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Query: UMLS:C0024530 (malaria)
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At least four doses of quinine followed by a single dose of mefloquine or by a single dose of sulfadoxine-pyrimethamine are two highly effective regimens for chloroquine-resistant falciparum malaria. Mefloquine alone is valuable in ambulant patients. Chloroquine-sensitive falciparum malaria can be treated with a course of chloroquine. Vivax and all other types of malaria should be treated with sequential chloroquine and primaquine. Quinine, by intravenous infusion, is the most effective drug for severe falciparum malaria. The optimum intravenous dose varies between 5 mg/kg and 10 mg/kg administered over four hours. Intravenous or oral quinine should be administered about every 12 hours and the total daily dose of quinine should rarely exceed 20 mg/kg. Intravenous fluid input should be controlled in falciparum malaria to prevent pulmonary oedema. Established renal failure is best treated by dialysis. The value of adrenocortical steroids for falciparum coma has not been established. Fresh blood transfusion may be helpful in small doses for severe anaemia and to replace clotting factors. Anticoagulants, such as heparin, should not be used in falciparum malaria.
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PMID:The treatment of malaria. 76 37

Chloroquine and amodiaquine are demonstrably still the most reliable drugs for the treatment of malaria, except in the south east Asia area, and in parts of south and central America where an altered sensitivity of falciparum plasmodia has been confirmed. The present position of malaria prophylaxis is, unfortunately, anything but satisfactory. But there are already some good preparations which, if correctly used with consideration of all available information, contribute considerably to the prevention of an infection.
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PMID:[Chemotherapy and chemoprophylaxis of malaria (author's transl)]. 82 13

Chloroquine resistance is a well established entity in South East Asia, and presents a problem of increasing importance. Strains of P. falciparum resistant to chloroquine have also been found to be resistant to amodiaquine and a combination of pyrimethamine and sulphadoxine. Knowledge of the drug sensitivity of the strains of malaria parasite in a given locality is important so that the right choice of drugs can be made in treatment of the disease. The treatment of chloroquine resistant malaria in West Malaysia is a subject of another paper but suffice it to say that increased doses of chloroquine have still been found to be effective in treating many cases of falciparum malaria from areas of chloroquine resistance.
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PMID:Chloroquine resistant malaria in West Malaysia. 109 76

Amodiaquine cured 38% (13/34) of patients with falciparum malaria in Southeast Thailand. Chloroquine cured 0% (0/13). The cure rates with amodiaquine were the same whether a 1.5 g or 2.0 g course was used. Most patients were resistant to amodiaquine at the RI level and to chloroquine at the RII level. In hospital, amodiaquine cleared parasitemia more frequently than did chloroquine. With the 2.0 g course of amodiaquine, the parasite clearance time was 77 hours; the fever clearance time of 36 hours was low and suggests that amodiaquine does not cause a drug fever. Because of resistance, chloroquine should not be used for falciparum malaria in Thailand. Routine use of amodiaquine is not indicated because more effective drugs are available.
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PMID:Amodiaquine resistant falciparum malaria in Thailand. 109 99

Data are presented on the causal prophylactic action of about 100 compounds of various types against Plasmodium yoelii nigeriensis N67 in mice. Examples are given to show how action against pre-erythrocytic schizonts may be differentiated from action on emerging erythrocytic stages. In a series of 35 8-aminoquinolines, all but 10 showed definite causal prophylactic activity at tolerated doses. The data permit the compounds to be ranked in order of activity, and many are shown to be more active in this test system than primaquine. Marked causal prophylactic activity is displayed by a variety of quinone structures, several of which show a significant residual action on blood stages. A high level of activity is found in dihydrofolate reductase inhibitors within several chemical classes. Rorguanil is more effective as a causal prophylactic than a blood schizontocide in the mouse as in man. Sulphonamides and sulphones are also effective in this system. The active levels are influenced by the content of PABA in the diet of the hosts. Causal prophylactic action has been detected in a number of experimental compounds including some antibiotics (such as tetracycline and clindamycin). The pyrocatechol RC 12 shows only slight activity at the maximum tolerated dose. Chloroquine, mepacrine, quinine, quinolinemethanols and phenanthrenemethanols are inactive as causal prophylactics. It is concluded that a rodent malaria-mouse model does provide a relatively simple model for the screening of drugs for causal prophylaxis, and the data so obtained are of relevance to the detection of causal prophylactics against human malaria.
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PMID:The chemotherapy of rodent malaria, XXIII Causal prophylaxis, part II: Practical experience with Plasmodium yoelii nigeriensis in drug screening. 109 90

The duration of action of the drug Antemal, a combination of Pyrimethamine and Sulfametopyrazine, was eveluated in Bobo-Dioulasso, Upper Volta, West Africa, and endemic zone for Plasmodium falciparum malaria. The study was held during the season of maximum malaria transmission. 79 persons presenting with an acute attack of malaria were studied; 37 persons received a single dose of chloroquine sulfate (Nivaquine), at a dose of 15 mg./kg.; 42 persons received a single dose of Antemal at a dose of one tablet (75 mg. of Pyrimethamine and 25 mg. of Sulfametopyrazine) per 10 kg. Clinical and parasitological studies of all subjects occurred on days one, two, three, 10, 17, 24 and 31. Only one of 37 (2.7%) subjects on Antemal had a reappearance of trophozoites, occurring on day 17. Eight of 42 (19.0%) patients taking nivaquine had reappearance of trophozoites, observed between day 23 and 31. Gametocytes were observed in eight of 37 (21.6 %) persons on Antemal and in only one of 42 (2.3 %) persons on Nivaquine. These observations suggest an extended duration of protection from Antemal in semi-immune individuals. Nivaquine appeared as a potent inhibitor of gametocytogenesis.
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PMID:[Duration of action of the pyrimethamine-sulfametopyrazine combination in a Plasmodium falciparum endemic zone]. 110 Feb 87

The efficacy of chloroquine in the treatment of falciparum malaria was studied in two villages in Northeast Thailand, an area endemic for chloroquine-resistant falciparum infections. Chloroquine did not appear to reduce the duration or density of parasitemias experienced by asymptomatic villagers, but did benefit, usually temporarily, many subjects with symptomatic or high-density infections. These observations suggest that the high prevalence of chloroquine-resistant infections in the villages is similar to data from the hospital and clinics serving the area. The question whether chloroquine should remain available to this population should be evaluated.
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PMID:Longitudinal malaria studies in rural Northeast Thailand. Chloroquine treatment of falciparum malaria infections. 110 87

Chloroquine in a concentration range from 5 ng to 2 mug per ml of biological fluid can be determined in plasma and urine by the spectrofluorometric methods. The spectrodensitometric method is less sensitive and should be used when other drugs are interfering with the chloroquine determination in solution. After extraction from urine and separation from interfering drugs and metabolites by TL-chromatography chloroquine can be determined by spectrodensitometry in a minimum concentration of 5 mug per ml of urine. Chloroquine should be determined in plasma and urine of patients suffering from malaria with an impaired renal function. Whether the fluorometric determination of chloroquine should be used in field investigations will depend on the problem to be investigated and the regional facilities.
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PMID:Spectrofluorometric and spectrodensitometric determination of chloroquine in plasma and urine. 118 23

Chloroquine increases the inhibition of cultured lymphocytes by high concentrations of phytohemagglutinin (PHA) or concanavalin A (Con A). The inhibition is also increased by complement. Thus chloroquine and complement have similar effects. Time-course studies show that chloroquine increases the rate of onset of the complement-dependent inhibition. In serum preheated to inactivate complement, chloroquine can partially simulate the effect of complement. It is suggested that at certain stages in malaria or autoimmune disease the rate of clearance of parasitized erythrocytes or autoreactive lymphocytes is limited by the concentration of complement. Under these conditions a drug such as chloroquine, which could enhance or simulate the action of complement, might be of therapeutic value.
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PMID:Evidence for a relationship between chloroquine and complement from studies with lymphocyte mitogens: possible implications for the mechanism of action of chloroquine in disease. 123 60

We carried out in 1989 a non randomized comparative study in French army units which had been in Central Africa (Central African Republic and Gabon) for 4 months, in order to compare in 758 men on return from malaria areas the usual strategy of chemoprophylaxis with chloroquine and a radical cure by halofantrine (Halfan). Chloroquine was taken by 278 men (100 mg daily for 6 weeks after their return to France); the other 480 men were given two doses of 1,500 mg halofantrine on the third and on the tenth day after their return to France. In Africa both of the units were on chloroquine prophylaxis (100 mg daily for 4 months). The Plasmodium falciparum attack rates were, during a period of 5 months after the return to France, 0.2% in the halofantrine group (1/480) and 4.7% (13/228) in the chloroquine group (P < 10(-4)). The radical cure by halofantrine was more effective than chloroquine prophylaxis in preventing falciparum malaria on return from malaria areas.
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PMID:[Efficacy of radical treatment with halofantrine on the prevention of imported Plasmodium falciparum malaria]. 129 22


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