Clinical and parasitological response to oral chloroquine and primaquine in uncomplicated human Plasmodium knowlesi infections

Background: Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs. Methods: A prospective observational study of oral chloroquine and primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group. Results: Of 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT50) and 90% (PCT90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR. Conclusions: Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance. Further studies using alternative anti-malarial drugs, including artemisinin derivatives, would be desirable to define optimal management strategies for P. knowlesi.Publisher PDFPeer reviewe

Magnetic Anisotropy in Quantum Hall Ferromagnets

We show that the sign of magnetic anisotropy energy in quantum Hall ferromagnets is determined by a competition between electrostatic and exchange energies. Easy-axis ferromagnets tend to occur when Landau levels whose states have similar spatial profiles cross. We report measurements of integer QHE evolution with magnetic-field tilt. Reentrant behavior observed for the $\nu = 4$ QHE at high tilt angles is attributed to easy-axis anisotropy. This interpretation is supported by a detailed calculation of the magnetic anisotropy energy.Comment: 12 pages, 3 figures, submitted to Phys. Rev. Let

Spins, charges and currents at Domain Walls in a Quantum Hall Ising Ferromagnet

We study spin textures in a quantum Hall Ising ferromagnet. Domain walls between ferro and unpolarized states at $\nu=2$ are analyzed with a functional theory supported by a microscopic calculation. In a neutral wall, Hartree repulsion prevents the appearance of a fan phase provoked by a negative stiffness. For a charged system, electrons become trapped as solitons at the domain wall. The size and energy of the solitons are determined by both Hartree and spin-orbit interactions. Finally, we discuss how electrical transport takes place through the domain wall.Comment: 4 pages, 3 figures include

Magnetoresistivity in a Tilted Magnetic Field in p-Si/SiGe/Si Heterostructures with an Anisotropic g-Factor: Part II

The magnetoresistance components $\rho_{xx}$ and $\rho_{xy}$ were measured in two p-Si/SiGe/Si quantum wells that have an anisotropic g-factor in a tilted magnetic field as a function of temperature, field and tilt angle. Activation energy measurements demonstrate the existence of a ferromagnetic-paramagnetic (F-P) transition for a sample with a hole density of $p$=2$\times10^{11}$\,cm$^{-2}$. This transition is due to crossing of the 0$\uparrow$ and 1$\downarrow$ Landau levels. However, in another sample, with $p$=7.2$\times10^{10}$\,cm$^{-2}$, the 0$\uparrow$ and 1$\downarrow$ Landau levels coincide for angles $\Theta$=0-70$^{\text{o}}$. Only for $\Theta$ > 70$^{\text{o}}$ do the levels start to diverge which, in turn, results in the energy gap opening.Comment: 5 pages, 6 figure

Unusual conductance collapse in one-dimensional quantum structures

We report an unusual insulating state in one-dimensional quantum wires with a non-uniform confinement potential. The wires consist of a series of closely spaced split gates in high mobility GaAs/AlGaAs heterostructures. At certain combinations of wire widths, the conductance abruptly drops over three orders of magnitude, to zero on a linear scale. Two types of collapse are observed, one occurring in multi-subband wires in zero magnetic field and one in single subband wires in an in-plane field. The conductance of the wire in the collapse region is thermally activated with an energy of the order of 1 K. At low temperatures, the conductance shows a steep rise beyond a threshold DC source-drain voltage of order 1 mV, indicative of a gap in the density of states. Magnetic depopulation measurements show a decrease in the carrier density with lowering temperature. We discuss these results in the context of many-body effects such as charge density waves and Wigner crystallization in quantum wires.Comment: 5 pages, 5 eps figures, revte

Green tea extract only affects markers of oxidative status postprandially: lasting antioxidant effect of flavonoid-free diet

Epidemiological studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease and cancer. The objective of the present study was to investigate the effect of green tea extract (GTE) used as a food antioxidant on markers of oxidative status after dietary depletion of flavonoids and catechins. The study was designed as a 2×3 weeks blinded human cross-over intervention study (eight smokers, eight non-smokers) with GTE corresponding to a daily intake of 18·6 mg catechins/d. The GTE was incorporated into meat patties and consumed with a strictly controlled diet otherwise low in flavonoids. GTE intervention increased plasma antioxidant capacity from 1·35 to 1·56 (P<0·02) in postprandially collected plasma, most prominently in smokers. The intervention did not significantly affect markers in fasting blood samples, including plasma or haemoglobin protein oxidation, plasma oxidation lagtime, or activities of the erythrocyte superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase. Neither were fasting plasma triacylglycerol, cholesterol, α-tocopherol, retinol, β-carotene, or ascorbic acid affected by intervention. Urinary 8-oxo-deoxyguanosine excretion was also unaffected. Catechins from the extract were excreted into urine with a half-life of less than 2 h in accordance with the short-term effects on plasma antioxidant capacity. Since no long-term effects of GTE were observed, the study essentially served as a fruit and vegetables depletion study. The overall effect of the 10-week period without dietary fruits and vegetables was a decrease in oxidative damage to DNA, blood proteins, and plasma lipids, concomitantly with marked changes in antioxidative defenc

Spin instabilities and quantum phase transitions in integral and fractional quantum Hall states

The inter-Landau-level spin excitations of quantum Hall states at filling factors nu=2 and 4/3 are investigated by exact numerical diagonalization for the situation in which the cyclotron (hbar*omega_c) and Zeeman (E_Z) splittings are comparable. The relevant quasiparticles and their interactions are studied, including stable spin wave and skyrmion bound states. For nu=2, a spin instability at a finite value of epsilon=hbar*omega_c-E_Z leads to an abrupt paramagnetic to ferromagnetic transition, in agreement with the mean-field approximation. However, for nu=4/3 a new and unexpected quantum phase transition is found which involves a gradual change from paramagnetic to ferromagnetic occupancy of the partially filled Landau level as epsilon is decreased.Comment: 4 pages, 5 figures, submitted to Phys.Rev.Let

Highly Anisotropic Transport in the Integer Quantum Hall Effect

At very large tilt of the magnetic (B) field with respect to the plane of a two-dimensional electron system the transport in the integer quantum Hall regime at $\nu$ = 4, 6, and 8 becomes strongly anisotropic. At these filling factors the usual {\em deep minima} in the magneto-resistance occur for the current flowing {\em perpendicular} to the in-plane B field direction but develop into {\em strong maxima} for the current flowing {\em parallel} to the in-plane B field. The origin of this anisotropy is unknown but resembles the recently observed anisotropy at half-filled Landau levels.Comment: 4 pages, 4 figure

Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region