title: Variation in Plasmodium falciparum Histidine-Rich Protein 2 (Pfhrp2) and Plasmodium falciparum Histidine-Rich Protein 3 (Pfhrp3) Gene Deletions in Guyana and Suriname.
abstract: Guyana and Suriname have made important progress in reducing the burden of malaria. While both countries use microscopy as the primary tool for clinical diagnosis, malaria rapid diagnostic tests (RDTs) are useful in remote areas of the interior where laboratory support may be limited or unavailable. Recent reports indicate that histidine-rich protein 2 (PfHRP2)-based diagnostic tests specific for detection of P. falciparum may provide false negative results in some parts of South America due to the emergence of P. falciparum parasites that lack the pfhrp2 gene, and thus produce no PfHRP2 antigen. Pfhrp2 and pfhrp3 genes were amplified in parasite isolates collected from Guyana and Suriname to determine if there were circulating isolates with deletions in these genes. Pfhrp3 deletions were monitored because some monoclonal antibodies utilized in PfHRP2-based RDTs cross-react with the PfHRP3 protein. We found that all 97 isolates from Guyana that met the inclusion criteria were both pfhrp2- and pfhrp3-positive. In Suriname (N = 78), 14% of the samples tested were pfhrp2-negative while 4% were pfhrp3-negative. Furthermore, analysis of the genomic region proximal to pfhrp2 and pfhrp3 revealed that genomic deletions extended to the flanking genes. We also investigated the population substructure of the isolates collected to determine if the parasites that had deletions of pfhrp2 and pfhrp3 belonged to any genetic subtypes. Cluster analysis revealed that there was no predominant P. falciparum population substructure among the isolates from either country, an indication of genetic admixture among the parasite populations. Furthermore, the pfhrp2-deleted parasites from Suriname did not appear to share a single, unique genetic background.
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 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, Atlanta, Georgia, United States of America.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Abdallah
authors.affiliation: Pan American Health Organization-Guyana, Georgetown, Guyana.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ceron
authors.affiliation: Department of Biochemistry, Anton de Kom (ADEK) University of Suriname, Paramaribo, Suriname.
authors.forename: Malti R
authors.initials: MR
authors.lastname: Adhin
authors.affiliation: Guyana Ministry of Health, Georgetown, Guyana.
authors.forename: Javin
authors.initials: J
authors.lastname: Chandrabose
authors.affiliation: Guyana Ministry of Health, Georgetown, Guyana.
authors.forename: Karanchand
authors.initials: K
authors.lastname: Krishnalall
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 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, Atlanta, Georgia, United States of America.
authors.forename: Ira F
authors.initials: IF
authors.lastname: Goldman
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Macedo de Oliveira
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics*; D003955:Diagnostic Tests, Routine / Q000379:methods; D017353:Gene Deletion; D006172:Guyana; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D013532:Suriname
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; C578339:HRP3 protein, Plasmodium falciparum; D015800:Protozoan Proteins