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

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-ß, 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-ß levels were negatively correlated with parasitemia, while IL-10 and TGF-ß 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.

Effect of compression pressure, preservative, and storage with potassium chloride on the microbiological quality of tablets formulated with Terminalia randii Gum (Combretaceae).

Gums are used as binders in tablets and also as emulsion stabilisers, suspending agents and thickeners in syrups. The need for other natural gums apart from the conventional gums to be employed as binding agents in tablets formulation led to this study. A gum obtained from the incised trunk of Terminalia randii (Combretaceae) was evaluated for the effect of compression pressure, methyl paraben preservative and storage with potassium chloride, on the microbial load of tablets formulated with the gum. The microbial load was determined by surface spread method on the processed gum at suitable dilutions, and tablets formulated from the gum at different compression pressures. The formulated tablets were evaluated for microbial load, also when stored in potassium chloride for 8 and 12 weeks with and without preservation with 1% Methyl Paraben. In each case the compressed tablets were incubated in 0.1% peptone water as control. The microbial load recorded reflected generally, reduction in microbial counts in tablets formulated with the gum as a binder both in terms of compression at different pressures and when the different compression pressures were associated with or without 1% methyl paraben in the presence of potassium chloride. Comparatively, the processed gum showed higher microbial load than the pressure compressed tablets. Besides the different compression pressures, duration of storage was also found to cause reduction of microbial load, particularly in the formulated tablets compressed with methyl paraben stored in potassium chloride such that after 8 weeks, the microbial load was zero. The studies showed that compression pressures and duration of storage caused marked reduction in microbial load of the tablets formulated with the processed gum of Terminalia randii as a binder.