Dissection of haplotype-specific drug response phenotypes in multiclonal malaria isolates

Natural infections of Plasmodium falciparum, the parasite responsible for the deadliest form of human malaria, often comprise multiple parasite lineages (haplotypes). Multiclonal parasite isolates may exhibit variable phenotypes including different drug susceptibility profiles over time due to the presence of multiple haplotypes. To test this hypothesis, three P. falciparum Cambodian isolates IPC_3445 (MRA-1236), IPC_5202 (MRA-1240) and IPC_6403 (MRA-1285) suspected to be multiclonal were cloned by limiting dilution, and the resulting clones genotyped at 24 highly polymorphic single nucleotide polymorphisms (SNPs). Isolates harbored up to three constituent haplotypes, and exhibited significant variability (p