Spliced-Leader RNA as a Dynamic Marker for Monitoring Viable Leishmania Parasites During and After Treatment

Author:

Hendrickx Rik1,Melkamu Roma2,Tadesse Dagimawie3,Teferi Tedla4,Feijens Pim-Bart1,Vleminckx Margot1,van Henten Saskia5ORCID,Alves Fabiana6,Shibru Tamiru3,van Griensven Johan5ORCID,Caljon Guy1ORCID,Pareyn Myrthe5ORCID

Affiliation:

1. Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp , Antwerp , Belgium

2. Leishmaniasis Research and Treatment Center, University of Gondar Hospital , Gondar

3. College of Medicine and Health Sciences, Arba Minch University

4. Malaria and Leishmaniasis Research and Treatment Center, Arba Minch General Hospital , Arba Minch , Ethiopia

5. Clinical Sciences Department, Institute of Tropical Medicine Antwerp , Antwerp , Belgium

6. Drugs for Neglected Diseases initiative , Geneva , Switzerland

Abstract

Abstract Accurate detection of viable Leishmania parasites is critical for evaluating visceral leishmaniasis (VL) treatment response at an early timepoint. We compared the decay of kinetoplast DNA (kDNA) and spliced-leader RNA (SL-RNA) in vitro, in vivo, and in a VL patient cohort. An optimized combination of blood preservation and nucleic acid extraction improved efficiency for both targets. SL-RNA degraded more rapidly during treatment than kDNA, and correlated better with microscopic examination. SL-RNA quantitative polymerase chain reaction emerges as a superior method for dynamic monitoring of viable Leishmania parasites. It enables individualized treatment monitoring for improved prognoses and has potential as an early surrogate endpoint in clinical trials.

Funder

University of Antwerp

Directorate-General Development Cooperation and Humanitarian Aid

Institute of Tropical Medicine

University of Gondar

Publisher

Oxford University Press (OUP)

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