Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia.

BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia threatens malaria treatment efficacy. Mutations in a kelch protein encoded on P. falciparum chromosome 13 (K13) have been associated with resistance in vitro and in field samples from Cambodia. METHODS: P. falciparum infections from artesunate efficacy trials in Bangladesh, Cambodia, Laos, Myanmar, and Vietnam were genotyped at 33 716 genome-wide single-nucleotide polymorphisms (SNPs). Linear mixed models were used to test associations between parasite genotypes and parasite clearance half-lives following artesunate treatment. K13 mutations were tested for association with artemisinin resistance, and extended haplotypes on chromosome 13 were examined to determine whether mutations arose focally and spread or whether they emerged independently. RESULTS: The presence of nonreference K13 alleles was associated with prolonged parasite clearance half-life (P = 1.97 × 10(-12)). Parasites with a mutation in any of the K13 kelch domains displayed longer parasite clearance half-lives than parasites with wild-type alleles. Haplotype analysis revealed both population-specific emergence of mutations and independent emergence of the same mutation in different geographic areas. CONCLUSIONS: K13 appears to be a major determinant of artemisinin resistance throughout Southeast Asia. While we found some evidence of spreading resistance, there was no evidence of resistance moving westward from Cambodia into Myanmar

Building a climate of trust during organizational change: The mediating role of justice perceptions and emotion

Over the years, research has shown that, although there are various factors which contribute to failed change, one of the key reasons people resist change is due to the inability of leaders to convince employees to support change and to commit the energy and effort necessary to implement it. Senior management can ensure an organization is change-ready by developing and maintaining a supportive culture and climate that positively influence the emotional health and welfare of employees. Despite the obvious importance of leadership to change efforts, little previous research has investigated, holistically and in the context of major change, the relationship between senior management actions and employee responses. Furthermore, the change literature largely ignores the role that emotions play in employee responses to change initiatives. This chapter addresses both areas, and develops a model of organizational change from a justice and emotions perspective, which depicts employees’ justice perceptions related to senior executives as affecting trust directly and indirectly, through associated emotional responses