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)

1. A method is described for the measurement of phenobarbitone (PB) by reversed phase high performance liquid chromatography (h.p.l.c.) from small samples of whole blood dried onto filter paper strips. 2. The disposition of PB given prophylactically to young children with severe malaria on parenteral quinine is contrasted with that in aparasitaemic Kenyan children on no antimalarial drugs. There were no differences in the disposition of PB between the two groups. 3. Peak blood PB concentrations were equal to or greater than 15 mg l-1 in 27% of the patients on quinine and 23% of those not on quinine; a concentration of 10 mg l-1 was achieved or exceeded by 100% and 92% of each group, respectively, and was maintained for 39 +/- 24 h (mean +/- s.d.), and 33 +/- 21 h, respectively. 4. In an open, dose-finding study, the progress of young children with cerebral malaria given prophylactic PB (10 mg kg-1), was contrasted with that of controls given no seizure prophylaxis. 5. The drug had no apparent effect on depth or duration of coma, but neither was the incidence of seizures reduced. 6. A controlled trial of prophylactic PB in young children with cerebral malaria is needed, but a larger dose than 10 mg kg-1 should be studied.
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PMID:Prophylactic phenobarbitone in young children with severe falciparum malaria: pharmacokinetics and clinical effects. 155 Jun 96

Opening lumbar cerebrospinal fluid (CSF) pressure was measured with a paediatric spinal fluid manometer in 26 of 61 Kenyan children (mean age 39 months) with cerebral malaria. In all cases pressure was above normal (mean [SD]22.6 [7.4] cm CSF, range 10.5-36). Clinical features of our patients suggest that intracranial hypertension is important in the pathogenesis of cerebral malaria in children, especially as a cause of death. We suggest that raised intracranial pressure is secondary to increased cerebral blood volume. Lowering intracranial pressure may significantly reduce the mortality and morbidity of cerebral malaria. The potential risks and benefits of lumbar puncture should be considered carefully in patients with suspected cerebral malaria.
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PMID:Intracranial pressure in African children with cerebral malaria. 167 76

In 1981, Kenyan authorities attempted eradication of tsetse (Glossina pallidipes) from the Lambwe valley, by sequential aerial spraying of endosulfan. Fly populations were reduced by over 99.9% in the main habitats, but recovered to their original levels within one year. In 1986, an Argentine research team attempted local elimination of domestic Triatominae (Triatoma infestans) in an area of Santiago del Estero. House infestation rates were reduced to an apparent zero, but recovered to pre-control levels in two years. In Sri Lanka, a combination of mosquito control with active case detection and treatment reduced malaria incidence to just 17 cases in 1964. Interruption of the programme then saw case incidence return to over 500,000 by 1969. These three examples-from African trypanosomiasis, South American Chagas disease and malaria-all illustrate the same process. Vector populations, infestation rates, and rates of disease transmission, can be reduced. The real problem is not in achieving the initial reduction, but in subsequently either driving the disease to extinction or maintaining it below acceptable levels. And this problem takes us beyond the simple analysis of interventions, into the complex realms of population behaviour set in its political, social and economic context. It seems that we have been too rarely concerned to plan and implement the long term surveillance and selective interventions that are required to translate initial gains into real success. In biological terms, we tend to ignore the complexity and robustness of vector populations and disease transmission cycles, especially their varied capacity to recover from interference. Moreover, in socio-political terms, a reduced problem-even one representing potential for future catastrophe-tends to claim less priority than present problems, even though premature redeployment of resources may abnegate gains already achieved. The problem is strongly compounded by methods of economic analysis where the benefits of avoiding future problems are strongly discounted in favour of short-term temporary gains. This paper seeks to open discussion on these long-term planning issues.
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PMID:Vector population responses to control interventions. 179 71

Although erythromycin has been reported to be active against Plasmodium falciparum in vitro and P. berghei in vivo and in vitro when given alone or with chloroquine, it has been difficult to demonstrate a beneficial effect for the combination of erythromycin and chloroquine when used for the treatment of P. falciparum infections in humans. We developed a seven-day test of parasite sensitivity to a 4-aminoquinoline and erythromycin combination in vitro. Eight isolates of P. falciparum from the Kenyan coast were culture-adapted and exposed to erythromycin with chloroquine or with amodiaquine. The interaction of the drugs was evaluated by plotting the concentration of each drug needed to inhibit parasite growth. In seven isolates the combination of chloroquine and erythromycin was antagonistic; one isolate showed slight synergy The combination of amodiaquine and erythromycin was synergistic in three isolates but antagonistic in five. An antagonistic interaction may explain why erythromycin does not enhance chloroquine treatment of malaria in vivo in Kenya.
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PMID:Plasmodium falciparum sensitivity to erythromycin and 4-aminoquinoline combinations in vitro. 179 64

Quantification of human peripheral blood NK subsets has been made in a group of Kenyan adults and children with acute P. falciparum malaria. Results were compared with data obtained from three age- and sex-matched control cohorts: parasitaemic but asymptomatic children; aparasitaemic children and adults; and adult Caucasians with no previous history of malaria. Separated NK subsets were tested in vitro for cytotoxicity to erythrocytic schizonts of P. falciparum in the presence and absence of cytokines. There was a statistically significant quantitative and qualitative depression of the CD3-CD56+ subset in patients with acute malaria and this was accompanied by an expansion of the 'non-functional' CD3-CD57+CD16-CD56- subset. Both CD3-CD16+ and CD3-CD56+ NK cells from all patients and donors lysed schizonts, and this cytotoxicity was enhanced by the addition of recombinant interferon-alpha and/or IL-2, notably with the CD3-CD56+ subset. Interestingly, asymptomatic donors had the highest levels of CD3-CD56+ NK cells, which also demonstrated an enhanced response to cytokine stimulation. Cytotoxicity to schizonts was accompanied by the release of soluble NK cell lytic factors. Neomycin suppressed cytotoxicity in a dose-dependent manner, indicating that the lysis of schizonts by NK cells involves phospholipase C-mediated phosphoinositide metabolism. Our findings define a role for NK cells in immunity to malaria through the lysis of infected erythrocytes as a first-line defence against the parasite.
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PMID:Cytotoxicity of human natural killer (NK) cell subsets for Plasmodium falciparum erythrocytic schizonts: stimulation by cytokines and inhibition by neomycin. 183

Extensive metabolizers (EM) and poor metabolizers (PM) of the malaria chemoprophylactic drug proguanil have been identified by measuring the proguanil/cycloguanil ratio in urine following a single dose of the pro-drug. The pharmacokinetic characteristics of proguanil were similar in 8 EM and 8 PM subjects, but there were significant differences between the 2 groups with respect to cycloguanil pharmacokinetics. In none of the PM subjects could cycloguanil be detected in whole blood samples at any time after proguanil dosage. Plasma cycloguanil was measureable in only 2 of 8 PM subjects, despite an analytical sensitivity in the high-performance liquid chromatographic assay of 1 ng/ml cycloguanil. A comparatively high proportion of Black Kenyan adults appear to metabolize proguanil poorly, possibly because they lack the specific mixed function oxidase which will accept proguanil as substrate.
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PMID:Variability in the metabolism of proguanil to the active metabolite cycloguanil in healthy Kenyan adults. 209 35

An enzyme-linked immunosorbent assay (ELISA) was developed to detect antibody in human sera to a synthetic peptide, Asn-Ala-Asn-Pro (NANP)3, derived from the repeating amino acid sequence found in the surface circumsporozoite protein of Plasmodium falciparum sporozoites. One hundred four sera from U.S. residents were used to determine a cut-off value for reactivity. Test sera were considered reactive when the absorbance was greater than that at the 95th percentile of the control sera. Sera from 112 Kenyans living in an area of holoendemic malaria transmission were tested. Of the total number of sera, 65% had detectable antibody to (NANP)3. The percentage of reactive sera increased from 41% in sera from children under 4 years of age to 85% in sera from adults 20 to 39 years of age. The high exposure to malaria parasites of the Kenyans was reflected in indirect fluorescent antibody assay titers to blood stage P. falciparum parasites. All of the Kenyan sera had antibody present at titers greater than 1:256.
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PMID:Detection of antibodies in human sera to the repeating epitope of the circumsporozoite protein of Plasmodium falciparum using the synthetic peptide (NANP)3 in an enzyme-linked immunosorbent assay (ELISA). 244 Mar 27

The relationships between S. haematobium, hookworm, malaria, hemoglobin level, splenomegaly, and hepatomegaly before and 8 months after treatment with a single dose of metrifonate or praziquantel were studied in Kenyan primary schoolchildren in an area where anemia, S. haematobium, and hookworm are common and malaria is holoendemic. Children with light to moderate S. haematobium infection were examined (Exam 1), assigned at random to groups receiving placebo (PL, n = 104), metrifonate (MT, n = 103, dose 10 mg/kg body weight) or praziquantel (PR, n = 105, dose 40 mg/kg body weight), treated, and examined 8 months later (Exam 2). At Exam 2, 62% of the MT group still passed S. haematobium eggs vs. 13% in the PR group. Egg reduction rates were substantial in both groups, but greater in the PR group; geometric mean egg counts in both groups were very low. Prevalence and intensity in the PL group had not changed between exams. Hookworm egg counts were significantly reduced in the MT group (59% egg reduction rate); malarial infection had increased in all 3 groups, presumably due to the long rainy season between exams. Hookworm egg count was the most significant predictor of initial hemoglobin level, followed by S. haematobium egg count and presence of malarial infection. Treatment with a single dose of MT or PR can produce substantial decreases in S. haematobium infection 8 months later.
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PMID:Single dose metrifonate or praziquantel treatment in Kenyan children. I. Effects on Schistosoma haematobium, hookworm, hemoglobin levels, splenomegaly, and hepatomegaly. 250 1

In a 5-month study of Salmonella septicaemias in Kenyan children carried out during the annual peak infection period, Salmonella typhimurium septicaemias occurred seven times more frequently than typhoid or other non-typhoid infections. Salmonella typhimurium infections were predominantly community acquired, malnourished infants from rural malaria endemic areas with poor water supply were especially vulnerable. Typical clinical features of fever, diarrhoea, and severe anaemia resembled P. falciparum malaria which often co-existed. Mortality was 18 per cent. Isolates exhibited a wide range of multidrug resistance. Typhoid affected older children, was less severe and drug sensitive.
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PMID:Salmonella septicaemias in Kenyan children. 265 90

Mefloquine pharmacokinetics were studied in Kenyan African normal volunteers and in patients with severe acute attack of Plasmodium falciparum malaria. Peak concentrations were achieved in both groups at 20-24 hours. The mean half-life of elimination was 385 +/- 150 hours (mean +/- SD) in normal subjects while in severe malaria it was 493 +/- 215 hours which was significantly longer (P less than or equal to 0.001). The volume of distribution was significantly smaller in severe malaria where it was 30.76 +/- 10.50 l/kg (mean +/- SD) while in the normal subjects it was 40.90 +/- 20.70 l/kg (mean +/- SD) (P less than or equal to 0.001). The total body clearance in severe malaria was 3.75 +/- 1.51 l/h (mean +/- SD). This was significantly lower than in the normal subjects where it was 5.15 +/- 1.50 l/h (mean +/- SD) (P less than or equal to 0.001).
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PMID:Mefloquine disposition in normals and in patients with severe Plasmodium falciparum malaria. 266 7


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