Relapse and Reinfection in Tuberculosis
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| CFLC01.dat.gz | Other | |||
| CFLC01.fasta.gz | Fasta.gz | |||
| CFLC01.master.dat | Other | |||
| CFNY01.dat.gz | Other | |||
| CFNY01.fasta.gz | Fasta.gz |
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Project description:Use of whole-genome sequencing to distinguish relapse from reinfection in a completed tuberculosis clinical trial
| PRJEB18529 | ENA
Project description:Background Identification of patients at risk of tuberculosis relapse following treatment would revolutionize clinical trials of new drugs and regimens and facilitate clinical management. The study aim was to determine whether tuberculosis patients who subsequently suffer relapse have different immune responses to mycobacteria in vitro compared to patients who remain cured for two years post-treatment. Methods First episode pulmonary tuberculosis patients were recruited into a surrogate marker study in Cape Town, South Africa. Peripheral blood samples were collected at diagnosis and after two and four weeks of tuberculosis treatment. Diluted blood was cultured with live Mycobacterium tuberculosis for six days and cellular RNA was frozen. Gene expression in samples from ten patients who subsequently relapsed, confirmed by stain genotyping, was compared to those who remained cured using Affymetrix microarrays. Results At diagnosis, the expression of 668 genes was significantly different in samples from patients who subsequently relapsed compared to successfully cured patients, and these differences persisted for at least four weeks. Gene Ontology and biological pathways analyses revealed the most significant difference was up-regulation of genes involved in cytotoxic cell-mediated killing, such as perforin, granulysin and fas ligand. Results were confirmed by qRT-PCR in a wider patient cohort. Conclusions These data show that patients who will subsequently relapse exhibit altered immune responses at diagnosis, including excessively robust cytolytic responses to M. tuberculosis in vitro, compared to patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited for patient stratification in drugs trials, or for host-directed therapy development.
2015-09-10 | GSE67589 | GEO
Project description:Background Identification of patients at risk of tuberculosis relapse following treatment would revolutionize clinical trials of new drugs and regimens and facilitate clinical management. The study aim was to determine whether tuberculosis patients who subsequently suffer relapse have different immune responses to mycobacteria in vitro compared to patients who remain cured for two years post-treatment. Methods First episode pulmonary tuberculosis patients were recruited into a surrogate marker study in Cape Town, South Africa. Peripheral blood samples were collected at diagnosis and after two and four weeks of tuberculosis treatment. Diluted blood was cultured with live Mycobacterium tuberculosis for six days and cellular RNA was frozen. Gene expression in samples from ten patients who subsequently relapsed, confirmed by stain genotyping, was compared to those who remained cured using Affymetrix microarrays. Results At diagnosis, the expression of 668 genes was significantly different in samples from patients who subsequently relapsed compared to successfully cured patients, and these differences persisted for at least four weeks. Gene Ontology and biological pathways analyses revealed the most significant difference was up-regulation of genes involved in cytotoxic cell-mediated killing, such as perforin, granulysin and fas ligand. Results were confirmed by qRT-PCR in a wider patient cohort. Conclusions These data show that patients who will subsequently relapse exhibit altered immune responses at diagnosis, including excessively robust cytolytic responses to M. tuberculosis in vitro, compared to patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited for patient stratification in drugs trials, or for host-directed therapy development. Venous blood samples were diluted in culture medium and stimulated with live M. tuberculosis for 6 days. Samples from 10 TB patients who subsequently relapsed and 10 patients whore remained disease-free for 2 years. Samples collected at TB diagnosis and after 2 weeks or 4 weeks of treatment of first TB episode.
2015-09-10 | E-GEOD-67589 | biostudies-arrayexpress
Project description:In individuals highly exposed to hepatitis C virus (HCV), reinfection is common, suggesting that natural development of sterilising immunity is difficult. In those that are reinfected, some will develop a persistent infection, while a small proportion repeatedly clear the virus, suggesting natural protection is possible. The aim of this study was to characterise immune responses associated with rapid natural clearance of HCV reinfection. Broad neutralising antibodies (BnAbs) and Envelope 2 (E2)-specific memory B cell (MBCs) responses were examined longitudinally in 15 subjects with varied reinfection outcomes. BnAb responses were associated with MBC recall, but not with reinfection clearance. Strong evidence of antigen imprinting was found, and the B cell receptor repertoire showed a high level of clonality with ongoing somatic hypermutation of many clones over subsequent reinfection events. Single cell transcriptomic analyses showed that cleared reinfections featured an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection. MBC quality, but not necessarily breadth of nAb responses, is important for protection against antigenically diverse variants, which is encouraging for HCV vaccine development.
2024-06-13 | GSE269792 | GEO
Project description:Whole Genome Sequencing Demonstrates Fidaxomicin is Superior to Vancomycin for Prevention of Clostridium difficile Relapse and Reinfection
| PRJEB4638 | ENA
Project description:Recurrent tuberculosis is an important indicator of the effectiveness of tuberculosis control and can occur by relapse or exogenous reinfection. We conducted a retrospective cohort study on all bacteriologically confirmed tuberculosis cases that were successfully treated between 2000 and 2012 in Shanghai, an urban area with a high number but a low prevalence rate of tuberculosis cases and a low prevalence of HIV infection. Genotyping the Mycobacterium tuberculosis from clinical isolates was used to distinguish between relapse and reinfection. In total, 5.3% (710/13,417) of successfully treated cases had a recurrence, a rate of 7.55 (95% CI 7.01-8.13) episodes per 1000 person-years, more than 18 times the rate of tuberculosis in the general population. Patients who were male, age 30-59, retreatment cases, had cavitation, diabetes, drug-resistant or multidrug-resistant tuberculosis in their initial episode of tuberculosis, were at high risk for a recurrence. Among 141 recurrent cases that had paired isolates, 59 (41.8%) had different genotypes, indicating reinfection with a different strain. Patients who completed treatment were still at high risk of another episode of tuberculosis and exogenous reinfection contributed a significant proportion of the recurrent tuberculosis cases. Targeted control strategies are needed to prevent new tuberculosis infections in this setting.
| S-EPMC5638046 | biostudies-literature
Project description:Tuberculosis (TB) recurrence can result from either relapse of an original infection or exogenous reinfection with a new strain of Mycobacterium tuberculosis (MTB). The aim of this study was to assess the roles of relapse and reinfection among recurrent TB cases characterized by a high prevalence rate of drug-resistant TB within a hospital setting. After 58 paired recurrent TB cases were genotyped to distinguish relapse from reinfection, 37 (63.8%) were demonstrated to be relapse cases, while the remaining 21 were classified as reinfection cases. Statistical analysis revealed that male gender was a risk factor for TB reinfection, odds ratios and 95% confidence interval (OR [95% CI]: 4.188[1.012-17.392], P = 0.049). Of MTB isolates obtained from the 37 relapse cases, 11 exhibited conversion from susceptible to resistance to at least one antibiotic, with the most frequent emergence of drug resistance observed to be levofloxacin. For reinfection cases, reemergence of rifampicin-resistant isolates harboring double gene mutations, of codon 531 of rpoB and codon 306 of embB, were observed. In conclusion, our data demonstrate that relapse is a major mechanism leading to TB recurrence in Beijing Chest Hospital, a national hospital specialized in TB treatment. Moreover, male patients are at higher risk for reinfection. The extremely high rate of multidrug-resistant tuberculosis (MDR-TB) among reinfection cases reflects more successful transmission of MDR-TB strains versus non-resistant strains overall.
| S-EPMC6102324 | biostudies-literature
Project description:The antimicrobials isoniazid and pyrazinamide, used for the treatment of tuberculosis are known to cause drug-induced liver injury in humans. This limits the effectiveness of tuberculosis treatment, resulting in incomplete cure, relapse and the development of antimicrobial resistance. MicroRNAs are known to be good biomarkers of disease, with the microRNA miR-122 being diagnostic for liver injury. In this study zebrafish larvae were exposed to the anti-tuberculosis drugs isoniazid and pyrazinamide at concentrations which demonstrated liver injury by microscopy and histology. The aim of this study is to understand small RNA changes occurring in anti-tuberculosis drug-induced liver injury and to attempt to identify novel microRNA biomarkers of liver injury.
2023-12-25 | GSE146260 | GEO
Project description:Recurrence of TB in an individual can occur due to relapse of the same strain or reinfection by a different strain. The contribution of reinfection and relapse to TB incidence, and the factors associated with each are unknown. We aimed to quantify and describe cases attributable to relapse or reinfection, and identify associated risk factors in order to reduce recurrence. We categorised recurrent TB cases from notifications in London (2002-2015) as relapse or reinfection using molecular (MIRU VNTR strain type) and epidemiological information (hierarchical approach using time since notification, site of disease and method of case finding). Factors associated with each outcome were determined using logistic regression in Stata Version 13.1 (2009-2015 only). Of 43,465 TB cases, 1.4% (618) were classified as relapse and 3.8% (1,637) as reinfection. The proportion with relapse decreased from 2002 (2.3%) to 2015 (1.3%), while the proportion of reinfection remained around 4%. Relapse was more common among recent migrants (<1 year, odds ratio (OR) = 1.99, p = 0.005), those with a social risk factor (OR = 1.51, p = 0.033) and those with central nervous system, spinal, miliary or disseminated TB (OR = 1.75, p = 0.001). Reinfection was more common among long term migrants (>11 years, OR = 1.67, p = <0.001), those with a social risk factor (OR = 1.96, p = <0.001) and within specific areas in London. Patients with social risk factors were at increased risk of both relapse and reinfection. Characterising those with relapsed disease highlights patients at risk and factors associated with reinfection suggest groups where transmission is occurring. This will inform TB control programs to target appropriate treatment and interventions in order to reduce the risk of recurrence.
| S-EPMC6377187 | biostudies-literature
Project description:B cell characteristics define HCV reinfection outcome
| PRJNA1123702 | ENA