initiated but also reduced time to treatment initiation. We also recommend improved tracking of all diagnosed patients as early as possible.

Project description:BackgroundSequence matching is extremely important for applications throughout biology, particularly for discovering information such as functional and evolutionary relationships, and also for discriminating between unimportant and disease mutants. At present the functions of a large fraction of genes are unknown; improvements in sequence matching will improve gene annotations. Universal amino acid substitution matrices such as Blosum62 are used to measure sequence similarities and to identify distant homologues, regardless of the structure class. However, such single matrices do not take into account important structural information evident within the different topologies of proteins and treats substitutions within all protein folds identically. Others have suggested that the use of structural information can lead to significant improvements in sequence matching but this has not yet been very effective. Here we develop novel substitution matrices that include not only general sequence information but also have a topology specific component that is unique for each CATH topology. This novel feature of using a combination of sequence and structure information for each protein topology significantly improves the sequence matching scores for the sequence pairs tested. We have used a novel multi-structure alignment method for each homology level of CATH in order to extract topological information.ResultsWe obtain statistically significant improved sequence matching scores for 73 % of the alpha helical test cases. On average, 61 % of the test cases showed improvements in homology detection when structure information was incorporated into the substitution matrices. On average z-scores for homology detection are improved by more than 54 % for all cases, and some individual cases have z-scores more than twice those obtained using generic matrices. Our topology specific similarity matrices also outperform other traditional similarity matrices and single matrix based structure methods. When default amino acid substitution matrix in the Psi-blast algorithm is replaced by our structure-based matrices, the structure matching is significantly improved over conventional Psi-blast. It also outperforms results obtained for the corresponding HMM profiles generated for each topology.ConclusionsWe show that by incorporating topology-specific structure information in addition to sequence information into specific amino acid substitution matrices, the sequence matching scores and homology detection are significantly improved. Our topology specific similarity matrices outperform other traditional similarity matrices, single matrix based structure methods, also show improvement over conventional Psi-blast and HMM profile based methods in sequence matching. The results support the discriminatory ability of the new amino acid similarity matrices to distinguish between distant homologs and structurally dissimilar pairs.

Project description:Background:Laminitis is a common equine disease characterized by foot pain, and is commonly diagnosed using a five-grade Obel system developed in 1948 using sepsis-related cases. However, endocrinopathic laminitis is now the most common form of the disease and clinical signs may be mild, or spread across two Obel grades. This paper describes a modified method which assigns scores to discreet clinical signs, providing a wider scale suitable for use in a research setting. Methods:The "modified Obel" method was developed using an iterative process. First, a prototype method was developed during the detailed observation of 37 ponies undergoing a laminitis induction experiment. The final method was refined and validated using video footage taken during the induction study and from a clinical trial of naturally occurring endocrinopathic laminitis cases. The Obel method was deconstructed and key laminitis signs were evaluated to develop a three-stage, five criteria method that employs a severity scale of 0-12. Veterinarians (n = 28) were recruited to watch and assess 15 video recordings of cases of varying severity, using the Obel and "modified Obel" methods. The inter-observer agreement (reproducibility) was determined using Kendall's coefficient of concordance (Kendall W) and Krippendorf's alpha reliability coefficient. A total of 14 veterinarians repeated the exercise 2-4 weeks after their original assessment, to determine intra-observer agreement (repeatability), assessed using a weighted kappa statistic (kw). Agreement between methods was calculated by converting all "modified Obel" scores to Obel grades and calculating the mean and distribution of the differences. Results:The "modified Obel" and Obel methods showed excellent and similar inter-observer agreement based on the Kendall W value (0.87, P < 0.001 vs. 0.85, P < 0.001) and Krippendorf's alpha (95% CI) value (0.83 [0.53-0.90] vs. 0.77 [0.55-0.85]). Based on the kw value, the "modified Obel" method also had substantial repeatability, although slightly less than the Obel method, (0.80 vs. 0.91). Excellent agreement between the methods was found, with the mean difference (95% CI), comparing the Obel grade, with the "modified Obel" score converted to an Obel grade, being -0.12 (-0.19 to -0.06) grades. The Obel and converted "modified Obel" grades were identical 62% of the time (259/420) and a difference of one grade (higher or lower) occurred in 35% of cases (148/420). Conclusion:Both methods show excellent agreement, reproducibility and repeatability when used to diagnose endocrinopathic laminitis. The "modified Obel" method is a three-step examination process for severity-scoring of endocrinopathic laminitis, initially proposed for use within a research setting. When using the modified method a diagnosis of laminitis also requires clinical acumen. The allocation of scores for specific clinical signs should be particularly useful in research trials monitoring laminitis recovery.

Project description:BackgroundIncreasing incidence of multidrug-resistant Mycobacterium tuberculosis infections is hampering global tuberculosis control efforts. Kuwait is a low-tuberculosis-incidence country, and ~?1% of M. tuberculosis strains are resistant to rifampicin and isoniazid (MDR-TB). This study detected mutations in seven genes predicting resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin in MDR-TB strains. Sequence data were combined with spoligotypes for detecting local transmission of MDR-TB in Kuwait.MethodsNinety-three MDR-TB strains isolated from 12 Kuwaiti and 81 expatriate patients and 50 pansusceptible strains were used. Phenotypic drug susceptibility was determined by MGIT 460 TB/960 system. Mutations conferring resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin were detected by genotype MTBDRplus assay and/or PCR sequencing of three rpoB regions, katG codon 315 (katG315)?+?inhA regulatory region, pncA, three embB regions and rpsL?+?rrs-500-900 regions. Spoligotyping kit was used, spoligotypes were identified by SITVIT2, and phylogenetic tree was constructed by using MIRU-VNTRplus software. Phylogenetic tree was also constructed from concatenated sequences by MEGA7 software. Additional PCR sequencing of gidB and rpsA was performed for cluster isolates.ResultsPansusceptible isolates contained wild-type sequences. Mutations in rpoB and katG and/or inhA were detected in 93/93 and 92/93 MDR-TB strains, respectively. Mutations were also detected for pyrazinamide resistance, ethambutol resistance and streptomycin resistance in MDR-TB isolates in pncA, embB and rpsL?+?rrs, respectively. Spoligotyping identified 35 patterns with 18 isolates exhibiting unique patterns while 75 isolates grouped in 17 patterns. Beijing genotype was most common (32/93), and 11 isolates showed nine orphan patterns. Phylogenetic analysis of concatenated sequences showed unique patterns for 51 isolates while 42 isolates grouped in 16 clusters. Interestingly, 22 isolates in eight clusters by both methods were isolated from TB patients typically within a span of 2 years. Five of eight clusters were confirmed by additional gidB and rpsA sequence data.ConclusionsOur study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified several potential clusters of local transmission of MDR-TB involving 2-6 subjects which had escaped detection by routine surveillance studies. Prospective detection of resistance-conferring mutations can identify possible cases of local transmission of MDR-TB in low MDR-TB settings.

Dataset Information

SEVERITY OF TB CLASSIFIED BY MODIFIED BANDIM TB SCORING ASSOCIATES WITH THE SPECIFIC SEQUENCE OF ESXA GENES IN MDR-TB PATIENTS.

Publications

SEVERITY OF TB CLASSIFIED BY MODIFIED BANDIM TB SCORING ASSOCIATES WITH THE SPECIFIC SEQUENCE OF ESXA GENES IN MDR-TB PATIENTS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets