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)

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

In adult patients with acute falciparum malaria in Ho Chi Minh City, Vietnam, a more rapid reduction in parasite count (50% clearance in 11.3 h) and complete clearance (41.8 h) was obtained in 32 adult patients randomly assigned to received artemisinine suppositories than was obtained with 30 patients receiving oral quinine (20.8 h and 68.1 h). There were higher degrees of resistance (RII, 3 cases; RI early, 1 case) with quinine than with artemisinine but in a subgroup of patients quinine reduced parasitaemia as rapidly as artemisinine (50% clearance 13.6 h and 10.1 h respectively). Recrudescence (RI, delayed), occurred in 16 patients receiving artemisinine compared with 6 receiving quinine. Artemisinine suppositories, because of ease of administration, efficacy, and lack of side effects or risk of overdose, have advantages for the early treatment of falciparum malaria by possibly reducing the morbidity and mortality associated with a high or sustained parasitaemia.
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PMID:A randomized comparative study of artemisinine (qinghaosu) suppositories and oral quinine in acute falciparum malaria. 209 37

Qinghaosu, an anti-malaria drug, has been found to kill not only asexual blood stages but also the early stages of gametocytes of Plasmodium falciparum. The effect of qinghaosu in vitro depends on the concentration of the drug as well as on the initial parasitemia level (IC50 = 10-20 nM with 1% initial parasitemia). Resistance of P. falciparum to other anti-malaria drugs, e.g., chloroquine and pyrimethamine, did not affect susceptibility of its asexual and sexual stages to qinghaosu. Gametocytocidal effect of qinghaosu may play a role in the interruption of malaria transmission.
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PMID:Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum. 217 46

Artemisinin (Qinghaosu) is a potent antimalarial sesquiterpene lactone isolated from the Chinese herb Artemisia annua. Arteether, a potent semisynthetic analogue of dihydroartemisinin is being developed by the World Health Organization as the artemisinin derivative of choice for the treatment of malaria. All three agents in doses of 400 and 600 mg/kg body weight were found to exhibit marked suppression of humoral responses, as measured by the hemolytic plaque assay, with arteether being the most potent. These agents did not alter the delayed-type hypersensitivity response to sheep erythrocytes at the same dose levels. In addition, all three agents were found not to possess any anti-inflammatory activity when tested on carrageenan-induced oedema. These results indicated that these agents have a selective immunosuppressive activity. They did not exhibit immunostimulating activity in contrast to what has been reported for sodium artesunate.
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PMID:Effects of artemisinin, dihydroartemisinin and arteether on immune responses of normal mice. 220 89

Qinghaosu (QHS), also known as artemisinine and arteannuin, is isolated from the Chinese herb Artemisia annua L. It is highly active against both chloroquine-sensitive and chloroquine-resistant strains of P. berghei and has been approved by the Ministry of Health for the treatment of malaria. When QHS is treated with sodium borohydride, dihydroqinghaosu (DH QHS) is resulted with the antimalarial activity enhanced several fold. This paper reports the pharmacokinetics of DHQHS studied with the radioimmunoassay method. When the drug was given orally in tablet form to rabbits at doses of 10, 20 and 30 mg/kg, peak serum levels of 0.03, 0.05 and 0.13 micrograms/ml, respectively, were obtained in 1 to 2 h. The corresponding T1/2 of the drug were found to be 1.19, 1.00 and 1.10 h and the MRTs were 1.73, 1.36 and 1.53 h. No significant difference between dosages used was observed. When dogs were given DHQHS tablets at the dose of 20 mg/kg, a peak serum concentration of 0.13 micrograms/ml wes reached in about 2 h with a T1/2 of 2.10 h and an MRT of 3.04 h. However, when dogs were given QHS tablets at the dose of 70 mg/kg, no drug was detected in the serum. It would appear that the bioavailability of DHQHS tablets is much higher than that of QHS when given orally to the dog.
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PMID:[The pharmacokinetics of dihydroqinghasu given orally to rabbits and dogs]. 223 23

The A.A. weight present criteria of choice in order to set right a correct and effective anti-malarial prophylaxis. In the last ten years, a progressive increase of tropical diseases has been observed. This is due to the considerable growth of intercontinental traffic and of the number of persons moving to or from tropical areas where such diseases are endemic. Among these, malaria represent the most alarming problem, both because of the incidence cases and the difficulties related to the efficacy of pharmacological remedies for the chemoprophylaxis. In particular, three are now various pharmacological possibilities for malarial prophylaxis. Undoubtedly Chloroquine is the most efficacious even if there are many Plasmodium falciparum species resistant to Chloroquine and to other available medicines (multi-resistance). Most authors recommend to associate Chloroquine to others pharmacological substances to avoid pharmaco-resistance phenomena. Among the most famous pharmacological products used elsewhere are Fansidar, Maloprim, Paludrine and Lapudrine, not all are available in Italy. In China, for the therapy of resistant forms of malaria, the Qinghaosu a "schizont-killer" acting on multiresistant plasmodium falciparum has been utilizing for years. The Qinghaosu is not responsible for the crossing-reactions with other anti-malarial medicines. Various substances with Ca-antagonist action (Verapamil) are being experimented. It is supposed that Verapamil associated with Chloroquine can stop the flow of chlorine from plasmodium cells. The same mechanism is expected to be valid also for Desipramine, an experimental tricyclic anti-depressive when associated to Chloroquine. To the people moving to endemic areas, the A.A., at the end, suggest a series of practical norms to prevent infection and, therefore, the incidence of imported cases, still increasing at the moment, due to the absence of efficacious vaccine.
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PMID:[A current problem: the prevention of malaria]. 248 2

Qinghaosu, also known as artemisinin and arteannuin, is a new type of antimalarial drug isolated from Artemisa annua L. Its low solubility in water and oil limited its widespread clinical use. Artesunate (sodium dihydroqinghaosu hydrogen hemisuccinate monoester) is easily soluble in water and is used iv in the treatment of acute cerebral and malignant malaria. However, artesunate was shown to have a very short half-life when given iv in animals as well as in human beings. A transdermal dosage form of artesunic acid had been prepared and was reported to have reliable suppressing and killing effects on plasmobium berghei in mice. This paper reports results of pharmacokinetic studies of this preparation when applied onto a fixed area of the shaved skin of mice and rabbits. Serum concentration of the drug was determined by a method of radioimmunoassay. The drug was found to be easily absorbed from the skin. The serum concentration-time curve is depicted in figures 1. Peak concentration of 1.8 micrograms/ml was reached at about 2 h when a dose of 25 mg/kg was given to rabbits. For mice, peak serum concentrations of 2.05 and 7.11 micrograms/ml were attained in about 0.5 h after doses of 31.3 and 71.4 mg/kg, respectively, while at a dose of 6.7 mg/kg a peak level of 0.82 micrograms/ml (a concentration more than 5000 times the IC50 of artesunate in in vitro tests on plasmodium berghei for antimalarial activity) was attained at about 4 h after application of the drug. The half-lives of the drug were found to be more than 2 h for both mice and rabbits.
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PMID:[The pharmacokinetics of a transdermal preparation of artesunate in mice and rabbits]. 261 77

Artemisinin, developed by Chinese scientists, is a new type of anti-malarial drug with quick effect and low toxicity. Since its solubility in water or oil is very low, it cannot be made into a clear injection to be given intramuscularly or intravenously for emergency use. The artemisinin suppositories used in the study was provided by the institute of Chinese Materia Medica in 1982. Phase I and Phase II clinical trials of the drug were made by Guangzhou College of TCM. The results showed that the therapeutic effect of Artemisinin suppositories was satisfactory with no apparent side effects. The total dosage recommended was 2800-3200 mg. In 1986, fifty-six adults with falciparum malaria were treated with a total dose of 2800 mg Artemisinin suppositories for 3 days and randomly compared with a control group of Piperaquine phosphate in the Dongfang Town Hospital, Dongfang ( ) County of Hainan Island. The parasite clearance time in Artemisinin suppositories group (71.8 +/- 16.0 hrs) was significantly faster than that of Piperaquine phosphate group (100.3 +/- 20.3hrs), but recrudescence rate by 28 days (48.2%) was much higher than that of Piperaquine phosphate (17.0%). Artemisinin suppositories is simple to administrate and therefore it could be applied in endemic area of remote countryside and to the patients of incapable of oral dosing.
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PMID:[Comparative study of artemisinin suppositories and piperaquine phosphate in the treatment of falciparum malaria]. 268 37

In the treatment of severe Plasmodium falciparum infection antimalarial drugs should, ideally, be given by controlled rate intravenous infusion until the patient is able to swallow tablets. In cases where infection has been acquired in a chloroquine resistant area, and where it has broken through chloroquine prophylaxis or where the geographical origin or species are uncertain, quinine is the treatment of choice. When access to parenteral quinine is likely to be delayed, parenteral quinidine is an effective alternative. A loading dose of quinine is recommended in order to achieve therapeutic plasma concentrations as quickly as possible. In the case of chloroquine sensitive P. falciparum infection, chloroquine, which can be given safely by slow intravenous infusion, may be more rapidly effective and has fewer toxic effects than quinine. There is limited experience with parenteral administration of pyrimethamine sulphonamide combinations such as Fansidar, and resistance to these drugs has developed in South East Asia and elsewhere. Mefloquine and halofantrine cannot be given parenterally. Qinghaosu derivatives are not readily available and have not been adequately tested outside China. Supportive treatment includes the prevention or early detection and treatment of complications, strict attention to fluid balance, provision of adequate nursing for unconscious patients and avoidance of harmful ancillary treatments. Anaemia is inevitable and out of proportion to detectable parasitaemia. Hypotension and shock ('algid malaria') are often attributable to secondary gram-negative septicaemia requiring appropriate antimicrobial therapy and haemodynamic resuscitation. Many patients with severe falciparum malaria are hypovolaemic on admission to hospital and require cautious fluid replacement. Failure to rehydrate these patients may lead to circulatory collapse, lactic acidosis, renal failure and severe hyponatraemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of severe malaria. 269 26

The most recent acquisitions on chemotherapy and chemoprophylaxis of malaria are reviewed. With regard to chemotherapy, candidate antimalarial compounds have been divided into four groups, according to their stages of development. Mefloquine and the combination of mefloquine with sulfadoxine/pyrimethamine belong to the first group: they have completed clinical trials and have been registered in several countries for routine clinical use. The second group is characterized by chemical compounds which are in an advanced stage of development, including clinical trials. The compounds considered in this group are: a) the 9-phenanthrenemethanols, among which halofantrine is the most promising one; b) the sesquiterpene lactones such as Qinghaosu, artemether, artesunate, artesunic acid and arteether which must be further tested in order to find more effective drug regimens capable of eliminating recrudescences and for the completion of toxicity studies; c) pyronaridine, which appears to be a promising antimalarial, effective also against chloroquine-resistant P. falciparum, but still requiring further investigations on resistance and cross-resistance, as well as its pharmacokinetics, tolerability and bioavailability; d) enpiroline, another promising compound, which needs to be further studied in Phase II and Phase III investigations with naturally acquired malaria. The third group is composed of seven chemical classes of compounds that are in an advanced pre-clinical development, namely: the 4-aminoquinolines, such as dabechin, piperaquine, hydroxypiperaquine, tripiperaquine, dichlor-quinazine and the Mannich base compounds, the 8-aminoquinolines, the 4-quinolinemethanols, the quinolones, the naphthoquinones, the quinazolines and the dihydrotriazines. Among the many antimalarial compounds of interest, which can be considered at the moment as leads for further studies, only the acridandione derivatives such as floxacrine, the antibiotics, antifungal agents or their metabolites, plant substances such as Yingzhaosu A and quassinoids have been mentioned. Malaria chemoprophylaxis, especially in chloroquine-resistant P. falciparum areas, has become a real problem. The attempts to secure protection under these circumstances with the utilization of amodiaquine, the combination of sulfadoxine/pyrimethamine (Fansidar), sulfalene/pyrimethamine (Metakelfin), of pyrimethamine/dapsone (Maloprim), with or without chloroquine, had to be abandoned or to be used with caution in view of the severe complications following the weekly administration of these drugs. The combination of chloroquine with proguanil or chlorproguanil, which could be recommended on theoretical bases, did not meet the expectations when tested in the field. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recent acquisitions on chemotherapy and chemoprophylaxis of malaria. 269 8


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