%0 Journal Article
%T Plasmodium falciparum Treated with Artemisinin-based Combined Therapy Exhibits Enhanced Mutation, Heightened Cortisol and TNF-¦Á Induction
%A Abel Olusola Idowu
%A Anthony Ajayi Azenabor
%A Carolyn Black
%A Joseph Igietseme
%A Sanjib Bhattacharyya
%A Steve Gradus
%A Wellington Oyibo
%A Zenas George
%J International Journal of Medical Sciences
%D 2018
%R 10.7150/ijms.27350
%X 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-¦Á, IL-12p70, IL-10, TGF-¦Â, IFN-¦Ã) and corticosteroids (cortisol and dexamethasone) levels. The treated patients exhibited higher levels of parasitemia, TNF-¦Á, and cortisol, increased incidence of parasite genetic mutations, and greater number of mutant alleles per patient. In addition, corticosteroid levels declined with increasing number of mutant alleles. TGF-¦Â levels were negatively correlated with parasitemia, while IL-10 and TGF-¦Â were negatively correlated with increasing number of mutant alleles. However, IL-12 displayed slight positive correlation and TNF-¦Á 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-¦Á to account for ACT post-treatment syndrome.
%K Proinflammation
%K corticosteroids
%K cortisol
%K dexamethasone
%K gene polymorphism
%K persistent malaria
%K ACT.
%U http://www.medsci.org/v15p1449.htm