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

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

The toxicities of antimalarial drugs vary because of the differences in the chemical structures of these compounds. Quinine, the oldest antimalarial, has been used for 300 years. Of the 200 to 300 compounds synthesised since the first synthetic antimalarial, primaquine in 1926, 15 to 20 are currently used for malaria treatment, most of which are quinoline derivatives. Quinoline derivatives, particularly quinine and chloroquine, are highly toxic in overdose. The toxic effects are related to their quinidine-like actions on the heart and include circulatory arrest, cardiogenic shock, conduction disturbances and ventricular arrhythmias. Additional clinical features are obnubilation, coma, convulsions, respiratory depression. Blindness is a frequent complication in quinine overdose. Hypokalaemia is consistently present, although apparently self-correcting, in severe chloroquine poisoning and is a good index of severity. Recent toxicokinetic studies of quinine and chloroquine showed good correlations between dose ingested, serum concentrations and clinical features, and confirmed the inefficacy of haemodialysis, haemoperfusion and peritoneal dialysis for enhancing drug removal. The other quinoline derivatives appear to be less toxic. Amodiaquine may induce side effects such as gastrointestinal symptoms, agranulocytosis and hepatitis. The main feature of primaquine overdose is methaemoglobinaemia. No cases of mefloquine and piperaquine overdose have been reported. Overdose with quinacrine, an acridine derivative, may result in nausea, vomiting, confusion, convulsion and acute psychosis. The dehydrofolate reductase inhibitors used in malaria treatment are sulfadoxine, dapsone, proguanil (chloroguanide), trimethoprim and pyrimethamine. Most of these drugs are given in combination. Proguanil is one of the safest antimalarials. Convulsion, coma and blindness have been reported in pyrimethamine overdose. Sulfadoxine can induce Lyell and Stevens-Johnson syndromes. The main feature of dapsone poisoning is severe methaemoglobinaemia which is related to dapsone and to its metabolites. Recent toxicokinetic studies confirmed the efficacy of oral activated charcoal, haemodialysis and haemoperfusion in enhancing removal of dapsone and its metabolites. No overdose has been reported with artemesinine, a new antimalarial tested in the People's Republic of China. The general management of antimalarial overdose include gastric lavage and symptomatic treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical features and management of poisoning due to antimalarial drugs. 330 66

The widespread emergence of chloroquine-resistant Plasmodium falciparum led to the formulation of an effective, fixed combination of two antimalarial agents, pyrimethamine and the long-acting sulfonamide sulfadoxine, for prophylaxis and treatment. These drugs act at sequential steps to inhibit the formation of tetrahydrofolate in the parasite. Recently, their use for malaria prophylaxis has been associated with severe, at times fatal, cutaneous reactions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. These reactions have necessitated a major reassessment of the indications for pyrimethamine-sulfadoxine use and increased the search for pharmacologic, immunologic and behavioral approaches to the prophylaxis and treatment of infection with P. falciparum. Pyrimethamine-sulfadoxine may be effective in preventing recurrent pneumonia caused by Pneumocystis carinii in patients with the acquired immunodeficiency syndrome, but life-threatening cutaneous reactions have also been reported in this setting.
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PMID:Use of pyrimethamine-sulfadoxine (Fansidar) in prophylaxis against chloroquine-resistant Plasmodium falciparum and Pneumocystis carinii. 355 13

To the best of our knowledge, Stevens-Johnson syndrome (SJS) has not been reported previously as an adverse reaction to Malarone, which is a combination of atovaquone and proguanil hydrochloride used for antimalarial prophylaxis and therapy. We describe a 65-year-old patient who had SJS with typical clinical and histopathological findings associated with the use of Malarone prophylaxis for malaria. This report should alert physicians to this severe cutaneous reaction, and Malarone should be added to the list of drugs that can potentially cause SJS.
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PMID:Stevens-Johnson syndrome associated with Malarone antimalarial prophylaxis. 1283 Apr 30

Malaria, caused mostly by Plasmodium falciparum and P. vivax, remains one of the most important infectious diseases in the world. Antimalarial drug toxicity is one side of the risk-benefit equation and is viewed differently depending upon whether the clinical indication for drug administration is malaria treatment or prophylaxis. Drug toxicity must be acceptable to patients and cause less harm than the disease itself. Research that leads to drug registration tends to omit two important groups who are particularly vulnerable to malaria--very young children and pregnant women. Prescribing in pregnancy is a particular problem for clinicians because the risk-benefit ratio is often very unclear. The number of antimalarial drugs in use is very small. Despite its decreasing efficacy against P. falciparum, chloroquine continues to be used widely because of its low cost and good tolerability. It remains the drug of first choice for treating P. vivax malaria. Pruritus is a common adverse effect in African patients. As prophylaxis, chloroquine is usually combined with proguanil. This combination has good overall tolerability but mouth ulcers and gastrointestinal upset are more common than with other prophylactic regimens. Sulfadoxine/pyrimethamine is well tolerated as treatment and when used as intermittent preventive treatment in pregnant African women. Sulfadoxine/pyrimethamine is no longer used as prophylaxis because it may cause toxic epidermal necrolysis and Stevens Johnson syndrome. Mefloquine remains a valuable drug for prophylaxis and treatment. Tolerability is acceptable to most patients and travellers despite the impression given by the lay press. Dose-related serious neuropsychiatric toxicity can occur; mefloquine is contraindicated in individuals with a history of epilepsy or psychiatric disease. Quinine is the mainstay for treating severe malaria in many countries. Cardiovascular or CNS toxicity is rare, but hypoglycaemia may be problematic and blood glucose levels should be monitored. Halofantrine is unsuitable for widespread use because of its potential for cardiotoxicity. There is renewed interest in two old drugs, primaquine and amodiaquine. Primaquine is being developed as prophylaxis, and amodiaquine, which was withdrawn from prophylactic use because of neutropenia and hepatitis, is a potentially good partner drug for artesunate against falciparum malaria. Atovaquone/proguanil is a new antimalarial combination with good efficacy and tolerability as prophylaxis and treatment. The most important class of drugs that could have a major impact on malaria control is the artemisinin derivatives. They have remarkable efficacy and an excellent safety record. They have no identifiable dose-related adverse effects in humans and only very rarely produce allergic reactions. Combining an artemisinin derivative with another efficacious antimalarial drug is increasingly being viewed as the optimal therapeutic strategy for malaria.
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PMID:Antimalarial drug toxicity: a review. 1472 85

We estimated the frequency of clinically diagnosed Stevens-Johnson syndrome and toxic epidermal necrolysis associated with sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (CTX) in Blantyre District, Malawi. Cases were detected by passive surveillance at 22 health centers from March 2001 through September 2002. Denominators were estimated from the Malawi national census for Blantyre District and the frequency of SP and CTX use reported in five household surveys. Crude rates of adverse reactions were estimated to be 1.2 per 100,000 exposures for SP and 1.5 per 100,000 exposures for CTX. Rates were higher in adults (1.7 cases per 100,000 SP exposures and 2.6 cases per 100,000 CTX exposures) and in persons positive for human immunodeficiency virus (4.9 cases per 100,000 SP exposures and 8.4 cases per 100,000 CTX exposures). Infrequent treatment doses with SP are associated with a low risk of an adverse cutaneous reaction, and SP can be recommended for treatment of malaria in areas where P. falciparum is susceptible.
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PMID:Severe cutaneous reactions to sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole in Blantyre District, Malawi. 1668 72

The causative factors and ocular complications of Stevens-Johnson syndrome and toxic epidermal necrolysis are reported here. Six out of seven patients developed the syndrome secondary to ingestion of sulphadoxine/pyrimethamine while one developed it as a complication of HAART (highly active antiretroviral therapy). The ocular complications were ankyloblepharon, symblepharon, chronic conjunctivitis, corneal vascularization and conjunctivalization, and blindness. One patient died. A shift to the WHO-recommened artemisin-based combination therapy for the treatment of malaria is advised. Early referral to the ophthalmologist will help to reduce the complications.
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PMID:Ocular complications of Stevens-Johnson syndrome and toxic epidermal necrolysis. 2055 46

Two female patients aged 25 and 12 years suffering from malaria presented with picture of Stevens Johnson syndrome. Each of them had received daily doses of chloroquine phosphate by intramuscular injection for 3 days. They progressed to toxic epidermal necrolysis and could not be saved despite best of efforts.
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PMID:Chloroquine-induced toxic epidermal necrolysis. 2094 26

Intermittent preventive treatment with sulfadoxine/pyrimethamine (SP) is recommended for malaria prevention in infants (IPTi-SP). Serious adverse events, including Stevens-Johnson syndrome (SJS), have been reported following exposure to SP, but few infant-specific data exist. The safety of IPTi-SP was evaluated as part of a pilot implementation programme in southern Tanzania using three methods: spontaneous adverse event reporting to capture suspected adverse drug reactions (ADR); a census survey documenting rash-related hospital admissions among children < 2 years of age; and verbal autopsies (VA) completed for rash-related deaths in 2-11-month-olds. Approximately 82 000 IPTi-SP doses were administered to approximately 29 000 children. In total, 119 suspected ADRs were reported, 13 in children aged <2 years, only one of whom had received IPTi-SP. The census involved 243 612 households. Only one rash-related admission was reported amongst 1292 children aged 2-11 months, but this child had no history of exposure to SP. Moreover, 30 of 699 deaths in 2-11-month-olds were said to have been associated with a skin rash. The rates of rash-associated death were 0.59/1000 person-years at risk (PYAR) and 1.17/1000 PYAR in intervention and comparison areas, respectively (P = 0.79). VAs did not suggest SJS or any other ADR. We conclude that IPTi-SP is associated with a very low incidence of severe skin reactions. [ClinicalTrials.gov identifier: NCT00152204].
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PMID:Safety of sulfadoxine/pyrimethamine for intermittent preventive treatment of malaria in infants: evidence from large-scale operational research in southern Tanzania. 2403 64