1. Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests
- Author
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Mei-Fong Ho, James S. McCarthy, Jane Cunningham, John W. Barnwell, Jennifer Luchavez, Didier Menard, Sina Nhem, Nanhua Chen, David Bell, Michelle L. Gatton, Anita Pelecanos, Myat Phone Kyaw, Wellington Oyibo, Frédéric Ariey, Qin Cheng, Shan Qing Wang, Pamela Onyor, Claribel Murillo, Jeffery Hii, Audrey Albertini, Djibrine Djalle, Dionicia Gamboa, Diego F. Echeverry, Bernhards Ogutu, Salim Abdullah, Christopher Membi, Joanne Baker, Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, School of Population Health, University of Queensland [Brisbane], Clinical Tropical Medicine Laboratory, Queensland Institute of Medical Research-University of Queensland [Brisbane], Malaria Drug Resistance and Chemotherapy Laboratory, Queensland Institute of Medical Research, Bagamoyo, Ifakara Health Research and Development Centre, Foundation for Innovative New Diagnostics (FIND), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Centre for Disease Control and Prevention, Global Malaria Programme, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-UNICEF Headquarters-World Bank Group-United Nations Development Programme (UNDP), Institut Pasteur de Bangui, Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Instituto de Medicina Tropical 'Alexander von Humboldt' (IMT AvH), Universidad Peruana Cayetano Heredia (UPCH), Departamento de Bioquimica, Biologia Molecular y Farmacologia, FACULTAD DE CIENCIAS Y FILOSOFIA, Western Pacific Regional Office of the World Health Organization, Department of Medical Research, Research Institute for Tropical Medicine, Institut Pasteur de Madagascar, Kenya Medical Research Institute (KEMRI), College of Medicine, University of Lagos, and Hainan Provincial Centre for Disease Control and Prevention
- Subjects
MESH: Sequence Analysis, DNA ,MESH: Reagent Kits, Diagnostic ,Protozoan Proteins ,Polymerase Chain Reaction ,law.invention ,Exon ,0302 clinical medicine ,law ,MESH: Animals ,MESH: Genetic Variation ,Malaria, Falciparum ,MESH: Protozoan Proteins ,Polymerase chain reaction ,MESH: Plasmodium falciparum ,Genetics ,Immunoassay ,0303 health sciences ,biology ,MESH: Malaria, Falciparum ,3. Good health ,Infectious Diseases ,MESH: Immunoassay ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Sequence analysis ,030231 tropical medicine ,Plasmodium falciparum ,MESH: DNA, Protozoan ,Antigens, Protozoan ,Sensitivity and Specificity ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Genetic variation ,parasitic diseases ,medicine ,Animals ,Humans ,lcsh:RC109-216 ,Gene ,030304 developmental biology ,MESH: Humans ,Research ,Genetic Variation ,MESH: Polymerase Chain Reaction ,Sequence Analysis, DNA ,DNA, Protozoan ,medicine.disease ,biology.organism_classification ,MESH: Sensitivity and Specificity ,Parasitology ,Reagent Kits, Diagnostic ,Malaria ,MESH: Antigens, Protozoan - Abstract
Background Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region. Methods The pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs. Results Sequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified. Conclusions The results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.
- Published
- 2010
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