Warfarin pharmacogenetics: development of a dosing algorithm for Omani patients

International audienceThe objective of our present study was to develop a warfarin dosing algorithm for the Omani patients, as performances of warfarin dosing algorithms vary across populations with impact on the daily maintenance dose. We studied the functional polymorphisms of CYP2C9, CYP4F2 and VKORC1 genes to evaluate their impact on the warfarin maintenance dose in an admixed Omani patient cohort with Caucasian, African and Asian ancestries. We observed a 64-fold inter-patient variability for warfarin to achieve stable international normalized ratio in these patients. Univariate analysis revealed that age, gender, weight, atrial fibrillation, deep vein thrombosis/pulmonary embolism and variant genotypes of CYP2C9 and VKORC1 loci were significantly associated with warfarin dose in the studied patient population. However, multiple regression model showed that only the atrial fibrillation, and homozygous CYP2C9 variant genotypes (*2/*3 and *3/*3) and VKORC1 GA and AA genotypes remained significant. A multivariate model, which included demographic, clinical and pharmacogenetic variables together explained 63% of the overall inter-patient variability in warfarin dose requirement in this microgeographically defined, ethnically admixed Omani patient cohort on warfarin. This locally developed model performed much better than the International Warfarin Pharmacogenetics Consortium (IWPC) model as the latter could only explain 34% of the inter-patient variability in Omani patients. VKORC1 3673G>A polymorphism emerged as the single most important predictor of warfarin dose variability, even in this admixed population (partial R(2)=0.45)

Carriage of critically important antimicrobial resistant bacteria and zoonotic parasites amongst camp dogs in remote Western Australian indigenous communities

Camp dogs in indigenous communities in the Western Australian Kimberley Region, share the domestic environment with humans and have the potential to act as carriers of, and sentinels for, a wide range of zoonotic agents, including intestinal parasites and antimicrobial resistant bacteria. In this study, we investigated the carriage of extended-spectrum-cephalosporin-resistant (ESC-resistant) Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA) and species of hookworm and Giardia among camp dogs in remote Western Australian Aboriginal communities. A total of 141 canine faecal samples and 156 nasal swabs were collected from dogs in four communities of the Western Australian Kimberley region. Overall, ESC-resistant E. coli was detected in 16.7% of faecal samples and MRSA was isolated from 2.6% of nasal swabs. Of most significance was the presence of the community-associated Panton-Valentine leucocidin (PVL)-positive MRSA ST93 and ST5 clones and ESC-resistant E. coli ST38 and ST131. The most prevalent zoonotic intestinal parasite infection was Ancylostoma caninum (66%). The prevalence of Giardia was 12.1%, with the main genotypes of Giardia detected being dog specific assemblages C and D, which are unlikely to cause disease in humans