SummaryBackgroundEmergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations.MethodsWe did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar.FindingsOverall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations.InterpretationArtemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided.FundingWellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.

Multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates harboring New Delhi metallo-β-lactamase (NDM-1) were isolated from a patient who had returned to Canada from India. The NDM-1 gene was found on closely related incompatibility group A/C type plasmids. The occurrence of NDM-1 in North America is a major public health concern.

Kinetoplastid glycosomes contain a variety of metabolic activities, such as glycolysis, ␤-oxidation of fatty acids, lipid biosynthesis, and purine salvage. One advantage of sequestering metabolic activities is the avoidance of cellular oxidative damage by reactive oxygen species produced as a by-product of metabolism. Little is known about how glycosomes themselves withstand these toxic metabolites. We previously isolated an iron superoxide dismutase from Leishmania chagasi that is expressed at low levels in the early logarithmic promastigote stage and increases toward the stationary promastigote and amastigote stages. We have since identified a second highly homologous Lcfesodb gene that is expressed at high levels in the early logarithmic promastigote stage and decreases toward the stationary promastigote and amastigote stages. Localization studies using green fluorescent protein fusions have revealed that LcFeSODB1 and LcFeSODB2 are localized within the glycosomes by the last three amino acids of their carboxyl termini. To better understand the specific role that FeSODB plays in parasite growth and survival, a single-allele knockout of the Lcfesodb1 gene was generated. The parasites with these genes exhibited a significant reduction in growth when endogenous superoxide levels were increased with paraquat in culture. Furthermore, the FeSODB1-deficient parasites exhibited a significant reduction in survival within human macrophages. Our results suggest that LcFeSODB plays an important role in parasite growth and survival by protecting glycosomes from superoxide toxicity.Despite the evolution of a complex mammalian immune response against foreign pathogens, Leishmania continues to plague humans, causing death and disease worldwide. This places an emphasis on elucidating the molecular mechanisms employed by Leishmania to establish a successful infection. Leishmania is an intracellular protozoan parasite that infects mammalian macrophages. These parasites possess a digenic life cycle, consisting of an extracellular promastigote form that multiplies and develops within the alimentary tract of the sand fly vector and an intracellular amastigote form that resides and multiplies within the phagosome of the mammalian host macrophage.Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are toxic metabolites that damage all living cells. The superoxide anion (O 2˙Ϫ ) is produced by the reduction of oxygen and is the fundamental oxidant among a battery of reactive intermediates, as it is involved in numerous reactions generating a plethora of increasingly toxic intermediates, including hydrogen peroxide (H 2 O 2 ), hydroxyl radicals (˙OH), and peroxynitrite (ONOO Ϫ ). Collectively, these prooxidants are toxic to DNA and can cause peroxidation of lipids and the inactivation of iron-sulfur enzymatic centers of dehydratases (15 order to adapt to their new environment. Numerous genes have been shown to be differentially expressed in the promastigote and amastigote stages, and many morphological and metabolic chan...