Background: Diversity in Plasmodium falciparum poses a major threat to malaria control and elimination interventions. This study utilized 12 polymorphic microsatellite (MS) markers and the Msp2 marker to examine diversity, multiplicity of infection (MOI) as well as the population structure of parasites circulating in two sites separated by about 92 km and with varying malaria transmission intensities within the Greater Accra Region of Ghana. Methods: The diversity and MOI of P. falciparum parasites in 160 non-symptomatic volunteers living in Obom (high malaria transmission intensity) and Asutsuare (low malaria transmission intensity) aged between 8 and 60 years was determined using Msp2 genotyping and microsatellite analysis. Results: The prevalence of asymptomatic P. falciparum carriers as well as the parasite density of infections was significantly higher in Obom than in Asutsuare. Samples from Asutsuare and Obom were 100% and 65% clonal, respectively, by Msp2 genotyping but decreased to 50% and 5%, respectively, when determined by MS analysis. The genetic composition of parasites from Obom and Asutsuare were highly distinct, with parasites from Obom being more diverse than those from Asutsuare. Conclusion: Plasmodium falciparum parasites circulating in Obom are genetically more diverse and distinct from those circulating in Asutsuare. The MOI in samples from both Obom and Asutsuare increased when assessed by MS analysis relative to MSP2 genotyping. The TA40 and TA87 loci are useful markers for estimating MOI in high and low parasite prevalence settings.

No abstract

Recent reports of resistance to artemisinin-based combination drugs necessitate the need to discover novel antimalarial compounds. The present study was aimed at identifying novel antimalarial compounds from natural product libraries using computational methods. Plasmodium falciparum is highly dependent on the pyrimidine biosynthetic pathway, a de novo pathway responsible for the production of pyrimidines, and the parasite lacks the pyrimidine salvage enzymes. The P. falciparum thymidylate monophosphate kinase (PfTMPK) is an important protein necessary for rapid DNA replication; however, due to its broad substrate specificity, the protein is distinguished from its homologs, making it a suitable drug target. Compounds from AfroDB, a database of natural products originating from Africa, were screened virtually against PfTMPK after filtering the compounds for absorption, distribution, metabolism, excretion, and toxicity (ADMET)-acceptable compounds with FAF-Drugs4. Thirteen hits with lower binding energies than thymidine monophosphate were selected after docking. Among the thirteen compounds, ZINC13374323 and ZINC13365918 with binding energies of −9.4 and −8.9 kcal/mol, respectively, were selected as plausible lead compounds because they exhibited structural properties that ensure proper binding at the active site and inhibitory effect against PfTMPK. ZINC13374323 (also called aurantiamide acetate) is known to exhibit anti-inflammatory and antiviral activities, and ZINC13365918 exhibits antileishmanial activity. Furthermore, aurantiamide acetate, which is commercially available, is a constituent of Artemisia annua, the herb from which artemisinin was derived. The compound also shares interactions with several residues with a potent thymidine analog inhibitor of PfTMPK. The anti-plasmodial activity of aurantiamide acetate was evaluated in vitro, and the mean half-maximal inhibitory concentration (IC50) was 69.33 μM when synchronized P. falciparum 3D7 culture was used as compared to IC50 > 100 μM with asynchronized culture. The significance of our findings within the context of malaria treatment strategies and challenges is discussed.

No abstract