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 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Thirty-nine percent (36 of 92) of children in Limbe, Cameroon, treated with chloroquine (10 mg/kg body weight on days 1 and 2, and 5 mg/kg on day 3) for falciparum malaria failed to respond within 7 d of treatment. Twenty-two of these children with chloroquine-resistant malaria were successfully treated with Fansidar [one-half tablet (250 mg sulfadoxine and 25 mg pyrimethamine) per 10 kg body weight], while the other 14 children were cured with mefloquine (25 mg/kg body weight). In vitro, a combination of verapamil at 1.0 x 10(-6) M with chloroquine or desethylchloroquine reversed resistance to the antimalarial drug and its primary metabolite in each of the 2 isolates successfully adapted and maintained in continuous culture. Similar combinations had no effect on susceptibilities of a sensitive reference clone, D6, used as control. Both chloroquine-resistant isolates from Cameroon were significantly more susceptible to mefloquine and halofantrine in vitro than the chloroquine-sensitive reference clone. Clinical observation, and in vitro confirmation, of chloroquine-resistant falciparum malaria in these indigenous children from Cameroon, and the current socio-economic condition in West Africa, underscore the need for pragmatic health management policies for efficient use of alternative antimalarial drugs in controlling drug resistant Plasmodium falciparum in the region. This observation of reversal of chloroquine resistance in isolates of P. falciparum obtained from West Africa, and a previous report on clones obtained from south-east Asia and South America, suggest that the mechanism(s) of resistance to chloroquine may be identical in resistant parasites from the 3 continents.
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PMID:Chloroquine resistant Plasmodium falciparum in indigenous residents of Cameroon. 269 61

Malaria, particularly that due to chloroquine-resistant Plasmodium falciparum, which requires management with antimalarial drugs capable of protecting against multiresistant strains, has emerged in Malaysia. A study was carried out to assess the efficacy and tolerability of 2 dosages of mefloquine/sulfadoxine/pyrimethamine (MSP; RO 13-5112) compared to Fansidar in a malaria endemic area. 914 subjects in 3 random groups were studied. Occurrence of malaria was assessed both clinically as well as by blood films. Plasma drug levels were also measured. The results showed that the low dose of MSP was completely effective in suppressing parasitaemia. 2.7% of the study population reported adverse drug reactions, the lowest incidence being in subjects on the low dose; their blood chemical profiles were also the least affected. The plasma levels of pyrimethamine and sulfadoxine achieved in the low dose group were slightly higher than expected, but there was no significant difference in bioavailability. The study showed that, for chemoprophylaxis, a low dose of MSP provided effective protection with minimal side effects.
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PMID:Chemosuppression of malaria by the triple combination mefloquine/sulfadoxine/pyrimethamine: a field trial in an endemic area in Malaysia. 269 9

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

The effect of primaquine as a gametocytocidal drug was investigated in 218 P. falciparum (Pf) malaria cases detected during passive case detection (PCD) from August to December 1985 in two coastal villages of North Sumatra, where chloroquine-resistant and Fansidar-sensitive Pf was prevalent. Sulfonamide + pyrimethamine (SP) in combination with primaquine (Pr) was administered in Kuala Tanjung village and SP alone in Nana Siam village. Parasitologically confirmed Pf cases were followed up to observe the fluctuation of gametocytemia after the treatment. In 87 cases treated with SP alone, no significant change was observed in gametocyte positivity rate (GPR) and density on day 2 and day 7. In 131 cases treated with SP and Pr, no significant change was found on day 2 but significant reduction was observed in GPR and density on day 7. The gametocyte positive cases on day 7 were followed up weekly until gametocytes disappeared. SP alone did not reduce GPR from day 0 to week 2, then afterward GPR began to decline but was still 11.5% at week 5. On the other hand, SP with Pr reduced GPR from 77% on day 0 to 30% on day 7, after which GPR declined further to 7% at week 3. Reduction of parasite rate was observed in Kuala Tanjung after the PCD activities, reflecting a reduction in Pf prevalence rate from 18.6% in August 1985 to 2.9% in January 1986. These data indicate that a single dose of Pr 45 mg with SP was partially effective in reducing gametocytes and reducing malaria prevalence rate when administered through PCD activities.
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PMID:Gametocytocidal effect of primaquine in a chemotherapeutic malaria control trial in North Sumatra, Indonesia. 269 82

A patient developed eosinophilic peripheral pulmonary infiltrates while receiving malaria prophylaxis with sulfadoxine-pyrimethamine (Fansidar). Withdrawal of Fansidar and treatment with corticosteroids led to rapid recovery. No exacerbation occurred after cessation of corticosteroids. Lymphocyte transformation testing gave a positive result in the presence of sulfadoxine but not pyrimethamine. It is concluded that drug hypersensitivity to sulfadoxine was the cause of the eosinophilic pneumonia in this patient.
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PMID:Sulfadoxine specific lymphocyte transformation in a patient with eosinophilic pneumonia induced by sulfadoxine-pyrimethamine (Fansidar). 276 33

The itinerary of international travelers will largely determine the amount of pretravel counseling number of immunizations and type of malaria prophylaxis they will need. The countries visited are also the best predictor of traveler's diarrhea. Only yellow fever and cholera vaccines are required for entry into certain countries; the latter generally given only to satisfy entry requirements. Polio vaccine is important for some areas and is frequently neglected. For most malarious areas, chloroquine once per week is recommended. Fansidar should be prescribed weekly for very few travelers. Traveler's diarrhea is best prevented by avoiding high risk foods and beverages. Antibiotics, generally not recommended for prophylaxis, are very effective in treatment. Travelers should be reminded to advise physicians of their travel history during future medical encounters so that diseases, possibly contracted during travel, may be considered in diagnoses.
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PMID:Counseling the international traveler. 279 6

Two randomised double-blind trials were conducted to examine the activity and tolerability of mefloquine alone and in combination with sulfadoxine/pyrimethamine (MSP). In one trial mefloquine was compared with chloroquine in 40 patients with Plasmodium vivax malaria and in the other one mefloquine was compared with MSP in 40 patients with P falciparum malaria. The former trial showed that both a single oral dose of 250 mg mefloquine and a single oral dose of 450 mg chloroquine (base) were highly effective in relieving symptoms of malaria and in clearing P vivax parasitaemia. No side-effects and no changes in laboratory variables attributable to the test drugs were observed. The other trial showed that a single oral dose of 750 mg mefloquine and a single oral dose of MSP (750 mg mefloquine plus 3 tablets of 'Fansidar', were equally effective in the treatment of falciparum malaria. 2/4 treatment failures in the mefloquine group and 2/3 treatment failures in the MSP group were due to low plasma drug levels resulting from vomiting soon after ingestion of the tablets. Gametocytes of P falciparum were unaffected by either mefloquine or MSP. 5 patients in each group had side-effects such as vomiting, skin rash, diarrhoea, and transient mental confusion. Mefloquine was well tolerated by patients with glucose-6-phosphate dehydrogenase deficiency or heterozygous haemoglobin E.
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PMID:Trials of mefloquine in vivax and of mefloquine plus 'fansidar' in falciparum malaria. 285 43

The disposition of sulfadoxine was studied in the presence of pyrimethamine in 18 healthy Thai subjects who had been suffering from falciparum malaria in the 6 months prior to the study, and in 12 Thai patients with acute malaria. The volunteers were administered an oral dose of 500 mg sulfadoxine + 25 mg pyrimethamine (1 Fansidar tablet). They were classified retrospectively as responders (Group I, n = 8) or nonresponders (Group II, n = 10) according to previous response to treatment with Fansidar. The patients were treated with 3 Fansidar tablets corresponding to 1500 mg sulfadoxine and 75 mg pyrimethamine. Five of them were completely cured. Seven patients showed R I or R II resistance. In all cases blood samples were collected up to 288 h post dose. The resultant plasma was analyzed for active (i.e. unchanged) and total sulfadoxine using a modified Bratton-Marshall method. In the healthy volunteers the plasma concentration time course of total sulfadoxine was similar for responding and nonresponding subjects. However, in nonresponders active sulfadoxine tended to show shorter half-lives (harmonic means were 212 h vs 267 h, respectively). Furthermore, significantly higher amounts of metabolites (mainly N4-acetylsulfadoxine) were present in plasma of nonresponders. In contrast to these findings, in malaria patients, plasma concentrations of active and total sulfadoxine were even higher in nonresponders as compared to the subjects who could be successfully cured. Furthermore, in this case there was no increase of the amount of metabolites in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma concentrations of sulfadoxine in healthy and malaria infected Thai subjects. 290 23

In 1982, the fixed combination of pyrimethamine and sulfadoxine (Fansidar) became available in the United States, and was recommended for use in travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum. Prior to that time, no reports of severe cutaneous reactions had appeared in the medical literature despite widespread use for more than 8 years in both Europe and malarious areas of the developing world. In the fall of 1984, the Centers for Disease Control received reports of 4 cases of toxic epidermal necrolysis (including 3 fatalities) among Americans who had used pyrimethamine-sulfadoxine (PYR/SDX) for the prevention of malaria. Subsequent investigation into severe cutaneous reactions associated with the use of this drug by American travelers detected 24 cases of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Twenty-three of the 24 patients concurrently used chloroquine. Seven patients died. No risk factors in the development of these reactions other than the use of PYR/SDX could be identified. Among American travelers, we estimate that these reactions occur in 1 per 5,000-8,000 users, and that fatal reactions occur in 1 per 11,000-25,000 users. This higher than expected incidence necessitates that the use of PYR/SDX for the prevention of malaria be reconsidered. In the United States it is now recommended that the routine weekly use of the drug be reserved for those travelers at highest risk of acquiring chloroquine-resistant P. falciparum, when alternate prophylactic regimens are not deemed appropriate.
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PMID:Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis. 293 35


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