Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests

Ho, Mei-Fong, Baker, Joanne, Lee, Nelson, Luchavez, Jennifer, Ariey, Frederic, Nhem, Sina, Oyibo, Wellington, Bell, David, Gonzalez, Iveth, Chiodini, Peter, Gatton, Michelle L., Cheng, Qin, & McCarthy, James S. (2014) Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests. Malaria Journal, 13, p. 480.

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Background Rapid diagnostic tests (RDTs) for detection of Plasmodium falciparum infection that target P. falciparum histidine-rich protein 2 (PfHRP2), a protein that circulates in the blood of patients infected with this species of malaria, are widely used to guide case management. Understanding determinants of PfHRP2 availability in circulation is therefore essential to understanding the performance of PfHRP2-detecting RDTs.

Methods The possibility that pre-formed host anti-PfHRP2 antibodies may block target antigen detection, thereby causing false negative test results was investigated in this study.

Results Anti-PfHRP2 antibodies were detected in 19/75 (25%) of plasma samples collected from patients with acute malaria from Cambodia, Nigeria and the Philippines, as well as in 3/28 (10.7%) asymptomatic Solomon Islands residents. Pre-incubation of plasma samples from subjects with high-titre anti-PfHRP2 antibodies with soluble PfHRP2 blocked the detection of the target antigen on two of the three brands of RDTs tested, leading to false negative results. Pre-incubation of the plasma with intact parasitized erythrocytes resulted in a reduction of band intensity at the highest parasite density, and a reduction of lower detection threshold by ten-fold on all three brands of RDTs tested.

Conclusions These observations indicate possible reduced sensitivity for diagnosis of P. falciparum malaria using PfHRP2-detecting RDTs among people with high levels of specific antibodies and low density infection, as well as possible interference with tests configured to detect soluble PfHRP2 in saliva or urine samples. Further investigations are required to assess the impact of pre-formed anti-PfHRP2 antibodies on RDT performance in different transmission settings.

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ID Code: 79463
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Plasmodium falciparum, rapid diagnostic test, histidine-rich protein 2, antibodies
DOI: 10.1186/1475-2875-13-480
ISSN: 1475-2875
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Infectious Agents (060502)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL MICROBIOLOGY (110800) > Medical Parasitology (110803)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PUBLIC HEALTH AND HEALTH SERVICES (111700) > Public Health and Health Services not elsewhere classified (111799)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Schools > School of Public Health & Social Work
Copyright Owner: Copyright 2014 Ho et al.
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Deposited On: 14 Dec 2014 22:58
Last Modified: 15 Dec 2014 21:55

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