The predictive value of molecular markers of resistance is best assessed in the context of in vivo field trials using the WHO in vivo model. The association of molecular markers with in vivo resistance is confounded by several factors. First, in vivo studies are often carried out in regions where malaria is hyperendemic and adaptive immunity (premunition) exists. Such immunity may confound the interpretation of drug efficacy because premunition may facilitate clearance of drug-resistant parasites. Second, technical issues may confound interpretation. Many studies fail to check for drug levels to ensure that adequate drug absorption has occurred, thereby overestimating the number of resistant infections. In addition, studies often fail to use techniques to ensure that treatment failures are true recrudescences rather than reinfections.[31,32]

Most current models of resistance assume single-gene models; however, resistance may be multigenic particularly with respect to 4-aminoquinoline drugs such as MQ, and implicated genes and mutations still require further in vivo validation. In contrast, ATQ and SP mechanisms of action are better defined, allowing for a clearer understanding of the role of mutations in key proteins such as CYTb and DHFR/DHPS in mediating resistance. Ultimately, the use of validated genetic markers of drug resistance will facilitate molecular surveillance and global monitoring for emerging drug-resistant malaria, and will potentially serve in predicting treatment outcome.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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