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- Title
Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation.
- Authors
Aleka, Yetemwork; Ibarra-Meneses, Ana Victoria; Workineh, Meseret; Tajebe, Fitsumbrhan; Kiflie, Amare; Tessema, Mekibib Kassa; Melkamu, Roma; Tadesse, Azeb; Moreno, Javier; van Griensven, Johan; Carrillo, Eugenia; Adriaensen, Wim
- Abstract
Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-γ, TNF-α, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with soluble Leishmania antigen, we observed an early, robust, and incremental increase of IFN-γ, TNF-α, and IP-10 levels in all patients during treatment. Moreover, based on the IFN-γ levels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two main Leishmania species. The levels of IFN-γ, IP-10, or TNF-α also seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN-γ and IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases.
- Subjects
ETHIOPIA; TREATMENT effectiveness; VISCERAL leishmaniasis; CELLULAR immunity; CROSS-sectional method; BLOOD; CYTOKINES; PILOT projects; LEISHMANIASIS; IMMUNIZATION; CELL culture; LEISHMANIA; PUBLIC health; PATIENT monitoring; LONGITUDINAL method
- Publication
Journal of Immunology Research, 2020, p1
- ISSN
2314-8861
- Publication type
journal article
- DOI
10.1155/2020/8385672