Plasmodium falciparum Treated with Artemisinin-based Combined Therapy Exhibits Enhanced Mutation, Heightened Cortisol and TNF-α Induction
No Thumbnail Available
Date
2018-09-09
Authors
Idowu, A.O.
Bhattacharyya, S.
Gradus, S.
Oyibo, W.A.
George, Z.
Black, C.
Igietseme, J.
Azenabor, A.A.
Journal Title
Journal ISSN
Volume Title
Publisher
International Journal of Medical Sciences
Abstract
The artemisinin-based combined therapy (ACT) post-treatment illness in Plasmodium falciparum-endemic areas is characterized by vague malaria-like symptoms. The roles of treatment modality, persistence of parasites and host proinflammatory response in disease course are unknown. We investigated the hypothesis that ACT post-treatment syndrome is driven by parasite genetic polymorphisms and proinflammatory response to persisting mutant parasites. Patients were categorized as treated, untreated, and malaria-negative. Malaria-positive samples were analyzed for Pfcrt, Pfmdr1, K13 kelch gene polymorphisms, while all samples were evaluated for cytokines (TNF-α, IL-12p70, IL-10, TGF-β, IFN-γ) and corticosteroids (cortisol and dexamethasone) levels. The treated patients exhibited higher levels of parasitemia, TNF-α, and cortisol, increased incidence of parasite genetic mutations, and a greater number of mutant alleles per patient. In addition, corticosteroid levels declined with increasing number of mutant alleles. TGF-β levels were negatively correlated with parasitemia, while IL-10 and TGF-β were negatively correlated with increasing number of mutant alleles. However, IL-12 displayed a slight positive correlation and TNF-α exhibited moderate positive correlation with increasing number of mutant alleles. Since post-treatment management ultimately results in patient recovery, the high parasite gene polymorphism may act in concert with induced cortisol and TNF-α to account for ACT post-treatment syndrome.
Description
Scholarly articles
Keywords
Proinflamation , Cortisol , Corticosteroids , Gene , Research Subject Categories::MEDICINE
Citation
Idowu AO, Bhattacharyya S, Gradus S, Oyibo W, George Z, Black C, Igietseme J, Azenabor AA. Plasmodium falciparum Treated with Artemisinin-based Combined Therapy Exhibits Enhanced Mutation, Heightened Cortisol and TNF-α Induction. Int J Med Sci 2018; 15(13):1449-1457. doi:10.7150/ijms.27350.