**7.5 Origins and spread of sulfadoxine-pyrimethamine resistance**

Resistance to pyrimethamine was observed in the 1950s after it was used in mass drug administration and/or prophylaxis for malaria in most malaria-endemic regions [68]. Resistance to pyrimethamine led to it been used mostly as a first-line treatment option in sulfadoxine-pyrimethamine combination therapy in Thailand in the late 1960s, and most malaria-endemic countries in Southeast Asia, and South America in the 1970s and later in Africa [86].
