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Int J Med Sci. 2018 Sep 7;15(13):1449-1457. doi: 10.7150/ijms.27350. eCollection 2018.

Plasmodium falciparum Treated with Artemisinin-based Combined Therapy Exhibits Enhanced Mutation, Heightened Cortisol and TNF-α Induction.

Author information

1
Department of Biomedical Sciences, University of Wisconsin, Milwaukee WI 53211 USA.
2
Department of Pharmaceutics and Pharmaceutical Technology, University of Lagos, Nigeria.
3
City of Milwaukee Health Department Laboratories, Milwaukee, WI 53202 USA.
4
Department of Medical Microbiology and Parasitology, University of Lagos, Nigeria.
5
Molecular Pathogenesis laboratory, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

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 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 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.

KEYWORDS:

ACT.; Proinflammation; corticosteroids; cortisol; dexamethasone; gene polymorphism; persistent malaria

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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