Bead-based immunoassay allows sub-picogram detection of histidine-rich protein 2 from Plasmodium falciparum and estimates reliability of malaria rapid diagnostic tests

• Published in: PloS one Vol. 12; no. 2; p. e0172139
• Main Authors: Rogier, Eric, Plucinski, Mateusz, Lucchi, Naomi, Mace, Kimberly, Chang, Michelle, Lemoine, Jean Frantz, Candrinho, Baltazar, Colborn, James, Dimbu, Rafael, Fortes, Filomeno, Udhayakumar, Venkatachalam, Barnwell, John
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.02.2017; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Analysis; Angola - epidemiology; Antigens; Antigens, Protozoan - analysis; Biology and Life Sciences; Care and treatment; Child; Child, Preschool; Cross-Sectional Studies; Diagnosis; Diagnostic systems; Diagnostic tests; Diagnostic Tests, Routine - methods; Disease control; Disease prevention; Endemic Diseases; Erythrocytes; Haiti - epidemiology; Health aspects; Health Surveys - methods; Health Surveys - statistics & numerical data; Histidine; Host-Parasite Interactions; Humans; Immunoassay; Immunoassay - methods; Immunoassays; Immunoglobulins; Infant; Infections; Malaria; Malaria, Falciparum - diagnosis; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Medical diagnosis; Medicine and Health Sciences; Microscopy; Middle Aged; Mozambique - epidemiology; Parasites; Parasitic diseases; People and Places; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - metabolism; Plasmodium falciparum - physiology; Polyvinyl alcohol; Product testing; Proteins; Protozoan Proteins - analysis; Protozoan Proteins - genetics; Reproducibility of Results; Research and Analysis Methods; Sensitivity and Specificity; Vector-borne diseases; Womens health; Young Adult; Atlanta Georgia; United States > US; Angola; ASW, Caribbean Sea, Greater Antilles, Haiti; ASE, Angola; Mozambique
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0172139

Detection of histidine-rich protein 2 (HRP2) from the malaria parasite Plasmodium falciparum provides evidence for active or recent infection, and is utilized for both diagnostic and surveillance purposes, but current laboratory immunoassays for HRP2 are hindered by low sensitivities and high costs. Here we present a new HRP2 immunoassay based on antigen capture through a bead-based system capable of detecting HRP2 at sub-picogram levels. The assay is highly specific and cost-effective, allowing fast processing and screening of large numbers of samples. We utilized the assay to assess results of HRP2-based rapid diagnostic tests (RDTs) in different P. falciparum transmission settings, generating estimates for true performance in the field. Through this method of external validation, HRP2 RDTs were found to perform well in the high-endemic areas of Mozambique and Angola with 86.4% and 73.9% of persons with HRP2 in their blood testing positive by RDTs, respectively, and false-positive rates of 4.3% and 0.5%. However, in the low-endemic setting of Haiti, only 14.5% of persons found to be HRP2 positive by the bead assay were RDT positive. Additionally, 62.5% of Haitians showing a positive RDT test had no detectable HRP2 by the bead assay, likely indicating that these were false positive tests. In addition to RDT validation, HRP2 biomass was assessed for the populations in these different settings, and may provide an additional metric by which to estimate P. falciparum transmission intensity and measure the impact of interventions.