The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times.
Bibliographical noteFunding Information:
We wish to thank all members of the study team who originally contributed to the collection of samples and study participants for their permission to use these samples. We acknowledge funding support from the Amazon Malaria Initiative which is supported by the U.S. Agency for International Development. S.A. and T.H. were supported by the American Society of Microbiology/CDC Postdoctoral Fellowship Program. D.G. is supported by DGCD (Framework Agreement 03, 2008–2013, Project 95502); D.G. and J.B. are supported by the Peru/Brazil International Center of Excellence in Malaria Research U19AI089681 (NIH/NIAID, United States Public Health Service, USA). K.T. is supported by the NIH/Fogarty International Center Global Infectious Diseases Training Grant D43TW007120 (IMTAvH-UCSD). A.M.O., C.L., J.W.B. and V.U. are employees of the U.S. Government and D.J.B. is a military service member. This work was prepared as part of their official duties. We thank Dr. Fredrik Vannberg of the Georgia Institute of Technology and Mr. Ira F. Goldman of the Centers for Disease Control and Prevention for critical review of the manuscript.