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

In different countries opinions differ as to which chemotherapeutic methods should be used for malaria prophylaxis. It has long been the opinion of the Nordic countries, that WHO should give an official recommendation and the result is reflected now in the publication "Vaccination certificate requirements and health advice for internation travel." The malaria-endemic regions of the world are divided into 3 categories: regions without risk and no need for prophylaxis, low risk regions (A) with predominantly vivax inflections, risk regions (B) with predominantly chloroquine sensitive P. falciparum, and high risk regions (C) with often both chloroquine as well as sulfa/pyrimethamine resistance. Chloroquine is a sufficient prophylaxis for A-regions. For B-regions proguanil should be added and for C-regions only mefloquine is given. Proguanil was reintroduced basically because of Swedish research results in Liberia. An American initiative recommends for all regions, A-C, chemorprophylaxis as an alternative. However, a precondition is an observant traveller and clear instructions for self-treatment. Travellers who fall ill in a B-region should choose between Fansidar, mefloquine and quinine for self-treatment. Mefloquine has the least serious side effects, whereas quinine is therapeutically more safe. Fansidar very seldom gives any side effects. For C-regions only mefloquine is recommended for self-treatment. Nordic colleagues have recommended to double prophylaxis (chloroquine + Paludrine) treatment for the entire African tropical region. For short-time travellers to Kenya, Tanzania and Uganda, 6 tablets Lariam should be added. Only chloroquine is recommended for India and the Amazon region of South America. No chemoprophylaxis can guarantee full protection. Insect protection is therefore more important than ever. Malaria decreases the unspecific immune defense system. Surprisingly, repeated tests have shown that the AIDS frequency is not higher in patients with chronic malaria than for persons without plasmodia in the blood. In WHO's new little yellow booklet, a page concerning prophylaxis against AIDS appears. Equipment that is not new should be steamed or cooked for a least 20 minutes or treated with chemical disinfectants for at least 30 minutes. These measures should be enough to prevent HIV-infection.
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PMID:[Malaria and HIV prevention in WHO's "little gem"]. 338 44

Immunologically intact and T cell-deprived CBA mice were infected with Plasmodium chabaudi and treated with chloroquine, pyrimethamine or quinine. Chloroquine and pyrimethamine rapidly reduced the levels of parasitaemia in both types of host, but whereas the normal mice remained free of blood parasites thereafter, the deprived mice suffered recrudescences of the infection. Quinine was therapeutically more effective in the intact mice than in the deprived mice early after initiation of treatment and, while the normal mice suffered a transient recrudescence after quinine, the deprived mice retained a high parasitaemia during and after treatment. The results indicate that the immune response may contribute to effective chemotherapy of malaria.
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PMID:Reduced efficacy of chemotherapy of Plasmodium chabaudi in T cell-deprived mice. 350 36

We conducted a randomized controlled trial to evaluate the antibody response of freshman veterinary students to intradermal human diploid-cell rabies vaccine administered concurrently with chloroquine, a drug frequently used for chemoprophylaxis against malaria. Fifty-one students who had not been vaccinated against rabies were enrolled: 26 received 300 mg of chloroquine base per week (the recommended dose for malaria prophylaxis); 25 did not receive chloroquine and served as controls. All subjects received 0.1 ml of rabies vaccine intradermally on days 0, 7, and 28. Chloroquine was administered weekly to the treatment group, beginning nine days before the first dose of vaccine and continuing until day 48. The mean rabies-neutralizing antibody titer for the chloroquine group was significantly lower than that for the control group on each day of testing--i.e., day 28 (P = 0.0094), day 49 (P = 0.0008), and day 105 (P = 0.0002)--although both groups had neutralizing antibody titers on days 49 and 105, according to the criteria of the Centers for Disease Control. The blood concentrations of chloroquine and desethylchloroquine (the major metabolite of chloroquine, which also has antimalarial properties) were negatively associated with log antibody titers. These results indicate that chloroquine taken in the dose recommended for malaria prophylaxis can reduce the antibody response to primary immunization with intradermal human diploid-cell rabies vaccine.
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PMID:Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine. 351 Mar 93

The effects of chloroquine, amodiaquine and pyrimethamine-sulfadoxine (SP) (Fansidar) on the infection rate and density of Plasmodium falciparum gametocytes were studied in 198 patients with falciparum malaria from an area in the Punjab where malaria is endemic but seasonally transmitted. One month following treatment of 100 patients, SP had reduced the gametocyte carrier rate from 37% to 6% and the mean gametocyte density from 80 to 1.4 per mm3 of blood. Chloroquine and amodiaquine were much less effective. Since SP has no gametocytocidal properties and the reduction in gametocytes coincided with clearance of asexual parasitemias, gametocytes were probably reduced subsequent to the cure of the asexual malaria infections. If used during the nontransmission season, SP might be an effective component of an integrated program for reducing malaria transmission in the Punjab and other areas where 4-aminoquinoline-resistant and SP-sensitive falciparum malaria exists.
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PMID:Effects of chloroquine, amodiaquine and pyrimethamine-sulfadoxine on Plasmodium falciparum gametocytemia. 351 44

Intraerythrocytic malaria parasites feed on their host cell cytosol. We show that human red blood cells infected with the malaria parasite Plasmodium falciparum, produce free amino acids the composition of which resembles that of globin, the most abundant red blood cell protein. The rate of amino acid production is almost equal to the rate of efflux of these acids from the infected cell. Production of amino acids increases with parasite age: the rates of production at the young ring and the mature trophozoite stages were 3.3 and 13.5 nmol/10(8) infected cells per min at 37 degrees, respectively, compared with 0.04 nmol/10(8) cells per min in uninfected cells. The quinoline-containing antimalarial drugs, chloroquine, quinine and mefloquine, inhibit amino acid production at the same concentrations at which they inhibit parasite growth, but have no effect on the endogenous parasite protein degradation. We suggest that parasite feeding on host cell cytosol is the primary target for the antimalarial action of these drugs. Chloroquine accumulation, the rate of amino acid production by infected cells and the inhibitory effect of the drug, were determined simultaneously at the different stages of parasite development. At all stages the rate of amino acid production and chloroquine accumulation were directly related and both were inversely related to the inhibitory efficiency of the drug. The lysosomotropic agents methylamine and NH4Cl at millimolar concentrations also inhibit amino acid production, suggesting that the process is pH dependent and localized in the vacuole. Host cytosol degradation and drug accumulation both take place in the parasite food vacuole. Our observations imply that the metabolically dependent acidification of this parasite organelle is involved in both processes.
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PMID:Digestion of the host erythrocyte by malaria parasites is the primary target for quinoline-containing antimalarials. 352 76

Adults with malaria in Sri Lanka were treated with parenteral chloroquine diphosphate, either 2.5 mg base/kg intramuscularly at 0, 1, 12, 13, 24, and 25 hours or 5 mg base/kg subcutaneously at 0, 12, and 24 hours. Both regimens were completed with oral chloroquine phosphate, 5 mg base/kg, at 36 and 48 hours. Mean peak chloroquine concentrations in the first 12 hours, which were 0.5 (range 0.3-0.6) mg/l (1.4 (0.9-1.7) mu mol/l) [corrected] with the intramuscular regimen and 0.3 (0.2-0.4) mg/l (1.0 (0.7-1.3) mu mol/l) [corrected] with the subcutaneous regimen (p less than 0.05), were reached in median times of 90 (65-90) minutes and 30 (30-60) minutes respectively (p less than 0.05) after the start of treatment. The mean area under the plasma concentration curve for the first 12 hours was 1.4 (0.9-2.1) mg/l.h (4.5 (2.8-6.4) mu mol/l.h) [corrected] after intramuscular administration and 1.8 (0.8-2.3) mg/l.h (5.7 (2.7-7.2) mu mol/l.h) [corrected] after subcutaneous administration (p greater than 0.1). Mean maximum plasma concentrations were higher after intramuscular administration (0.6 (0.4-0.8) mg/l (1.7 (1.3-2.5) mu mol/l)) [corrected] than after subcutaneous administration (0.4 (0.4-0.5) mg/l (1.3 (1.3-1.5) mu mol/l)) [corrected] (p less than 0.05), but both regimens produced satisfactory plasma profiles. Chloroquine resistance was found in the only case of Plasmodium falciparum malaria. Chloroquine is absorbed rapidly after divided dose intramuscular injection and single dose subcutaneous injection and does not cause hypotension or neurotoxicity in adults. Similar regimens should be evaluated in children before the parenteral use of this drug is abandoned.
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PMID:Divided dose intramuscular regimen and single dose subcutaneous regimen for chloroquine: plasma concentrations and toxicity in patients with malaria. 352 44

Chloroquine-resistant Plasmodium falciparum malaria contracted in Mozambique by a patient taking correct prophylaxis is reported. The fact that misdiagnosis of malaria still occurs, the need to have intravenous quinine readily available country-wide, and the fact that a P. falciparum strain resistant to chloroquine is present across our border are stressed.
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PMID:Chloroquine-resistant malaria. A case report. 352 56

Sixty-eight cases of vivax and 30 cases of falciparum malaria patients were treated with a combination of sulfamonomethoxine-pyrimethamine (MP tablet with 500 mg of sulfamonomethoxine and 25 mg of pyrimethamine) and the results were compared with those with chloroquine, Fansidar and quinine. Vivax malaria: Fever and parasites were cleared by the 4th day of treatment in 94 and 92% of the patients, respectively. Chloroquine was the most effective drug and Fansidar and MP tablets shared the next position. Falciparum malaria: Fever and asexual parasites were cleared by the 4th day of treatment in 67 and 78% of the patients, respectively. MP tablets were effective in chloroquine-resistant falciparum malaria contracted in Kalimantan (Indonesia) and Oceanian countries (Vanuatu etc.). Fever and parasite clearance times were shorter with chloroquine or with Fansidar than with MP tablets. Defective preschizonts used to appear following administration of MP tablets both in vivax and falciparum malarias. They were the premonitory laboratory indications that the asexual parasites will be soon eradicated.
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PMID:A combination of sulfamonomethoxine and pyrimethamine versus other drugs for the treatment of malaria. 354 42

The development of new sensitive and specific assays (HPLC) have enabled the pharmacokinetics of antimalarial drugs to be studied. Parameters such as half-life distribution volume, clearance and bioavailability, are defined. In healthy subjects, quinine is rapidly eliminated (t1/2 beta: 6-12 h). Hepatic biotransformation accounts for approximately 80% of its total clearance. In malaria, the pharmacokinetic properties of quinine (decrease in the apparent volume of distribution, prolongation of the t1/2 beta, reduction in systemic clearance), are altered in proportion to the severity of infection. Red cell concentrations and plasma binding are increased. Parenteral quinine should be given by slow intravenous infusion and a loading dose is recommended in severe infections. Chloroquine (t1/2 beta: 6-50 days) and mefloquine (t1/2 beta: 6-33 days) have extensive tissue distribution and prolonged activity after a single dose. Both drugs are concentrated in erythrocytes and are bound considerably to plasma proteins. Amodiaquine is not found in the blood after oral administration. Hepatic biotransformation accounts for almost all orally administered drug. Its antiplasmodial activity is thus almost entirely due to monodesethylamodiaquine, the main metabolite. In healthy subjects, the t1/2 beta of this metabolite is 9 to 18 days in plasma. Amodiaquine is concentrated in erythrocytes. The protein binding of this drug has not been studied to date. For prophylaxis, it has been suggested that the dosage of 10 mg/kg/wk should be spread over the week (3.5 mg/kg every other day, or 1.5 every day). Halofantrine has an elimination half-life of between 1.3 and 6.6 days. This drug has been suggested as a single-dose treatment. No pharmacokinetic studies of qinghaosu have been reported in humans. In rabbits, the elimination half-life in plasma was found to be 40 min. Although rapidly eliminated, this drug appears to be highly effective. More information is required on the pharmacokinetics of these drugs in malaria, during pregnancy, in children and in renal and hepatic failure.
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PMID:[Pharmacokinetics of antimalarials: quinine and mefloquine, halofantrine, qinghaosu, amino-4-quinolines]. 354 4

Over the last decade, chloroquine-resistant falciparum malaria has spread to other areas from its original foci in Southeast Asia and South America. Additionally, new knowledge about the life-cycle of the malaria parasite, and about the pharmacokinetic properties of antimalarial drugs, has emerged. It is appropriate to reassess our approach to prevention and management of malaria with these factors in mind. Antimalarial drugs can be classified in two ways: biologically as tissue schizontocides, hypnozoitocides, blood schizontocides, gametocytocides or sporontocides; or by a mixed chemical/biological classification as 8-aminoquinolines, antimetabolites and (again) blood schizontocides. Chloroquine resistance in P. falciparum can now be found in most areas where malaria occurs. Malarial strains moderately resistant to the chloroquine group of drugs (chloroquine and mepacrine) are generally susceptible to the aryl amino alcohols such as quinine. Indeed, quinine is the most widely used drug for treating malaria due to chloroquine-resistant strains, followed by a 7-day course of tetracycline where some resistance to quinine is also found. Alternatively, the course of quinine may be followed by sulfadoxine/pyrimethamine or the newer quinoline derivative, mefloquine. Quinidine has also shown activity against quinine-resistant strains. Prophylaxis of chloroquine-resistant strains is best undertaken with daily proguanil (chloroguanide), and weekly chloroquine. In severe malaria, including cerebral malaria, an intravenous loading dose of quinine should be considered, and plasma concentration monitoring may be advisable to assist with dosage adjustment. In patients with severe renal insufficiency, there is evidence that the elimination of chloroquine is prolonged, and dosage adjustments may be necessary. Other recent findings on the pharmacodynamic properties, mechanisms of action and toxicity of antimalarial drugs are also discussed.
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PMID:Antimalarial drugs. An update. 354 65


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