title: Systematic review of biomarkers to monitor therapeutic response in leishmaniasis.
abstract: Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred 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 patients with visceral, cutaneous, and post-kala-azar dermal leishmaniasis, 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 and therefore lacked specificity. Macrophage-related markers demonstrate favorable sensitivity and times to normalcy, 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 molecular or antigenic targets to increase the 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.
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, Amsterdam, the Netherlands.
authors.forename: Anke E
authors.initials: AE
authors.lastname: Kip
authors.affiliation: Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
authors.forename: Manica
authors.initials: M
authors.lastname: Balasegaram
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Slotervaart Hospital, Amsterdam, the Netherlands.
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands Department of Clinical Pharmacology, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.affiliation: Division of Internal Medicine, Tergooiziekenhuizen, Hilversum, the Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: de Vries
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, the Netherlands t.p.c.dorlo@uu.nl.
authors.forename: Thomas P C
authors.initials: TP
authors.lastname: Dorlo
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000243:Adenosine Deaminase / Q000378:metabolism; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007893:Leishmania donovani / Q000276:immunology / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000209:Acute-Phase Proteins; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015415:Biomarkers; D016207:Cytokines; D008565:Membrane Proteins; D000243:Adenosine Deaminase