Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests
Identifieur interne : 003B38 ( Main/Exploration ); précédent : 003B37; suivant : 003B39Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests
Auteurs : Mei-Fong Ho [Australie] ; Joanne Baker [Australie] ; Nelson Lee [Australie] ; Jennifer Luchavez ; Frédéric Ariey [Cambodge, France] ; Sina Nhem [Cambodge] ; Wellington Oyibo [Nigeria] ; David Bell [Suisse, États-Unis] ; Iveth González [Suisse] ; Peter Chiodini [Royaume-Uni] ; Michelle L. Gatton [Australie] ; Qin Cheng [Australie] ; James S. Mccarthy [Australie]Source :
- Malaria Journal [ 1475-2875 ] ; 2014.
Abstract
Rapid diagnostic tests (RDTs) for detection of
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.
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.
These observations indicate possible reduced sensitivity for diagnosis of
The online version of this article (doi:10.1186/1475-2875-13-480) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/1475-2875-13-480
PubMed: 25481825
PubMed Central: 4295572
Affiliations:
- Australie, Cambodge, France, Nigeria, Royaume-Uni, Suisse, États-Unis
- Angleterre, Grand Londres, Washington (État), Île-de-France
- Londres, Paris
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Le document en format XML
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histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests</title>
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histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests</title>
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<author><name sortKey="Nhem, Sina" sort="Nhem, Sina" uniqKey="Nhem S" first="Sina" last="Nhem">Sina Nhem</name>
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<country xml:lang="fr">Cambodge</country>
<wicri:regionArea>Pasteur Institute of Cambodia, Phnom Penh</wicri:regionArea>
<wicri:noRegion>Phnom Penh</wicri:noRegion>
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<author><name sortKey="Oyibo, Wellington" sort="Oyibo, Wellington" uniqKey="Oyibo W" first="Wellington" last="Oyibo">Wellington Oyibo</name>
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<country xml:lang="fr">Nigeria</country>
<wicri:regionArea>College of Medicine, University of Lagos, Odoaraba, Lagos</wicri:regionArea>
<wicri:noRegion>Lagos</wicri:noRegion>
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<author><name sortKey="Bell, David" sort="Bell, David" uniqKey="Bell D" first="David" last="Bell">David Bell</name>
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<author><name sortKey="Gonzalez, Iveth" sort="Gonzalez, Iveth" uniqKey="Gonzalez I" first="Iveth" last="González">Iveth González</name>
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<author><name sortKey="Chiodini, Peter" sort="Chiodini, Peter" uniqKey="Chiodini P" first="Peter" last="Chiodini">Peter Chiodini</name>
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<placeName><settlement type="city">Londres</settlement>
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<region type="région" nuts="1">Grand Londres</region>
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<author><name sortKey="Gatton, Michelle L" sort="Gatton, Michelle L" uniqKey="Gatton M" first="Michelle L" last="Gatton">Michelle L. Gatton</name>
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<country xml:lang="fr">Australie</country>
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<wicri:noRegion>Brisbane</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="Aff11">QUT University, Kelvin Grove, Brisbane, Australia</nlm:aff>
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<wicri:regionArea>QUT University, Kelvin Grove, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
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<author><name sortKey="Cheng, Qin" sort="Cheng, Qin" uniqKey="Cheng Q" first="Qin" last="Cheng">Qin Cheng</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>QIMR Berghofer Medical Research Institute, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<wicri:noRegion>Brisbane</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="Aff3">School of Population Health, University of Queensland, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Population Health, University of Queensland, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
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<author><name sortKey="Mccarthy, James S" sort="Mccarthy, James S" uniqKey="Mccarthy J" first="James S" last="Mccarthy">James S. Mccarthy</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">QIMR Berghofer Medical Research Institute, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>QIMR Berghofer Medical Research Institute, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="Aff3">School of Population Health, University of Queensland, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<wicri:noRegion>Brisbane</wicri:noRegion>
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<series><title level="j">Malaria Journal</title>
<idno type="eISSN">1475-2875</idno>
<imprint><date when="2014">2014</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Rapid diagnostic tests (RDTs) for detection of <italic>Plasmodium falciparum</italic>
infection that target <italic>P. falciparum</italic>
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.</p>
</sec>
<sec><title>Methods</title>
<p>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.</p>
</sec>
<sec><title>Results</title>
<p>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.</p>
</sec>
<sec><title>Conclusions</title>
<p>These observations indicate possible reduced sensitivity for diagnosis of <italic>P. falciparum</italic>
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.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/1475-2875-13-480) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<name sortKey="Cheng, Qin" sort="Cheng, Qin" uniqKey="Cheng Q" first="Qin" last="Cheng">Qin Cheng</name>
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<name sortKey="Gatton, Michelle L" sort="Gatton, Michelle L" uniqKey="Gatton M" first="Michelle L" last="Gatton">Michelle L. Gatton</name>
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<country name="France"><region name="Île-de-France"><name sortKey="Ariey, Frederic" sort="Ariey, Frederic" uniqKey="Ariey F" first="Frédéric" last="Ariey">Frédéric Ariey</name>
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<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Chiodini, Peter" sort="Chiodini, Peter" uniqKey="Chiodini P" first="Peter" last="Chiodini">Peter Chiodini</name>
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