Abstract
Treatment efficacy is difficult to evaluate in extrapulmonary tuberculosis (EPTB) patients. Interferon-γ inducible protein (IP-)10 has been suggested as a biomarker for response to treatment. We have investigated if IP-10 from dried plasma spots (DPS) or dried blood spots (DBS) can be used in treatment monitoring of EPTB patients in a low-resource setting of Zanzibar. IP-10 levels in plasma, DPS and DBS samples collected before, during (2 months) and after TB treatment of 36 EPTB patients (6 culture and/or Xpert MTB/RIF positive and 30 clinically diagnosed) and 8 pulmonary tuberculosis (PTB) patients, were quantified by an enzyme-linked immunosorbent assay. There was a high positive correlation between IP-10 measured in plasma and DPS and DBS, respectively. We found a significant decline in IP-10 levels from baseline to end of treatment in plasma, DPS and DBS, both in EPTB and PTB patients. The declines were observed already after 2 months in HIV negative patients. In conclusion, the DPS/DBS IP-10 assay allows for easy and manageable monitoring in low-resource settings and our findings suggest that IP-10 may serve as a biomarker for treatment efficacy in EPTB patients, albeit further studies in cohorts of patients with treatment failure and relapse are needed.
Highlights
Tuberculosis (TB) is a global health problem with an estimated 10.0 million new cases of active TB and 1.6 million deaths because of TB in 20171
We have evaluated the potential of the dried plasma spots (DPS)/dried blood spots (DBS) inducible protein (IP-)10 assay compared to measuring IP-10 in plasma, for assessing treatment responses in extrapulmonary tuberculosis (EPTB) patients in a clinical setting where diagnostic tools and resources are limited
We demonstrate that IP-10 is readily detectable both in unstimulated plasma and DPS/DBS filter paper samples
Summary
Tuberculosis (TB) is a global health problem with an estimated 10.0 million new cases of active TB and 1.6 million deaths because of TB in 20171. Rapid and robust tests for TB diagnosis and treatments efficacy are needed to achieve global TB control. Smear microscopy and culture are frequently used to assess treatment responses, the sensitivity of these methods is low in paucibacillary disease[2], and they have limited ability to predict treatment outcomes[3,4,5]. As smear or culture conversion cannot be used to monitor treatment efficacy in EPTB patients, clinicians must rely on clinical evaluation to detect treatment failure, which is often challenging due to the nonspecific symptoms in EPTB disease. IP-10 is a robust marker expressed at higher levels than many other candidate biomarkers[20,27], which allows for IP-10 detection using simple test platforms
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