**7.8 Route 3: south America**

Resistance to pyrimethamine was first recorded in South America in the 1950s shortly after its introduction in Venezuela [68]. *In vitro* resistance to pyrimethamine was confirmed in Brazil in the mid 1960s [93] and Columbia in 1981 [68]. Since then, sulfadoxine-pyrimethamine-resistant parasites have spread to other countries in South America [94]. Parasites with *pfdhfr* evolved indigenously in South America. Two distinct *pfdhfr* lineages resistant to pyrimethamine have been confirmed in South America. The *pfdhfr* RICNI triple mutant has been confirmed in Venezuela [95], Bolivia [96], and Brazil [97]. The *pfdhfr* RICNI triple mutant

#### **Figure 2.**

*Origins and spread of pyrimethamine resistance. (A) A resistant lineage having a double mutation (CNRNI), from the Thai-Cambodia border, evolved into triple (CIRNI and CNRNL) and quartet (CIRNL) types and spread to other regions in Asia and Africa. Three indigenous lineages of the dhfr triple mutant evolved in Africa. In the Pacific region, two resistant lineages having the CNRNI type have been reported: An indigenous lineage and the lineage that migrated from Southeast Asia. Capital letters are abbreviations of amino acids at positions 50, 51, 59, 108, and 164 in dhfr. Red-colored letters represent mutations. (B) Two distinct lineages of pyrimethamine resistance have been detected in South America in Venezuela and Peru. The two triple mutants (RICNI and CICNL) lineages sequentially evolved from different lineages of the CICNI type of dhfr double mutant. Abbreviations are the same as in (A). Adapted from [68].*

is taught to have evolved from the CICNI double mutant. The second lineage, the CICNL triple mutant is found in Peru and Bolivia. The CICNL triple mutant has been suggested to evolve from the CICNI double mutant [96, 98].

P. falciparum *and Its Molecular Markers of Resistance to Antimalarial Drugs DOI: http://dx.doi.org/10.5772/intechopen.98372*
