Individualizing management of extensively drug-resistant tuberculosis: diagnostics, treatment, and biomarkers

Alffenaar, Jan‐Willem C.; Akkerman, Onno W.; Anthony, Richard; Tiberi, Simon; Heysell, Scott K; Grobusch, Martin P.; Cobelens, Frank; Soolingen, Dick van

doi:10.1080/14787210.2017.1247692

Cited by 21 publications

(14 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results presented here demonstrate that robust signals from host protein biomarkers are able to reproducibly distinguish TB from non-TB subjects. Additionally, suites of markers were identified which correlated with early treatment response and which could be useful for detection and monitoring of drug-resistant TB ( 29 – 31 ).…”

Section: Introductionmentioning

confidence: 99%

Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis

et al. 2017

View full text Add to dashboard Cite

New non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of the highest priority for global TB control. We performed in-depth proteomic analysis using the 4,000-plex SOMAscan assay on 1,470 serum samples from seven countries where TB is endemic. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled out for TB by culture and clinical follow-up. HIV coinfection was present in 34% of samples, and 25% were sputum smear negative. Serum protein biomarkers were identified by stability selection using L1-regularized logistic regression and by Kolmogorov-Smirnov (KS) statistics. A naive Bayes classifier using six host response markers (HR6 model), including SYWC, kallistatin, complement C9, gelsolin, testican-2, and aldolase C, performed well in a training set (area under the sensitivity-specificity curve [AUC] of 0.94) and in a blinded verification set (AUC of 0.92) to distinguish TB and non-TB samples. Differential expression was also highly significant (P < 10−20) for previously described TB markers, such as IP-10, LBP, FCG3B, and TSP4, and for many novel proteins not previously associated with TB. Proteins with the largest median fold changes were SAA (serum amyloid protein A), NPS-PLA2 (secreted phospholipase A2), and CA6 (carbonic anhydrase 6). Target product profiles (TPPs) for a non-sputum biomarker test to diagnose active TB for treatment initiation (TPP#1) and for a community-based triage or referral test (TPP#2) have been published by the WHO. With 90% sensitivity and 80% specificity, the HR6 model fell short of TPP#1 but reached TPP#2 performance criteria. In conclusion, we identified and validated a six-marker signature for active TB that warrants diagnostic development on a patient-near platform.

show abstract

Section: Introductionmentioning

confidence: 99%

Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Such poor treatment outcomes may be in part a consequence of pharmacokinetic variability rendering subtherapeutic drug concentrations [4–6]. Serum area under the concentration curve (AUC) is the pharmacokinetic parameter correlative with efficacy for most concentration-dependent TB drugs [7, 8] and AUC/minimum inhibitory concentration (MIC) ratio can be further used to predict treatment response [9]. However, relatively few studies have examined the pharmacokinetics of MDR-TB drugs, and none from HIV-infected patients in the Russian Federation.…”

Section: To the Editormentioning

confidence: 99%

Pharmacokinetics of tuberculosis drugs in HIV-infected patients from Irkutsk, Russian Federation: redefining drug activity

et al. 2018

View full text Add to dashboard Cite

“…However a personalised approach appears to give the best outcomes [124], with careful clinical and laboratory monitoring remaining essential for the correct management of these complex cases.…”

Section: Mdr-tb Is Caused By Mycobacterial Strains Resistant To At Lementioning

confidence: 99%

The cursed duet today: Tuberculosis and HIV-coinfection

et al. 2017

Self Cite

View full text Add to dashboard Cite

The tuberculosis (TB) and HIV syndemic continues to rage and are a major public health concern worldwide. This deadly association raises complexity and represent a significant barrier towards TB elimination. TB continues to be the leading cause of death amongst HIV-infected people. This paper reports the challenges that lay ahead and outlines some of the current and future strategies that may be able to address this co-epidemic efficiently. Improved diagnostics, cheaper and more effective drugs, shorter treatment regimens for both drug-sensitive and drug-resistant TB are discussed. Also, special topics on drug interactions, TB-IRIS and TB relapse are also described. Notwithstanding the defeats and meagre investments, diagnosis and management of the two diseases have seen significant and unexpected improvements of late. On the HIV side, expansion of ART coverage, development of new updated guidelines aimed at the universal treatment of those infected, and the increasing availability of newer, more efficacious and less toxic drugs are an essential element to controlling the two epidemics. On the TB side, diagnosis of MDR-TB is becoming easier and faster thanks to the new PCR-based technologies, new anti-TB drugs active against both sensitive and resistant strains (i.e. bedaquiline and delamanid) have been developed and a few more are in the pipeline, new regimens (cheaper, shorter and/or more effective) have been introduced (such as the "Bangladesh regimen") or are being tested for MDR-TB and drug-sensitive-TB. However, still more resources will be required to implement an integrated approach, install new diagnostic tests, and develop simpler and shorter treatment regimens.

show abstract

Individualizing management of extensively drug-resistant tuberculosis: diagnostics, treatment, and biomarkers

Cited by 21 publications

References 114 publications

Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis

Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis

Pharmacokinetics of tuberculosis drugs in HIV-infected patients from Irkutsk, Russian Federation: redefining drug activity

The cursed duet today: Tuberculosis and HIV-coinfection

Contact Info

Product

Resources

About