Lineage-Specific Expansion of Plasmodium falciparum Parasites With pfhrp2 Deletion in the Greater Mekong Subregion

• Published in: The Journal of infectious diseases 2020-10, Vol.222 (9), p.1561-1569
• Main Authors: Gibbons, Justin, Qin, Junling, Malla, Pallavi, Wang, Zenglei, Brashear, Awtum, Wang, Chengqi, Miao, Jun, Adams, John H, Kim, Kami, Jiang, Rays, Cui, Liwang
• Format: Article
• Language: English
• Subjects: Antigens, Protozoan - genetics; China - epidemiology; False Negative Reactions; Gene Deletion; Genome, Protozoan - genetics; Humans; Major and Brief Reports; Malaria, Falciparum - diagnosis; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Myanmar - epidemiology; Phylogeny; Plasmodium falciparum - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Prevalence; Protozoan Proteins - genetics; Sequence Alignment
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiaa250

Deletion of the pfhrp2 gene in Plasmodium falciparum can lead to false-negative rapid diagnostic test (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% of samples, respectively, with no samples harboring deletions of both genes. The pfhrp2 deletions showed 2 distinct breakpoints, representing 2 different chromosomal deletion events. A phylogenetic analysis performed using genome-wide single-nucleotide polymorphisms revealed that the 2 pfhrp2 breakpoint 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 a plan for switching of RDTs pending the survey results.