Evidence map›Paper›PMID 38640118›Full record

ArticlePLoS neglected tropical diseases2024

Leishmania blood parasite dynamics during and after treatment of visceral leishmaniasis in Eastern Africa: A pharmacokinetic-pharmacodynamic model.

Luka Verrest, Séverine Monnerat, Ahmed M Musa, Jane Mbui, Eltahir A G Khalil, Joseph Olobo, Monique Wasunna, Wan-Yu Chu, Alwin D R Huitema, Henk D F H Schallig and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 9 institutions in 6 countries.

Luka VerrestDepartment of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, the Netherlands.
Séverine MonneratDrugs for Neglected Diseases initiative, Geneva, Switzerland.
Ahmed M MusaInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Jane MbuiCentre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Eltahir A G KhalilInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Joseph OloboDepartment of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda.
Monique WasunnaDrugs for Neglected Diseases initiative (DNDi), Nairobi, Kenya.
Wan-Yu ChuDepartment of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, the Netherlands.
Alwin D R HuitemaDepartment of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, the Netherlands.
Henk D F H SchalligDepartment of Medical Microbiology and Infection Prevention, Laboratory for Experimental Parasitology, Academic Medical Center, Amsterdam, the Netherlands.
Fabiana AlvesDrugs for Neglected Diseases initiative, Geneva, Switzerland.
Thomas P C DorloDepartment of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID 0000-0003-3076-8435
Drugs for Neglected Diseases Initiative · CHUniversity of Khartoum · SDUppsala University · SEAmsterdam UMC Location University of Amsterdam · NLKenya AIDS Vaccine Initiative · KEKenya Medical Research Institute · KEMakerere University · UGThe Netherlands Cancer Institute · NLUtrecht University · NL

Funding

European Union Seventh Framework Programme AfricoleishWorld Health Organization
6 · The paper itself

Abstract

backgroundWith the current treatment options for visceral leishmaniasis (VL), recrudescence of the parasite is seen in a proportion of patients. Understanding parasite dynamics is crucial to improving treatment efficacy and predicting patient relapse in cases of VL. This study aimed to characterize the kinetics of circulating Leishmania parasites in the blood, during and after different antileishmanial therapies, and to find predictors for clinical relapse of disease.

methodsData from three clinical trials, in which Eastern African VL patients received various antileishmanial regimens, were combined in this study. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during, and up to six months after treatment. An integrated population pharmacokinetic-pharmacodynamic model was developed using non-linear mixed effects modelling.

resultsParasite proliferation was best described by an exponential growth model, with an in vivo parasite doubling time of 7.8 days (RSE 12%). Parasite killing by fexinidazole, liposomal amphotericin B, sodium stibogluconate, and miltefosine was best described by linear models directly relating drug concentrations to the parasite elimination rate. After treatment, parasite growth was assumed to be suppressed by the host immune system, described by an Emax model driven by the time after treatment. No predictors for the high variability in onset and magnitude of the immune response could be identified. Model-based individual predictions of blood parasite load on Day 28 and Day 56 after start of treatment were predictive for clinical relapse of disease.

conclusionThis semi-mechanistic pharmacokinetic-pharmacodynamic model adequately captured the blood parasite dynamics during and after treatment, and revealed that high blood parasite loads on Day 28 and Day 56 after start of treatment are an early indication for VL relapse, which could be a useful biomarker to assess treatment efficacy of a treatment regimen in a clinical trial setting.

Indexed as

Antiprotozoal AgentsLeishmaniasis, VisceralNitroimidazolesAdolescentAdultAfrica, EasternAmphotericin BAntimony Sodium GluconateChildChild, PreschoolDNA, KinetoplastDNA, ProtozoanFemaleHumansMaleMiddle AgedAmphotericin BAntimony Sodium GluconateAntiprotozoal AgentsDNA, KinetoplastDNA, Protozoanfexinidazoleliposomal amphotericin BmiltefosineNitroimidazolesPhosphorylcholine

Identifiers

PMID38640118
PMCPMC11062534
OpenAlexW4394951349

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.