Measuring the Plasmodium falciparum HRP2 protein in blood from artesunate-treated malaria patients predicts post-artesunate delayed hemolysis.
Identifieur interne : 000820 ( Main/Exploration ); précédent : 000819; suivant : 000821Measuring the Plasmodium falciparum HRP2 protein in blood from artesunate-treated malaria patients predicts post-artesunate delayed hemolysis.
Auteurs : Papa Alioune Ndour [France] ; Sébastien Larréché [France] ; Oussama Mouri [France] ; Nicolas Argy [France] ; Frédérick Gay [France] ; Camille Roussel [France] ; Stéphane Jauréguiberry [France] ; Claire Perillaud [France] ; Dominique Langui [France] ; Sylvestre Biligui [France] ; Nathalie Chartrel [France] ; Audrey Mérens [France] ; Eric Kendjo [France] ; Aniruddha Ghose [Bangladesh] ; Md Mahtab Uddin Hassan [Bangladesh] ; Md Amir Hossain [Bangladesh] ; Hugh W F. Kingston [Thaïlande] ; Katherine Plewes [Thaïlande] ; Arjen M. Dondorp [Thaïlande] ; Martin Danis [France] ; Sandrine Houzé [France] ; Serge Bonnefoy [France] ; Marc Thellier [France] ; Charles J. Woodrow [Thaïlande] ; Pierre A. Buffet [France]Source :
- Science translational medicine [ 1946-6242 ] ; 2017.
Abstract
Artesunate, the recommended drug for severe malaria, rapidly clears the malaria parasite from infected patients but frequently induces anemia-called post-artesunate delayed hemolysis (PADH)-for which a simple predictive test is urgently needed. The underlying event in PADH is the expulsion of artesunate-exposed parasites from their host erythrocytes by pitting. We show that the histidine-rich protein 2 (HRP2) of the malaria parasite Plasmodium falciparum persists in the circulation of artesunate-treated malaria patients in Bangladesh and in French travelers who became infected with malaria in Africa. HRP2 persisted in whole blood (not plasma) of artesunate-treated patients with malaria at higher levels compared to quinine-treated patients. Using an optimized membrane permeabilization method, HRP2 was observed by immunofluorescence, Western blotting, and electron microscopy to persist in once-infected red blood cells from artesunate-treated malaria patients. HRP2 was deposited at the membrane of once-infected red blood cells in a pattern similar to that for ring erythrocyte surface antigen (RESA), a parasite invasion marker. On the basis of these observations, we developed a semiquantitative titration method using a widely available HRP2-based rapid diagnostic dipstick test. Positivity on this test using a 1:500 dilution of whole blood from artesunate-treated patients with malaria collected shortly after parasite clearance predicted subsequent PADH with 89% sensitivity and 73% specificity. These results suggest that adapting an existing HRP2-based rapid diagnostic dipstick test may enable prediction of PADH several days before it occurs in artesunate-treated patients with malaria.
DOI: 10.1126/scitranslmed.aaf9377
PubMed: 28679662
Affiliations:
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<author><name sortKey="Roussel, Camille" sort="Roussel, Camille" uniqKey="Roussel C" first="Camille" last="Roussel">Camille Roussel</name>
<affiliation wicri:level="1"><nlm:affiliation>Institut National de la Transfusion Sanguine, Université Paris Descartes/INSERM UMR_S 1134, 6 rue Alexandre Cabanel, 75015 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Transfusion Sanguine, Université Paris Descartes/INSERM UMR_S 1134, 6 rue Alexandre Cabanel, 75015 Paris</wicri:regionArea>
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</author>
<author><name sortKey="Jaureguiberry, Stephane" sort="Jaureguiberry, Stephane" uniqKey="Jaureguiberry S" first="Stéphane" last="Jauréguiberry">Stéphane Jauréguiberry</name>
<affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Perillaud, Claire" sort="Perillaud, Claire" uniqKey="Perillaud C" first="Claire" last="Perillaud">Claire Perillaud</name>
<affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Langui, Dominique" sort="Langui, Dominique" uniqKey="Langui D" first="Dominique" last="Langui">Dominique Langui</name>
<affiliation wicri:level="4"><nlm:affiliation>Université Pierre et Marie Curie, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Pierre et Marie Curie, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
</affiliation>
</author>
<author><name sortKey="Biligui, Sylvestre" sort="Biligui, Sylvestre" uniqKey="Biligui S" first="Sylvestre" last="Biligui">Sylvestre Biligui</name>
<affiliation wicri:level="4"><nlm:affiliation>Université Pierre et Marie Curie, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Pierre et Marie Curie, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
</affiliation>
</author>
<author><name sortKey="Chartrel, Nathalie" sort="Chartrel, Nathalie" uniqKey="Chartrel N" first="Nathalie" last="Chartrel">Nathalie Chartrel</name>
<affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Merens, Audrey" sort="Merens, Audrey" uniqKey="Merens A" first="Audrey" last="Mérens">Audrey Mérens</name>
<affiliation wicri:level="3"><nlm:affiliation>Département de Biologie Médicale, Hôpital d'Instruction Des Armées Bégin, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Département de Biologie Médicale, Hôpital d'Instruction Des Armées Bégin, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kendjo, Eric" sort="Kendjo, Eric" uniqKey="Kendjo E" first="Eric" last="Kendjo">Eric Kendjo</name>
<affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ghose, Aniruddha" sort="Ghose, Aniruddha" uniqKey="Ghose A" first="Aniruddha" last="Ghose">Aniruddha Ghose</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Chittagong Medical College Hospital, Chittagong, Bangladesh.</nlm:affiliation>
<country xml:lang="fr">Bangladesh</country>
<wicri:regionArea>Department of Medicine, Chittagong Medical College Hospital, Chittagong</wicri:regionArea>
<wicri:noRegion>Chittagong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hassan, Md Mahtab Uddin" sort="Hassan, Md Mahtab Uddin" uniqKey="Hassan M" first="Md Mahtab Uddin" last="Hassan">Md Mahtab Uddin Hassan</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Chittagong Medical College Hospital, Chittagong, Bangladesh.</nlm:affiliation>
<country xml:lang="fr">Bangladesh</country>
<wicri:regionArea>Department of Medicine, Chittagong Medical College Hospital, Chittagong</wicri:regionArea>
<wicri:noRegion>Chittagong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hossain, Md Amir" sort="Hossain, Md Amir" uniqKey="Hossain M" first="Md Amir" last="Hossain">Md Amir Hossain</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Chittagong Medical College Hospital, Chittagong, Bangladesh.</nlm:affiliation>
<country xml:lang="fr">Bangladesh</country>
<wicri:regionArea>Department of Medicine, Chittagong Medical College Hospital, Chittagong</wicri:regionArea>
<wicri:noRegion>Chittagong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kingston, Hugh W F" sort="Kingston, Hugh W F" uniqKey="Kingston H" first="Hugh W F" last="Kingston">Hugh W F. Kingston</name>
<affiliation wicri:level="1"><nlm:affiliation>Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Plewes, Katherine" sort="Plewes, Katherine" uniqKey="Plewes K" first="Katherine" last="Plewes">Katherine Plewes</name>
<affiliation wicri:level="1"><nlm:affiliation>Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dondorp, Arjen M" sort="Dondorp, Arjen M" uniqKey="Dondorp A" first="Arjen M" last="Dondorp">Arjen M. Dondorp</name>
<affiliation wicri:level="1"><nlm:affiliation>Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Danis, Martin" sort="Danis, Martin" uniqKey="Danis M" first="Martin" last="Danis">Martin Danis</name>
<affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Houze, Sandrine" sort="Houze, Sandrine" uniqKey="Houze S" first="Sandrine" last="Houzé">Sandrine Houzé</name>
<affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Assistance Publique-Hôpitaux de Paris, Centre National de Référence du Paludisme, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bonnefoy, Serge" sort="Bonnefoy, Serge" uniqKey="Bonnefoy S" first="Serge" last="Bonnefoy">Serge Bonnefoy</name>
<affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Thellier, Marc" sort="Thellier, Marc" uniqKey="Thellier M" first="Marc" last="Thellier">Marc Thellier</name>
<affiliation wicri:level="4"><nlm:affiliation>Université Pierre et Marie Curie, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Pierre et Marie Curie, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
</affiliation>
</author>
<author><name sortKey="Woodrow, Charles J" sort="Woodrow, Charles J" uniqKey="Woodrow C" first="Charles J" last="Woodrow">Charles J. Woodrow</name>
<affiliation wicri:level="1"><nlm:affiliation>Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Buffet, Pierre A" sort="Buffet, Pierre A" uniqKey="Buffet P" first="Pierre A" last="Buffet">Pierre A. Buffet</name>
<affiliation wicri:level="1"><nlm:affiliation>Institut National de la Transfusion Sanguine, Université Paris Descartes/INSERM UMR_S 1134, 6 rue Alexandre Cabanel, 75015 Paris, France. pabuffet@gmail.com ndourmail@yahoo.fr.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Transfusion Sanguine, Université Paris Descartes/INSERM UMR_S 1134, 6 rue Alexandre Cabanel, 75015 Paris</wicri:regionArea>
<wicri:noRegion>75015 Paris</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Science translational medicine</title>
<idno type="eISSN">1946-6242</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
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<front><div type="abstract" xml:lang="en">Artesunate, the recommended drug for severe malaria, rapidly clears the malaria parasite from infected patients but frequently induces anemia-called post-artesunate delayed hemolysis (PADH)-for which a simple predictive test is urgently needed. The underlying event in PADH is the expulsion of artesunate-exposed parasites from their host erythrocytes by pitting. We show that the histidine-rich protein 2 (HRP2) of the malaria parasite Plasmodium falciparum persists in the circulation of artesunate-treated malaria patients in Bangladesh and in French travelers who became infected with malaria in Africa. HRP2 persisted in whole blood (not plasma) of artesunate-treated patients with malaria at higher levels compared to quinine-treated patients. Using an optimized membrane permeabilization method, HRP2 was observed by immunofluorescence, Western blotting, and electron microscopy to persist in once-infected red blood cells from artesunate-treated malaria patients. HRP2 was deposited at the membrane of once-infected red blood cells in a pattern similar to that for ring erythrocyte surface antigen (RESA), a parasite invasion marker. On the basis of these observations, we developed a semiquantitative titration method using a widely available HRP2-based rapid diagnostic dipstick test. Positivity on this test using a 1:500 dilution of whole blood from artesunate-treated patients with malaria collected shortly after parasite clearance predicted subsequent PADH with 89% sensitivity and 73% specificity. These results suggest that adapting an existing HRP2-based rapid diagnostic dipstick test may enable prediction of PADH several days before it occurs in artesunate-treated patients with malaria.</div>
</front>
</TEI>
<affiliations><list><country><li>Bangladesh</li>
<li>France</li>
<li>Thaïlande</li>
</country>
<region><li>Île-de-France</li>
</region>
<settlement><li>Paris</li>
</settlement>
<orgName><li>Université Pierre-et-Marie-Curie</li>
</orgName>
</list>
<tree><country name="France"><region name="Île-de-France"><name sortKey="Ndour, Papa Alioune" sort="Ndour, Papa Alioune" uniqKey="Ndour P" first="Papa Alioune" last="Ndour">Papa Alioune Ndour</name>
</region>
<name sortKey="Argy, Nicolas" sort="Argy, Nicolas" uniqKey="Argy N" first="Nicolas" last="Argy">Nicolas Argy</name>
<name sortKey="Biligui, Sylvestre" sort="Biligui, Sylvestre" uniqKey="Biligui S" first="Sylvestre" last="Biligui">Sylvestre Biligui</name>
<name sortKey="Bonnefoy, Serge" sort="Bonnefoy, Serge" uniqKey="Bonnefoy S" first="Serge" last="Bonnefoy">Serge Bonnefoy</name>
<name sortKey="Buffet, Pierre A" sort="Buffet, Pierre A" uniqKey="Buffet P" first="Pierre A" last="Buffet">Pierre A. Buffet</name>
<name sortKey="Chartrel, Nathalie" sort="Chartrel, Nathalie" uniqKey="Chartrel N" first="Nathalie" last="Chartrel">Nathalie Chartrel</name>
<name sortKey="Danis, Martin" sort="Danis, Martin" uniqKey="Danis M" first="Martin" last="Danis">Martin Danis</name>
<name sortKey="Gay, Frederick" sort="Gay, Frederick" uniqKey="Gay F" first="Frédérick" last="Gay">Frédérick Gay</name>
<name sortKey="Houze, Sandrine" sort="Houze, Sandrine" uniqKey="Houze S" first="Sandrine" last="Houzé">Sandrine Houzé</name>
<name sortKey="Jaureguiberry, Stephane" sort="Jaureguiberry, Stephane" uniqKey="Jaureguiberry S" first="Stéphane" last="Jauréguiberry">Stéphane Jauréguiberry</name>
<name sortKey="Kendjo, Eric" sort="Kendjo, Eric" uniqKey="Kendjo E" first="Eric" last="Kendjo">Eric Kendjo</name>
<name sortKey="Langui, Dominique" sort="Langui, Dominique" uniqKey="Langui D" first="Dominique" last="Langui">Dominique Langui</name>
<name sortKey="Larreche, Sebastien" sort="Larreche, Sebastien" uniqKey="Larreche S" first="Sébastien" last="Larréché">Sébastien Larréché</name>
<name sortKey="Merens, Audrey" sort="Merens, Audrey" uniqKey="Merens A" first="Audrey" last="Mérens">Audrey Mérens</name>
<name sortKey="Mouri, Oussama" sort="Mouri, Oussama" uniqKey="Mouri O" first="Oussama" last="Mouri">Oussama Mouri</name>
<name sortKey="Perillaud, Claire" sort="Perillaud, Claire" uniqKey="Perillaud C" first="Claire" last="Perillaud">Claire Perillaud</name>
<name sortKey="Roussel, Camille" sort="Roussel, Camille" uniqKey="Roussel C" first="Camille" last="Roussel">Camille Roussel</name>
<name sortKey="Thellier, Marc" sort="Thellier, Marc" uniqKey="Thellier M" first="Marc" last="Thellier">Marc Thellier</name>
</country>
<country name="Bangladesh"><noRegion><name sortKey="Ghose, Aniruddha" sort="Ghose, Aniruddha" uniqKey="Ghose A" first="Aniruddha" last="Ghose">Aniruddha Ghose</name>
</noRegion>
<name sortKey="Hassan, Md Mahtab Uddin" sort="Hassan, Md Mahtab Uddin" uniqKey="Hassan M" first="Md Mahtab Uddin" last="Hassan">Md Mahtab Uddin Hassan</name>
<name sortKey="Hossain, Md Amir" sort="Hossain, Md Amir" uniqKey="Hossain M" first="Md Amir" last="Hossain">Md Amir Hossain</name>
</country>
<country name="Thaïlande"><noRegion><name sortKey="Kingston, Hugh W F" sort="Kingston, Hugh W F" uniqKey="Kingston H" first="Hugh W F" last="Kingston">Hugh W F. Kingston</name>
</noRegion>
<name sortKey="Dondorp, Arjen M" sort="Dondorp, Arjen M" uniqKey="Dondorp A" first="Arjen M" last="Dondorp">Arjen M. Dondorp</name>
<name sortKey="Plewes, Katherine" sort="Plewes, Katherine" uniqKey="Plewes K" first="Katherine" last="Plewes">Katherine Plewes</name>
<name sortKey="Woodrow, Charles J" sort="Woodrow, Charles J" uniqKey="Woodrow C" first="Charles J" last="Woodrow">Charles J. Woodrow</name>
</country>
</tree>
</affiliations>
</record>
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