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Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests
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Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests
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Journal Article
Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests
2014
Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V
Subject
/ Adult
/ Aged
/ Antibodies, Protozoan - blood
/ Antigens
/ Antigens, Protozoan - analysis
/ Antigens, Protozoan - immunology
/ Biomedical and Life Sciences
/ Cambodia
/ Child
/ Diagnostic Tests, Routine - methods
/ Female
/ Humans
/ Malaria
/ Malaria, Falciparum - diagnosis
/ Malaria, Falciparum - immunology
/ Male
/ Nigeria
/ Protozoan Proteins - analysis
