Dapsone malaria

The sulfas also remain clinically useful in the treatment of chancroid, lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and the fungus-related nocardiosis (7). In combination with pyrimethamine, they are recommended for toxoplasmosis (8) and have been used for chloroquine-resistant falciparium malaria (4,9). There has also been some use of sulfas for the prophylaxis of rheumatic fever. The sulfone, dapsone, remains an accepted treatment for all forms of leprosy (4). 

Acedapsone (127), which is conveniently prepared by acetylation of dapsone, was intended to be a prodrug. Leprous patients being treated with dapsone were observed to have a lower incidence of malaria and acedapsone was made to capitalize on this observation. It, indeed, has both antileprotic and antimalarial activity. 

Dapsone (p. 280) has several therapeutic uses besides treatment of leprosy, it is used for prevention/prophylaxis of malaria, toxoplasmosis, and actinomycosis. 

In treating resistant forms of malaria, tetracycline is also nsed in combination with pyrimethamine, snlfonamides, snlfones, and dapsone, which is widely used for treating leprosy (as a rnle, in combination with pyrimethamine). 

VI.a.2.4. Diaminopyrimidines. Pyrimethamine is a dihydrofolate reductase inhibitor, like the biguanides, and is structurally related to trimethoprim. It is seldom used alone. Pyrimethamine in fixed combinations with dapsone or sulfadoxine is used for treatment and prophylaxis of chloroquine-resistant falciparum malaria. The synergistic activities of pyrimethamine and sulfonamides are similar to those of trimethoprim/sulfonamide combinations. Resistant strains of Plasmodium falciparum have appeared world wide. Prophylaxis against falciparum... 

Although dapsone (Avlosulfon) was once used in the treatment and prophylaxis of chloroquine-resistant P. falciparum malaria, the toxicities associated with its administration (e.g., agranulocytosis, methemoglobinemia, hemolytic anemia) have severely reduced its use. 

Pyrimethamine is combined with dapsone (Malo-prim) (see p. 271) for prophylaxis of Plasmodium falciparum malaria. 

Two cases of pulmonary eosinophilia attributed to dapsone were reported in 1998. Four cases had previously been reported, in which the fixed combination of dapsone and pyrimethamine (a malaria prophylactic) had been implicated, but only one previous report had implicated dapsone alone. 

Since chlorproguanil + dapsone exerts lower resistance pressure on Plasmodium falciparum than does pyrimethamine -I- sulfadoxine, a randomized trial in outpatients with uncomplicated falciparum malaria was conducted in Africa in 910 children (1). Treatment failure was more common... 

Sulo J, Chimpeni P, Hatcher J, Kublin JG, Plowe CV, Molyneux ME, Marsh K, Taylor TE, Watkins WM, Winstanley PA. Chlorproguanil-dapsone versus sulfadox-ine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi a randomised clinical trial. Lancet 2002 360(9340) 1136 3. 

Although the hematological complications of pyrimethamine are generally a consequence of therapeutic use, long-term prophylactic treatment with pyrimethamine and dapsone in malaria could well involve an increased risk of megaloblastic anemia in patients whose nutritional state is not optimal (SEDA-13, 812). 

Three patients developed a hypersensitivity syndrome after taking pyrimethamine 12.5 mg + dapsone 100 mg weekly as malaria prophylaxis (16). The diagnosis was based on the presence of fever, lymphadenopathy, a maculopapular rash, and hepatitis. A mild Coombs -positive hemolytic anemia was also observed in one of the patients. All the clinical, hematological, and biochemical abnormalities normalized within 3 months of tapering regimens of moderate-dose prednisolone. 

Dapsone is also the drug of choice for dermatitis herpetiformis and is sometimes used with pyrimethamine for treatment of malaria and with trimethoprim for PCP. 

Dapsone, a sulfone with chemical sunilarities to sul-fapyridine, has been used for over 50 years for the treatment of susceptible forms of leprosy, as well as for quinine-resistant Plasmodium falciparum malaria. Dapsone is currently used for the primary treatment of dermatitis herpetiform, and can be replaced by sulfapyridine in patients with intolerance to the sulfone [183]. Dapsone in combination with trimethoprim it is also used... 

Another class of drugs that has proven clinically valuable against malaria are the antifolates. Sulfonamides such as pyridoxine and sulfones like dapsone inhibit the plasmodial enzyme dihydropteroate synthetase on the pathway of folic acid biosynthesis (48). The 2,4-... 

During the most active period of investigation of sulfanilamide derivatives, 1935—1944, for systemic bacterial infections, the antimycobacterial activity of 4,4 -diaminodiphenylsulfone [80-08-8] (DDS, dapsone) was discovered (14). Although neither this compound nor its derivatives proved to be clinically useful for human tuberculosis, it did evolve into the most important type of compound for leprosy (15). The A1,A1 -diacetyl derivative has also found use against certain resistant strains of falcipamm malaria. 

A large number of diphenylsulfone analogues have been developed for the treatment of leprosy. Incidentlly one such member chemically known as 4,4 -diaminodiphenyl sulfone (dapsone) exhibited prophylactic activity against resistant/ falciparum. Dapsone in conjimction with pyrimethamine has been effectively used in the treatment of malaria due to chloroquine resistant P. falciparum. 

Dapsone possesses limited therapeutic value in the treatment of malaria, except when combined with other agents for the treatment of chloroquine-resistant cases. 

Haemoglobinuria after a single dose treatment with dapsone and pyrimethamine for falciparum malaria in a patient with glucose-6-phosphate dehydrogenase deficiency. 

Dapsone is an antibiotic used to treat leprosy and for prophylaxis against malaria and Pneumocystis carinii infections in patients with AIDS and other immunodeficiency disorders. It is also used In rheumatologic and rate dermatologic disorders. 

No pharmacokinetic interaction appears to occur between dapsone and proguanil, and they have been successfully used together for malaria prophylaxis. 

Black RH. Malaria in die Australian army in South Vietnam. Successful use of a pr< uanil-dapsone combination for chemoprophylaxis of chloroquine-resislant Mciparum malaria. Med... 

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