Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa
| Autor: | Brima M. Younis, Anke E. Kip, Gerard J. Schoone, Lilian Were, Thomas P. C. Dorlo, Joseph Olobo, Robert Kimutai, Jane Mbui, Eltahir A G Khalil, Isra Cruz, Henk D. F. H. Schallig, Luka Verrest, Ahmed Eleojo Musa, Séverine Monnerat, Fabiana Alves, Monique Wasunna |
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| Přispěvatelé: | Medical Microbiology and Infection Prevention, AII - Infectious diseases, Unión Europea. Comisión Europea. 7 Programa Marco, World Health Organization (WHO/OMS), French Development Agency, Government of the United Kingdom, Federal Ministry of Education & Research (Alemania), Medicor Foundation, Médecins Sans Frontières, Swiss Agency for Development and Cooperation, Ministry of Foreign Affairs (Holanda), Ministry of Foreign Affairs and International Development (Francia), Rockefeller Foundation, Fundación BBVA, Unión Europea, Dutch Research Council (Holanda) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
medicine.medical_specialty Parasitemia Parasite load Gastroenterology Parasite Load Internal medicine medicine pharmacodynamics Animals Humans visceral leishmaniasis Parasites parasitemia Whole blood Visceral leishmaniasis business.industry Surrogate endpoint Area under the curve Biomarker Africa Eastern medicine.disease Regimen Major Articles and Commentaries qPCR Infectious Diseases AcademicSubjects/MED00290 Pharmacodynamics Biomarker (medicine) Leishmaniasis Visceral biomarker business Biomarkers |
| Zdroj: | Clinical infectious diseases, 73(5), 775-782. Oxford University Press Repisalud Instituto de Salud Carlos III (ISCIII) Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America |
| ISSN: | 1058-4838 |
| Popis: | 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. Blood Leishmania parasite load, determined by qPCR, is a promising early biomarker to predict relapse in visceral leishmaniasis patients and might particularly be useful in the context of dose finding studies of new chemical entities. |
| Databáze: | OpenAIRE |
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