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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors recorded clinical histories and tested serum for the presence of malaria fluorescent antibodies in 160 healthy Europeans who had been living for more than 4 weeks in West or Central Africa. Malaria or fever of unknown origin occurred in 37 of 50 subjects who were careless about taking prophylactic drugs while abroad. Out of 110 people regularly taking suppressive amino-4-quinoline therapy, 21 had presented febrile attacks but serological tests were only positive in 8 cases. Positive serological reactions at low titers were obtained in 3 subjects with no history of past infection and who had faithfully taken suppressive medications. These results confirm the value of the malaria immunofluorescence test for the detection of occult malaria in blood donors outside endemic areas, and explain the necessity to consider previous regular, irregular or absent chemoprophylaxis before interpreting the serological results of a febrile patient returning from overseas.
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PMID:[Anti-malaria chemical prophylaxis in Europeans and anti-Plasmodium fluorescence antibodies]. 40 Jan 22

Quinine was compared with a 9-phenanthrene methanol (WR33063) and a 4-quinoline methanol (WR30090) for the treatment of 207 patients with falciparum malaria in Southeast Thailand. Quinine eradicated parasitaemia (average 70 hours) more rapidly than either WR30090 (72 hours) or WR33063 (77 hours). But WR33063 had a higher cure rate (92%) than WR30090 (86%) or quinine (85%). The mean duration of fever and of parasitaemia were combined with the failure rate to form an arbitrary efficacy index. Using this concept WR33063 was the most effective drug. The recrudescence rate correlated with the degree and duration of parasitaemia and with the duration of fever. WR33063 was the least toxic drug. Side effects associated with WR30090 appeared to be headache, backache and urticaria. Quinine was the most toxic drug. All 3 drugs were inconvenient in having to be administered every 8 hours for 6 days. One patient did not respond to oral quinine but did respond to an intravenous quinine infusion (IVQ). A "Medication Ward Round" was perfected during the study and comprised sequential history, drug administration, physical examination, dose notation and patient observation. Falciparum nephrosis was diagnosed in one patient.
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PMID:Comparison of a 9-phenanthrene methanol (WR33063), a 4-quinoline methanol (WR30090), and quinine for falciparum malaria in Thailand. 110 64

Tropical disease physicians are challenged by drug-resistant Plasmodium falciparum. Well-documented effects of resistance on malaria morbidity and mortality among people in tropical countries do not exist. Observed resistant malaria in these countries may consist of true and false positive cases particularly in urban and suburban areas of sub-Saharan Africa. WHO recommends systematic treatment with an antimalarial drug for persons with fever in these areas. Yet clinicians should have more information to diagnose malaria. Fever may be due to something other than malaria or to malaria but not due to resistance. So clinicians who cannot confirm malaria should modify antimalarial treatment. If trophozoites are still present, clinicians tend to claim resistance but false positives can occur if the blood smear is thick. A low trophozoite load may even indicate weak resistance. Thus they need to distinguish between true treatment failure (clinical resistance) or clinical cure with low residual parasite load (parasitological resistance). In sub-Saharan Africa, amino-4-quinoline resistance occurs often but the degree of resistance is not high. Indeed its frequency is slowing. So clinicians should use these inexpensive and well-tolerated drugs for uncomplicated malaria among natives. As false positives increase, so will the number of people who undergo unnecessary treatment thus increasing the chances of drug toxicity, overdose, or complications from home IV therapy. Reliable studies indicate that antimalarials may be clinically effective and malaria-related mortality low in as much as 70% of P. falciparum strains considered to be resistant. National programs should see to improved competence, technical ability, and their authority to stop this harmful trend. They should also have power over continuous training, health education, assessment of drug resistance and iatrogenic disease, and biological quality controls for detection of P. falciparum.
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PMID:"Pseudo-resistant" malaria in tropical countries. 136 Jan 33

During its intraerythrocytic development, the malarial parasite devours most of the hemoglobin in its host cell. This enormous catabolic process is achieved through an ordered, efficient degradative pathway that takes place in a specialized organelle, the digestive vacuole. The amino acids generated are used by the parasite for its growth and maturation; the heme released is polymerized into a crystalline matrix called hemozoin. We are beginning to understand the special enzymes that participate in this pathway. We do not yet fully understand the relative importance of exogenous versus catabolically generated amino acids, the function of hemozoin, the mechanism of action of quinoline drugs that concentrate in the digestive vacuole, or the mechanism of protection from malaria of variant hemoglobin gene carriers.
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PMID:Plasmodial hemoglobin degradation: an ordered pathway in a specialized organelle. 136 47

The aim of this research was to document the incidence of malaria and infant and child mortality among children residing in suburban areas of Brazzaville, the Congo, which are known for a high transmission of malaria. The study population included all children born between January 1, 1981, and June 30, 1987, in the maternity department of Linzolo Hospital and whose mothers resided in Brazzaville at the time of delivery. Interviews were conducted with 2424 mothers who were traced to the present homes during the second quarter of 1989. Information on 75% of the recorded births in the region was obtained directly from mothers. On the average, 21-29% of families had migrated or had an incorrect address each year. The results yielded rates of infant mortality of 33-52/1000 for children born during 1981-87. There were similar rates of mortality for children aged 1-2 years and 0-5 years. Not only was there low mortality, but there was low malaria mortality. These rates were less than the estimated rates for an urban area of Brazzaville of 69/1000 in 1980 and 57/1000 in 1984. Rural rates around Brazzaville were 62/1000 in 1984. Low malaria mortality rates were found in 1983; i.e., .43/1000 among 0-4 year olds and .08/1000 in the 5-9 year old age group. Rates did not appear to vary by district. Malaria rates are considered low for sub-Saharan Africa. This is attributed to access to drugs such as amino-4-quinoline. a more recent study of malaria mortality in Brazzaville, with lower transmission levels, showed a slight increase, which may be due to lower drug sensitivity to amino-4-quinoline for combating the local strains of P. falciparum. This pattern of drug resistance was observed in Kinshasa, Zaire. There would appear to be a high level of malaria immunity and early treatment of malaria fever in suburban areas of Brazzaville.
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PMID:Infant and child mortality and malaria in the Congo. The trend in the suburbs of Brazzaville between 1981 and 1988. 147 Aug 38

The incidence of human malaria has increased during the past 20 years; 270 million people are now estimated to be infected with the parasite. An important contribution to this increase has been the appearance of malaria organisms resistant to quinoline-containing antimalarials such as chloroquine and quinine. These drugs accumulate in the acid food vacuoles of the intraerythrocytic-stage malaria parasite, although the mechanism of their specific toxicity in this organelle is uncertain. The primary function of the food vacuole is the proteolysis of ingested red cell haemoglobin to provide the growing parasite with essential amino acids. Haemoglobin breakdown in the food vacuole releases haem, which if soluble can damage biological membranes and inhibit a variety of enzymes. Rather than degrading or excreting the haem, the parasite has evolved a novel pathway for its detoxification by incorporating it into an insoluble crystalline material called haemozoin or malaria pigment. These crystals form in the food vacuole of the parasite concomitant with haemoglobin degradation, where they remain until the infected red cell bursts. The structure of haemozoin comprises a polymer of haems linked between the central ferric ion of one haem and a carboxylate side-group oxygen of another. This structure does not form spontaneously from either free haem or haemoglobin under physiological conditions, and the biochemistry of its formation is unclear. Here we report the identification and characterization of a haem polymerase enzyme activity from extracts of Plasmodium falciparum trophozoites, and show that this enzyme is inhibited by quinoline-containing drugs such as chloroquine and quinine. This provides a possible explanation for the highly stage-specific antimalarial properties of these drugs.
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PMID:Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. 172 45

Malaria constitutes one of the major health threats in the tropical and sub-tropical areas of the world. Yet, few advances were made in recent years in revealing the mode of action of the common and most economically affordable antimalarial drugs, the schizontocidal 4-aminoquinolines. Data presented indubitably repudiate the previous notions that these drugs act by either halting the feeding of the parasite on its host erythrocyte cytosol or repressing nucleic acid synthesis due to intercalation into the parasite's DNA. A novel target for drugs is outlined, i.e. they are shown to inhibit in vitro the release of iron from acidified host cell cytosol, consisting mostly of hemoglobin, a process that could provide this trace element to the parasite. Resistance to quinoline-containing drugs is the principal reason for the present resurgence of malaria. Drug-resistant parasites accumulate less of these weak base-like drugs in the acidic digestive vacuoles. A kinetic model is presented, indicating that diminishing drug accumulation is due to decreased vacuolar proton pump activity and is not a result of a putative multidrug resistance (MDR) efflux pump. Findings to date on the molecular biology of parasite mdr genes are reviewed. These indicate no correlation between gene expression or mutations and phenotypic drug resistance. Reversal of parasite drug resistance by relevant compounds in MDR cancer cells seems to involve mechanism(s) different from the inhibition of the MDR pump in cancer cells.
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PMID:Quinoline-containing antimalarials--mode of action, drug resistance and its reversal. An update with unresolved puzzles. 173 99

Paludism can occur quite easily in pregnant women in endemic zones, above all those who are primiparous or in their 2nd or 3rd terms. The onset of paludal attacks can be serious for both the mother and the child. That is to say, besides the obviously imperative therapeutic action, a prophylaxis is also a necessity. The use of antipaludial substances at our disposal has been complicated during the last few years as a result of chloroquine-resistance extension. Besides a few nuances of kinetic nature observed in pregnant women, a good knowledge of teratogenous or embryotoxic effects is necessary. But this remains fragmentary. Among the principal antipaludial medications is quinine (Q), reported to be abortifacient but in reality it is not: it is often poorly tolerated by the mother (hypoglycemia), but is not responsible for abnormalities in children, except under large doses. Chloroquine (CQ), considered to be without harmful effects, can be used in women without large restrictions, even if toxic effects have been observed in animals. The pyrimethamine-sulfanilamide (P-S) combination contains two substances which are a potential risk. Nevertheless, experiments have never showed harmful effects in pregnant women, particularly when under cover of a joint prescription of folinic acid. Proguanil is without doubt the only molecule which can be used without restriction. Two new medications, quinoline methanol, Mefloquine (MQ) and Halofantrine (HF) are contra-indicated for lack of experimentation and because of some abnormalities observed at high doses in animals. Artemisinine and amino-8-quinoline are contra-indicated, and cyclines are strongly inadvised. From the practical point of view, the present use of antipaludial medication in pregnancy should take into account the surrounding risk, namely that of paludism and of treatments. Curatively, Q remains a serious treatment in any form. In CQ-sensitive zones CQ is usable unreservedly in simple attacks. In CQ resistance zones the use of Q seems preferable to that of Fansidar proposed by certain people. MQ and HF, although contra-indicated, have already been employed without inconvenience. By way of prevention, it is important first of all to avoid all leisure stays in endemic zones. If travel is unavoidable or for indigenous people, a chemoprophylaxis, judged according to the local risk of impaludation, is desirable: CQ in sensitive zones, PG+CQ in resistant zones, P-S, as proposed by some people, is normally contra-indicated; MQ and HF are contra-indicated. Protection against nocturnal mosquito bites is still strongly applied (Mosquito net, repellents, insecticides).
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PMID:[Antimalarials and pregnancy]. 181 22

Using a presumptive animal model of the pruritus produced by chloroquine or amodiaquine in patients with malaria, the ability of mono de-ethylated chloroquine, chloroquine, mono de-ethylated amodiaquine, bi-de-ethylated amodiaquine and normal saline (placebo) to be differentiated in their pruritogenic potentials were determined. The six-hour totals of the visually-monitored pruritic activity showed that the mono de-ethylated chloroquine was no more pruritogenic than placebo (normal saline) and sedated the animals, unlike the mono-de-ethylated and the bi-de-ethylated amodiaquine metabolites which retained the known pruritogenic activity of their parent compound. It is concluded that 4-aminoquinolines with a simple aliphatic side group, like chloroquine, on losing an ethyl group (de-alkylation) have a significant reduction in the pruritogenic effect, but with a more complex aromatic side group, like amodiaquine, even the loss of both ethyl groups does not appreciably decrease their pruritogenic qualities. Thus, the dog model is apparently sensitive enough to be used as a biological animal screen for pruritogenic potentials among quinoline antimalarial drug candidates, and for structure-activity relationship studies in pruritus research.
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PMID:Structure activity relationships in the pruritogenicity of chloroquine and amodiaquine metabolites in a dog model. 206 3

Mefloquine, a quinoline-methanol antimalarial, is effective single dose therapy for all species of malaria infecting humans, including multi-drug-resistant Plasmodium falciparum. It is used both in prophylaxis and treatment. Mefloquine is available either as the hydrochloride salt alone, or in a combined preparation with sulfadoxine and pyrimethamine. There is no parenteral formulation. Several assay methodologies have been developed, but high performance liquid chromatography has been the most used in recent pharmacokinetic studies. These have shown in healthy volunteers that mefloquine is absorbed with a half-life of 1 to 4 hours and a time to peak concentration of 7 to 24 hours (median 16.7 hours). Mean peak blood concentrations have ranged between 50 and 110 (median 83) ng/ml/mg/kg. Estimates of total apparent volume of distribution (Vd/f) have ranged from 13.3 to 40.9 (median 19.2) L/kg, systemic clearance (CL/f) from 0.022 to 0.073 L/h/kg (median 0.026 L/h/kg), and terminal elimination half-life from 13.8 to 40.9 days (median 20 days). Systemic clearance appears to be increased in late pregnancy. In uncomplicated falciparum malaria, peak blood concentrations are 2 to 3 times higher than those in healthy subjects ranging from 112 to 209 (median 144) ng/ml/mg/kg because of contraction in the total apparent volume of distribution. Systemic clearance is usually reduced but elimination rates are increased (possibly because of reduced enterohepatic recycling). Mefloquine absorption appears to be reduced in severe falciparum malaria; plasma protein binding exceeds 98% in both healthy subjects and patients. No important drug interactions have been identified as yet, but the potential for serious interactions with quinine has not been adequately investigated. More studies are needed on the disposition of mefloquine in children.
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PMID:Clinical pharmacokinetics of mefloquine. 220 97


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