Biomarkers to monitor therapeutic response in leishmaniasis: a systematic review

Abstract

Since a few years there is a renewed interest in the development of new drugs for the treatment of leishmaniasis. This propitiates the need for pharmacodynamic markers to monitor and compare therapies, specifically for visceral leishmaniasis in which the primary recrudescence of parasites is a particularly long-term event that remains difficult to predict. We performed a systematic review of studies evaluating biomarkers in human visceral, cutaneous and post-kala-azar dermal leishmaniasis patients, which yielded a total of 170 studies in which 53 potential pharmacodynamic biomarkers were identified. In conclusion, the large majority of these biomarkers constituted universal indirect markers of activation and subsequent waning of cellular immunity, therefore lacking specificity. Macrophage-related markers demonstrate favourable sensitivity and time-to-normal, but more evidence is required to establish a link between these markers and clinical outcome. Most promising are the markers directly related to the parasite burden, but future effort should be focused on optimization of the molecular or antigenic target to increase sensitivity of these markers. In general, future research should focus on the longitudinal evaluation of the pharmacodynamic biomarkers during treatment with an emphasis on the correlation of studied biomarkers and clinical parameters