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Blood Parasite Load...
Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa.
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Verrest, Luka (author)
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Kip, Anke E (author)
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Musa, Ahmed M (author)
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Schoone, Gerard J (author)
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Schallig, Henk D F H (author)
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Mbui, Jane (author)
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Khalil, Eltahir A G (author)
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Younis, Brima M (author)
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Olobo, Joseph (author)
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Were, Lilian (author)
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Kimutai, Robert (author)
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Monnerat, Séverine (author)
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Cruz, Isra (author)
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Wasunna, Monique (author)
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Alves, Fabiana (author)
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- Dorlo, Thomas P C (author)
- Netherlands Cancer Institute
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(creator_code:org_t)
- 2021-02-13
- 2021
- English.
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 73:5, s. 775-782
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- BACKGROUND: To expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes.METHODS: Data from 3 clinical trials were combined in this study, in which Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative polymerase chain reaction (qPCR) before, during, and up to 6 months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at 6 months.RESULTS: The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within 6 months of follow-up at a cutoff of 20 parasites/mL (area under the curve 0.92, specificity 0.91, sensitivity 0.89). Blood parasite loads correlated well with tissue parasite loads (ρ = 0.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a > 80% power to detect a difference in cure rate between treatment regimens if this difference was high (> 50%) and when minimally 30 patients were included per regimen.CONCLUSIONS: Blood Leishmania parasite load determined by qPCR is a promising early biomarker to predict relapse in VL patients. Once optimized, it might be useful in dose finding studies of new chemical entities.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- biomarker
- parasitemia
- pharmacodynamics
- qPCR
- visceral leishmaniasis
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Verrest, Luka
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Kip, Anke E
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Musa, Ahmed M
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Schoone, Gerard ...
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Schallig, Henk D ...
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Mbui, Jane
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show more...
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Khalil, Eltahir ...
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Younis, Brima M
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Olobo, Joseph
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Were, Lilian
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Kimutai, Robert
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Monnerat, Séveri ...
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Cruz, Isra
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Wasunna, Monique
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Alves, Fabiana
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Dorlo, Thomas P ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
- Articles in the publication
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Clinical Infecti ...
- By the university
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Uppsala University