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Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

ABSTRACT: Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a second cohort from Uganda/Brazil consisting of 17 relapse and 23 cured patients. Thirty markers changed significantly with different response patterns during TB treatment in cured patients. The serum biosignature distinguished cured from relapse patients and a combination of two clinical (time to positivity in liquid culture and BMI) and four immunological parameters (TNF-?, sIL-6R, IL-12p40 and IP-10) at diagnosis predicted relapse with a 75% sensitivity (95%CI 0.38-1) and 85% specificity (95%CI 0.75-0.93). This biosignature was validated in an independent Uganda/Brazil cohort correctly classifying relapse patients with 83% (95%CI 0.58-1) sensitivity and 61% (95%CI 0.39-0.83) specificity. A characteristic biosignature with value as predictor of TB relapse was identified. The repeatability and robustness of these biomarkers require further validation in well-characterized cohorts.

SUBMITTER: Ronacher K

PROVIDER: S-EPMC6839616 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

Ronacher Katharina K Chegou Novel N NN Kleynhans Léanie L Djoba Siawaya Joel F JF du Plessis Nelita N Loxton André G AG Maasdorp Elizna E Tromp Gerard G Kidd Martin M Stanley Kim K Kriel Magdalena M Menezes Angela A Gutschmidt Andrea A van der Spuy Gian D GD Warren Robin M RM Dietze Reynaldo R Okwera Alphonse A Thiel Bonnie B Belisle John T JT Cliff Jacqueline M JM Boom W Henry WH Johnson John L JL van Helden Paul D PD Dockrell Hazel M HM Walzl Gerhard G

Tuberculosis (Edinburgh, Scotland) 20190812

Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a sec ...[more]

PMID: 31434026

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Project description:Cavitary pulmonary tuberculosis (TB) is associated with poor outcomes, treatment recurrence, higher transmission rates, and the development of drug resistance. However, reports on its clinical characteristics, associated factors, and treatment outcomes are lacking. Hence, this study sought to evaluate the clinical factors associated with cavitary pulmonary TB and its treatment outcomes. We retrospectively evaluated 410 patients with drug-susceptible pulmonary TB in a university hospital in Korea between 2014 and 2019. To evaluate the factors associated with cavitary TB, multivariable logistic regression was performed with adjustments for potential confounders. We also compared the treatment outcomes between patients with cavitary TB and those without cavitary TB. Of the 410 patients, 244 (59.5%) had non-cavitary TB and 166 (40.5%) had cavitary TB. Multivariable logistic analysis with forward selection method showed that body mass index (BMI) (adjusted OR = 0.88, 95% CI: 0.81-0.97), previous history of TB (adjusted OR = 3.45, 95% CI: 1.24-9.59), ex- or current smoker (adjusted OR = 1.77, 95% CI: 1.01-3.13), diabetes mellitus (adjusted OR = 2.72, 95% CI: 1.36-5.44), and positive results on the initial sputum acid-fast bacilli (AFB) smear (adjusted OR = 2.24, 95% CI: 1.26-3.98) were significantly associated with cavitary TB. Although treatment duration was significantly longer in patients with cavitary TB than in those with non-cavitary TB (248 (102-370 days) vs. 202 (98-336 days), p < 0.001), the recurrence rate after successful treatment was significantly higher in the patients with cavitary TB than in those with non-cavitary TB (0.4% vs. 3.0% p = 0.042). In conclusion, ex- or current smoker, lower BMI, previous history of TB, diabetes mellitus, and positivity of the initial AFB smear were associated with cavitary TB. The patients with cavitary TB had more AFB culture-positive results at 2 months, longer treatment duration, and higher recurrence rates than those with non-cavitary TB.

Project description:ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants.Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed.The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively.In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.

Project description:BackgroundTuberculosis (TB) is the leading cause of death from an infectious disease in Ethiopia, killing more than 30 thousand people every year. This study aimed to determine whether the rates of poor TB treatment outcome varied geographically across Ethiopia at district and zone levels and whether such variability was associated with socioeconomic, behavioural, health care access, or climatic conditions.MethodsA geospatial analysis was conducted using national TB data reported to the health management information system (HMIS), for the period 2015-2017. The prevalence of poor TB treatment outcomes was calculated by dividing the sum of treatment failure, death and loss to follow-up by the total number of TB patients. Binomial logistic regression models were computed and a spatial analysis was performed using a Bayesian framework. Estimates of parameters were generated using Markov chain Monte Carlo (MCMC) simulation. Geographic clustering was assessed using the Getis-Ord Gi* statistic, and global and local Moran's I statistics.ResultsA total of 223,244 TB patients were reported from 722 districts in Ethiopia during the study period. Of these, 63,556 (28.5%) were cured, 139,633 (62.4%) completed treatment, 6716 (3.0%) died, 1459 (0.7%) had treatment failure, and 12,200 (5.5%) were lost to follow-up. The overall prevalence of a poor TB treatment outcome was 9.0% (range, 1-58%). Hot-spots and clustering of poor TB treatment outcomes were detected in districts near the international borders in Afar, Gambelia, and Somali regions and cold spots were detected in Oromia and Amhara regions. Spatial clustering of poor TB treatment outcomes was positively associated with the proportion of the population with low wealth index (OR: 1.01; 95%CI: 1.0, 1.01), the proportion of the population with poor knowledge about TB (OR: 1.02; 95%CI: 1.01, 1.03), and higher annual mean temperature per degree Celsius (OR: 1.15; 95% CI: 1.08, 1.21).ConclusionsThis study showed significant spatial variation in poor TB treatment outcomes in Ethiopia that was related to underlying socioeconomic status, knowledge about TB, and climatic conditions. Clinical and public health interventions should be targeted in hot spot areas to reduce poor TB treatment outcomes and to achieve the national End-TB Strategy targets.

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Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

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Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

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