quinine + sulfadoxine-pyrimethamine

The combination of quinine with sulfadoxine-pyrimethamine is an antimalarial treatment regimen that has been used particularly in areas with chloroquine-resistant malaria. This sequential therapy typically involves a short course of quinine (usually 3-7 days) followed by a single dose of sulfadoxine-pyrimethamine (also known by the brand name Fansidar). ## Therapeutic Use and Efficacy This combination has been studied extensively for treating uncomplicated falciparum malaria. In Bangladesh, a study showed an overall cure rate of 87.3% in a 42-day follow-up after PCR adjustment when using 3 days of quinine plus a single dose of sulfadoxine-pyrimethamine[1]. The combination has been considered an affordable alternative to artemisinin-based combination therapies (ACTs) in regions where ACTs might not be available[1][4]. The treatment regimen typically consists of: * Quinine: 650 mg every 8 hours for 3-7 days * Sulfadoxine-pyrimethamine: 2-3 tablets as a single dose given on the last day of quinine treatment[2][10] A study in Thailand demonstrated that a short course of quinine (average 4 doses, equivalent to 2 g base) followed by a single dose of pyrimethamine-sulfadoxine cured 92% of patients with falciparum malaria[8]. ## Mechanism of Action The combination works through complementary mechanisms: **Quinine** acts by interfering with the parasite's ability to digest hemoglobin. It is derived from the bark of the cinchona tree and has been used to treat malaria for centuries[4]. **Sulfadoxine-pyrimethamine** works by inhibiting two enzymes involved in the folate biosynthesis pathway of the parasite: * Pyrimethamine inhibits dihydrofolate reductase (DHFR) * Sulfadoxine inhibits dihydropteroate synthase (DHPS) This dual inhibition blocks the synthesis of folate, which is essential for parasite DNA synthesis and reproduction[7]. ## Resistance Concerns The efficacy of this combination has been declining in certain regions, particularly in East Africa, due to increasing resistance to sulfadoxine-pyrimethamine[6]. A study in Kenya found a treatment failure rate of 13.9% when using quinine followed by sulfadoxine-pyrimethamine for severe malaria[6]. Resistance to pyrimethamine has been observed in Plasmodium vivax, making this combination less effective against P. vivax infections[3]. The development of resistance is associated with mutations in the parasite's dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes[6]. ## Safety and Side Effects Sulfadoxine-pyrimethamine can cause severe adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis[5]. Treatment should be discontinued at the first appearance of skin rash, significant reduction in blood cell counts, or upon the occurrence of active bacterial or fungal infections[5]. This combination is not recommended for infants under 2 months of age and should be used with caution in breastfeeding women due to potential harmful effects on the infant[5].

Brand names

Fansidar