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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 : 003B39

Circulating 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 :

RBID : PMC:4295572

Abstract

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.

Electronic supplementary material

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:


Links toward previous steps (curation, corpus...)


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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<title xml:lang="en" level="a" type="main">Circulating antibodies against
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histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests</title>
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<name sortKey="Luchavez, Jennifer" sort="Luchavez, Jennifer" uniqKey="Luchavez J" first="Jennifer" last="Luchavez">Jennifer Luchavez</name>
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<wicri:noCountry code="subfield">The Philippines</wicri:noCountry>
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<name sortKey="Ariey, Frederic" sort="Ariey, Frederic" uniqKey="Ariey F" first="Frédéric" last="Ariey">Frédéric Ariey</name>
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<nlm:aff id="Aff5">Pasteur Institute of Cambodia, Phnom Penh, Cambodia</nlm:aff>
<country xml:lang="fr">Cambodge</country>
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<wicri:noRegion>Phnom Penh</wicri:noRegion>
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<nlm:aff id="Aff9">6GGIV Unit, Parasitology and Mycology Department, Institute Pasteur, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
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<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<name sortKey="Nhem, Sina" sort="Nhem, Sina" uniqKey="Nhem S" first="Sina" last="Nhem">Sina Nhem</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff5">Pasteur Institute of Cambodia, Phnom Penh, Cambodia</nlm:aff>
<country xml:lang="fr">Cambodge</country>
<wicri:regionArea>Pasteur Institute of Cambodia, Phnom Penh</wicri:regionArea>
<wicri:noRegion>Phnom Penh</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Oyibo, Wellington" sort="Oyibo, Wellington" uniqKey="Oyibo W" first="Wellington" last="Oyibo">Wellington Oyibo</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff6">College of Medicine, University of Lagos, Odoaraba, Lagos, Nigeria</nlm:aff>
<country xml:lang="fr">Nigeria</country>
<wicri:regionArea>College of Medicine, University of Lagos, Odoaraba, Lagos</wicri:regionArea>
<wicri:noRegion>Lagos</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Bell, David" sort="Bell, David" uniqKey="Bell D" first="David" last="Bell">David Bell</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff7">Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Foundation for Innovative New Diagnostics (FIND), Geneva</wicri:regionArea>
<wicri:noRegion>Geneva</wicri:noRegion>
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<nlm:aff id="Aff10">Global Good Fund/Intellectual Ventures Laboratory, Bellevue, WA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Global Good Fund/Intellectual Ventures Laboratory, Bellevue</wicri:cityArea>
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<name sortKey="Gonzalez, Iveth" sort="Gonzalez, Iveth" uniqKey="Gonzalez I" first="Iveth" last="González">Iveth González</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff7">Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Foundation for Innovative New Diagnostics (FIND), Geneva</wicri:regionArea>
<wicri:noRegion>Geneva</wicri:noRegion>
</affiliation>
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<name sortKey="Chiodini, Peter" sort="Chiodini, Peter" uniqKey="Chiodini P" first="Peter" last="Chiodini">Peter Chiodini</name>
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<nlm:aff id="Aff8">Hospital for Tropical Diseases, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Hospital for Tropical Diseases, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
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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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<nlm:aff id="Aff1">QIMR Berghofer Medical Research Institute, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<wicri:noRegion>Brisbane</wicri:noRegion>
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<nlm:aff id="Aff11">QUT University, Kelvin Grove, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>QUT University, Kelvin Grove, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
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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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<nlm:aff id="Aff1">QIMR Berghofer Medical Research Institute, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<wicri:noRegion>Brisbane</wicri:noRegion>
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<nlm:aff id="Aff2">Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
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<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>
</affiliation>
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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>
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<nlm:aff id="Aff1">QIMR Berghofer Medical Research Institute, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<wicri:noRegion>Brisbane</wicri:noRegion>
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<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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<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>
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<name sortKey="Gonzalez, Iveth" sort="Gonzalez, Iveth" uniqKey="Gonzalez I" first="Iveth" last="González">Iveth González</name>
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<country name="États-Unis">
<region name="Washington (État)">
<name sortKey="Bell, David" sort="Bell, David" uniqKey="Bell D" first="David" last="Bell">David Bell</name>
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</country>
<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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</record>

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