Okoth, R. | Search bioRxiv

bioRxiv2020

Evidence of interaction between humoral immunity and drug half-life in determining treatment outcome for artemisinin combination therapy in high transmission settings in western Kenya

The role of humoral immunity on the efficacy of artemisinin combination therapy (ACT) has not been investigated, yet naturally acquired immunity is key determinant of antimalarial therapeutic response. We conducted a therapeutic efficacy study in high transmission settings of western Kenya, which showed artesunate-mefloquine (ASMQ) and dihydroartemisinin-piperaquine (DP) were more efficacious than artemether-lumefantrine (AL). To investigate the underlying prophylactic mechanism, we compared a broad range of humoral immune responses in cohort I study participants treated with ASMQ or AL, and applied machine-learning (ML) models using immunoprofile data to analyze individual participants treatment outcome. We showed ML models could predict treatment outcome for ASMQ but no AL with high (72-92%) accuracy. Simulated PK profiling provided evidence demonstrating specific humoral immunity confers protection in the presence of sub-therapeutic residual mefloquine concentration. We concluded patient humoral immunity and partner drug interact to provide long prophylactic effect of ASMQ.

bioinformatics↗

bioRxiv2018

A 7-member SNP Assay on the iPlex MassARRAY Platform Provides a Rapid and Affordable Alternative to Typing Major African Staphylococcus aureus Types

BackgroundData on the clonal distribution of Staphylococcus aureus in Africa is scanty, partly due to high costs and long turnaround times imposed by conventional genotyping methods such as spa and multilocus sequence typing (MLST) warranting the need for alternative typing approaches. This study applied and evaluated the accuracy, cost and time of using iPlex massARRAY genotyping method on Kenyan staphylococcal isolates.\n\nMethodsFifty four clinical S. aureus isolates from three counties were characterized using iPlex massARRAY, spa and MLST typing methods. Ten Single Nucleotide Polymorphisms (SNPs) from the S. aureus MLST database were assessed by iPlex massARRAY.\n\nResultsThe iPlex massARRAY assay grouped the isolates into 14 SNP genotypes with 9/10 SNPs interrogated showing high detection rates (average 89%). spa and MLST typing revealed 22 spa types and 21 STs that displayed unique regional distribution. spa type t355 (ST152) was the dominant type and t2029 and t037 (ST 241) were observed among MRSA strains. MassARRAY showed 83% and 82% accuracy against spa and MLST typing respectively in isolate classification. Moreover, massARRAY identified all MRSA strains and a novel spa type. MassARRAY had reduced turnaround time (<12 hrs) compared to spa (3 days) and MLST (20 days) typing. The iPlex massARRAY cost approximately 18 USD compared to spa (30 USD) and MLST (126 USD) typing based on consumable costs/isolate.\n\nConclusionUpon validation with a larger collection of isolates, iPlex massARRAY could provide a faster, more affordable and fairly accurate method of resolving African S.aureus isolates especially in large surveillance studies.

microbiology↗