Back to Search
Start Over
Dormant Plasmodium falciparum Parasites in Human Infections Following Artesunate Therapy.
- Source :
-
Journal of Infectious Diseases . May2021, Vol. 223 Issue 9, p1631-1638. 8p. - Publication Year :
- 2021
-
Abstract
- <bold>Background: </bold>Artemisinin monotherapy of Plasmodium falciparum infection is frequently ineffective due to recrudescence. Artemisinin-induced dormancy, shown in vitro and in animal models, provides a plausible explanation. To date, direct evidence of artemisinin-induced dormancy in humans is lacking.<bold>Methods: </bold>Blood samples were collected from Plasmodium falciparum 3D7- or K13-infected participants before and 48-72 hours after single-dose artesunate (AS) treatment. Parasite morphology, molecular signature of dormancy, capability and dynamics of seeding in vitro cultures, and genetic mutations in the K13 gene were investigated.<bold>Results: </bold>Dormant parasites were observed in post-AS blood samples of 3D7- and K13-infected participants. The molecular signature of dormancy, an up-regulation of acetyl CoA carboxylase, was detected in 3D7 and K13 samples post-AS, but not in pre-AS samples. Posttreatment samples successfully seeded in vitro cultures, with a significant delay in time to reach 2% parasitemia compared to pretreatment samples.<bold>Conclusions: </bold>This study provides strong evidence for the presence of artemisinin-induced dormant parasites in P. falciparum infections. These parasites are a likely reservoir for recrudescent infection following artemisinin monotherapy and artemisinin combination therapy (ACT). Combination regimens that target dormant parasites or remain at therapeutic levels for a sufficient time to kill recovering parasites will likely improve efficacy of ACTs. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PLASMODIUM falciparum
*GENETIC mutation
*PARASITES
*ARTEMISININ
*BLOOD sampling
Subjects
Details
- Language :
- English
- ISSN :
- 00221899
- Volume :
- 223
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Journal of Infectious Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 150453501
- Full Text :
- https://doi.org/10.1093/infdis/jiaa562