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1. Genomic analysis of Plasmodium vivax describes patterns of connectivity and putative drivers of adaptation in Ethiopia

Author

Kebede, Alebachew Messele, Sutanto, Edwin, Trimarsanto, Hidayat, Benavente, Ernest Diez, Barnes, Mariana, Pearson, Richard D., Siegel, Sasha V., Erko, Berhanu, Assefa, Ashenafi, Getachew, Sisay, Aseffa, Abraham, Petros, Beyene, Lo, Eugenia, Mohammed, Rezika, Yilma, Daniel, Rumaseb, Angela, Nosten, Francois, Noviyanti, Rintis, Rayner, Julian C., Kwiatkowski, Dominic P., Price, Ric N., Golassa, Lemu, and Auburn, Sarah

Published
2023
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2. Genomics of Plasmodium vivax in Colombia reveals evidence of local bottle-necking and inter-country connectivity in the Americas

Author

Sutanto, Edwin, Pava, Zuleima, Echeverry, Diego F., Lopera-Mesa, Tatiana M., Montenegro, Lidia Madeline, Yasnot-Acosta, Maria F., Benavente, Ernest Diez, Pearson, Richard D., Herrera, Sócrates, Arévalo-Herrera, Myriam, Trimarsanto, Hidayat, Rumaseb, Angela, Noviyanti, Rintis, Kwiatkowski, Dominic P., Price, Ric N., and Auburn, Sarah

Published
2023
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3. Tafenoquine co-administered with dihydroartemisinin–piperaquine for the radical cure of Plasmodium vivax malaria (INSPECTOR): a randomised, placebo-controlled, efficacy and safety study

Author

Sutanto, Inge, Soebandrio, Amin, Ekawati, Lenny L, Chand, Krisin, Noviyanti, Rintis, Satyagraha, Ari Winasti, Subekti, Decy, Santy, Yulia Widya, Crenna-Darusallam, Chelzie, Instiaty, Instiaty, Budiman, Waras, Prasetya, Catur Bidik, Lardo, Soroy, Elyazar, Iqbal, Duparc, Stephan, Cedar, Eve, Rolfe, Katie, Fernando, Disala, Berni, Alessandro, Jones, Siôn, Kleim, Jörg-Peter, Fletcher, Kim, Sharma, Hema, Martin, Ana, Taylor, Maxine, Goyal, Navin, Green, Justin A, Tan, Lionel K, and Baird, J Kevin

Published
2023
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4. On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity

Author

Edgar, Rebecca C. S., primary, Malcolm, Tess R., additional, Siddiqui, Ghizal, additional, Giannangelo, Carlo, additional, Counihan, Natalie A., additional, Challis, Matthew, additional, Duffy, Sandra, additional, Chowdhury, Mrittika, additional, Marfurt, Jutta, additional, Dans, Madeline, additional, Wirjanata, Grennady, additional, Noviyanti, Rintis, additional, Daware, Kajal, additional, Suraweera, Chathura D., additional, Price, Ric N., additional, Wittlin, Sergio, additional, Avery, Vicky M., additional, Drinkwater, Nyssa, additional, Charman, Susan A., additional, Creek, Darren J., additional, de Koning-Ward, Tania F., additional, Scammells, Peter J., additional, and McGowan, Sheena, additional

Published
2024
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5. Implementation of a Randomized, Placebo-Controlled Trial of Live Attenuated Malaria Sporozoite Vaccines in an Indonesian Military Study Population

Author

Indrihutami, Khoriah, primary, Chand, Krisin, additional, Fahmia, Rizka, additional, Rahardjani, Mutia, additional, Wulandari, Fitria, additional, Subekti, Decy, additional, Noviyanti, Rintis, additional, Soebandrio, Amin, additional, Mallisa, Noch T., additional, Mardika, I Made, additional, Budiman, Waras, additional, Suriswan, Irwan, additional, Ertanto, Yogi, additional, Chen, Mei-Chun, additional, Murshedkar, Tooba, additional, Abebe, Yonas, additional, Sim, B. Kim Lee, additional, Hoffman, Stephen L., additional, Richie, Thomas L., additional, Chen, Sky, additional, Elyazar, Iqbal R. F., additional, Ekawati, Lenny L., additional, Baird, J. Kevin, additional, and Nelwan, Erni J., additional

Published
2024
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9. A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria

Author

Trimarsanto, Hidayat, Amato, Roberto, Pearson, Richard D., Sutanto, Edwin, Noviyanti, Rintis, Trianty, Leily, Marfurt, Jutta, Pava, Zuleima, Echeverry, Diego F., Lopera-Mesa, Tatiana M., Montenegro, Lidia M., Tobón-Castaño, Alberto, Grigg, Matthew J., Barber, Bridget, William, Timothy, Anstey, Nicholas M., Getachew, Sisay, Petros, Beyene, Aseffa, Abraham, Assefa, Ashenafi, Rahim, Awab G., Chau, Nguyen H., Hien, Tran T., Alam, Mohammad S., Khan, Wasif A., Ley, Benedikt, Thriemer, Kamala, Wangchuck, Sonam, Hamedi, Yaghoob, Adam, Ishag, Liu, Yaobao, Gao, Qi, Sriprawat, Kanlaya, Ferreira, Marcelo U., Laman, Moses, Barry, Alyssa, Mueller, Ivo, Lacerda, Marcus V. G., Llanos-Cuentas, Alejandro, Krudsood, Srivicha, Lon, Chanthap, Mohammed, Rezika, Yilma, Daniel, Pereira, Dhelio B., Espino, Fe E. J., Chu, Cindy S., Vélez, Iván D., Namaik-larp, Chayadol, Villegas, Maria F., Green, Justin A., Koh, Gavin, Rayner, Julian C., Drury, Eleanor, Gonçalves, Sónia, Simpson, Victoria, Miotto, Olivo, Miles, Alistair, White, Nicholas J., Nosten, Francois, Kwiatkowski, Dominic P., Price, Ric N., and Auburn, Sarah

Published
2022
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10. Laboratory challenges of Plasmodium species identification in Aceh Province, Indonesia, a malaria elimination setting with newly discovered P. knowlesi.

Author

Coutrier, Farah, Tirta, Yusrifar, Cotter, Chris, Zarlinda, Iska, González, Iveth, Schwartz, Alanna, Maneh, Cut, Marfurt, Jutta, Murphy, Maxwell, Herdiana, Herdiana, Anstey, Nicholas, Greenhouse, Bryan, Hsiang, Michelle, and Noviyanti, Rintis

Subjects
Disease Eradication, Humans, Indonesia, Laboratories, Malaria, Nucleic Acid Amplification Techniques, Plasmodium, Plasmodium knowlesi, Polymerase Chain Reaction
Abstract

The discovery of the life-threatening zoonotic infection Plasmodium knowlesi has added to the challenges of prompt and accurate malaria diagnosis and surveillance. In this study from Aceh Province, Indonesia, a malaria elimination setting where P. knowlesi endemicity was not previously known, we report the laboratory investigation and difficulties encountered when using molecular detection methods for quality assurance of microscopically identified clinical cases. From 2014 to 2015, 20 (49%) P. falciparum, 16 (39%) P. vivax, 3 (7%) P. malariae, and 2 (5%) indeterminate species were identified by microscopy from four sentinel health facilities. At a provincial-level reference laboratory, loop-mediated isothermal amplification (LAMP), a field-friendly molecular method, was performed and confirmed Plasmodium in all samples though further species-identification was limited by the unavailability of non-falciparum species-specific testing with the platform used. At a national reference laboratory, several molecular methods including nested PCR (nPCR) targeting the 18 small sub-unit (18S) ribosomal RNA, nPCR targeting the cytochrome-b (cytb) gene, a P. knowlesi-specific nPCR, and finally sequencing, were necessary to ultimately classify the samples as: 19 (46%) P. knowlesi, 8 (20%) P. falciparum, 14 (34%) P. vivax. Microscopy was unable to identify or mis-classified up to 56% of confirmed cases, including all cases of P. knowlesi. With the nPCR methods targeting the four human-only species, P. knowlesi was missed (18S rRNA method) or showed cross-reactivity for P. vivax (cytb method). To facilitate diagnosis and management of potentially fatal P. knowlesi infection and surveillance for elimination of human-only malaria in Indonesia and other affected settings, new detection methods are needed for testing at the point-of-care and in local reference laboratories.

Published
2018

11. Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia

Author

Marfurt, Jutta, Wirjanata, Grennady, Prayoga, Pak, Chalfein, Ferryanto, Leonardo, Leo, Sebayang, Boni F., Apriyanti, Dwi, Sihombing, Maic A.E.M., Trianty, Leily, Suwanarusk, Rossarin, Brockman, Alan, Piera, Kim A., Luo, Irene, Rumaseb, Angela, MacHunter, Barbara, Auburn, Sarah, Anstey, Nicholas M., Kenangalem, Enny, Noviyanti, Rintis, Russell, Bruce, Poespoprodjo, Jeanne R., and Price, Ric N.

Published
2021
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12. Updating estimates of Plasmodium knowlesi malaria risk in response to changing land use patterns across Southeast Asia

Author

Tobin, Ruarai J., primary, Harrison, Lucinda E., additional, Tully, Meg K., additional, Lubis, Inke N. D., additional, Noviyanti, Rintis, additional, Anstey, Nicholas M., additional, Rajahram, Giri S., additional, Grigg, Matthew J., additional, Flegg, Jennifer A., additional, Price, David J., additional, and Shearer, Freya M., additional

Published
2024
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15. Retention of uninfected red blood cells causing congestive splenomegaly is the major mechanism of anemia in malaria

Author

Kho, Steven, primary, Siregar, Nurjati C., additional, Qotrunnada, Labibah, additional, Fricot, Aurélie, additional, Sissoko, Abdoulaye, additional, Shanti, Putu A. I., additional, Candrawati, Freis, additional, Kambuaya, Noy N., additional, Rini, Hasrini, additional, Andries, Benediktus, additional, Hardy, David, additional, Margyaningsih, Nur I., additional, Fadllan, Fauziyah, additional, Rahmayenti, Desandra A., additional, Puspitasari, Agatha M., additional, Aisah, Amelia R., additional, Leonardo, Leo, additional, Yayang, Bagus T. G., additional, Margayani, Dewi S., additional, Prayoga, Pak, additional, Trianty, Leily, additional, Kenangalem, Enny, additional, Price, Ric N., additional, Yeo, Tsin W., additional, Minigo, Gabriela, additional, Noviyanti, Rintis, additional, Poespoprodjo, Jeanne R., additional, Anstey, Nicholas M., additional, and Buffet, Pierre A., additional

Published
2023
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16. On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity

Author

Edgar, Rebecca C.S., primary, Malcolm, Tess R., additional, Siddiqui, Ghizal, additional, Giannangelo, Carlo, additional, Counihan, Natalie A., additional, Challis, Matthew, additional, Duffy, Sandra, additional, Chowdhury, Mrittika, additional, Marfurt, Jutta, additional, Dans, Madeline, additional, Wirjanata, Grennady, additional, Noviyanti, Rintis, additional, Daware, Kajal, additional, Suraweera, Chathura D., additional, Price, Ric N, additional, Wittlin, Sergio, additional, Avery, Vicky M., additional, Drinkwater, Nyssa, additional, Charman, Susan A., additional, Creek, Darren J., additional, de Koning-Ward, Tania F., additional, Scammells, Peter J., additional, and McGowan, Sheena, additional

Published
2023
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17. Genomic analysis of Plasmodium vivax identifies putative drivers of adaptation and connectivity across diverse districts in Ethiopia

Author

Kebede, Alebachew Messele, primary, Sutanto, Edwin, additional, Trimarsanto, Hidayat, additional, Benavente, Ernest Diez, additional, Barnes, Mariana, additional, Pearson, Richard, additional, Siegel, Sasha, additional, Erko, Berhanu, additional, Assefa, Ashenafi, additional, Getachew, Sisay, additional, Aseffa, Abraham, additional, Petros, Beyene, additional, Lo, Eugenia, additional, Mohammed, Rezika, additional, Yilma, Daniel, additional, Rumaseb, Angela, additional, Nosten, Francois, additional, Noviyanti, Rintis, additional, Rayner, Julian, additional, Kwiatkowski, Dominic, additional, Price, Ric, additional, Golassa, Lemu, additional, and Auburn, Sarah, additional

Published
2023
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18. Plasmodium knowlesi detection methods for human infections—Diagnosis and surveillance

Author

Grigg, Matthew J., primary, Lubis, Inke N., additional, Tetteh, Kevin K.A., additional, Barber, Bridget E., additional, William, Timothy, additional, Rajahram, Giri S., additional, Tan, Angelica F., additional, Sutherland, Colin J., additional, Noviyanti, Rintis, additional, Drakeley, Chris J., additional, Britton, Sumudu, additional, and Anstey, Nicholas M., additional

Published
2021
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19. A novel multiple-stage antimalarial agent that inhibits protein synthesis

Author

Baragaña, Beatriz, Hallyburton, Irene, Lee, Marcus CS, Norcross, Neil R, Grimaldi, Raffaella, Otto, Thomas D, Proto, William R, Blagborough, Andrew M, Meister, Stephan, Wirjanata, Grennady, Ruecker, Andrea, Upton, Leanna M, Abraham, Tara S, Almeida, Mariana J, Pradhan, Anupam, Porzelle, Achim, Martínez, María Santos, Bolscher, Judith M, Woodland, Andrew, Luksch, Torsten, Norval, Suzanne, Zuccotto, Fabio, Thomas, John, Simeons, Frederick, Stojanovski, Laste, Osuna-Cabello, Maria, Brock, Paddy M, Churcher, Tom S, Sala, Katarzyna A, Zakutansky, Sara E, Jiménez-Díaz, María Belén, Sanz, Laura Maria, Riley, Jennifer, Basak, Rajshekhar, Campbell, Michael, Avery, Vicky M, Sauerwein, Robert W, Dechering, Koen J, Noviyanti, Rintis, Campo, Brice, Frearson, Julie A, Angulo-Barturen, Iñigo, Ferrer-Bazaga, Santiago, Gamo, Francisco Javier, Wyatt, Paul G, Leroy, Didier, Siegl, Peter, Delves, Michael J, Kyle, Dennis E, Wittlin, Sergio, Marfurt, Jutta, Price, Ric N, Sinden, Robert E, Winzeler, Elizabeth A, Charman, Susan A, Bebrevska, Lidiya, Gray, David W, Campbell, Simon, Fairlamb, Alan H, Willis, Paul A, Rayner, Julian C, Fidock, David A, Read, Kevin D, and Gilbert, Ian H

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Biotechnology, Infectious Diseases, Malaria, Orphan Drug, Vector-Borne Diseases, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Animals, Antimalarials, Drug Discovery, Female, Gene Expression Regulation, Life Cycle Stages, Liver, Male, Models, Molecular, Peptide Elongation Factor 2, Plasmodium, Plasmodium berghei, Plasmodium falciparum, Plasmodium vivax, Protein Biosynthesis, Quinolines, General Science & Technology
Abstract

There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

Published
2015

22. Implementing parasite genotyping into national surveillance frameworks: feedback from control programmes and researchers in the Asia–Pacific region

Author

Noviyanti, Rintis, Miotto, Olivo, Barry, Alyssa, Marfurt, Jutta, Siegel, Sasha, Thuy-Nhien, Nguyen, Quang, Huynh Hong, Anggraeni, Nancy Dian, Laihad, Ferdinand, Liu, Yaobao, Sumiwi, Maria Endang, Trimarsanto, Hidayat, Coutrier, Farah, Fadila, Nadia, Ghanchi, Najia, Johora, Fatema Tuj, Puspitasari, Agatha Mia, Tavul, Livingstone, Trianty, Leily, Utami, Retno Ayu Setya, Wang, Duoquan, Wangchuck, Kesang, Price, Ric N., and Auburn, Sarah

Published
2020
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24. 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

25. Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study

Author

Kho, Steven, Qotrunnada, Labibah, Leonardo, Leo, Andries, Benediktus, Wardani, Putu A. I., Fricot, Aurelie, Henry, Benoit, Hardy, David, Margyaningsih, Nur I., Apriyanti, Dwi, Puspitasari, Agatha M., Prayoga, Pak, Trianty, Leily, Kenangalem, Enny, Chretien, Fabrice, Brousse, Valentine, Safeukui, Innocent, del Portillo, Hernando A., Fernandez-Becerra, Carmen, Meibalan, Elamaran, Marti, Matthias, Price, Ric N., Woodberry, Tonia, Ndour, Papa A., Russell, Bruce M., Yeo, Tsin W., Minigo, Gabriela, Noviyanti, Rintis, Poespoprodjo, Jeanne R., Siregar, Nurjati C., Buffet, Pierre A., and Anstey, Nicholas M.

Subjects
Spleen -- Health aspects -- Physiological aspects, Plasmodium vivax -- Physiological aspects, Erythrocytes -- Health aspects -- Physiological aspects, Malaria -- Physiological aspects -- Complications and side effects, Carrier state (Communicable diseases) -- Physiological aspects -- Complications and side effects, Host-parasite relationships -- Physiological aspects, Biological sciences
Abstract

Background A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P. vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival. Methods and findings We examined spleen tissue in 22 mostly untreated individuals naturally exposed to P. vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia (2015 to 2017). Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. Nine non-endemic control spleens from individuals undergoing spleno-pancreatectomy in France (2017 to 2020) were also examined for reticulocyte densities. There were no exclusion criteria or sample size considerations in both patient cohorts for this demanding approach. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P. vivax, 13 P. falciparum, and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Accordingly, in France, reticulocyte concentrations in the splenic effluent were higher than in peripheral blood. Greater rigidity of reticulocytes in splenic than in peripheral blood, and their higher densities in splenic cords both suggest a mechanical retention process. Asexual-stage P. vivax-infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and median total splenic parasite loads 81 (IQR: 14 to 205) times greater, accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P. vivax biomass. More reticulocytes were in contact with sinus lumen endothelial cells in P. vivax- than in P. falciparum-infected spleens. Histological analyses revealed 96% of P. vivax rings/trophozoites and 46% of schizonts colocalised with 92% of immature reticulocytes in the cords and sinus lumens of the red pulp. Larger splenic cohort studies and similar investigations in untreated symptomatic malaria are warranted. Conclusions Immature CD71.sup.+ reticulocytes and splenic P. vivax-infected erythrocytes of all asexual stages accumulate in the same splenic compartments, suggesting the existence of a cryptic endosplenic lifecycle in chronic P. vivax infection. Findings provide insight into P. vivax-specific adaptions that have evolved to maximise survival and replication in the spleen., Author(s): Steven Kho 1, Labibah Qotrunnada 2, Leo Leonardo 3, Benediktus Andries 3, Putu A. I. Wardani 4, Aurelie Fricot 5, Benoit Henry 5, David Hardy 6, Nur I. Margyaningsih [...]

Published
2021
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27. 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

28. SARS-CoV-2 Antibody Seroprevalence in Jakarta, Indonesia

Author

Ariawan, Iwan, primary, Jusril, Hafizah, additional, N Farid, Muhammad, additional, Riono, Pandu, additional, Wahyuningsih, Wiji, additional, Widyastuti, Widyastuti, additional, Handayani, Dwi Oktavia T L, additional, Wahyuningsih, Endang Sri, additional, Daulay, Rebekka, additional, Henderiawati, Retno, additional, Malik, Safarina G, additional, Noviyanti, Rintis, additional, Trianty, Leily, additional, Fadila, Nadia, additional, Myint, Khin Saw Aye, additional, Yudhaputri, Frilasita A., additional, Venkateswaran, Neeraja, additional, Venkateswaran, Kodumudi, additional, Udhayakumar, Venkatachalam, additional, Hawley, William A., additional, Morgan, Juliette, additional, and Pronyk, Paul M, additional

Published
2022
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29. Hypnozoite depletion in successive Plasmodium vivax relapses

Author

Noviyanti, Rintis, primary, Carey-Ewend, Kelly, additional, Trianty, Leily, additional, Parobek, Christian, additional, Puspitasari, Agatha Mia, additional, Balasubramanian, Sujata, additional, Park, Zackary, additional, Hathaway, Nicholas, additional, Utami, Retno A. S., additional, Soebianto, Saraswati, additional, Jeny, Jeny, additional, Yudhaputri, Frilasita, additional, Perkasa, Aditya, additional, Coutrier, Farah N., additional, Tirta, Yusrifar K., additional, Ekawati, Lenny, additional, Tjahyono, Bagus, additional, Sutanto, Inge, additional, Nelwan, Erni J., additional, Sudoyo, Herawati, additional, Baird, J. Kevin, additional, and Lin, Jessica T., additional

Published
2022
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31. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples

Author

Adam, Ishag, Alam, Mohammad Shafiul, Alemu, Sisay, Amaratunga, Chanaki, Amato, Roberto, Andrianaranjaka, Voahangy, Anstey, Nicholas M, Aseffa, Abraham, Ashley, Elizabeth, Assefa, Ashenafi, Auburn, Sarah, Barber, Bridget E, Barry, Alyssa, Batista Pereira, Dhelio, Cao, Jun, Chau, Nguyen Hoang, Chotivanich, Kesinee, Chu, Cindy, Dondorp, Arjen M, Drury, Eleanor, Echeverry, Diego F, Erko, Berhanu, Espino, Fe, Fairhurst, Rick, Faiz, Abdul, Fernanda Villegas, María, Gao, Qi, Golassa, Lemu, Goncalves, Sonia, Grigg, Matthew J, Hamedi, Yaghoob, Hien, Tran Tinh, Htut, Ye, Johnson, Kimberly J, Karunaweera, Nadira, Khan, Wasif, Krudsood, Srivicha, Kwiatkowski, Dominic P, Lacerda, Marcus, Ley, Benedikt, Lim, Pharath, Liu, Yaobao, Llanos-Cuentas, Alejandro, Lon, Chanthap, Lopera-Mesa, Tatiana, Marfurt, Jutta, Michon, Pascal, Miotto, Olivo, Mohammed, Rezika, Mueller, Ivo, Namaik-Larp, Chayadol, Newton, Paul N, Nguyen, Thuy-Nhien, Nosten, Francois, Noviyanti, Rintis, Pava, Zuleima, Pearson, Richard D, Petros, Beyene, Phyo, Aung P, Price, Ric N, Pukrittayakamee, Sasithon, Rahim, Awab Ghulam, Randrianarivelojosia, Milijaona, Rayner, Julian C, Rumaseb, Angela, Siegel, Sasha V, Simpson, Victoria J, Thriemer, Kamala, Tobon-Castano, Alberto, Trimarsanto, Hidayat, Urbano Ferreira, Marcelo, Vélez, Ivan D, Wangchuk, Sonam, Wellems, Thomas E, White, Nicholas J, William, Timothy, Yasnot, Maria F, Yilma, Daniel, Alam, Mohammad Shafiul [0000-0001-8330-5499], Ashley, Elizabeth [0000-0002-7620-4822], Barber, Bridget E [0000-0003-1066-7960], Batista Pereira, Dhelio [0000-0002-7761-5498], Chu, Cindy [0000-0001-9465-8214], Dondorp, Arjen M [0000-0001-5190-2395], Echeverry, Diego F [0000-0003-0301-4478], Espino, Fe [0000-0003-1690-1711], Faiz, Abdul [0000-0002-3460-7535], Golassa, Lemu [0000-0002-1216-8711], Grigg, Matthew J [0000-0001-9914-8352], Karunaweera, Nadira [0000-0003-3985-1817], Kwiatkowski, Dominic P [0000-0002-5023-0176], Ley, Benedikt [0000-0002-5734-0845], Miotto, Olivo [0000-0001-8060-6771], Nguyen, Thuy-Nhien [0000-0002-4101-5706], Nosten, Francois [0000-0002-7951-0745], Pearson, Richard D [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], Urbano Ferreira, Marcelo [0000-0002-5293-9090], Wellems, Thomas E [0000-0003-3899-8454], Yasnot, Maria F [0000-0001-8081-4212], Yilma, Daniel [0000-0001-6058-2696], and Apollo - University of Cambridge Repository

Subjects
parasitic diseases, Genomics, Genomic Epidemiology, Plasmodium vivax, Malaria, Data Resource
Abstract

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.

Published
2022

32. Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria

Author

Studniberg, Stephanie I, primary, Ioannidis, Lisa J, additional, Utami, Retno A S, additional, Trianty, Leily, additional, Liao, Yang, additional, Abeysekera, Waruni, additional, Li‐Wai‐Suen, Connie S N, additional, Pietrzak, Halina M, additional, Healer, Julie, additional, Puspitasari, Agatha M, additional, Apriyanti, Dwi, additional, Coutrier, Farah, additional, Poespoprodjo, Jeanne R, additional, Kenangalem, Enny, additional, Andries, Benediktus, additional, Prayoga, Pak, additional, Sariyanti, Novita, additional, Smyth, Gordon K, additional, Cowman, Alan F, additional, Price, Ric N, additional, Noviyanti, Rintis, additional, Shi, Wei, additional, Garnham, Alexandra L, additional, and Hansen, Diana S, additional

Published
2022
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34. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples

Author

MalariaGEN, Adam, Ishag, Alam, Mohammad Shafiul, Alemu, Sisay, Amaratunga, Chanaki, Amato, Roberto, Andrianaranjaka, Voahangy, Anstey, Nicholas M, Aseffa, Abraham, Ashley, Elizabeth, Assefa, Ashenafi, Auburn, Sarah, Barber, Bridget E, Barry, Alyssa, Batista Pereira, Dhelio, Cao, Jun, Chau, Nguyen Hoang, Chotivanich, Kesinee, Chu, Cindy, Dondorp, Arjen M, Drury, Eleanor, Echeverry, Diego F, Erko, Berhanu, Espino, Fe, Fairhurst, Rick, Faiz, Abdul, Fernanda Villegas, María, Gao, Qi, Golassa, Lemu, Goncalves, Sonia, Grigg, Matthew J, Hamedi, Yaghoob, Hien, Tran Tinh, Htut, Ye, Johnson, Kimberly J, Karunaweera, Nadira, Khan, Wasif, Krudsood, Srivicha, Kwiatkowski, Dominic P, Lacerda, Marcus, Ley, Benedikt, Lim, Pharath, Liu, Yaobao, Llanos-Cuentas, Alejandro, Lon, Chanthap, Lopera-Mesa, Tatiana, Marfurt, Jutta, Michon, Pascal, Miotto, Olivo, Mohammed, Rezika, Mueller, Ivo, Namaik-Larp, Chayadol, Newton, Paul N, Nguyen, Thuy-Nhien, Nosten, Francois, Noviyanti, Rintis, Pava, Zuleima, Pearson, Richard D, Petros, Beyene, Phyo, Aung P, Price, Ric N, Pukrittayakamee, Sasithon, Rahim, Awab Ghulam, Randrianarivelojosia, Milijaona, Rayner, Julian C, Rumaseb, Angela, Siegel, Sasha V, Simpson, Victoria J, Thriemer, Kamala, Tobon-Castano, Alberto, Trimarsanto, Hidayat, Urbano Ferreira, Marcelo, Vélez, Ivan D, Wangchuk, Sonam, Wellems, Thomas E, White, Nicholas J, William, Timothy, Yasnot, Maria F, Yilma, Daniel, AII - Infectious diseases, Intensive Care Medicine, MalariaGEN, Alam, Mohammad Shafiul [0000-0001-8330-5499], Ashley, Elizabeth [0000-0002-7620-4822], Barber, Bridget E [0000-0003-1066-7960], Batista Pereira, Dhelio [0000-0002-7761-5498], Chu, Cindy [0000-0001-9465-8214], Dondorp, Arjen M [0000-0001-5190-2395], Echeverry, Diego F [0000-0003-0301-4478], Espino, Fe [0000-0003-1690-1711], Faiz, Abdul [0000-0002-3460-7535], Golassa, Lemu [0000-0002-1216-8711], Karunaweera, Nadira [0000-0003-3985-1817], Kwiatkowski, Dominic P [0000-0002-5023-0176], Ley, Benedikt [0000-0002-5734-0845], Miotto, Olivo [0000-0001-8060-6771], Nguyen, Thuy-Nhien [0000-0002-4101-5706], Nosten, Francois [0000-0002-7951-0745], Pearson, Richard D [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], Urbano Ferreira, Marcelo [0000-0002-5293-9090], Wellems, Thomas E [0000-0003-3899-8454], Yasnot, Maria F [0000-0001-8081-4212], Yilma, Daniel [0000-0001-6058-2696], and Apollo - University of Cambridge Repository

Subjects
Data resource, parasitic diseases, Medicine (miscellaneous), Genomics, Genomic epidemiology, Plasmodium vivax, General Biochemistry, Genetics and Molecular Biology, Malaria
Abstract

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.

Published
2022

35. Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia: A longitudinal surveillance study

Author

Kenangalem, Enny, Poespoprodjo, Jeanne Rini, Douglas, Nicholas M., Burdam, Faustina Helena, Gdeumana, Ketut, Chalfein, Ferry, Prayoga, Thio, Franciscus, Devine, Angela, Marfurt, Jutta, Waramori, Govert, Yeung, Shunmay, Noviyanti, Rintis, Penttinen, Pasi, Bangs, Michael J., Sugiarto, Paulus, Simpson, Julie A., Soenarto, Yati, Anstey, Nicholas M., and Price, Ric N.

Subjects
Artemisinin -- Usage, Longitudinal studies -- Usage, Malaria -- Drug therapy -- Control -- Patient outcomes -- Risk factors, Mortality, Hospital admission and discharge, Morbidity, Intelligence gathering, Plasmodium falciparum, Liver, Pyrimethamine, Biological sciences
Abstract

Background Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species. Methods and findings A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9% (95% confidence interval [CI] -13.5% to -12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = -0.21% [95% CI -0.34 to -0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = -0.05% [95% CI -0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95% CI 0.48-0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95% CI 0.71-0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy. Conclusions In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria., Author(s): Enny Kenangalem 1,2, Jeanne Rini Poespoprodjo 1,2,3,4, Nicholas M. Douglas 5, Faustina Helena Burdam 1,2, Ketut Gdeumana 6, Ferry Chalfein 1, Prayoga 1, Franciscus Thio 1,4, Angela Devine 5,7, [...]

Published
2019
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36. Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1

Author

Rambhatla, Janavi S., primary, Tonkin-Hill, Gerry Q., additional, Takashima, Eizo, additional, Tsuboi, Takafumi, additional, Noviyanti, Rintis, additional, Trianty, Leily, additional, Sebayang, Boni F., additional, Lampah, Daniel A., additional, Marfurt, Jutta, additional, Price, Ric N., additional, Anstey, Nicholas M., additional, Papenfuss, Anthony T., additional, Damelang, Timon, additional, Chung, Amy W., additional, Duffy, Michael F., additional, and Rogerson, Stephen J., additional

Published
2022
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37. High-dimensional mass cytometry identifies T cell and B cell signatures predicting reduced risk of Plasmodium vivax malaria

Author

Ioannidis, Lisa J., primary, Pietrzak, Halina M., additional, Ly, Ann, additional, Utami, Retno A.S., additional, Eriksson, Emily M., additional, Studniberg, Stephanie I., additional, Abeysekera, Waruni, additional, Li-Wai-Suen, Connie S.N., additional, Sheerin, Dylan, additional, Healer, Julie, additional, Puspitasari, Agatha M., additional, Apriyanti, Dwi, additional, Coutrier, Farah N., additional, Poespoprodjo, Jeanne R., additional, Kenangalem, Enny, additional, Andries, Benediktus, additional, Prayoga, Pak, additional, Sariyanti, Novita, additional, Smyth, Gordon K., additional, Trianty, Leily, additional, Cowman, Alan F., additional, Price, Ric N., additional, Noviyanti, Rintis, additional, and Hansen, Diana S., additional

Published
2021
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38. The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance

Author

Murithi, James M., primary, Pascal, Cécile, additional, Bath, Jade, additional, Boulenc, Xavier, additional, Gnädig, Nina F., additional, Pasaje, Charisse Flerida A., additional, Rubiano, Kelly, additional, Yeo, Tomas, additional, Mok, Sachel, additional, Klieber, Sylvie, additional, Desert, Paul, additional, Jiménez-Díaz, María Belén, additional, Marfurt, Jutta, additional, Rouillier, Mélanie, additional, Cherkaoui-Rbati, Mohammed H., additional, Gobeau, Nathalie, additional, Wittlin, Sergio, additional, Uhlemann, Anne-Catrin, additional, Price, Ric N., additional, Wirjanata, Grennady, additional, Noviyanti, Rintis, additional, Tumwebaze, Patrick, additional, Cooper, Roland A., additional, Rosenthal, Philip J., additional, Sanz, Laura M., additional, Gamo, Francisco Javier, additional, Joseph, Jayan, additional, Singh, Shivendra, additional, Bashyam, Sridevi, additional, Augereau, Jean Michel, additional, Giraud, Elie, additional, Bozec, Tanguy, additional, Vermat, Thierry, additional, Tuffal, Gilles, additional, Guillon, Jean-Michel, additional, Menegotto, Jérôme, additional, Sallé, Laurent, additional, Louit, Guillaume, additional, Cabanis, Marie-José, additional, Nicolas, Marie Françoise, additional, Doubovetzky, Michel, additional, Merino, Rita, additional, Bessila, Nadir, additional, Angulo-Barturen, Iñigo, additional, Baud, Delphine, additional, Bebrevska, Lidiya, additional, Escudié, Fanny, additional, Niles, Jacquin C., additional, Blasco, Benjamin, additional, Campbell, Simon, additional, Courtemanche, Gilles, additional, Fraisse, Laurent, additional, Pellet, Alain, additional, Fidock, David A., additional, and Leroy, Didier, additional

Published
2021
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39. Hidden Biomass of Intact Malaria Parasites in the Human Spleen

Author

Kho, Steven, primary, Qotrunnada, Labibah, additional, Leonardo, Leo, additional, Andries, Benediktus, additional, Wardani, Putu A.I., additional, Fricot, Aurelie, additional, Henry, Benoit, additional, Hardy, David, additional, Margyaningsih, Nur I., additional, Apriyanti, Dwi, additional, Puspitasari, Agatha M., additional, Prayoga, Pak, additional, Trianty, Leily, additional, Kenangalem, Enny, additional, Chretien, Fabrice, additional, Safeukui, Innocent, additional, del Portillo, Hernando A., additional, Fernandez-Becerra, Carmen, additional, Meibalan, Elamaran, additional, Marti, Matthias, additional, Price, Ric N., additional, Woodberry, Tonia, additional, Ndour, Papa A., additional, Russell, Bruce M., additional, Yeo, Tsin W., additional, Minigo, Gabriela, additional, Noviyanti, Rintis, additional, Poespoprodjo, Jeanne R., additional, Siregar, Nurjati C., additional, Buffet, Pierre A., additional, and Anstey, Nicholas M., additional

Published
2021
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40. SARS CoV-2 Antibody Seroprevalence in Jakarta, Indonesia: March 2021

Author

Ariawan, Iwan, primary, Jusril, Hafizah, additional, Farid, Muhammad N., additional, Riono, Pandu, additional, Wahyuningsih, Wiji, additional, Oktavia, Dwi, additional, Wahyuningsih, Endang Sri, additional, Daulay, Rebekka, additional, Henderiawati, Retno, additional, Malik, Safarina G., additional, Noviyanti, Rintis, additional, Trianty, Leily, additional, Fadila, Nadia, additional, Myint, Khin Saw Aye, additional, Yudhaputri, Frilasita Aisyah, additional, Hawley, William A., additional, Udhayakumar, Venkatachalam, additional, Morgan, Juliette, additional, Venkateswaran, Neeraja, additional, Venkateswaran, Kodumudi, additional, and Pronyk, Paul M., additional

Published
2021
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41. Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea

Author

Miotto, Olivo, primary, Sekihara, Makoto, additional, Tachibana, Shin-Ichiro, additional, Yamauchi, Masato, additional, Pearson, Richard D., additional, Amato, Roberto, additional, Gonçalves, Sonia, additional, Mehra, Somya, additional, Noviyanti, Rintis, additional, Marfurt, Jutta, additional, Auburn, Sarah, additional, Price, Ric N., additional, Mueller, Ivo, additional, Ikeda, Mie, additional, Mori, Toshiyuki, additional, Hirai, Makoto, additional, Tavul, Livingstone, additional, Hetzel, Manuel W., additional, Laman, Moses, additional, Barry, Alyssa E., additional, Ringwald, Pascal, additional, Ohashi, Jun, additional, Hombhanje, Francis, additional, Kwiatkowski, Dominic P., additional, and Mita, Toshihiro, additional

Published
2020
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42. Defining malaria risks among forest workers in Aceh, Indonesia: a formative assessment

Author

Ekawati, Lenny Lia, primary, Johnson, Kelly C., additional, Jacobson, Jerry O., additional, Cueto, Carmen A., additional, Zarlinda, Iska, additional, Elyazar, Iqbal RF, additional, Fatah, Abdul, additional, Sumiwi, Maria E., additional, Noviyanti, Rintis, additional, Cotter, Chris, additional, Smith, Jennifer L., additional, Coutrier, Farah N., additional, and Bennett, Adam, additional

Published
2020
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43. Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling

Author

Le Bihan, Amélie, de Kanter, Ruben, Angulo-Barturen, Iñigo, Binkert, Christoph, Boss, Christoph, Brun, Reto, Brunner, Ralf, Buchmann, Stephan, Burrows, Jeremy, Dechering, Koen J., Delves, Michael, Ewerling, Sonja, Ferrer, Santiago, Fischli, Christoph, Gamo-Benito, Francisco Javier, Gnädig, Nina F., Heidmann, Bibia, Jiménez-Díaz, María Belén, Leroy, Didier, Martínez, Maria Santos, Meyer, Solange, Moehrle, Joerg J., Ng, Caroline L., Noviyanti, Rintis, Ruecker, Andrea, Sanz, Laura María, Sauerwein, Robert W., Scheurer, Christian, Schleiferboeck, Sarah, Sinden, Robert, Snyder, Christopher, Straimer, Judith, Wirjanata, Grennady, Marfurt, Jutta, Price, Ric N., Weller, Thomas, Fischli, Walter, Fidock, David A., Clozel, Martine, and Wittlin, Sergio

Subjects
Antimalarials -- Models -- Usage -- Analysis -- Dosage and administration -- Complications and side effects, Plasmodium falciparum -- Models -- Analysis -- Physiological aspects -- Research, Malaria -- Analysis -- Models -- Drug therapy -- Research, Biological sciences
Abstract

Background Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. Method and Findings The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3-4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11-16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39). The compound's preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as survival) in relation to area under the concentration versus time curve (AUC), maximum observed plasma concentration (C.sub.max ), and time above a threshold concentration. The determination of the dose-efficacy relationship of ACT-451840 under curative conditions in rodent malaria models allowed prediction of the human efficacious exposure. Conclusion The dual activity of ACT-451840 against asexual and sexual stages of P. falciparum and the activity on P. vivax have the potential to meet the specific profile of a target compound that could replace the fast-acting artemisinin component and harbor additional gametocytocidal activity and, thereby, transmission-blocking properties. The fast parasite reduction ratio (PRR) and gametocytocidal effect of ACT-451840 were recently also confirmed in a clinical proof-of-concept (POC) study., Author(s): Amélie Le Bihan 1, Ruben de Kanter 1, Iñigo Angulo-Barturen 2, Christoph Binkert 1, Christoph Boss 1, Reto Brun 3,4, Ralf Brunner 1,3,4, Stephan Buchmann 1, Jeremy Burrows 5, [...]

Published
2016
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44. Corrigendum: A novel multiple-stage antimalarial agent that inhibits protein synthesis

Author

Baragaa, Beatriz, Hallyburton, Irene, Lee, Marcus C. S., Norcross, Neil R., Grimaldi, Raffaella, Otto, Thomas D., Proto, William R., Blagborough, Andrew M., Meister, Stephan, Wirjanata, Grennady, Ruecker, Andrea, Upton, Leanna M., Abraham, Tara S., Almeida, Mariana J., Pradhan, Anupam, Porzelle, Achim, Martnez, Mara Santos, Bolscher, Judith M., Woodland, Andrew, Luksch, Torsten, Norval, Suzanne, Zuccotto, Fabio, Thomas, John, Simeons, Frederick, Stojanovski, Laste, Osuna-Cabello, Maria, Brock, Paddy M., Churcher, Tom S., Sala, Katarzyna A., Zakutansky, Sara E., Jimnez-Daz, Mara Beln, Sanz, Laura Maria, Riley, Jennifer, Basak, Rajshekhar, Campbell, Michael, Avery, Vicky M., Sauerwein, Robert W., Dechering, Koen J., Noviyanti, Rintis, Campo, Brice, Frearson, Julie A., Angulo-Barturen, Iigo, Ferrer-Bazaga, Santiago, Gamo, Francisco Javier, Wyatt, Paul G., Leroy, Didier, Siegl, Peter, Delves, Michael J., Kyle, Dennis E., Wittlin, Sergio, Marfurt, Jutta, Price, Ric N., Sinden, Robert E., Winzeler, Elizabeth A., Charman, Susan A., Bebrevska, Lidiya, Gray, David W., Campbell, Simon, Fairlamb, Alan H., Willis, Paul A., Rayner, Julian C., Fidock, David A., Read, Kevin D., and Gilbert, Ian H.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Beatriz Baragaa; Irene Hallyburton; Marcus C. S. Lee; Neil R. Norcross; Raffaella Grimaldi; Thomas D. Otto; William R. Proto; Andrew M. Blagborough; Stephan Meister; Grennady Wirjanata; Andrea Ruecker; Leanna [...]

Published
2016
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45. Molecular surveillance over 14 years confirms reduction of Plasmodium vivax and falciparum transmission after implementation of Artemisinin-based combination therapy in Papua, Indonesia

Author

Pava, Zuleima, primary, Puspitasari, Agatha M., additional, Rumaseb, Angela, additional, Handayuni, Irene, additional, Trianty, Leily, additional, Utami, Retno A. S., additional, Tirta, Yusrifar K., additional, Burdam, Faustina, additional, Kenangalem, Enny, additional, Wirjanata, Grennady, additional, Kho, Steven, additional, Trimarsanto, Hidayat, additional, Anstey, Nicholas M., additional, Poespoprodjo, Jeanne Rini, additional, Noviyanti, Rintis, additional, Price, Ric N., additional, Marfurt, Jutta, additional, and Auburn, Sarah, additional

Published
2020
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46. A molecular barcode and online tool to identify and map imported infection with Plasmodium vivax

Author

Trimarsanto, Hidayat, primary, Amato, Roberto, additional, Pearson, Richard D, additional, Sutanto, Edwin, additional, Noviyanti, Rintis, additional, Trianty, Leily, additional, Marfurt, Jutta, additional, Pava, Zuleima, additional, Echeverry, Diego F, additional, Lopera-Mesa, Tatiana M, additional, Montenegro, Lidia Madeline, additional, Tobón-Castaño, Alberto, additional, Grigg, Matthew J, additional, Barber, Bridget, additional, William, Timothy, additional, Anstey, Nicholas M, additional, Getachew, Sisay, additional, Petros, Beyene, additional, Aseffa, Abraham, additional, Assefa, Ashenafi, additional, Rahim, Awab Ghulam, additional, Chau, Nguyen Hoang, additional, Hien, Tran Tinh, additional, Alam, Mohammad Shafiul, additional, Khan, Wasif A, additional, Ley, Benedikt, additional, Thriemer, Kamala, additional, Wangchuck, Sonam, additional, Hamedi, Yaghoob, additional, Adam, Ishag, additional, Liu, Yaobao, additional, Gao, Qi, additional, Sriprawat, Kanlaya, additional, Ferreira, Marcelo U, additional, Barry, Alyssa, additional, Mueller, Ivo, additional, Drury, Eleanor, additional, Goncalves, Sonia, additional, Simpson, Victoria, additional, Miotto, Olivo, additional, Miles, Alistair, additional, White, Nicholas J, additional, Nosten, Francois, additional, Kwiatkowski, Dominic P, additional, Price, Ric N, additional, and Auburn, Sarah, additional

Published
2019
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47. A tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance

Author

O'Neill, Paul M., Amewu, Richard K., Charman, Susan A., Sabbani, Sunil, Gnädig, Nina F., Straimer, Judith, Fidock, David A., Shore, Emma R., Roberts, Natalie L., Wong, Michael H.-L., Hong, W. David, Pidathala, Chandrakala, Riley, Chris, Murphy, Ben, Aljayyoussi, Ghaith, Gamo, Francisco Javier, Sanz, Laura, Rodrigues, Janneth, Cortes, Carolina Gonzalez, Herreros, Esperanza, Angulo-Barturén, Iñigo, Jiménez-Díaz, María Belén, Bazaga, Santiago Ferrer, Martínez-Martínez, María Santos, Campo, Brice, Sharma, Raman, Ryan, Eileen, Shackleford, David M., Campbell, Simon, Smith, Dennis A., Wirjanata, Grennady, Noviyanti, Rintis, Price, Ric N., Marfurt, Jutta, Palmer, Michael J., Copple, Ian M., Mercer, Amy E., Ruecker, Andrea, Delves, Michael J., Sinden, Robert E., Siegl, Peter, Davies, Jill, Rochford, Rosemary, Kocken, Clemens H. M., Zeeman, Anne-Marie, Nixon, Gemma L., Biagini, Giancarlo A., and Ward, Stephen A.

Subjects
Male, Erythrocytes, Science, Plasmodium falciparum, Drug Resistance, Protozoan Proteins, Mice, SCID, qv_38, wc_765, Article, Rats, Sprague-Dawley, Antimalarials, Mice, Dogs, Mice, Inbred NOD, qx_600, parasitic diseases, qv_256, Animals, Humans, Transgenes, Dose-Response Relationship, Drug, Artemisinins, wc_750, Rats, qx_20, Mutation, Female, Plasmodium vivax, Tetraoxanes, Half-Life
Abstract

K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P. falciparum and P. vivax in vitro, is efficacious against P. falciparum in in vivo rodent models, produces parasite reduction ratios equivalent to dihydroartemisinin and has pharmacokinetic and pharmacodynamic characteristics compatible with a single-dose cure. In vitro studies with transgenic parasites expressing variant forms of K13 show no cross-resistance with the C580Y mutation, the primary variant observed in Southeast Asia. E209 is a superior next generation endoperoxide with combined pharmacokinetic and pharmacodynamic features that overcome the liabilities of artemisinin derivatives., Artemisinin-resistant Plasmodium is an increasing problem. Here, using a medicinal chemistry programme, the authors identify a tetraoxane-based drug candidate that shows no cross-resistance with an artemisinin-resistant strain (PfK13-C580Y) and is efficient in Plasmodium mouse models.

Published
2017

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