**7.6 Route 1: southeast Asia to Africa**

*P. falciparum* resistance to SP was first reported in the 1960s at the Thai-Cambodia. Mutations in *pfdhfr* at codons 50,51,59,108, and 164 are CNRNI → CIRNI or CNRNL→CIRNL. These mutations have spread to other countries in Southeast Africa due to sulfadoxine-pyrimethamine pressure (**Figure 2A**) [87]. The *pfdhfr* quartet CIRNL mutant is dominant in Thailand [58], while the CIRNI mutant is found predominantly in Cambodia and Vietnam. The CNRNL mutant is found dominantly in Myanmar [87], while the CNRNI is found in Laos [88, 89]. Three additional genotypes, which are CNCNI, CICNI, and CICNL are also found in Southeast Asia at a very low prevalence of 5% [87]. The *pfdhfr* CIRNI mutant is predominant in many Africa countries such as South Africa, Benin, Cameroon, The Comoros, Congo, Gabon, Ghana, Guinea, Ivory Coast, Mali, Senegal, and Uganda (**Figure 2A**) [90]. This mutant is taught to have migrated to Africa from Asia [90]. It remains unknown when parasites resistant to pyrimethamine migrated to Africa, although some studies indicate the Asian origin triple mutant arrived in Kenya in 1987 [91].
