|Rabna, Paulo. 2008. Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Marker of Tuberculosis Treatment Efficacy and Potential Prognostic marker for Survival in individuals with a TB negative diagnosis. A prospective, Longitudinal Cohort Study in Suspected Pulmonary Tuberculosis patients in Guinea-Bissau. Bandim Health Project, Statens Serum Institut. Faculty of Health Sciences, University of Copenhagen.
The aim of this thesis was to investigate if suPAR levels are prognostic of TB treatment efficacy and to investigate whether suPAR can be used to identify aTBneg individuals with high mortality risk.
Currently, microscopy and culture are traditionally the methods used to monitor the efficacy of TB treatment recommended by the WHO and IUATLD. However, monitoring TB treatment by smear microscopy has limitations such as low sensitivity. Culturing of mycobacterium increases sensitivity but adds weeks to the process of diagnosing primary infections, as well as evaluating TB resistance and treatment effectiveness.
Use of biomarkers, such as suPAR measurements, is a developing field that has the potential to provide considerable insights for the monitoring of TB treatment response as well as HIV disease progression and for identifying individuals with a high mortality risk among individuals assumed to be TB-negative.
The problem is that TB is quite difficult to diagnose, especially in cases without presence of bacteria in direct microscopy,
Patients that are diagnosed with active TB are immediately treated with a course of medication lasting approximately 6-8 months. Prior to the end of the treatment regime, there exists very little indication of the efficacy of the particular treatment, and thus infected individuals can complete a treatment regimen without knowing if the infection has been eradicated.
Recently, a validated and CE/IVD labeled assay for measuring suPAR became available (suPARnostic®, ViroGates, Denmark).
In our aTBneg study, (paper I), we observed an increased mortality rate among individuals who were aTBneg compared to the general population. This increased mortality was most profound for individuals younger than 55 years old.
The third study (paper III) examined whether urine suPAR (U-suPAR) can be used as a prognostic marker in aTBneg individuals. We found that U-suPAR carried significant prognostic information on mortality for HIV-infected subjects. For HIV-negative individuals, little or no prognostic effect was observed. However, in both HIV positives and negatives, the predictive effect of U-suPAR was found to be inferior to that of P-suPAR.
Conclusion and future perspectives
In conclusion the plasma suPAR carries strong prognostic information on mortality in aTBneg suggesting that suPAR could be used to identify individuals with high mortality risk. Identification of individuals with high suPAR or individuals with increasing suPAR levels should lead to further clinical and diagnostic procedures in order to reduce the high mortality among these individuals.