Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison.

BACKGROUND: Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefloquine is widely recommended in southeast Asia, but its high cost and tolerability profile remain obstacles to widespread deployment. To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefloquine, we compared the safety, tolerability, efficacy, and effectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar (Burma). METHODS: We did an open randomised comparison of 3-day regimens of artesunate-mefloquine (12/25 mg/kg) versus dihydroartemisinin-piperaquine (6.3/50 mg/kg) for the treatment of children aged 1 year or older and in adults with uncomplicated falciparum malaria in Rakhine State, western Myanmar. Within each group, patients were randomly assigned supervised or non-supervised treatment. The primary endpoint was the PCR-confirmed parasitological failure rate by day 42. Failure rates at day 42 were estimated by Kaplan-Meier survival analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN27914471. FINDINGS: Of 652 patients enrolled, 327 were assigned dihydroartemisinin-piperaquine (156 supervised and 171 not supervised), and 325 artesunate-mefloquine (162 and 163, respectively). 16 patients were lost to follow-up, and one patient died 22 days after receiving dihydroartemisinin-piperaquine. Recrudescent parasitaemias were confirmed in only two patients; the day 42 failure rate was 0.6% (95% CI 0.2-2.5) for dihydroartemisinin-piperaquine and 0 (0-1.2) for artesunate-mefloquine. Whole-blood piperaquine concentrations at day 7 were similar for patients with observed and non-observed dihydroartemisinin-piperaquine treatment. Gametocytaemia developed more frequently in patients who had received dihydroartemisinin-piperaquine than in those on artesunate-mefloquine: day 7, 18 (10%) of 188 versus five (2%) of 218; relative risk 4.2 (1.6-11.0) p=0.011. INTERPRETATION: Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups. The effectiveness of the unsupervised treatment, as in the usual context of use, equalled its supervised efficacy, indicating good adherence without supervision. Dihydroartemisinin-piperaquine is a good alternative to artesunate-mefloquine

Detection of asymptomatic malaria in Asian countries: a meta-analysis of diagnostic accuracy

Background: Achieving malaria elimination requires the targeting of the human reservoir of infection, including those patients with asymptomatic infection. The objective was to synthesise evidence on the accuracy of the rapid- onsite diagnostic tests (RDTs) and microscopy for the detection of asymptomatic malaria as part of the surveillance activities in Asian countries. Methods: This was a meta-analysis of diagnostic test accuracy. Relevant studies that evaluated the diagnostic per- formance of RDTs and microscopy for detection of asymptomatic malaria were searched in health-related electronic databases. The methodological quality of the studies included was assessed using the QUADAS-2 tool. Results: Ten studies assessing RDT and/or microscopy were identified. The diagnostic accuracies in all these stud- ies were verified by PCR. Overall, the pooled sensitivities of RDT, as well as microscopy for detection of any malaria parasites in asymptomatic participants, were low, while their pooled specificities were almost ideal. For the detection of Plasmodium falciparum, pooled sensitivity by RDT (59%, 95%CI:16-91%) or microscopy (55%, 95%CI: 25-82%) were almost comparable. For detection of Plasmodium vivax, pooled sensitivity of RDT (51%, 95% CI:7-94%) had also the comparable accuracy of microscopy (54%, 95%CI,11-92%). Of note are the wide range of sensitivity and specificity. Conclusion: The findings of this meta-analysis suggest that RDTs and microscopy have limited sensitivity and are inappropriate for the detection of asymptomatic Plasmodium infections. Other methods including a combination of PCR-based strategies, Loop-Mediated Isothermal Amplification (LAMP) technique must be considered to target these infections, in order to achieve malaria elimination. However, more data is needed for the wide acceptance and feasi- bility of these approaches. Studies to explore the role of asymptomatic and sub-patent infections in the transmission of malaria are of critical importance and are recommend

Optimization of Phosphorus Fertilizer in Supplemental Feed‐Fed Based Nile Tilapia (Oreochromis niloticus) Ponds

An experiment was conducted in earthen ponds at the Asian Institute of Technology, Thailand to determine different phosphorus fertilizer dose effects on Nile tilapia production, water quality variables, nutrient utilization and cost‐benefit under supplemental feeding. Five phosphorus fertilization rates were used as treatments e.g. 100%, 75%, 50%, 25% and 0% of 7 kg P ha week−1. Nitrogen fertilization rate was fixed at 28 kg N ha week−1 for all the treatments. Sex‐reversed Nile tilapia were stocked at 3 fish m−2, and 30% CP floating feed fed at 50% satiation feeding rate. Nutrient budget showed higher phosphorus fertilizer input resulted in higher phosphorus sink in the sediment. Mean weight, mean weight gain, daily weight gain and net yield were not significantly different among treatments (P > 0.05). Total Kjeldahl nitrogen, total phosphorus and soluble reactive phosphorus were significantly different among treatments. Economic analysis showed phosphorus fertilization resulted in positive net returns. Though the gross income was not affected by different fertilization rates, significantly lowest cost was found in the treatment using 25% phosphorus fertilizer. It can be concluded from the research that 25% phosphorus fertilization might be used as an alternative strategy of Nile tilapia pond culture in terms of economic return and nutrient loss in sediment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115936/1/are12444.pd

Observations of Mkn 421 in 2004 with H.E.S.S. at large zenith angles

Mkn 421 was observed during a high flux state for nine nights in April and May 2004 with the fully operational High Energy Stereoscopic System (H.E.S.S.) in Namibia. The observations were carried out at zenith angles of 60$^\circ$--65$^\circ$, which result in an average energy threshold of 1.5 TeV and a collection area reaching 2~km$^2$ at 10~TeV. Roughly 7000 photons from Mkn~421 were accumulated with an average gamma-ray rate of 8 photons/min. The overall significance of the detection exceeds 100 standard deviations. The light-curve of integrated fluxes above 2~TeV shows changes of the diurnal flux up to a factor of 4.3. For nights of high flux, intra-night variability is detected with a decay time of less than 1 hour. The time averaged energy spectrum is curved and is well described by a power-law with a photon index \egamm and an exponential cutoff at \ecut~TeV and an average integral flux above 2~TeV of 3 Crab flux units. Significant variations of the spectral shape are detected with a spectral hardening as the flux increases. Contemporaneous multi-wavelength observations at lower energies (X-rays and gamma-rays above $\approx 300$~GeV) indicate smaller relative variability amplitudes than seen above 2~TeV during high flux state observed in April 2004.Comment: 5 pages, 4 figures, published in A&

Very high energy gamma rays from the direction of Sagittarius A*.

We report the detection of a point-like source of very high energy (VHE) -rays coincident within 1' of Sgr A *, obtained with the HESS array of Cherenkov telescopes. The -rays exhibit a power-law energy spectrum with a spectral index of and a flux above the 165 GeV threshold of m -2 s -1. The measured flux and spectrum differ substantially from recent results reported in particular by the CANGAROO collaboration

Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S

We report the discovery of very-high-energy (VHE) gamma-ray emission of the binary system PSR B1259-63/SS 2883 of a radio pulsar orbiting a massive, luminous Be star in a highly eccentric orbit. The observations around the 2004 periastron passage of the pulsar were performed with the four 13 m Cherenkov telescopes of the H.E.S.S. experiment, recently installed in Namibia and in full operation since December 2003. Between February and June 2004, a gamma-ray signal from the binary system was detected with a total significance above 13 sigma. The flux was found to vary significantly on timescales of days which makes PSR B1259-63 the first variable galactic source of VHE gamma-rays observed so far. Strong emission signals were observed in pre- and post-periastron phases with a flux minimum around periastron, followed by a gradual flux decrease in the months after. The measured time-averaged energy spectrum above a mean threshold energy of 380 GeV can be fitted by a simple power law F_0(E/1 TeV)^-Gamma with a photon index Gamma = 2.7+-0.2_stat+-0.2_sys and flux normalisation F_0 = (1.3+-0.1_stat+-0.3_sys) 10^-12 TeV^-1 cm^-2 s^-1. This detection of VHE gamma-rays provides unambiguous evidence for particle acceleration to multi-TeV energies in the binary system. In combination with coeval observations of the X-ray synchrotron emission by the RXTE and INTEGRAL instruments, and assuming the VHE gamma-ray emission to be produced by the inverse Compton mechanism, the magnetic field strength can be directly estimated to be of the order of 1 G.Comment: 10 pages, 8 figures, accepted in Astronomy and Astrophysics on 2 June 2005, replace: document unchanged, replaced author field in astro-ph entry - authors are all members of the H.E.S.S. collaboration and three additional authors (99+3, see document

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

World Health Organization Discontinues Its Drinking-Water Guideline for Manganese

Background: The World Health Organization (WHO) released the fourth edition of Guidelines for Drinking-Water Quality in July 2011. In this edition, the 400-µg/L drinking-water guideline for manganese (Mn) was discontinued with the assertion that because “this health-based value is well above concentrations of manganese normally found in drinking water, it is not considered necessary to derive a formal guideline value.

Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B

BACKGROUND: After perinatal transmission of hepatitis B virus, infants of anti-HBe positive HBsAg carrier mothers may develop fulminant hepatitis B. Previously it has been suggested, that fulminant hepatitis B in adults was associated with specific mutations in the HBV-genome. The aim of this study was to investigate, whether specific viral variants are associated with fulminant hepatitis B in young infants. METHODS: The complete HBV-genomes of five mothers and their infants with fulminant hepatitis were isolated from the sera, amplified and directly sequenced. RESULTS: Between 6 and 43 base pair exchanges between the HBV genomes of the infants and their mothers were identified. The mutations spread over the entire virus genome. Nucleotide exchanges in the basic core promotor and precore region were identified in all cases. A heterogeneous virus population was detected in four mothers. CONCLUSIONS: Many new mutations were proved to emerge during fulminant hepatitis B in infants, who had been perinatally infected. HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers. The data suggest that the selection of a specific HBeAg negative viral strain may be associated with the development of fulminant hepatitis B in children