Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was: 1) to measure tumour necrosis factor alpha (TNF) in the plasma of Plasmodium falciparum infected subjects; and 2) to correlate the presence of TNF to symptomatology. Plasma from 77 malaria infected individuals (with malaria parasites) were assayed for TNF by ELISA. The mean age of the subjects under study was 16.36 +/- 0.80 (mean +/- SEM) years. Thirty-nine (51%) subjects had measurable plasma TNF. Taking symptomatology into account, 10 (59%) of the 17 asymptomatics and 29 (48%) of the 60 symptomatics had measurable plasma TNF. A risk ratio of 0.9 was obtained for the association between the detection of plasma TNF and the presence of symptoms. In plasma from 13 healthy controls no TNF was detected. The results suggest that if TNF plays a negative role in the pathogenesis of malaria, it must be in the presence of other predisposing factors.
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PMID:Tumour necrosis factor alpha in uncomplicated malaria in young adults. 748 5

Clinical and experimental evidence suggests that iron-deficient hosts are less susceptible to severe malaria and that iron supplementation aggravates infection. In the present study, 60 weanling Wistar rats were fed standard diets with different iron concentrations: 21 mg/kg (group 1), 45 mg/kg (group 2) and 113 mg/kg (group 3). Ferrous sulfate (FeSO4 x 7H2O) was added to the normal-iron and iron-supplemented diets (groups 2 and 3, respectively). Data are reported as mean +/- SEM. After 16 days of regimen, eight rats from each group were killed to measure serum iron concentration (SI) and transferrin saturation capacity (TSC). At this moment, rats from group 1 were underweight and their dietary intake was significantly lower than that of animals from the other groups. Severe iron deficiency (SI = 49.2 +/- 4.5 micrograms/100 ml and TSC = 8.3 +/- 0.7%) was observed in rats from group 1, while the animals from the other groups were iron-sufficient (group 2: SI = 186.5 +/- 28.5 micrograms/100 ml and TSC = 27.3 +/- 3.4%; group 3: SI = 137.3 +/- 18.2 micrograms/100 ml and TSC = 21.3 +/- 2.3%). Nine animals from each group were then infected with the malaria parasite Plasmodium berghei, whereas three animals from each group were used as noninfected controls. Parasitemias (% of infected red blood cells) peaked 7 days post-infection in animals from groups 2 and 3 (mean values of 2.4% and 1.7%, respectively), but in animals from group 1 parasitemias increased until the 9th day post-infection (mean at peak, 2.3%) and parasite clearance was significantly slower than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of dietary iron on the course of Plasmodium berghei malaria in young rats. 813 31

The prompt identification of patients with falciparum malaria who are at risk of late therapeutic failure could help clinicians avoid the dangers of missed or delayed retreatment. Different methods for predicting late recrudescence were compared for 52 patients whose parasitemia initially cleared after treatment with either halofantrine or quinine. Parasites reappeared in the peripheral circulation of six individuals 17 to 28 days after the initiation of therapy. Transient rises in parasite counts on thick blood films were accurate (91% specific and 100% sensitive) and prompt indicators of eventual recrudescence. All six therapeutic failures had been predicted by the third day (mean time [+/- SEM], 51.5 +/- 3.6 hours) after initiation of treatment. Parasite clearance time, fever clearance time, rRNA probe, and the polymerase chain reaction had less practical prognostic value. Serial thick-film parasite counts are a simple, cheap, rapid, and reliable method for identifying patients at high risk of recrudescence.
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PMID:Prospective comparison of methods for the early prediction of treatment failure in patients with falciparum malaria. 864 94

An increase in parasitaemia is not uncommon after initiation of treatment for Plasmodium falciparum malaria, but its exact significance is unknown. The time-course of parasitaemia was assessed retrospectively in 33 patients with severe imported malaria. In 19 patients (group 1) mean parasitaemia (+/- SEM) fell promptly after starting quinine treatment, from 24.9 +/- 4.1% on day 0 to 9.7 +/- 2.3% on day 1 and 1.8 +/- 0.7% on day 2. In 14 other patients (group 2), parasitaemia did not change significantly or increased, with mean parasitaemia (+/- SEM) of 9.5 +/- 2.1% on day 0, 17.2 +/- 2.6% on day 1, and 3.7 +/- 1.8% on day 2. Simplified acute physiology scores on admission (mean +/- SEM) were 17.4 +/- 1.4 in group 1 and 11.7 +/- 1.0 in group 2 (P = 0.006). The mean number of complications of malaria per patient (+/- SEM) was 2.9 +/- 0.5 in group 1 and 1.6 +/- 0.3 in group 2 (P = 0.046). Two group 1 patients died. Initially, more than 95% of peripheral blood parasites were tiny and small rings in both groups, and this distribution was unchanged on day 1, suggesting that the parasitaemia increase in group 2 was not due to release of sequestered mature parasites. In severe falciparum malaria, a rise in parasitaemia after treatment initiation may be of favourable prognostic significance and should not lead to aggressive therapeutic approaches such as exchange transfusion.
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PMID:Possible prognostic significance of a brief rise in parasitaemia following quinine treatment of severe Plasmodium falciparum malaria. 888 83

Sequestration of infected erythrocytes in brain microvasculature contributes to cerebral malaria, a severe complication of Plasmodium falciparum infection. Sequestration likely involves cytoadherence of parasitized erythrocytes to cerebral microvascular endothelium. Elucidation of the receptors and ligands involved in cytoadherence will likely contribute to a more complete understanding of malaria pathophysiology. The integrin receptor alpha(v)beta3 is involved in several physiologic and pathologic adherence processes, but its role in cytoadherence has not been investigated. In this study, the ability of erythrocytes infected with P. falciparum to adhere to alpha(v)beta3 on human microvascular endothelium was investigated. Cytoadherence was quantified under continuous flow at a shear stress of 1.0 dyne/cm2 to mimic shear forces in the cerebral microcirculation. Adherence of erythrocytes infected with P. falciparum to human microvascular endothelial cells was 7-270-fold greater than uninfected erythrocytes. Pretreatment of microvascular endothelial cells with anti-alpha(v) antibody inhibited P. falciparum-infected erythrocyte adherence by 45 +/- 6% (mean +/- SEM). These data suggest that in addition to other endothelial receptors previously described, P. falciparum parasitized red blood cells may bind to the integrin alpha(v)beta3 on microvascular endothelial cells.
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PMID:Short report: Plasmodium falciparum: cytoadherence to alpha(v)beta3 on human microvascular endothelial cells. 968 32

A high-performance liquid chromatography (HPLC) method was developed for the simultaneous analysis of trimethoprim (TMP), sulphamethoxazole (SMX), and acetylsulphamethoxazole (AcSMX) in small amounts of blood. The method involved precipitation with 50 microL trichloracetic acid (1M) to 125 microL plasma or serum sample. 60 microL supernatant was added to 60 microL mobile phase, modified with 50microL 1 M sodium hydroxide/mL. The mobile phase consisted of 20% acetonitrile and 80% phosphate buffer adjusted to pH 6.15. Using 125 microL of the sample, limits of quantitation were 0.1 microg/mL for TMP, 1.0 microg/mL for SMX, and 1.0 microg/mL for AcSMX. The precision of the method was 2% to 11% over the range of concentrations tested, 0.5-30 microg/mL for TMP, 5-300 microg/mL for SMX, and 2.5-150 microg/mL for AcSMX, respectively. No interference with other commonly used drugs was observed. The method is rapid, simple, specific, and sensitive enough for pharmacokinetic studies. The small amount of blood required makes it suitable for pediatric patients. The method was used to analyze samples from Tanzanian children aged 6-59 months participating in a cotrimoxazole (TMP/SMX)/chloroquine randomized trial for the treatment of uncomplicated malaria. Venous blood samples from 68 children were collected 2 hours after the first dose of TMP/SMX (4 mg/kg TMP/20 mg/kg SMX at two divided doses for 5 days) and again at treatment day 4. Individual variations in plasma concentrations of TMP, SMX, and AcSMX were considerable. The mean and SEM plasma concentrations (g/mL) of TMP, SMX, and AcSMX 2 hours after the first treatment dose were 2.0 +/- 1.0 (range 0.5-6), 53 +/- 22 (range 24-146), and 13.5 +/- 12 (range 0-65), respectively. On the fourth day the attained plasma concentrations were not significantly different from samples collected after the first dose.
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PMID:A reversed-phase high-performance liquid chromatography method for the determination of cotrimoxazole (trimethoprim/ sulphamethoxazole) in children treated for malaria. 1060 20

1. It is known that grapefruit juice (GFJ) may interact with drugs concomitantly administered by inhibiting first-pass metabolism during the intestinal absorption phase. However, its interaction with chloroquine has not been studied previously. 2. Grapefruit juice (4 mL/kg) was given orally to mice 1 h prior to oral administration of chloroquine (100 mg/kg) and the concentration of the latter drug was measured fluorometrically in the plasma 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18 and 24 h after its administration. 3. The mean (+/-SEM) of area under the curve values after administration of water +/- control) and GFJ were 5.34 +/- 0.38 and 7.01 +/- 0.66 mg.h/L, respectively. The corresponding mean C(max) values were 763.4 +/- 39.1 and 859.2 +/- 45.2 mg/L and the corresponding T(max) values (median) were 2.65 and 2.95 h. 4. The results suggest that GFJ coingestion increased the plasma concentration of chloroquine and altered some kinetic parameters of chloroquine. The clinical significance of this interaction in patients with malaria needs to be investigated.
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PMID:Effect of grapefruit juice on plasma chloroquine kinetics in mice. 1210 3

Cardiotoxicity has become a major concern during treatment with antimalarial drugs. Lengthening of the QTc and severe cardiac arrhythmia have been observed, particularly after treatment with halofantrine for chloroquine-resistant Plasmodium falciparum malaria. The purpose of this prospective study was to evaluate whether antimalarial agents alter dispersion of the QTc and ventricular repolarization dynamicity. Sixty patients with uncomplicated falciparum malaria were randomly allocated in four groups of 15 patients and treated with quinine, mefloquine, artemether, or halofantrine at recommended doses. Patients in treatment groups were compared with a group including 15 healthy controls with no history of malaria and/or febrile illness within the last month. QTc dispersion was measured on surface electrocardiograms. Repolarization dynamicity was analyzed from Holter recordings, which allow automatic beat-to-beat measurement of QT and RR intervals. Plasma drug concentration was determined by reversed-phase high-performance liquid chromatography. No change in QTc dispersion was observed after treatment with quinine, mefloquine, or artemether. Treatment with halofantrine was followed by a significant increase in QTc dispersion at 9 hours (P < 0.0001) and 24 hours (P < 0.01). Assessment of QT heart rate variability by QT/RR nychtohemeral regression slope demonstrated no significant difference between the artemether (mean +/- SEM = 0.170 +/- 0.048), mefloquine (0.145 +/- 0.044), and the control groups (0.172 +/- 0.039). A significant decrease in the Q-eT/RR slope was observed in the quinine group compared with the control and artemether groups (0.135 +/- 0.057; P < 0.04). With halofantrine, a significant increase in the QT/RR regression slope (0.289 +/- 0.118) was observed (P < 0.0002). QTc interval, QT dispersion, and QT regression slope were significantly correlated with halofantrine and quinine plasma concentration. Mefloquine and artemether did not alter ventricular repolarization. Quinine induced a significant decrease in QT/RR slope of the same order of magnitude as those previously observed with quinidine. Both QTc dispersion and QT/RR slope were significantly modified by halofantrine. These repolarization changes were related to a class-III antiarrhythmic drug effect and may explain the occurrence of ventricular arrhythmia and/or sudden deaths reported after halofantrine intake.
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PMID:The effects of antimalarial drugs on ventricular repolarization. 1236 64

The mosquito sampling efficiency of a new bed net trap (the Mbita trap) was compared with that of the Centers for Disease Control miniature light trap (hung adjacent to an occupied bed net) and the human landing catch in western Kenya. Overall, the Mbita trap caught 48.7 +/- 4.8% (mean +/- SEM) the number of Anopheles gambiae Giles sensu lato caught in the human landing catch and 27.4 +/- 8.2% of the number caught by the light trap. The corresponding figures for Anopheles funestus Giles were 74.6 +/- 1.3% and 39.2 +/- 1.9%, respectively. Despite the clear differences in the numbers of mosquitoes caught by each method, both the Mbita trap and light trap catches were directly proportional to human landing catches regardless of mosquito density. No significant differences in parity or sporozoite incidence were observed between mosquitoes caught by the three methods for either An. gambiae s.l. or An. funestus. Identification of the sibling species of the An. gambiae complex by a polymerase chain reaction indicated that the ratio of An. gambiae Giles sensu stricto to An. arabiensis Patton did not vary according to the sampling method used. It is concluded that the Mbita trap is a promising tool for sampling malaria vector populations since its catch can be readily converted into equivalent human biting catch, it can be applied more intensively, it requires neither expensive equipment nor skilled personnel, and it samples mosquitoes in an exposure-free manner. Such intensive sampling capability will allow cost-effective surveillance of malaria transmission at much finer spatial and temporal resolution than has been previously possible.
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PMID:Comparative field evaluation of the Mbita trap, the Centers for Disease Control light trap, and the human landing catch for sampling of malaria vectors in western Kenya. 1497 95

A large proportion of people with latent tuberculosis live in malaria-endemic areas, so co-infection with these two organisms is likely to be common. To determine whether there might be a biologic interaction between these two pathogens in vivo, we infected mice with Mycobacterium tuberculosis and then with a non-lethal strain of Plasmodium yoelii eight weeks later. Mice chronically infected with M. tuberculosis simulate the equilibrium between pathogen and host thought to exist in human latent infection. Co-infected mice were less able to contain growth of M. tuberculosis in lung, spleen, and liver (mean +/- SEM log10 colony-forming units = 5.50 +/- 0.11 versus 5.12 +/- 0.08, 4.58 +/- 0.07 versus 4.13 +/- 0.10, and 2.86 +/- 0.10 versus 2.49 +/- 0.10, respectively) and had increased mortality. In populations where both diseases are endemic, there may be implications for increased incidence of clinically detectable tuberculosis.
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PMID:Short report: modulation of Mycobacterium tuberculosis infection by Plasmodium in the murine model. 1523 80


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