A Biomarker for Monitoring Tuberculosis Treatment Responses in HIV-Positive Patients

IP10 kinetics during the first week of TB treatment is associated with bacteriological confirmation at diagnosis in HIV-positive patients, according to a new study led by ISGlobal, an institution supported by the ”la Caixa” Foundation, and the Manhiça Health Research Center (CISM). The results, published in Scientific Reports, pave the way to a better diagnosis and disease management in these patients.

Tuberculosis (TB) remains a major global health problem (with around 10.4 new estimated cases in 2016), but the available tools to diagnose and manage patients during treatment are suboptimal.  The current diagnosis methods have several limitations: low sensitivity for sputum smears, low specificity for clinical criteria, and delay in results for bacteria culture assays). Because of this, clinically confirmed cases may start treatment without actually having TB or with the wrong therapy (in case they have drug resistant TB). Hence the importance of assays to confirm TB diagnosis and monitor TB treatment. Some studies have associated certain biomarkers such as the proinflammatory protein IP10 with bacteriological confirmation of diagnosis and good treatment response. 

In this study, the authors investigated whether changes in circulating IP10 levels correlated with bacteriological confirmation of TB and treatment outcome among adult HIV patients.  The study was carried out in Manhiça, Mozambique, where 40% of adults are HIV-positive and the prevalence of TB is high. For a total of 127 HIV patients that started treatment for pulmonary TB, they measured IP10 levels during the first week and after 2 months of treatment. Sputum analyses, culture assays, and molecular amplification (Xpert MTB/RIF) were also performed for all patients, as part of the diagnosis strategy.

The results show that bacteriologically confirmed patients were more likely to have high IP10 levels at day 0 and a steeper decline by day 7, as compared to clinically diagnosed cases.    

“IP10 kinetics could predict the bacteriological status in 2 out of 3 cases” says Alberto García-Basteiro, ISGlobal researcher and first author of the study, “therefore we believe that IP10 represents a promising tool to evaluate TB treatment responses, also in HIV-positive patients”.   

The authors point out that further work in combination with other biomarkers is needed to increase sensitivity and identify the 20% of bacteriologically confirmed patients without elevated IL10 levels.  

Reference:

García-Basteiro A, Mambuque E, den Hertog A, et al. IP-10 kinetics in the first week of therapy are strongly associated with bacteriological confirmation of tuberculosis diagnosis in HIV-infected patients. Sci Rep. Oct 30, 2017. doi:10.1038/s41598-017-13785-3