Mahidol University

About: Mahidol University is a education organization based out in Bangkok, Nakhon Pathom, Thailand. It is known for research contribution in the topics: Population & Malaria. The organization has 23758 authors who have published 39761 publications receiving 878781 citations.

Impact of guidelines and enhanced antibiotic stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium difficile infection

Abstract: Methods: This was a retrospective, quasi-experimental study using interrupted time series (ITS) over 12 months before and after the intervention. The setting was adult medical and surgical wards in University Hospital Lewisham, an acute general hospital in London. The intervention was introduced in April 2006. Revised guidelines avoided broad-spectrum antibiotics, e.g. fluoroquinolones, cephalosporins, clindamycin, amoxicillin and co-amoxiclav, as they were considered to be ‘high risk’ for CDI. Instead, ‘low risk’ antibiotics such as penicillin, clarithromycin, doxycycline, gentamicin, vancomycin, trimethoprim and nitrofurantoin were recommended. Changes in antibiotic usage and incidence of CDI before and after the intervention were compared using segmented regression analysis. The negative binomial model was used to analyse the time series to estimate the CDI incidence rate ratio (IRR) following the intervention. Results: The intervention was associated with a significant reduction in the use of fluoroquinolones by 105.33 defined daily doses (DDDs)/1000 occupied bed-days (OBDs) per month [95% confidence interval (CI) 34.18 –176.48, P,0.001] and cephalosporins by 45.93 DDDs/1000 OBDs/month (95% CI 24.11 –67.74, P,0.0001). There was no significant change in total antibiotic, clindamycin, amoxicillin or co-amoxiclav use. There was a significant decrease in CDI following the intervention [IRR 0.34 (0.20 –0.58), P, 0.0001]. Conclusions: Revised antibiotic guidelines and enhanced stewardship was associated with a significant stepwise reduction in the use of cephalosporins and fluoroquinolones and a significant decrease in the incidence of CDI.

Therapeutic Responses to Different Antimalarial Drugs in Vivax Malaria

Abstract: The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients with Plasmodium vivax malaria. This parasite does not cause marked sequestration, so parasite clearance can be used as a direct measure of antimalarial activity. The activities of these drugs in descending order were artesunate, artemether, chloroquine, mefloquine, quinine, halofantrine, primaquine, and pyrimethamine-sulfadoxine (PS). Therapeutic responses to PS were poor; parasitemias did not clear in 5 of the 12 PS-treated patients, whereas all the other patients made an initial recovery. Of 166 patients monitored for ≥28 days, 35% had reappearance of vivax malaria 11 to 65 days later and 7% developed falciparum malaria 5 to 21 days after the start of treatment. There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine, in which all vivax malaria reappearances developed >28 days after treatment, suggesting suppression of the first relapse by these slowly eliminated drugs. There was no evidence of chloroquine resistance. The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action.

Cosmic-ray electron-positron spectrum from 7 GeV to 2 TeV with the Fermi Large Area Telescope

Abstract: We present a measurement of the cosmic-ray electron+positron spectrum between 7 GeV and 2 TeV performed with almost seven years of data collected with the Fermi Large Area Telescope. We find that the spectrum is well fit by a broken power law with a break energy at about 50 GeV. Above 50 GeV, the spectrum is well described by a single power law with a spectral index of 3.07 ± 0.02 (stat+syst) ± 0.04 (energy measurement). An exponential cutoff lower than 1.8 TeV is excluded at 95% CL. PACS numbers: 98.70.Sa, 96.50.sb, 95.85.Ry, 95.55.Vj

Adaptive copy number evolution in malaria parasites.

Abstract: Copy number polymorphism (CNP) is ubiquitous in eukaryotic genomes, but the degree to which this reflects the action of positive selection is poorly understood The first gene in the Plasmodium folate biosynthesis pathway, GTP-cyclohydrolase I (gch1), shows extensive CNP We provide compelling evidence that gch1 CNP is an adaptive consequence of selection by antifolate drugs, which target enzymes downstream in this pathway (1) We compared gch1 CNP in parasites from Thailand (strong historical antifolate selection) with those from neighboring Laos (weak antifolate selection) Two percent of chromosomes had amplified copy number in Laos, while 72% carried multiple (2-11) copies in Thailand, and differentiation exceeded that observed at 73 synonymous SNPs (2) We found five amplicon types containing one to greater than six genes and spanning 1 to >11 kb, consistent with parallel evolution and strong selection for this gene amplification gch1 was the only gene occurring in all amplicons suggesting that this locus is the target of selection (3) We observed reduced microsatellite variation and increased linkage disequilibrium (LD) in a 900-kb region flanking gch1 in parasites from Thailand, consistent with rapid recent spread of chromosomes carrying multiple copies of gch1 (4) We found that parasites bearing dhfr-164L, which causes high-level resistance to antifolate drugs, carry significantly (p = 000003) higher copy numbers of gch1 than parasites bearing 164I, indicating functional association between genes located on different chromosomes but linked in the same biochemical pathway These results demonstrate that CNP at gch1 is adaptive and the associations with dhfr-164L strongly suggest a compensatory function More generally, these data demonstrate how selection affects multiple enzymes in a single biochemical pathway, and suggest that investigation of structural variation may provide a fast-track to locating genes underlying adaptation