title: Histidine-rich protein 2 (pfhrp2) and pfhrp3 gene deletions in Plasmodium falciparum isolates from select sites in Brazil and Bolivia.
abstract: More than 80% of available malaria rapid diagnostic tests (RDTs) are based on the detection of histidine-rich protein-2 (PfHRP2) for diagnosis of Plasmodium falciparum malaria. Recent studies have shown the genes that code for this protein and its paralog, histidine-rich protein-3 (PfHRP3), are absent in parasites from the Peruvian Amazon Basin. Lack of PfHRP2 protein through deletion of the pfhrp2 gene leads to false-negative RDT results for P. falciparum. We have evaluated the extent of pfhrp2 and pfhrp3 gene deletions in a convenience sample of 198 isolates from six sites in three states across the Brazilian Amazon Basin (Acre, Rondonia and Para) and 25 isolates from two sites in Bolivia collected at different times between 2010 and 2012. Pfhrp2 and pfhrp3 gene and their flanking genes on chromosomes 7 and 13, respectively, were amplified from 198 blood specimens collected in Brazil. In Brazil, the isolates collected in Acre state, located in the western part of the Brazilian Amazon, had the highest percentage of deletions for pfhrp2 25 (31.2%) of 79, while among those collected in Rondonia, the prevalence of pfhrp2 gene deletion was only 3.3% (2 out of 60 patients). In isolates from Para state, all parasites were pfhrp2-positive. In contrast, we detected high proportions of isolates from all 3 states that were pfhrp3-negative ranging from 18.3% (11 out of 60 samples) to 50.9% (30 out of 59 samples). In Bolivia, only one of 25 samples (4%) tested had deleted pfhrp2 gene, while 68% (17 out of 25 samples) were pfhrp3-negative. Among the isolates tested, P. falciparum pfhrp2 gene deletions were present mainly in those from Acre State in the Brazilian Amazon. These results indicate it is important to reconsider the use of PfHRP2-based RDTs in the western region of the Brazilian Amazon and to implement appropriate surveillance systems to monitor pfhrp2 gene deletions in this and other parts of the Amazon region.
authors.affiliation: Instituto Evandro Chagas - IEC/SVS/MS, Ananindeua, Pará, Brasil.
authors.forename: Giselle Maria
authors.initials: GM
authors.lastname: Rachid Viana
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.|Atlanta Research and Education Foundation, Decatur, Georgia, United States of America.
authors.forename: Luciana
authors.initials: L
authors.lastname: Silva-Flannery
authors.affiliation: Instituto Evandro Chagas - IEC/SVS/MS, Ananindeua, Pará, Brasil.
authors.forename: Danielle Regina
authors.initials: DR
authors.lastname: Lima Barbosa
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: 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: Lindsay C
authors.initials: LC
authors.lastname: Morton
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
authors.initials: C
authors.lastname: Huber
authors.affiliation: Pan American Health Organization, La Paz, Bolivia.
authors.forename: Arletta
authors.initials: A
authors.lastname: Anez
authors.affiliation: Instituto Evandro Chagas - IEC/SVS/MS, Ananindeua, Pará, Brasil.
authors.forename: Ricardo Luiz
authors.initials: RL
authors.lastname: Dantas Machado
authors.affiliation: ICB5/USP e Faculdade São Lucas, Porto Velho, Rondônia, Brasil.
authors.forename: Luís Marcelo
authors.initials: LM
authors.lastname: Aranha Camargo
authors.affiliation: Secretaria Estadual de Saúde do Acre, Hemonúcleo Cruzeiro do Sul, Cruzeiro do Sul, Acre, Brasil.
authors.forename: Suiane
authors.initials: S
authors.lastname: Costa Negreiros do Valle
authors.affiliation: Instituto Evandro Chagas - IEC/SVS/MS, Ananindeua, Pará, Brasil.
authors.forename: Marinete
authors.initials: M
authors.lastname: Marins Póvoa
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.identifier: http://orcid.org/0000-0003-0304-3383
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, Atlanta, Georgia, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics*; D001838:Bolivia; D001938:Brazil; D017353:Gene Deletion; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; C578339:HRP3 protein, Plasmodium falciparum; D015800:Protozoan Proteins