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

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

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

Interaction Effects in a One-Dimensional Constriction

We have investigated the transport properties of one-dimensional (1D) constrictions defined by split-gates in high quality GaAs/AlGaAs heterostructures. In addition to the usual quantized conductance plateaus, the equilibrium conductance shows a structure close to $0.7(2e^2/h)$, and in consolidating our previous work [K.~J. Thomas et al., Phys. Rev. Lett. 77, 135 (1996)] this 0.7 structure has been investigated in a wide range of samples as a function of temperature, carrier density, in-plane magnetic field $B_{\parallel}$ and source-drain voltage $V_{sd}$. We show that the 0.7 structure is not due to transmission or resonance effects, nor does it arise from the asymmetry of the heterojunction in the growth direction. All the 1D subbands show Zeeman splitting at high $B_{\parallel}$, and in the wide channel limit the $g$-factor is $\mid g \mid \approx 0.4$, close to that of bulk GaAs. As the channel is progressively narrowed we measure an exchange-enhanced $g$-factor. The measurements establish that the 0.7 structure is related to spin, and that electron-electron interactions become important for the last few conducting 1D subbands.Comment: 8 pages, 7 figures (accepted in Phys. Rev. B

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