From the Guidelines
Sulphadoxine and pyrimethamine are no longer recommended as a first-line treatment for falciparum malaria due to widespread resistance, but they still play a role in intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention programs. The combination of sulphadoxine and pyrimethamine, commonly administered as the combination drug Fansidar, works synergistically to block two sequential enzymes in the Plasmodium falciparum metabolic pathway: sulphadoxine inhibits dihydropteroate synthase while pyrimethamine targets dihydrofolate reductase 1. By disrupting folate synthesis, the drugs prevent the parasite from producing DNA and amino acids essential for its survival.
Key Considerations
- The adult treatment dose is a single administration of three tablets (each containing 500mg sulphadoxine and 25mg pyrimethamine) 1.
- For children, dosing is weight-based: 1/4 tablet for 5-10kg, 1/2 tablet for 11-20kg, 1 tablet for 21-30kg, and 2 tablets for 31-45kg.
- The medication should be used cautiously in patients with glucose-6-phosphate dehydrogenase deficiency or sulfa allergies, as it can cause severe adverse reactions including Stevens-Johnson syndrome in susceptible individuals.
Clinical Use
- Due to widespread resistance, this combination is now rarely used as monotherapy for treating acute malaria.
- Instead, it's primarily used in intermittent preventive treatment during pregnancy (IPTp) in malaria-endemic regions and as part of seasonal malaria chemoprevention programs.
- Alternative drugs such as tetracycline, quinine, and newer drugs like mefloquine should be considered, consistent with national malaria control policies in the host country 1.
From the Research
Role of Sulphadoxine and Pyrimethamine in Falciparum Malaria
- Sulphadoxine and pyrimethamine are used in combination with other drugs for the treatment of falciparum malaria, particularly in areas where resistance to these drugs is prevalent 2.
- The combination of artesunate and sulphadoxine-pyrimethamine has been shown to be effective in treating uncomplicated Plasmodium falciparum malaria, with a significant improvement in cure rates compared to sulphadoxine-pyrimethamine alone 2.
- However, the efficacy of sulphadoxine-pyrimethamine alone is limited due to widespread resistance, and its use as a monotherapy is no longer recommended 3, 4, 5, 6.
- Artemisinin-based combination therapies (ACTs), which include sulphadoxine-pyrimethamine as a partner drug, are now the recommended first-line treatment for uncomplicated falciparum malaria 3, 4, 5, 6.
- The use of sulphadoxine-pyrimethamine in combination with artemisinin derivatives has been shown to improve treatment outcomes and reduce the risk of resistance development 2.
Efficacy and Safety
- The combination of artesunate and sulphadoxine-pyrimethamine has been shown to be well tolerated and safe, with few adverse events reported 2.
- The efficacy of this combination has been demonstrated in several studies, with cure rates ranging from 74.4% to 84.6% at day 28 2.
- However, the use of sulphadoxine-pyrimethamine alone is associated with a higher risk of treatment failure and resistance development 3, 4, 5, 6.
Resistance and Limitations
- The widespread use of sulphadoxine-pyrimethamine has led to the development of resistance, which limits its efficacy as a monotherapy 3, 4, 5, 6.
- The combination of sulphadoxine-pyrimethamine with artemisinin derivatives can help to delay the development of resistance, but it is not a guarantee against resistance development 2.
- Therefore, the use of sulphadoxine-pyrimethamine should be carefully considered, and alternative treatments should be used in areas where resistance is prevalent 3, 4, 5, 6.