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Plasmodium falciparum finds the winning combination.

ABSTRACT: After 3 years of laboratory drug pressure in the presence of a picomolar inhibitor, the parasite Plasmodium falciparum developed a combination strategy of gene amplification and mutation to regain viability. The mutation observed led to a dysfunctional enzyme, but new research reveals the clever mechanism behind its success. Not that we needed a reminder of nature's creativity in the time of a pandemic.

SUBMITTER: Hengge AC

PROVIDER: S-EPMC8047455 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature

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Plasmodium falciparum finds the winning combination.

Hengge Alvan C AC

The Journal of biological chemistry 20210101

After 3 years of laboratory drug pressure in the presence of a picomolar inhibitor, the parasite Plasmodium falciparum developed a combination strategy of gene amplification and mutation to regain viability. The mutation observed led to a dysfunctional enzyme, but new research reveals the clever mechanism behind its success. Not that we needed a reminder of nature's creativity in the time of a pandemic. ...[more]

PMID: 34237898

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Project description:Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance.Data from a cohort of Ugandan children four to five years old, enrolled in a longitudinal, randomized, clinical trial comparing two leading ACT, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), were analysed. For all episodes of uncomplicated P. falciparum malaria over a 14-month period, daily blood smears were performed for three days following the initiation of therapy. Associations between pre-treatment variables of interest and persistent parasitaemia were estimated using multivariate, generalized, estimating equations with adjustment for repeated measures in the same patient.A total of 202 children were included, resulting in 416 episodes of malaria treated with AL and 354 episodes treated with DP. The prevalence of parasitaemia on days 1, 2, and 3 following initiation of therapy was 67.6, 5.6 and 0% in those treated with AL, and 52.2, 5.7 and 0.3% in those treated with DP. Independent risk factors for persistent parasitaemia on day 1 included treatment with AL vs DP (RR?=?1.34, 95% CI 1.20-1.50, p?<?0.001), having a temperature ?38.0°C vs?<?37.0°C (RR?=?1.19, 95% CI 1.05-1.35, p?=?0.007) and having a parasite density >20,000/?L vs <4,000/?L (RR?=?3.37, 95% CI 2.44-4.49, p?<?0.001). Independent risk factors for having persistent parasitaemia on day 2 included elevated temperature, higher parasite density, and being HIV infected.Among Ugandan children, parasite clearance following treatment with AL or DP was excellent with only one of 752 patients tested having a positive blood slide three days after initiation of therapy. The type of ACT given, pre-treatment temperature, pre-treatment parasite density and HIV status were associated with differences in persistent parasitaemia, one or two days following therapy.Current Controlled Trials Identifier NCT00527800.

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Plasmodium falciparum finds the winning combination.

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Plasmodium falciparum finds the winning combination.

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