Lineage-specific expansion of Plasmodium falciparum parasites with pfhrp2 deletion in the Greater Mekong Subregion.

: Deletion of the pfhrp2 gene in Plasmodium falciparum can lead to false negative RDT results, constituting a major challenge for evidence-based malaria treatment. Here we analyzed the whole genome sequences of 138 P. falciparum clinical samples collected from the China-Myanmar boarder for pfhrp2 and pfhrp3 gene deletions. We found pfhrp2 and pfhrp3 deletions in 9.4% and 3.6% samples, respectively, with no samples harboring deletions of both genes. The pfhrp2 deletions showed two distinct break points, representing two different chromosomal deletion events. A phylogenetic analysis performed using genome-wide single nucleotide polymorphisms revealed that the two pfhrp2 break point groups as well as all the pfhrp3-negative parasites formed separate clades, suggesting they might have resulted from clonal expansion of pfhrp2- and pfhrp3-negative parasites. These findings highlight the need for urgent surveys to determine the prevalence of pfhrp2-negative parasites causing false-negative RDT results and plan for switching of RDTs pending the survey results.