title: Deletion of Plasmodium falciparum Histidine-Rich Protein 2 (pfhrp2) and Histidine-Rich Protein 3 (pfhrp3) Genes in Colombian Parasites.
abstract: A number of studies have analyzed the performance of malaria rapid diagnostic tests (RDTs) in Colombia with discrepancies in performance being attributed to a combination of factors such as parasite levels, interpretation of RDT results and/or the handling and storage of RDT kits. However, some of the inconsistencies observed with results from Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-based RDTs could also be explained by the deletion of the gene that encodes the protein, pfhrp2, and its structural homolog, pfhrp3, in some parasite isolates. Given that pfhrp2- and pfhrp3-negative P. falciparum isolates have been detected in the neighboring Peruvian and Brazilian Amazon regions, we hypothesized that parasites with deletions of pfhrp2 and pfhrp3 may also be present in Colombia. In this study we tested 100 historical samples collected between 1999 and 2009 from six Departments in Colombia for the presence of pfhrp2, pfhrp3 and their flanking genes. Seven neutral microsatellites were also used to determine the genetic background of these parasites. In total 18 of 100 parasite isolates were found to have deleted pfhrp2, a majority of which (14 of 18) were collected from Amazonas Department, which borders Peru and Brazil. pfhrp3 deletions were found in 52 of the 100 samples collected from all regions of the country. pfhrp2 flanking genes PF3D7_0831900 and PF3D7_0831700 were deleted in 22 of 100 and in 1 of 100 samples, respectively. pfhrp3 flanking genes PF3D7_1372100 and PF3D7_1372400 were missing in 55 of 100 and in 57 of 100 samples. Structure analysis of microsatellite data indicated that Colombian samples tested in this study belonged to four clusters and they segregated mostly based on their geographic region. Most of the pfhrp2-deleted parasites were assigned to a single cluster and originated from Amazonas Department although a few pfhrp2-negative parasites originated from the other three clusters. The presence of a high proportion of pfhrp2-negative isolates in the Colombian Amazon may have implications for the use of PfHRP2-based RDTs in the region and may explain inconsistencies observed when PfHRP2-based tests and assays are performed.
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Carrera 125 #19-225 Av., La Maria, Cali, Colombia.
authors.forename: Claribel
authors.initials: C
authors.lastname: Murillo Solano
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, United States of America; Atlanta Research and Education Foundation, Decatur, Georgia, United States of America.
authors.forename: Sheila
authors.initials: S
authors.lastname: Akinyi Okoth
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, United States of America.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Abdallah
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Carrera 125 #19-225 Av., La Maria, Cali, Colombia.
authors.forename: Zuleima
authors.initials: Z
authors.lastname: Pava
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Carrera 125 #19-225 Av., La Maria, Cali, Colombia.
authors.forename: Erika
authors.initials: E
authors.lastname: Dorado
authors.affiliation: Foundation for Innovative New Diagnostics, Chemin des Mines, 1202, Geneva, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Incardona
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, United States of America.
authors.forename: Curtis S
authors.initials: CS
authors.lastname: Huber
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, United States of America.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Macedo de Oliveira
authors.affiliation: Foundation for Innovative New Diagnostics, Chemin des Mines, 1202, Geneva, Switzerland; Global Good Fund/Intellectual Ventures Lab, 1807 132nd Ave NE, Bellevue, Washington, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, United States of America.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics* / Q000378:metabolism; D003105:Colombia / Q000453:epidemiology; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D003955:Diagnostic Tests, Routine; D004587:Electrophoresis, Agar Gel; D017353:Gene Deletion; D005838:Genotype; D005843:Geography; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000453:epidemiology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; C578339:HRP3 protein, Plasmodium falciparum; D015800:Protozoan Proteins