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2. Identification of complex Plasmodium falciparum genetic backgrounds circulating in Africa: a multicountry genomic epidemiology analysis

Author

Miotto, Olivo, Amambua-Ngwa, Alfred, Amenga-Etego, Lucas N, Abdel Hamid, Muzamil M, Adam, Ishag, Aninagyei, Enoch, Apinjoh, Tobias, Awandare, Gordon A, Bejon, Philip, Bertin, Gwladys I, Bouyou-Akotet, Marielle, Claessens, Antoine, Conway, David J, D'Alessandro, Umberto, Diakite, Mahamadou, Djimdé, Abdoulaye, Dondorp, Arjen M, Duffy, Patrick, Fairhurst, Rick M, Fanello, Caterina I, Ghansah, Anita, Ishengoma, Deus S, Lawniczak, Mara, Maïga-Ascofaré, Oumou, Auburn, Sarah, Rosanas-Urgell, Anna, Wasakul, Varanya, White, Nina F D, Harrott, Alexandria, Almagro-Garcia, Jacob, Pearson, Richard D, Goncalves, Sonia, Ariani, Cristina, Bozdech, Zbynek, Hamilton, William L, Simpson, Victoria, and Kwiatkowski, Dominic P

Published
2024
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6. A complexPlasmodium falciparumcryptotype circulating at low frequency across the African continent

Author

Miotto, Olivo, primary, Amambua-Ngwa, Alfred, additional, Amenga-Etego, Lucas, additional, Abdel Hamid, Muzamil M, additional, Adam, Ishag, additional, Aninagyei, Enoch, additional, Apinjoh, Tobias, additional, Awandare, Gordon A, additional, Bejon, Philip, additional, Bertin, Gwladys I, additional, Bouyou-Akotet, Marielle, additional, Claessens, Antoine, additional, Conway, David J, additional, D’Alessandro, Umberto, additional, Diakite, Mahamadou, additional, Djimdé, Abdoulaye, additional, Dondorp, Arjen M, additional, Duffy, Patrick, additional, Fairhurst, Rick M, additional, Fanello, Caterina I, additional, Ghansah, Anita, additional, Ishengoma, Deus, additional, Lawniczak, Mara, additional, Maïga-Ascofaré, Oumou, additional, Auburn, Sarah, additional, Rosanas-Urgell, Anna, additional, Wasakul, Varanya, additional, White, Nina FD, additional, Almagro-Garcia, Jacob, additional, Pearson, Richard D, additional, Goncalves, Sonia, additional, Ariani, Cristina, additional, Bozdech, Zbynek, additional, Hamilton, William, additional, Simpson, Victoria, additional, and Kwiatkowski, Dominic P, additional

Published
2024
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7. Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

Author

MalariaGEN, Abdel Hamid, Muzamil Mahdi, Abdelraheem, Mohamed Hassan, Acheampong, Desmond Omane, Ahouidi, Ambroise, Ali, Mozam, Almagro-Garcia, Jacob, Amambua-Ngwa, Alfred, Amaratunga, Chanaki, Amenga-Etego, Lucas, Andagalu, Ben, Anderson, Tim, Andrianaranjaka, Voahangy, Aniebo, Ifeyinwa, Aninagyei, Enoch, Ansah, Felix, Ansah, Patrick O, Apinjoh, Tobias, Arnaldo, Paulo, Ashley, Elizabeth, Auburn, Sarah, Awandare, Gordon A, Ba, Hampate, Baraka, Vito, Barry, Alyssa, Bejon, Philip, Bertin, Gwladys I, Boni, Maciej F, Borrmann, Steffen, Bousema, Teun, Bouyou-Akotet, Marielle, Branch, Oralee, Bull, Peter C, Cheah, Huch, Chindavongsa, Keobouphaphone, Chookajorn, Thanat, Chotivanich, Kesinee, Claessens, Antoine, Conway, David J, Corredor, Vladimir, Courtier, Erin, Craig, Alister, D'Alessandro, Umberto, Dama, Souleymane, Day, Nicholas, Denis, Brigitte, Dhorda, Mehul, Diakite, Mahamadou, Djimde, Abdoulaye, Dolecek, Christiane, Dondorp, Arjen, Doumbia, Seydou, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Echeverry, Diego F, Egwang, Thomas G, Enosse, Sonia Maria Mauricio, Erko, Berhanu, Fairhurst, Rick M, Faiz, Abdul, Fanello, Caterina A, Fleharty, Mark, Forbes, Matthew, Fukuda, Mark, Gamboa, Dionicia, Ghansah, Anita, Golassa, Lemu, Goncalves, Sonia, Harrison, GL Abby, Healy, Sara Anne, Hendry, Jason A, Hernandez-Koutoucheva, Anastasia, Hien, Tran Tinh, Hill, Catherine A, Hombhanje, Francis, Hott, Amanda, Htut, Ye, Hussein, Mazza, Imwong, Mallika, Ishengoma, Deus, Jackson, Scott A, Jacob, Chris G, Jeans, Julia, Johnson, Kimberly J, Kamaliddin, Claire, Kamau, Edwin, Keatley, Jon, Kochakarn, Theerarat, Konate, Drissa S, Konaté, Abibatou, Kone, Aminatou, Kwiatkowski, Dominic P, Kyaw, Myat P, Kyle, Dennis, Lawniczak, Mara, Lee, Samuel K, Lemnge, Martha, Lim, Pharath, Lon, Chanthap, Loua, Kovana M, Mandara, Celine I, Marfurt, Jutta, Marsh, Kevin, Maude, Richard James, Mayxay, Mayfong, Maïga-Ascofaré, Oumou, Miotto, Olivo, Mita, Toshihiro, Mobegi, Victor, Mohamed, Abdelrahim Osman, Mokuolu, Olugbenga A, Montgomery, Jaqui, Morang'a, Collins Misita, Mueller, Ivo, Murie, Kathryn, Newton, Paul N, Ngo Duc, Thang, Nguyen, Thuy, Nguyen, Thuy-Nhien, Nguyen Thi Kim, Tuyen, Nguyen Van, Hong, Noedl, Harald, Nosten, Francois, Noviyanti, Rintis, Ntui, Vincent Ntui-Njock, Nzila, Alexis, Ochola-Oyier, Lynette Isabella, Ocholla, Harold, Oduro, Abraham, Omedo, Irene, Onyamboko, Marie A, Ouedraogo, Jean-Bosco, Oyebola, Kolapo, Oyibo, Wellington Aghoghovwia, Pearson, Richard, Peshu, Norbert, Phyo, Aung P, Plowe, Christopher V, Price, Ric N, Pukrittayakamee, Sasithon, Quang, Huynh Hong, Randrianarivelojosia, Milijaona, Rayner, Julian C, Ringwald, Pascal, Rosanas-Urgell, Anna, Rovira-Vallbona, Eduard, Ruano-Rubio, Valentin, Ruiz, Lastenia, Saunders, David, Shayo, Alex, Siba, Peter, Simpson, Victoria J, Sissoko, Mahamadou S, Smith, Christen, Su, Xin-Zhuan, Sutherland, Colin, Takala-Harrison, Shannon, Talman, Arthur, Tavul, Livingstone, Thanh, Ngo Viet, Thathy, Vandana, Thu, Aung Myint, Toure, Mahamoudou, Tshefu, Antoinette, Verra, Federica, Vinetz, Joseph, Wellems, Thomas E, Wendler, Jason, White, Nicholas J, Whitton, Georgia, Yavo, William, Van Der Pluijm, Rob W, Amenga-Etego, Lucas [0000-0003-4468-0506], Anderson, Tim [0000-0002-0191-0204], Ansah, Patrick O [0000-0002-3214-5621], Ashley, Elizabeth [0000-0002-7620-4822], Ba, Hampate [0000-0002-9299-5775], Baraka, Vito [0000-0001-9694-9293], Bejon, Philip [0000-0002-2135-7549], Bertin, Gwladys I [0000-0002-2218-9591], Boni, Maciej F [0000-0002-0830-9630], Bousema, Teun [0000-0003-2666-094X], Chookajorn, Thanat [0000-0003-2876-6203], Claessens, Antoine [0000-0002-4277-0914], Conway, David J [0000-0002-8711-3037], Craig, Alister [0000-0003-0914-6164], D'Alessandro, Umberto [0000-0001-6341-5009], Day, Nicholas [0000-0003-2309-1171], Diakite, Mahamadou [0000-0002-4268-8857], Djimde, Abdoulaye [0000-0003-0062-2283], Dondorp, Arjen [0000-0001-5190-2395], Drakeley, Chris [0000-0003-4863-075X], Echeverry, Diego F [0000-0003-0301-4478], Erko, Berhanu [0000-0003-1685-752X], Faiz, Abdul [0000-0002-3460-7535], Fanello, Caterina A [0000-0003-1932-9562], Gamboa, Dionicia [0000-0002-1420-7729], Golassa, Lemu [0000-0002-1216-8711], Healy, Sara Anne [0000-0003-3078-6094], Ishengoma, Deus [0000-0003-2040-3416], Jackson, Scott A [0000-0002-3172-1607], Kamaliddin, Claire [0000-0001-8198-6235], Kamau, Edwin [0000-0002-5761-7883], Konate, Drissa S [0000-0002-4177-9642], Kwiatkowski, Dominic P [0000-0002-5023-0176], Kyle, Dennis [0000-0002-0238-965X], Lawniczak, Mara [0000-0002-3006-2080], Loua, Kovana M [0000-0003-0571-0944], Marsh, Kevin [0000-0001-8377-5466], Mayxay, Mayfong [0000-0002-6056-4516], Miotto, Olivo [0000-0001-8060-6771], Mita, Toshihiro [0000-0001-8180-2344], Mobegi, Victor [0000-0002-1962-5583], Morang'a, Collins Misita [0000-0002-6988-150X], Nguyen, Thuy-Nhien [0000-0002-4101-5706], Nosten, Francois [0000-0002-7951-0745], Ntui, Vincent Ntui-Njock [0000-0002-7532-9930], Oduro, Abraham [0000-0002-4191-7419], Onyamboko, Marie A [0000-0002-7501-5931], Ouedraogo, Jean-Bosco [0000-0003-0412-8733], Oyebola, Kolapo [0000-0002-1003-2570], Pearson, Richard [0000-0002-7386-3566], Phyo, Aung P [0000-0002-0383-9624], Price, Ric N [0000-0003-2000-2874], Rayner, Julian C [0000-0002-9835-1014], Rosanas-Urgell, Anna [0000-0002-0432-5203], Shayo, Alex [0000-0002-7099-8537], Su, Xin-Zhuan [0000-0003-3246-3248], Vinetz, Joseph [0000-0001-8344-2004], Wellems, Thomas E [0000-0003-3899-8454], and Apollo - University of Cambridge Repository

Subjects
data resource, plasmodium falciparum, genomics, malaria, genomic epidemiology
Abstract

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.

Published
2023

8. Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

Author

Abdel Hamid, Muzamil Mahdi, Abdelraheem, Mohamed Hassan, Acheampong, Desmond Omane, Ahouidi, Ambroise, Ali, Mozam, Almagro-Garcia, Jacob, Amambua-Ngwa, Alfred, Amaratunga, Chanaki, Amenga-Etego, Lucas, Andagalu, Ben, Anderson, Tim, Andrianaranjaka, Voahangy, Aniebo, Ifeyinwa, Aninagyei, Enoch, Ansah, Felix, Ansah, Patrick, Apinjoh, Tobias, Arnaldo, Paulo, Ashley, Elizabeth, Auburn, Sarah, Awandare, Gordon, Ba, Hampate, Baraka, Vito, Barry, Alyssa, Bejon, Philip, Bertin, Gwladys, Boni, Maciej, Borrmann, Steffen, Bousema, Teun, Bouyou-Akotet, Marielle, Branch, Oralee, Bull, Peter, Cheah, Huch, Chindavongsa, Keobouphaphone, Chookajorn, Thanat, Chotivanich, Kesinee, Claessens, Antoine, Conway, David, Corredor, Vladimir, Courtier, Erin, Craig, Alister, d'Alessandro, Umberto, Dama, Souleymane, Day, Nicholas, Denis, Brigitte, Dhorda, Mehul, Diakite, Mahamadou, Djimde, Abdoulaye, Dolecek, Christiane, Dondorp, Arjen, Doumbia, Seydou, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Echeverry, Diego, Egwang, Thomas, Enosse, Sonia Maria Mauricio, Erko, Berhanu, Fairhurst, Rick, Faiz, Abdul, Fanello, Caterina, Fleharty, Mark, Forbes, Matthew, Fukuda, Mark, Gamboa, Dionicia, Ghansah, Anita, Golassa, Lemu, Goncalves, Sonia, Harrison, G, Healy, Sara Anne, Hendry, Jason, Hernandez-Koutoucheva, Anastasia, Hien, Tran Tinh, Hill, Catherine, Hombhanje, Francis, Hott, Amanda, Htut, Ye, Hussein, Mazza, Imwong, Mallika, Ishengoma, Deus, Jackson, Scott, Jacob, Chris, Jeans, Julia, Johnson, Kimberly, Kamaliddin, Claire, Kamau, Edwin, Keatley, Jon, Kochakarn, Theerarat, Konate, Drissa, Konaté, Abibatou, Kone, Aminatou, Kwiatkowski, Dominic, Kyaw, Myat, Kyle, Dennis, Lawniczak, Mara, Lee, Samuel, Lemnge, Martha, Lim, Pharath, Lon, Chanthap, Loua, Kovana, Mandara, Celine, Marfurt, Jutta, Marsh, Kevin, Maude, Richard James, Mayxay, Mayfong, Maïga-Ascofaré, Oumou, Miotto, Olivo, Mita, Toshihiro, Mobegi, Victor, Mohamed, Abdelrahim Osman, Mokuolu, Olugbenga, Montgomery, Jaqui, Morang'A, Collins Misita, Mueller, Ivo, Murie, Kathryn, Newton, Paul, Ngo Duc, Thang, Nguyen, Thuy, Nguyen, Thuy-Nhien, Nguyen Thi Kim, Tuyen, Nguyen Van, Hong, Noedl, Harald, Nosten, François, Noviyanti, Rintis, Ntui, Vincent Ntui-Njock, Nzila, Alexis, Ochola-Oyier, Lynette Isabella, Ocholla, Harold, Oduro, Abraham, Omedo, Irene, Onyamboko, Marie, Ouedraogo, Jean-Bosco, Oyebola, Kolapo, Oyibo, Wellington Aghoghovwia, Pearson, Richard, Peshu, Norbert, Phyo, Aung, Plowe, Christopher, Price, Ric, Pukrittayakamee, Sasithon, Quang, Huynh Hong, Randrianarivelojosia, Milijaona, Rayner, Julian, Ringwald, Pascal, Rosanas-Urgell, Anna, Rovira-Vallbona, Eduard, Ruano-Rubio, Valentin, Ruiz, Lastenia, Saunders, David, Shayo, Alex, Siba, Peter, Simpson, Victoria, Sissoko, Mahamadou, Smith, Christen, Su, Xin-Zhuan, Sutherland, Colin, Takala-Harrison, Shannon, Talman, Arthur, Tavul, Livingstone, Thanh, Ngo Viet, Thathy, Vandana, Thu, Aung Myint, Toure, Mahamoudou, Tshefu, Antoinette, Verra, Federica, Vinetz, Joseph, Wellems, Thomas, Wendler, Jason, White, Nicholas, Whitton, Georgia, Yavo, William, van der Pluijm, Rob, MalariaGEN, University of Khartoum, University of Cape Coast [Ghana], Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), The Wellcome Trust Sanger Institute [Cambridge], London School of Hygiene and Tropical Medicine [Fajara, Gambia], London School of Hygiene and Tropical Medicine (LSHTM), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), West African Centre for Cell Biology of Infectious Pathogens [Legon, Ghana] (WACCBIP), University of Ghana, Navrongo Health Research Centre [Navrongo, Ghana] (NHRC), Kenya Medical Research Institute (KEMRI), Texas Biomedical Research Institute [San Antonio, TX], Université d'Antananarivo, University of Buéa, Instituto Nacional de Saude [Maputo, Mozambique] (INS), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Menzies School of Health Research [Australia], Charles Darwin University [Australia], Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Institut de Recherche pour le Développement (IRD), Laboratory of Pathogen and Host Immunity [Montpellier] (LPHI), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)

Subjects
data resource, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], plasmodium falciparum, genomics, malaria, Medicine (miscellaneous), genomic epidemiology, General Biochemistry, Genetics and Molecular Biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Contains fulltext : 291985.pdf (Publisher’s version ) (Open Access) We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.

Published
2023
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10. Elevated plasma IL-8 as a risk factor for mortality in children presenting with cerebral malaria (NeuroCM study)

Author

Royo, Jade, primary, Vianou, Bertin, additional, Accrombessi, Manfred, additional, Kinkpé, Elisée, additional, Ayédadjou, Linda, additional, Dossou-Dagba, Ida, additional, Ladipo, Yélé, additional, Alao, Maroufou Jules, additional, Bertin, Gwladys I, additional, Cot, Michel, additional, Boumediene, Farid, additional, Houzé, Sandrine, additional, Faucher, Jean-François, additional, Aubouy, Agnès, additional, and group, collaborators NeuroCM, additional

Published
2022
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13. Additional file 1 of Non-traumatic coma in young children in Benin: are viral and bacterial infections gaining ground on cerebral malaria?

Author

Brisset, Josselin, Angendu Baki, Karl, Watier, Laurence, Kinkp��, Elis��e, Bailly, Justine, Ay��dadjou, Linda, Alao, Maroufou Jules, Dossou-Dagba, Ida, Bertin, Gwladys I., Cot, Michel, Boum��di��ne, Farid, Ajzenberg, Daniel, Aubouy, Agn��s, Houz��, Sandrine, and Faucher, Jean-Fran��ois

Abstract

Additional file 1: Figure S1. Map of Benin with focus on Cotonou and the 2 study sites. Figure S2. Coma etiologies: graphical presentation.

Published
2022
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16. An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples

Author

Ahouidi, Ambroise, Ali, Mozam, Almagro-Garcia, Jacob, Amambua-Ngwa, Alfred, Amaratunga, Chanaki, Amato, Roberto, Amenga-Etego, Lucas, Andagalu, Ben, Anderson, Tim JC, Andrianaranjaka, Voahangy, Apinjoh, Tobias, Ariani, Cristina, Ashley, Elizabeth A, Auburn, Sarah, Awandare, Gordon, Ba, Hampdate, Baraka, Vito, Barry, Alyssa E, Bejon, Philip, Bertin, Gwladys I, Boni, Maciej F, Borrmann, Steffen, Bousema, Teun, Branch, Oralee, Bull, Peter C, Busby, George BJ, Chookajorn, Thanat, Chotivanich, Kesinee, Claessens, Antoine, Conway, David, Craig, Alister, D'Alessandro, Umberto, Dama, Souleymane, Day, Nicholas PJ, Denis, Brigitte, Diakite, Mahamadou, Djimdé, Abdoulaye, Dolecek, Christiane, Dondorp, Arjen M, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Echeverry, Diego F, Egwang, Thomas G, Erko, Berhanu, Fairhurst, Rick M, Faiz, Abdul, Fanello, Caterina A, Fukuda, Mark M, Gamboa, Dionica, Ghansah, Anita, Golassa, Lemu, Goncalves, Sonia, Hamilton, William L, Harrison, GL Abby, Hart, Lee, Henrichs, Christa, Hien, Tran Tinh, Hill, Catherine A, Hodgson, Abraham, Hubbart, Christina, Imwong, Mallika, Ishengoma, Deus S, Jackson, Scott A, Jacob, Chris G, Jeffery, Ben, Jeffreys, Anna E, Johnson, Kimberly J, Jyothi, Dushyanth, Kamaliddin, Claire, Kamau, Edwin, Kekre, Mihir, Kluczynski, Krzysztof, Kochakarn, Theerarat, Konaté, Abibatou, Kwiatkowski, Dominic P, Kyaw, Myat Phone, Lim, Pharath, Lon, Chanthap, Loua, Kovana M, Maïga-Ascofaré, Oumou, Malangone, Cinzia, Manske, Magnus, Marfurt, Jutta, Marsh, Kevin, Mayxay, Mayfong, Miles, Alistair, Miotto, Olivo, Mobegi, Victor, Mokuolu, Olugbenga A, Montgomery, Jacqui, Mueller, Ivo, Newton, Paul N, Nguyen, Thuy, Nguyen, Thuy-Nhien, Noedl, Harald, Nosten, Francois, Noviyanti, Rintis, Nzila, Alexis, Ochola-Oyier, Lynette I, Ahouidi, Ambroise, Ali, Mozam, Almagro-Garcia, Jacob, Amambua-Ngwa, Alfred, Amaratunga, Chanaki, Amato, Roberto, Amenga-Etego, Lucas, Andagalu, Ben, Anderson, Tim JC, Andrianaranjaka, Voahangy, Apinjoh, Tobias, Ariani, Cristina, Ashley, Elizabeth A, Auburn, Sarah, Awandare, Gordon, Ba, Hampdate, Baraka, Vito, Barry, Alyssa E, Bejon, Philip, Bertin, Gwladys I, Boni, Maciej F, Borrmann, Steffen, Bousema, Teun, Branch, Oralee, Bull, Peter C, Busby, George BJ, Chookajorn, Thanat, Chotivanich, Kesinee, Claessens, Antoine, Conway, David, Craig, Alister, D'Alessandro, Umberto, Dama, Souleymane, Day, Nicholas PJ, Denis, Brigitte, Diakite, Mahamadou, Djimdé, Abdoulaye, Dolecek, Christiane, Dondorp, Arjen M, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Echeverry, Diego F, Egwang, Thomas G, Erko, Berhanu, Fairhurst, Rick M, Faiz, Abdul, Fanello, Caterina A, Fukuda, Mark M, Gamboa, Dionica, Ghansah, Anita, Golassa, Lemu, Goncalves, Sonia, Hamilton, William L, Harrison, GL Abby, Hart, Lee, Henrichs, Christa, Hien, Tran Tinh, Hill, Catherine A, Hodgson, Abraham, Hubbart, Christina, Imwong, Mallika, Ishengoma, Deus S, Jackson, Scott A, Jacob, Chris G, Jeffery, Ben, Jeffreys, Anna E, Johnson, Kimberly J, Jyothi, Dushyanth, Kamaliddin, Claire, Kamau, Edwin, Kekre, Mihir, Kluczynski, Krzysztof, Kochakarn, Theerarat, Konaté, Abibatou, Kwiatkowski, Dominic P, Kyaw, Myat Phone, Lim, Pharath, Lon, Chanthap, Loua, Kovana M, Maïga-Ascofaré, Oumou, Malangone, Cinzia, Manske, Magnus, Marfurt, Jutta, Marsh, Kevin, Mayxay, Mayfong, Miles, Alistair, Miotto, Olivo, Mobegi, Victor, Mokuolu, Olugbenga A, Montgomery, Jacqui, Mueller, Ivo, Newton, Paul N, Nguyen, Thuy, Nguyen, Thuy-Nhien, Noedl, Harald, Nosten, Francois, Noviyanti, Rintis, Nzila, Alexis, and Ochola-Oyier, Lynette I

Abstract

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed.  Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Published
2021

17. Sulfadoxine/pyrimethamine intermittent preventive treatment for malaria during pregnancy

Author

Deloron, Philippe, Bertin, Gwladys, Briand, Valerie, Massougbodji, Achille, and Cot, Michel

Subjects
Medicine, Preventive, Pregnancy, Antimalarials, Infection -- Drug therapy -- Genetic aspects, Public health, Preventive health services, Malaria -- Drug therapy -- Genetic aspects, Pregnant women -- Drug therapy, Plasmodium falciparum, Dihydrofolate reductase, Health, World Health Organization
Abstract

Malaria during pregnancy is a major cause of anemia and maternal death and one of the main causes of low birthweight (1,2). Consequently, the World Health Organization (WHO) recommends protection [...]

Published
2010
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18. PfEMP1 A-type ICAM-1-binding domains are not associated with cerebral Malaria in Beninese children

Author

Joste, V., Guillochon, E., Fraering, Jeremy, Vianou, B., Watier, L., Guemouri, Sayeh, Cot, Michel, Houze, S., Aubouy, Agnès, Faucher, J. F., Argy, N., Bertin, Gwladys, and NeuroCM Study Group

Subjects
dual receptor binding, ICAM-1-binding motif, var genes, parasitic diseases, cytoadherence, cerebral malaria
Abstract

PfEMP1 is the major antigen involved in Plasmodium falciparum-infected erythrocyte sequestration in cerebrovascular endothelium. While some PfEMP1 domains have been associated with clinical phenotypes of malaria, formal associations between the expression of a specific domain and the adhesion properties of clinical isolates are limited. In this context, 73 cerebral malaria (CM) and 98 uncomplicated malaria (UM) Beninese children were recruited. We attempted to correlate the cytoadherence phenotype of Plasmodium falciparum isolates with the clinical presentation and the expression of specific PfEMP1 domains. Cytoadherence level on Hbec-5i and CHO-ICAM-1 cell lines and var genes expression were measured. We also investigated the prevalence of the ICAM-1-binding amino acid motif and dual receptor-binding domains, described as a potential determinant of cerebral malaria pathophysiology. We finally evaluated IgG levels against PfEMP1 recombinant domains (CIDR alpha 1.4, DBL beta 3, and CIDR alpha 1.4-DBL beta 3). CM isolates displayed higher cytoadherence levels on both cell lines, and we found a correlation between CIDR alpha 1.4 DBL beta 1/3 domain expression and CHO-ICAM-1 cytoadherence level. Endothelial protein C receptor (EPCR)-binding domains were overexpressed in CM isolates compared to UM whereas no difference was found in ICAM-1-binding DBL beta 1/3 domain expression. Surprisingly, both CM and UM isolates expressed ICAM-1-binding motif and dual receptor-binding domains. There was no difference in IgG response against DBL beta 3 between CM and UM isolates expressing ICAM-1-binding DB4 beta/3 domain. It raises questions about the role of this motif in CM pathophysiology, and further studies are needed, especially on the role of DBL beta 1/3 without the ICAM-1-binding motif. IMPORTANCE Cerebral malaria pathophysiology remains unknown despite extensive research. PfEMP1 proteins have been identified as the main Plasmodium antigen involved in cerebrovascular endothelium sequestration, but it is unclear which var gene domain is involved in Plasmodium cytoadhesion. EPCR binding is a major determinant of cerebral malaria whereas the ICAM-1-binding role is still questioned. Our study confirmed the EPCR-binding role in CM pathophysiology with a major overexpression of EPCR-binding domains in CM isolates. In contrast, ICAM-1-binding involvement appears less obvious with A-type ICAM-1-binding and dual receptor-binding domain expression in both CM and UM isolates. We did not find any variations in ICAM-1-binding motif sequences in CM compared to UM isolates. UM and CM patients infected with isolates expressing the ICAM-1-binding motif displayed similar IgG levels against DBL beta 3 recombinant protein. Our study raises interrogations about the role of these domains in CM physiopathology and questions their use in vaccine strategies against cerebral malaria.

Published
2020

20. Comprehensive Analysis of Transcript and Protein Relative Abundance During Blood Stages of Plasmodium falciparum Infection

Author

Kamaliddin, Claire, primary, Guillochon, Emilie, additional, Salnot, Virginie, additional, Rombaut, David, additional, Huguet, Stéphanie, additional, Guillonneau, François, additional, Houzé, Sandrine, additional, Cot, Michel, additional, Deloron, Philippe, additional, Argy, Nicolas, additional, and Bertin, Gwladys I., additional

Published
2021
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22. Identification of Plasmodium falciparum and host factors associated with cerebral malaria : description of the protocol for a prospective, case-control study in Benin (NeuroCM)

Author

Joste, V., Maurice, L., Bertin, Gwladys, Aubouy, Agnès, Boumediene, F., Houze, S., Ajzenberg, D., Argy, N., Massougbodji, A., Dossou-Dagba, I., Alao, M. J., Cot, Michel, Deloron, Philippe, Faucher, J. F., Guemouri, Sayeh (collab.), Royo, Jade (collab.), and NeuroCM Group

Subjects
parasitic diseases
Abstract

Introduction In 2016, an estimated 216 million cases and 445 000 deaths of malaria occurred worldwide, in 91 countries. In Benin, malaria causes 26.8% of consultation and hospitalisation motif in the general population and 20.9% in children under 5 years old. The goal of the NeuroCM project is to identify the causative factors of neuroinflammation in the context of cerebral malaria. There are currently very few systematic data from West Africa on the aetiologies and management of non-malarial non-traumatic coma in small children, and NeuroCM will help to fill this gap. We postulate that an accurate understanding of molecular and cellular mechanisms involved in neuroinflammation may help to define efficient strategies to prevent and manage cerebral malaria. Methods and analysis This is a prospective, case-control study comparing cerebral malaria to uncomplicated malaria and non-malarial non-traumatic coma. This study takes place in Benin, precisely in Cotonou for children with coma and in So-Ava district for children with uncomplicated malaria. We aim to include 300 children aged between 24 and 71 months and divided in three different clinical groups during 12 months (from December 2017 to November 2018) with a 21 to 28 days follow-up for coma. Study data, including clinical, biological and research results will be collected and managed using CSOnline-Ennov Clinical. Ethics and dissemination Ethics approval for the NeuroCM study has been obtained from Comite National d'Ethique pour la Recherche en sante of Benin (n degrees 67/ MS/DC/SGM/DRFMT/CNERS/SA; 10/17/2017). NeuroCM study has also been approved by Comite consultatif de deontologie et d'ethique of Institut de Recherche pour le Developpement (IRD; 10/24/2017). The study results will be disseminated through the direct consultations with the WHO's Multilateral Initiative on Malaria (TDR-MIM) and Roll Back Malaria programme, through scientific meetings and peer-reviewed publications in scientific or medical journals, and through guidelines and booklets.

Published
2019

26. From genomic to LC-MS/MS evidence: Analysis of PfEMP1 in Benin malaria cases

Author

Kamaliddin, Claire, primary, Rombaut, David, additional, Guillochon, Emilie, additional, Royo, Jade, additional, Ezinmegnon, Sem, additional, Agbota, Gino, additional, Huguet, Stéphanie, additional, Guemouri, Sayeh, additional, Peirera, Céline, additional, Coppée, Romain, additional, Broussard, Cédric, additional, Alao, Jules M., additional, Aubouy, Agnès, additional, Guillonneau, François, additional, Deloron, Philippe, additional, and Bertin, Gwladys I., additional

Published
2019
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27. Identification of Plasmodium falciparum and host factors associated with cerebral malaria: description of the protocol for a prospective, case-control study in Benin (NeuroCM)

Author

Joste, Valentin, primary, Maurice, Laurine, additional, Bertin, Gwladys I, additional, Aubouy, Agnès, additional, Boumédiène, Farid, additional, Houzé, Sandrine, additional, Ajzenberg, Daniel, additional, Argy, Nicolas, additional, Massougbodji, Achille, additional, Dossou-Dagba, Ida, additional, Alao, Maroufou Jules, additional, Cot, Michel, additional, Deloron, Philippe, additional, and Faucher, Jean-François, additional

Published
2019
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28. Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin

Author

Massougbodji Achille, Carrieu Ambre, Bonaventure Diana, Briand Valérie, Bertin Gwladys, Cot Michel, and Deloron Philippe

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The prevention of malaria faces with the repeated emergence of Plasmodium falciparum resistance to drugs, often involving point mutations of the target gene. In the pregnant woman, currently the WHO recommendation is the administration of an intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine. Sulphadoxine-pyrimethamine (SP) resistance has increased for several years in Africa, stressing the need for alternative molecules. In this context, the first randomized clinical trial comparing the efficacy of SP and mefloquine for IPTp has been conducted recently in Benin. Using samples from this trial, the current study evaluated and quantified the prevalence of mutations on the pfdhfr and pfdhps genes as well as the copy number of the pfmdr1 gene in parasites from P. falciparum-infected pregnant women before first and second IPTp administration, and at delivery. Methods PCR-restriction fragment length polymorphism of polymorphic codons of the pfdhfr gene (51, 59, 108, and 164) was performed. The identification of mutations in three codons of the pfdhps gene (436, 437 and 540) was achieved by PCR and sequencing. Copy number quantification for pfmdr1 gene was performed using real-time PCR. Results Results show a high prevalence rate of mutant parasites in women taking IPTp with sulphadoxine-pyrimethamine or mefloquine. The prevalence of triple and quadruple mutants was high before first drug regimen administration (79/93, 85%), and remained similar until delivery. Infection with mutant parasites was not correlated with low birth weight nor placental infection. In all samples, the copy number of pfmdr1 gene was equal to one. Conclusions The clinical trial comparing SP and mefloquine efficacy during IPTp showed SP remained efficacious in preventing low birth weight. The present study shows a high prevalence of triple and quadruple mutations implicated in SP resistance. Although the pfdhfr/pfdhps triple and quadruple mutations were frequent, there was no evidence of correlation between these genotypes and the lack of efficacy of SP in the context of IPTp. Nevertheless, it is now obvious that SP will soon be compromised in whole Africa. Molecular markers have been recommended to monitor SP efficacy for IPTp, but given the current prevalence of mutant parasites their usefulness is questionable.

Published
2011
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29. PFI1785w : a highly conserved protein associated with pregnancy associated malaria

Author

Kamaliddin, Claire, Salnot, Virginie, Leduc, Marjorie, Ezinmegnon, Sem, Broussard, Cédric, Fievet, Nadine, Deloron, Philippe, Guillonneau, François, and Bertin, Gwladys I.

Subjects
Proteomics, Plasmodium, lcsh:Medicine, Protein Structure Prediction, Biochemistry, Mass Spectrometry, Protein Structure, Secondary, Database and Informatics Methods, Pregnancy, Macromolecular Structure Analysis, Medicine and Health Sciences, Malaria, Falciparum, lcsh:Science, Protozoans, Malarial Parasites, Eukaryota, Genomics, Phylogeography, embryonic structures, Female, Synthetic Biology, Sequence Analysis, Research Article, Protein Structure, Bioinformatics, Plasmodium falciparum, Antigens, Protozoan, Research and Analysis Methods, Parasite Groups, Malaria Vaccines, parasitic diseases, Genetics, Parasitic Diseases, Humans, Molecular Biology, lcsh:R, Organisms, Biology and Life Sciences, Proteins, Tropical Diseases, Parasitic Protozoans, Malaria, Pregnancy Complications, Parasitic, Mutation, lcsh:Q, Parasitology, Structural Genomics, Peptides, Sequence Alignment, Apicomplexa
Abstract

Pregnancy-associated malaria (PAM) is one of the severe forms of Plasmodium falciparum infection. The main antigen VAR2CSA is the target of vaccine development. However, the large size of VAR2CSA protein and its high degree of variability limit to the efficiency of the vaccination. Using quantitative mass spectrometry method, we detected and quantified proteotypic peptides from 5 predicted PAM associated proteins. Our results confirmed that PFI1785w is over-expressed in PAM samples. Then, we investigated PFI1785w variability among a set of parasite samples from various endemic areas. PFI1785w appear to be more conserved than VAR2CSA. PFB0115w, another PAM associated protein, seems also associated with the pathology. Further vaccination strategies could integrate other proteins in addition to the major VAR2CSA antigen to improve immune response to vaccination.

Published
2017

30. Preferential expression of domain cassettes 4, 8 and 13 of Plasmodium falciparum erythrocyte membrane protein 1 in severe malaria imported in France

Author

Argy, N., Bertin, Gwladys, Milet, Jacqueline, Hubert, V., Clain, J., Cojean, S., Houze, P., Tuikue Ndam, Nicaise, Kendjo, E., Deloron, Philippe, Houze, S., and CNRP Study Group (collab.)

Subjects
Severe malaria, DC8, parasitic diseases, DC4, Imported malaria, Domain cassette, Var, DC13, gene
Abstract

Objectives: Severe Plasmodium falciparum malaria (SM) involves cytoadhesion of parasitized red blood cells, mediated by P. falciparum erythrocyte membrane protein 1, which is encoded by var genes. Expression of var gene group A and B or encoding domain cassettes DC4, DC5, DC8 and DC13 has been implicated in SM in African children, but no data exist in the context of imported malaria. The aim of this study was to investigate var gene expression linked to clinical presentation and host factors in SM imported into France. Methods: Expression level of var gene groups A, B, C, var1, var2csa, var3 and var genes encoding DC4, DC5, DC8 and DC13 was measured by quantitative RT- PCR and expressed in transcript units. Seventy SM and 48 uncomplicated malaria (UM) P. falciparum cases were analysed according to disease severity, epidemiological characteristics (migrants or travellers) and anti- P. falciparum antibodies. Cluster analysis was performed to identify gene expression profiles. Results: Var1 and B/ C expression were higher in UM than SM (0.66 (0-1.1) and 1.88 (1.3-2.4); p < 0.04, respectively). Group C expression differed between migrants and travellers (0.21 (0-0.75) versus 0 (0e0); p 0.002). Group A differed in naive and pre- exposed patients (1.1 (0.7-1.5) versus 0.4 (0-1.1); p 0.01). Population clusters revealed increased expression from group A and B var genes, and DC4, DC8 and DC13 in SM. Conclusions: These results corroborate the implication of DC4, DC8 and DC13 in severe imported malaria cases as African children, and their expression depends of host factors.

Published
2017

31. Genomic from Plasmodium falciparum field isolates from Benin allows the identification of PfEMP1 variants by LC-MS/MS at the patient’s level

Author

Kamaliddin, Claire, primary, Rombaut, David, additional, Guillochon, Emilie, additional, Royo, Jade, additional, Ezinmegnon, Sem, additional, Huguet, Stéphanie, additional, Guemouri, Sayeh, additional, Peirera, Céline, additional, Broussard, Cédric, additional, Alao, Jules M, additional, Aubouy, Agnès, additional, Guillonneau, François, additional, Deloron, Philippe, additional, and Bertin, Gwladys, additional

Published
2018
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36. Prevalence of malaria in pregnancy in southern Laos: a cross-sectional survey

Author

Briand, Valérie, primary, Le Hesran, Jean-Yves, additional, Mayxay, Mayfong, additional, Newton, Paul N., additional, Bertin, Gwladys, additional, Houzé, Sandrine, additional, Keomany, Sommay, additional, Inthavong, Yom, additional, Vannavong, Nanthasane, additional, Chindavongsa, Keobouphaphone, additional, Hongvanthong, Bouasy, additional, and Fievet, Nadine, additional

Published
2016
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38. G6PD A-variant influences the antibody responses to Plasmodium falciparum MSP2

Author

Courtin, David, Milet, Jacqueline, Bertin, Gwladys, Vafa, M., Sarr, Jean Birame, Watier, L., Deloron, Philippe, Troye-Blomberg, M., Garcia, André, and Migot Nabias, Florence

Subjects
Sickle cell trait, HbAS, parasitic diseases, Plasmodium falciparum, MSP2, Antibody, Malaria, G6PD
Abstract

High antibody levels directed to Plasmodium falciparum merozoite surface proteins (MSP), including MSP2, as well as genetically related red blood cell defects, have previously been found to be associated with protection against malaria. Here, our main objective was to study the changes in MSP2-specific total IgG, IgG1 and IgG3 responses during a malaria transmission season in order to assess the impact of sickle-cell, alpha(+)-thalassemia and G6PD variants on antibody kinetics. Repeated parasitological assessments of a cohort of children were conducted during an 8-month period. Antibody responses to recombinant MSP2/3D7 and MSP2/FC27 proteins were measured at the beginning and at the end of transmission season. We found that (i) the period of last Plasmodium falciparum infection during the transmission season was associated with IgG3 anti-MSP2 change. Compared to the IgG3 levels of children infected in January 2003 (end of transmission season), the IgG3 level of children decreased with the length of the period without infection, (ii) G6PD A carriers had a lower increase of IgG3 levels to MSP2/FC27 and MSP2/3D7 during the transmission season than the noncarriers. This latter finding is suggestive of qualitative and/or quantitative reduction of exposure to malarial antigens related to this genetic variant, leading to weaker stimulation of specific antibody responses. We speculate that cellmediated immune activity may explain the clinical protection afforded by this genetic trait.

Published
2011

40. Receptor-binding studies of the DBL gamma domain of Plasmodium falciparum erythrocyte membrane protein 1 from a placental isolate

Author

Badaut, C., Faure, G., Tuikue Ndam, Nicaise, Bertin, Gwladys, Chaffotte, A., Khattab, A., Klinkert, M.Q., Deloron, Philippe, and Bentley, G.A.

Subjects
erythrocyte membrane protein 1, receptor binding, Plasmodium falciparum, surface plasmon resonance, duffy binding like domain, placental malaria, circular dichroism
Abstract

We have previously identified a number of DBL gamma domains in Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) transcripts obtained from placental parasite isolates, showing that they bind specifically to chondroitin sulfate A (CSA) (Khattab A, Kun J, Deloron P, Kremsner PG, Klinkert MQ. Variants of Plasmodium falciparum erythrocyte membrane protein I expressed by different placental parasites are closely related and adhere to chondroitin sulfate A. J Infect Dis 2001;183:1165-9). Here we give a more detailed physico-chemical and binding characterisation of the soluble, recombinant DBL gamma domain derived from one of these isolates. Results from circular dichroism and limited proteolysis experiments are consistent with the recombinant domain being expressed with the native fold. Specific binding of DBL gamma to placental cryosections was demonstrated by labeling with antibodies raised against the recombinant domain; binding was diminished after treatment of the cryosections with chondroitinase or by blocking with anti-CSA antibody, showing that CSA mediates the interaction. Binding of the DBL gamma domain to purified placental chondroitin sulfate proteoglycan (CSPG) was also studied using surface plasmon resonance techniques, with DBL gamma as analyte and CSPG immobilised on the sensor chip; these quantitative measurements gave an affinity constant in the mu-molar range under the conditions used. The native conformation of the DBL gamma domain is essential for CSPG recognition since binding to the sensor chip is abolished when the protein is irreversibly reduced. As with the placental cryosections, association was significantly reduced after treating the immobilised CSPG with chondroitinase. Together, these results demonstrate specific interaction between the DBL gamma domain and the placental receptor.

Published
2007

41. Involvement of connexin 43 in human trophoblast cell fusion and differentiation

Author

Frendo, Jean-Louis, Cronier, Laurent, Bertin, Gwladys, Guibourdenche, Jean, Vidaud, Michel, Evain-Brion, Danièle, Malassiné, André, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biomembranes et Signalisation Cellulaire (LBSC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Service de biochimie-hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biomembranes et Signalisation cellulaire, Université de Poitiers, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
MESH : Cell Communication, MESH: Cytoskeletal Proteins, MESH: Gap Jun, MESH : Fluorescence Recovery After Photobleaching, MESH : Desmoplakins, MESH: Desmoplakins, MESH: Chorionic Gonadotropin, MESH : Cells, Cultured, MESH: Cell Communication, MESH : Connexin 43, MESH : Female, MESH : Gap Jun, reproductive and urinary physiology, MESH : Chorionic Gonadotropin, MESH : Cell Fusion, MESH : Endogenous Retroviruses, MESH : Cytoskeletal Proteins, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, female genital diseases and pregnancy complications, MESH: Connexin 43, [ SDV.BDLR ] Life Sciences [q-bio]/Reproductive Biology, MESH : Chorionic Gonadotropin, beta Subunit, Human, MESH: Cell Fusion, embryonic structures, MESH: Chorionic Gonadotropin, beta Subunit, Human, sense organs, MESH: Female, MESH: Fluorescence Recovery After Photobleaching, MESH: Endogenous Retroviruses, MESH: Cells, Cultured
Abstract

The syncytiotrophoblast is the principal component of the human placenta involved in feto-maternal exchanges and hormone secretion. The syncytiotrophoblast arises from the fusion of villous cytotrophoblasts. We recently showed that functional gap junctional intercellular communication (GJIC) is an important prerequisite for syncytiotrophoblast formation and that connexin 43 (Cx43) is present in cytotrophoblasts and in the syncytiotrophoblast. To determine whether Cx43 is directly involved in trophoblast fusion, we used an antisense strategy in primary cultures of human villous cytotrophoblasts that spontaneously differentiate into the syncytiotrophoblast by cell fusion. We assessed the morphological and functional differentiation of trophoblasts by desmoplakin immunostaining, by quantifying hCG (human chorionic gonadotropin) production and by measuring the expression of specific trophoblast genes (hCG and HERV-W). Furthermore, we used the gap-FRAP (fluorescence recovery after photobleaching) method to investigate functional GJIC. Cytotrophoblasts treated with Cx43 antisense aggregated and fused poorly. Furthermore, less HERV-W env mRNA, hCGbeta mRNA and hCG secretion were detected in Cx43 antisense-treated cytotrophoblasts than in cells treated with scrambled antisense. Treatment with Cx43 antisense dramatically reduced the percentage of coupled trophoblast cells. Taken together, these results suggest that Cx43 is directly involved in human trophoblast cell-cell communication, fusion and differentiation.

Published
2003
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42. Expression of the domain cassette 8 Plasmodium falciparum erythrocyte membrane protein 1 is associated with cerebral malaria in Benin

Author

Bertin, Gwladys I, Lavstsen, Thomas, Guillonneau, François, Doritchamou, Justin, Wang, Christian W, Jespersen, Jakob S, Ezimegnon, Sem, Fievet, Nadine, Alao, Maroufou J, Lalya, Francis, Massougbodji, Achille, Ndam, Nicaise Tuikue, Theander, Thor G, Deloron, Philippe, Bertin, Gwladys I, Lavstsen, Thomas, Guillonneau, François, Doritchamou, Justin, Wang, Christian W, Jespersen, Jakob S, Ezimegnon, Sem, Fievet, Nadine, Alao, Maroufou J, Lalya, Francis, Massougbodji, Achille, Ndam, Nicaise Tuikue, Theander, Thor G, and Deloron, Philippe

Abstract

Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a highly polymorphic adherence receptor expressed on the surface of infected erythrocytes. Based on sequence homology PfEMP-1 variants have been grouped into three major groups A-C, the highly conserved VAR2CSA variants, and semi-conserved types defined by tandem runs of specific domains ("domain cassettes" (DC)). The PfEMP-1 type expressed determines the adherence phenotype, and is associated with clinical outcome of infection.

Published
2013

43. Expression of the Domain Cassette 8 Plasmodium falciparum Erythrocyte Membrane Protein 1 Is Associated with Cerebral Malaria in Benin

Author

Bertin, Gwladys I., primary, Lavstsen, Thomas, additional, Guillonneau, François, additional, Doritchamou, Justin, additional, Wang, Christian W., additional, Jespersen, Jakob S., additional, Ezimegnon, Sem, additional, Fievet, Nadine, additional, Alao, Maroufou J., additional, Lalya, Francis, additional, Massougbodji, Achille, additional, Ndam, Nicaise Tuikue, additional, Theander, Thor G., additional, and Deloron, Philippe, additional

Published
2013
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44. High level of var2csa transcription by Plasmodium falciparum isolated from the placenta

Author

Tuikue Ndam, Nicaise G, Salanti, Ali, Bertin, Gwladys, Dahlbäck, Madeleine, Fievet, Nadine, Turner, Louise, Gaye, Alioune, Theander, Thor, Deloron, Philippe, Tuikue Ndam, Nicaise G, Salanti, Ali, Bertin, Gwladys, Dahlbäck, Madeleine, Fievet, Nadine, Turner, Louise, Gaye, Alioune, Theander, Thor, and Deloron, Philippe

Abstract

Udgivelsesdato: 2005-Jul-15, Plasmodium falciparum parasites that bind to chondroitin sulphate A (CSA) express unique variant surface antigens that are involved in the placental sequestration that precipitates pregnancy-associated malaria (PAM). Two var gene subfamilies, var1csa and var2csa, have been associated with CSA binding. We show here that placental P. falciparum isolates highly transcribed var2csa but not var1csa. var2csa was not transcribed or was only minimally transcribed by parasites isolated from nonpregnant women. Placental parasites that effectively bound to placental chondroitin sulphate proteoglycans transcribed higher levels of var2csa. In pregnant women, levels of var2csa transcription and plasma anti-VAR2CSA immunoglobulin G were associated. These findings support the idea that VAR2CSA plays a crucial role in PAM and strengthen the rationale for the development of VAR2CSA-based vaccines.

Published
2005

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