The simian parasite Plasmodium knowlesi causes severe human malaria; the optimal treatment remains unknown. We describe the clinical features, disease spectrum, and response to antimalarial chemotherapy, including artemether-lumefantrine and artesunate, in patients with P. knowlesi malaria diagnosed by PCR during December 2007-November 2009 at a tertiary care hospital in Sabah, Malaysia. Fifty-six patients had PCR-confirmed P. knowlesi monoinfection and clinical records available for review. Twenty-two (39%) had severe malaria; of these, 6 (27%) died. Thirteen (59%) had respiratory distress; 12 (55%), acute renal failure; and 12, shock. None experienced coma. Patients with uncomplicated disease received chloroquine, quinine, or artemether-lumefantrine, and those with severe disease received intravenous quinine or artesunate. Parasite clearance times were 1-2 days shorter with either artemether-lumefantrine or artesunate treatment. P. knowlesi is a major cause of severe and fatal malaria in Sabah. Artemisinin derivatives rapidly clear parasitemia and are efficacious in treating uncomplicated and severe knowlesi malaria.
Matched MeSH terms: Quinine/administration & dosage; Quinine/therapeutic use
1. 1. Paris green was used as a larvicide on an inland hilly estate where A. maculatus was the carrier-and where most of the water treated was moving, more or less rapidly. 2. 2. Three different diluents were tried, viz., lime, talcum and soapstone powder. 3. 3. The strength of the mixture was one part of Paris green to ninety-nine parts of diluent by volume. 4. 4. Distribution was carried out by mechanical blowers and sprayers. 5. 5. The application was checked twenty-four hours afterwards. For one month it was checked forty-eight hours afterwards. 6. 6. There was an increase in breeding places-most of which were found in moving water. 7. 7. There was an increase in larvæ, many of them being over two days old. 8. 8. In spite of treatment of epidemics with plasmochin and quinine, the malaria rate was higher than during the previous year. The rise was more or less consistent, pointing to constant infections. 9. 9. The morbidity rate, death rate and infantile mortality were apparently not adversely affected, but in view of the treatments given with plasmochin, they are of no help in deciding the value of Paris green. 10. 10. There was a distinct fall in anti-larval costs, but the total anti-malarial costs were still high on account of the treatments necessary for epidemics of malaria. 11. 11. The advantages and disadvantages of Paris green are discussed.
Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed.
We report a previously undocumented drug interaction between cyclosporine A and quinine. A 39 year old Asian with a recent renal transplant was diagnosed to have a mild cerebral falciparum malaria. He was treated with seven days of oral quinine (600 mg, 8 hourly), followed by a stat dose of pyrimethamine (75 mg)--sulfadoxime (1200mg) because of a strong suspicion of chloroquine resistant falciparum malaria. Using a polyclonal radioimmunoassay method, we measured morning trough cyclosporine A level before, during and after the quinine treatment. Results showed a gradual decrease in the cyclosporine A level from a baseline value of 328 ng/ml to 107 ng/ml after seven days of oral quinine with a subsequent rise to pre-treatment level after discontinuation of quinine. There was no significant change in the dose of cyclosporine A administered during the period of quinine treatment (4.05 to 3.83 mg/kg body weight). Biochemical liver function tests, serum creatinine and hematological parameters were also essentially unchanged during this period. In vitro study showed no significant methodological interference in the cyclosporine assay by quinine dihydrochloride. These findings suggest an in vivo drug interaction between cyclosporine A and quinine. The mechanism of this interaction is not clear. Further studies are required to confirm the significance of this observation. Quinine and its stereoisomer, quinidine should be used with caution until further information is available.
A new multi-stacking pre-concentration procedure based on field-enhanced sample injection (FESI), field-amplified sample stacking, and transient isotachophoresis was developed and implemented in a compact microchip electrophoresis (MCE) with a double T-junction glass chip, coupled with an on-chip capacitively coupled contactless conductivity detection (C4 D) system. A mixture of the cationic target analyte and the terminating electrolyte (TE) from the two sample reservoirs was injected under FESI conditions within the two sample-loading channels. At the double T-junction, the stacked analyte zones were further concentrated under field-amplified stacking conditions and then subsequently focused by transient-isotachophoresis and separated along the separation channels. The proposed multi-stacking strategy was verified under a Universal Serial Bus (USB) fluorescence microscope employing Rhodamine 6G as the model analyte. This developed approach was subsequently used to monitor the target quinine present in human plasma samples. The total analysis time for quinine was approximately 200 s with a sensitivity enhancement factor of approximately 61 when compared to the typical gated injection. The detection and quantification limits of the developed approach for quinine were 3.0 μg/mL and 10 μg/mL, respectively, with intraday and interday repeatability (%RSDs, n = 5) of 3.6 and 4.4%. Recoveries in spiked human plasma were 98.1-99.8%.
1.This paper records the treatment by a continuous intravenous quinine drip technique of fifteen cases of heavy P. falciparum infection in malnourished prisoners of war in a Singapore camp. These cases were selected from a series of approximately 1,000.2.The efficiency of the method, its simplicity, and the ease with which it can be combined with blood transfusion or the slow administration of thiamin are stressed.3.Recovery by this method of treatment is recorded of three cases with a peripheral intensity of infection higher than has hitherto been reported in Malaya with survival.4.The author is of the opinion that this is a safe and effective method for the treatment of pernicious falciparum infections.
To determine whether glucose turnover is increased in acute falciparum malaria compared to enteric fever in children, steady-state 6,6-D2-glucose turnover was measured in 9 Malaysian children with uncomplicated malaria (6 males and 3 females; median age 10 years, body weight 22 kg) and in 12 with uncomplicated enteric fever (8 males and 4 females; median age 10 years, body weight 24 kg) in acute illness, after quinine (5 malaria patients) and in convalescence. Baseline plasma glucose concentrations in malaria and enteric fever were similar (all values are medians [ranges in brackets]) 5.6 [3.2-11.3] vs. 5.5 [4.2-8.0] mmol/L), as were serum insulin levels (5.6 [0.4-26.5] vs. 6.8 [1.1-22.5] milliunits/L; P > 0.4). Glucose turnover in the malaria patients was higher than in patients with enteric fever (6.27 [2.71-6.87] vs. 5.20 [4.50-6.08] mg/kg.min; P = 0.02) and in convalescence (4.74 [3.35-6.79] mg/kg.min; P = 0.05 vs. acute malaria study), and fell after quinine together with a rise in serum insulin (P = 0.03). Basal plasma lactate concentrations were higher in enteric fever than in malaria (3.4 [1.8-6.4] vs. 0.8 [0.3-3.8] mmol/L; P < 0.0001) and correlated inversely with glucose turnover in this group (rs = -0.60; n = 12; P = 0.02). These data suggest that glucose turnover is 20% greater in malaria than in enteric fever. This might reflect increased non-insulin-mediated glucose uptake in falciparum malaria and/or impaired gluconeogenesis in enteric fever, and may have implications for metabolic complications and their clinical management in both infections.
Matched MeSH terms: Quinine/metabolism; Quinine/therapeutic use
We report two patients who had cerebral malaria, heavy parasitemia, hyperbilirubinemia, hypercatabolism with rapid rises of blood urea and serum creatinine and acute renal failure. There was no evidence of intravascular hemolysis. Renal biopsy was consistent with acute tubular necrosis. Both patients responded to treatment with intravenous quinine and dialysis.
Potentiometric response characteristics were evaluated for quinine selective sensors based on a lipophilic ion-exchanger potassium tetrakis[3,5-bis(trifluoromethylphenyl)]borate (PTFB) immobilized together with plasticizing solvents in polyvinyl chloride membranes. The use of dioctyl phthalate (DOP), 2-nitrophenyl phenyl ether (NPPE), and bis(2-ethylhexyl)adipate (BEHA) plasticizers produced good quality quinine sensors that were sensitive and fast responding, and exhibited near Nernstian responses when used as batch-sensors. These membranes were further tested in a wall-jet flow-through potentiometric flow injection analysis (FIA) detector. Quinine sensors containing BEHA were the most suitable membrane, with no noticeable differences in sensitivity even after 5 h of continuous exposure to solutions. Interference by foreign species such as alkali, alkaline earth metal ions, sugars, and sodium benzoate was minimal in either the batch-mode (log selectivity coefficients
In 2007, a Finnish traveler was infected in Peninsular Malaysia with Plasmodium knowlesi, a parasite that usually causes malaria in monkeys. P. knowlesi has established itself as the fifth Plasmodium species that can cause human malaria. The disease is potentially life-threatening in humans; clinicians and laboratory personnel should become more aware of this pathogen in travelers.