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1. Field evaluation of the diagnostic performance of EasyScan GO: a digital malaria microscopy device based on machine-learning

Author

Das, Debashish, Vongpromek, Ranitha, Assawariyathipat, Thanawat, Srinamon, Ketsanee, Kennon, Kalynn, Stepniewska, Kasia, Ghose, Aniruddha, Sayeed, Abdullah Abu, Faiz, M. Abul, Netto, Rebeca Linhares Abreu, Siqueira, Andre, Yerbanga, Serge R., Ouédraogo, Jean Bosco, Callery, James J., Peto, Thomas J., Tripura, Rupam, Koukouikila-Koussounda, Felix, Ntoumi, Francine, Ong’echa, John Michael, Ogutu, Bernhards, Ghimire, Prakash, Marfurt, Jutta, Ley, Benedikt, Seck, Amadou, Ndiaye, Magatte, Moodley, Bhavani, Sun, Lisa Ming, Archasuksan, Laypaw, Proux, Stephane, Nsobya, Sam L., Rosenthal, Philip J., Horning, Matthew P., McGuire, Shawn K., Mehanian, Courosh, Burkot, Stephen, Delahunt, Charles B., Bachman, Christine, Price, Ric N., Dondorp, Arjen M., Chappuis, François, Guérin, Philippe J., and Dhorda, Mehul

Published
2022
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3. 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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4. 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

5. 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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6. 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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7. 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

8. KAF156 Is an Antimalarial Clinical Candidate with Potential for Use in Prophylaxis, Treatment, and Prevention of Disease Transmission

Author

Kuhen, Kelli L, Chatterjee, Arnab K, Rottmann, Matthias, Gagaring, Kerstin, Borboa, Rachel, Buenviaje, Jennifer, Chen, Zhong, Francek, Carolyn, Wu, Tao, Nagle, Advait, Barnes, S Whitney, Plouffe, David, Lee, Marcus CS, Fidock, David A, Graumans, Wouter, van de Vegte-Bolmer, Marga, van Gemert, Geert J, Wirjanata, Grennady, Sebayang, Boni, Marfurt, Jutta, Russell, Bruce, Suwanarusk, Rossarin, Price, Ric N, Nosten, Francois, Tungtaeng, Anchalee, Gettayacamin, Montip, Sattabongkot, Jetsumon, Taylor, Jennifer, Walker, John R, Tully, David, Patra, Kailash P, Flannery, Erika L, Vinetz, Joseph M, Renia, Laurent, Sauerwein, Robert W, Winzeler, Elizabeth A, Glynne, Richard J, and Diagana, Thierry T

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, HIV/AIDS, Orphan Drug, Infectious Diseases, Vector-Borne Diseases, Rare Diseases, Malaria, Prevention, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Animals, Antimalarials, Imidazoles, Inhibitory Concentration 50, Malaria, Falciparum, Mice, Mice, Inbred ICR, Piperazines, Plasmodium falciparum, Sporozoites, Microbiology, Pharmacology and Pharmaceutical Sciences, Medical microbiology, Pharmacology and pharmaceutical sciences
Abstract

Renewed global efforts toward malaria eradication have highlighted the need for novel antimalarial agents with activity against multiple stages of the parasite life cycle. We have previously reported the discovery of a novel class of antimalarial compounds in the imidazolopiperazine series that have activity in the prevention and treatment of blood stage infection in a mouse model of malaria. Consistent with the previously reported activity profile of this series, the clinical candidate KAF156 shows blood schizonticidal activity with 50% inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive and drug-resistant strains, as well as potent therapeutic activity in a mouse models of malaria with 50, 90, and 99% effective doses of 0.6, 0.9, and 1.4 mg/kg, respectively. When administered prophylactically in a sporozoite challenge mouse model, KAF156 is completely protective as a single oral dose of 10 mg/kg. Finally, KAF156 displays potent Plasmodium transmission blocking activities both in vitro and in vivo. Collectively, our data suggest that KAF156, currently under evaluation in clinical trials, has the potential to treat, prevent, and block the transmission of malaria.

Published
2014

9. 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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10. Evaluation of performance for malaria diagnosis in health facilities by five provincial reference laboratories of China

Author

Zhang, Xuan, primary, Jiang, Jingjing, additional, Sui, Yuan, additional, Yan, Hui, additional, Xia, Jing, additional, Liu, Ying, additional, Sun, Lingcong, additional, Wang, Xiaoxiao, additional, Marfurt, Jutta, additional, Lu, Shenning, additional, Li, Shizhu, additional, Ruan, Wei, additional, and Wang, Duoquan, additional

Published
2023
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11. 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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12. 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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13. The changing epidemiology of Plasmodium vivax: Insights from conventional and novel surveillance tools

Author

Auburn, Sarah, Cheng, Qin, Marfurt, Jutta, and Price, Ric N.

Subjects
Plasmodium vivax -- Distribution -- Health aspects, Malaria -- Causes of -- Diagnosis -- Demographic aspects, Company distribution practices, Biological sciences
Abstract

Author(s): Sarah Auburn 1,2,3,*, Qin Cheng 4,5, Jutta Marfurt 1, Ric N. Price 1,2,3 Summary points Renewed efforts to eliminate malaria have had greater impact on Plasmodium falciparum than Plasmodium [...]

Published
2021
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14. Glucose-6-phosphate dehydrogenase activity in individuals with and without malaria: Analysis of clinical trial, cross-sectional and case-control data from Bangladesh

Author

Ley, Benedikt, Alam, Mohammad Shafiul, Kibria, Mohammad Golam, Marfurt, Jutta, Phru, Ching Swe, Ami, Jenifar Quaiyum, Thriemer, Kamala, Auburn, Sarah, Jahan, Nusrat, Johora, Fatema Tuj, Hossain, Mohammad Sharif, Koepfli, Cristian, Khan, Wasif Ali, and Price, Ric N.

Subjects
Hemolysis and hemolysins -- Risk factors, Dehydrogenases -- Physiological aspects -- Health aspects, Malaria -- Physiological aspects, Biological sciences
Abstract

Background Glucose-6-phosphate dehydrogenase (G6PD) activity is dependent upon G6PD genotype and age of the red blood cell (RBC) population, with younger RBCs having higher activity. Peripheral parasitemia with Plasmodium spp. induces hemolysis, replacing older RBCs with younger cells with higher G6PD activity. This study aimed to assess whether G6PD activity varies between individuals with and without malaria or a history of malaria. Methods and findings Individuals living in the Chittagong Hill Tracts of Bangladesh were enrolled into 3 complementary studies: (i) a prospective, single-arm clinical efficacy trial of patients (n = 175) with uncomplicated malaria done between 2014 and 2015, (ii) a cross-sectional survey done between 2015 and 2016 (n = 999), and (iii) a matched case-control study of aparasitemic individuals with and without a history of malaria done in 2020 (n = 506). G6PD activity was compared between individuals with and without malaria diagnosed by microscopy, rapid diagnostic test (RDT), or polymerase chain reaction (PCR), and in aparasitemic participants with and without a history of malaria. In the cross-sectional survey and clinical trial, 15.5% (182/1,174) of participants had peripheral parasitemia detected by microscopy or RDT, 3.1% (36/1,174) were positive by PCR only, and 81.4% (956/1,174) were aparasitemic. Aparasitemic individuals had significantly lower G6PD activity (median 6.9 U/g Hb, IQR 5.2-8.6) than those with peripheral parasitemia detected by microscopy or RDT (7.9 U/g Hb, IQR 6.6-9.8, p < 0.001), but G6PD activity similar to those with parasitemia detected by PCR alone (submicroscopic parasitemia) (6.1 U/g Hb, IQR 4.8-8.6, p = 0.312). In total, 7.7% (14/182) of patients with malaria had G6PD activity < 70% compared to 25.0% (248/992) of participants with submicroscopic or no parasitemia (odds ratio [OR] 0.25, 95% CI 0.14-0.44, p < 0.001). In the case-control study, the median G6PD activity was 10.3 U/g Hb (IQR 8.8-12.2) in 253 patients with a history of malaria and 10.2 U/g Hb (IQR 8.7-11.8) in 253 individuals without a history of malaria (p = 0.323). The proportion of individuals with G6PD activity < 70% was 11.5% (29/253) in the cases and 15.4% (39/253) in the controls (OR 0.7, 95% CI 0.41-1.23, p = 0.192). Limitations of the study included the non-contemporaneous nature of the clinical trial and cross-sectional survey. Conclusions Patients with acute malaria had significantly higher G6PD activity than individuals without malaria, and this could not be accounted for by a protective effect of G6PD deficiency. G6PD-deficient patients with malaria may have higher than expected G6PD enzyme activity and an attenuated risk of primaquine-induced hemolysis compared to the risk when not infected., Author(s): Benedikt Ley 1,*, Mohammad Shafiul Alam 2, Mohammad Golam Kibria 2, Jutta Marfurt 1, Ching Swe Phru 2, Jenifar Quaiyum Ami 2, Kamala Thriemer 1, Sarah Auburn 1, Nusrat [...]

Published
2021
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17. No association between thePlasmodium vivax crt-oMS334 or In9pvcrtpolymorphisms and chloroquine failure in a clinical cohort from Malaysia

Author

Rumaseb, Angela, primary, Moraes Barros, Roberto R., additional, Sá, Juliana M., additional, Juliano, Jonathan J., additional, William, Timothy, additional, Braima, Kamil A., additional, Barber, Bridget E., additional, Anstey, Nicholas M, additional, Price, Ric N., additional, Grigg, Matthew J., additional, Auburn, Sarah, additional, and Marfurt, Jutta, additional

Published
2022
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18. Genomic characterization of recrudescent Plasmodium malariae after treatment with artemether/lumefantrine

Author

Rutledge, Gavin G., Marr, Ian, Huang, G. Khai Lin, Auburn, Sarah, Marfurt, Jutta, Sanders, Mandy, White, Nicholas J., Berriman, Matthew, Newbold, Chris I., Anstey, Nicholas M., Otto, Thomas D., and Price, Ric N.

Subjects
DNA sequencing -- Analysis -- Health aspects, Plasmodium falciparum -- Analysis -- Health aspects, Infection -- Analysis -- Health aspects, Genomes -- Analysis -- Health aspects, Malaria -- Analysis -- Health aspects, Genomics -- Analysis -- Health aspects, Health
Abstract

During the past decade, intensification of malaria control efforts has substantially reduced the global burden of malaria from Plasmodium falciparum. This trend has often been associated with increased recognition of [...]

Published
2017
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19. 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

20. Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group

Author

Thriemer, Kamala, Bobogare, Albino, Ley, Benedikt, Gudo, Clarice Samo, Alam, Mohammad Shafiul, Anstey, Nick M., Ashley, Elizabeth, Baird, J. Kevin, Gryseels, Charlotte, Jambert, Elodie, Lacerda, Marcus, Laihad, Ferdinand, Marfurt, Jutta, Pasaribu, Ayodhia Pitaloka, Poespoprodjo, Jeanne Rini, Sutanto, Inge, Taylor, Walter R., van den Boogaard, Christel, Battle, Katherine E., Dysoley, Lek, Ghimire, Prakash, Hawley, Bill, Hwang, Jimee, Khan, Wasif Ali, Mudin, Rose Nani Binti, Sumiwi, Maria Endang, Ahmed, Rukhsana, Aktaruzzaman, M. M., Awasthi, Kiran Raj, Bardaji, Azucena, Bell, David, Boaz, Leonard, Burdam, Faustina Helen, Chandramohan, Daniel, Cheng, Qin, Chindawongsa, Keobouphaphone, Culpepper, Janice, Das, Santasabuj, Deray, Raffy, Desai, Meghna, Domingo, Gonzalo, Duoquan, Wang, Duparc, Stephan, Floranita, Rustini, Gerth-Guyette, Emily, Howes, Rosalind E., Hugo, Cecilia, Jagoe, George, Sariwati, Elvieda, Jhora, Sanya Tahmina, Jinwei, Wu, Karunajeewa, Harin, Kenangalem, Enny, Lal, Bibek Kumar, Landuwulang, Chandra, Le Perru, Emmanuel, Lee, Sang-Eun, Makita, Leo Sora, McCarthy, James, Mekuria, Asrat, Mishra, Neelima, Naket, Esau, Nambanya, Simone, Nausien, Johnny, Duc, Thang Ngo, Thi, Thuan Nguyen, Noviyanti, Rinitis, Pfeffer, Daniel, Qi, Gao, Rahmalia, Annisa, Rogerson, Stephen, Samad, Iriani, Sattabongkot, Jetsumon, Satyagraha, Ari, Shanks, Dennis, Sharma, Surender Nath, Sibley, Carol Hopkins, Sungkar, Ali, Syafruddin, Din, Talukdar, Arunansu, Tarning, Joel, ter Kuile, Feiko, Thapa, Suman, Theodora, Minerva, Huy, Tho Tran, Waramin, Edward, Waramori, Govert, Woyessa, Adugna, Wongsrichanalai, Chansuda, Xa, Nguyen Xuan, Yeom, Joon Sup, Hermawan, Lukas, Devine, Angela, Nowak, Spike, Jaya, Indra, Supargiyono, Supargiyono, Grietens, Koen Peeters, and Price, Ric N.

Published
2018
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21. Low risk of recurrence following artesunate–Sulphadoxine–pyrimethamine plus primaquine for uncomplicated Plasmodium falciparum and Plasmodium vivax infections in the Republic of the Sudan

Author

Hamid, Muzamil Mahdi Abdel, Thriemer, Kamala, Elobied, Maha E., Mahgoub, Nouh S., Boshara, Salah A., Elsafi, Hassan M. H., Gumaa, Suhaib A., Hamid, Tassneem, Abdelbagi, Hanadi, Basheir, Hamid M., Marfurt, Jutta, Chen, Ingrid, Gosling, Roly, Price, Ric N., and Ley, Benedikt

Published
2018
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23. 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

24. 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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26. Additional file 2 of Field evaluation of the diagnostic performance of EasyScan GO: a digital malaria microscopy device based on machine-learning

Author

Das, Debashish, Vongpromek, Ranitha, Assawariyathipat, Thanawat, Srinamon, Ketsanee, Kennon, Kalynn, Stepniewska, Kasia, Ghose, Aniruddha, Sayeed, Abdullah Abu, Faiz, M. Abul, Netto, Rebeca Linhares Abreu, Siqueira, Andre, Yerbanga, Serge R., Ouédraogo, Jean Bosco, Callery, James J., Peto, Thomas J., Tripura, Rupam, Koukouikila-Koussounda, Felix, Ntoumi, Francine, Ong’echa, John Michael, Ogutu, Bernhards, Ghimire, Prakash, Marfurt, Jutta, Ley, Benedikt, Seck, Amadou, Ndiaye, Magatte, Moodley, Bhavani, Sun, Lisa Ming, Archasuksan, Laypaw, Proux, Stephane, Nsobya, Sam L., Rosenthal, Philip J., Horning, Matthew P., McGuire, Shawn K., Mehanian, Courosh, Burkot, Stephen, Delahunt, Charles B., Bachman, Christine, Price, Ric N., Dondorp, Arjen M., Chappuis, François, Guérin, Philippe J., and Dhorda, Mehul

Abstract

Additional file 2. Parasite Density Estimation.

Published
2022
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27. Additional file 1 of A fluorometric assay to determine the protective effect of glucose-6-phosphate dehydrogenase (G6PD) against a Plasmodium spp. infection in females heterozygous for the G6PD gene: proof of concept in Plasmodium falciparum

Author

Rumaseb, Angela, Marfurt, Jutta, Kho, Steven, Kahn, Maria, Price, Ric N., and Ley, Benedikt

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, hemic and lymphatic diseases, parasitic diseases, nutritional and metabolic diseases
Abstract

Additional file 1. Standard operating procedure for G6PD analysis in Plasmodium-infected red blood cells.

Published
2022
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28. Additional file 3 of Field evaluation of the diagnostic performance of EasyScan GO: a digital malaria microscopy device based on machine-learning

Author

Das, Debashish, Vongpromek, Ranitha, Assawariyathipat, Thanawat, Srinamon, Ketsanee, Kennon, Kalynn, Stepniewska, Kasia, Ghose, Aniruddha, Sayeed, Abdullah Abu, Faiz, M. Abul, Netto, Rebeca Linhares Abreu, Siqueira, Andre, Yerbanga, Serge R., Ouédraogo, Jean Bosco, Callery, James J., Peto, Thomas J., Tripura, Rupam, Koukouikila-Koussounda, Felix, Ntoumi, Francine, Ong’echa, John Michael, Ogutu, Bernhards, Ghimire, Prakash, Marfurt, Jutta, Ley, Benedikt, Seck, Amadou, Ndiaye, Magatte, Moodley, Bhavani, Sun, Lisa Ming, Archasuksan, Laypaw, Proux, Stephane, Nsobya, Sam L., Rosenthal, Philip J., Horning, Matthew P., McGuire, Shawn K., Mehanian, Courosh, Burkot, Stephen, Delahunt, Charles B., Bachman, Christine, Price, Ric N., Dondorp, Arjen M., Chappuis, François, Guérin, Philippe J., and Dhorda, Mehul

Abstract

Additional file 3. EasyScan Go.

Published
2022
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29. Additional file 1 of Field evaluation of the diagnostic performance of EasyScan GO: a digital malaria microscopy device based on machine-learning

Author

Das, Debashish, Vongpromek, Ranitha, Assawariyathipat, Thanawat, Srinamon, Ketsanee, Kennon, Kalynn, Stepniewska, Kasia, Ghose, Aniruddha, Sayeed, Abdullah Abu, Faiz, M. Abul, Netto, Rebeca Linhares Abreu, Siqueira, Andre, Yerbanga, Serge R., Ouédraogo, Jean Bosco, Callery, James J., Peto, Thomas J., Tripura, Rupam, Koukouikila-Koussounda, Felix, Ntoumi, Francine, Ong’echa, John Michael, Ogutu, Bernhards, Ghimire, Prakash, Marfurt, Jutta, Ley, Benedikt, Seck, Amadou, Ndiaye, Magatte, Moodley, Bhavani, Sun, Lisa Ming, Archasuksan, Laypaw, Proux, Stephane, Nsobya, Sam L., Rosenthal, Philip J., Horning, Matthew P., McGuire, Shawn K., Mehanian, Courosh, Burkot, Stephen, Delahunt, Charles B., Bachman, Christine, Price, Ric N., Dondorp, Arjen M., Chappuis, François, Guérin, Philippe J., and Dhorda, Mehul

Abstract

Additional file 1. STARD-2015-Checklist.

Published
2022
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30. Additional file 2 of A fluorometric assay to determine the protective effect of glucose-6-phosphate dehydrogenase (G6PD) against a Plasmodium spp. infection in females heterozygous for the G6PD gene: proof of concept in Plasmodium falciparum

Author

Rumaseb, Angela, Marfurt, Jutta, Kho, Steven, Kahn, Maria, Price, Ric N., and Ley, Benedikt

Subjects
parasitic diseases
Abstract

Additional file 2. Flow cytometry data from schizont and ring stages of P. falciparum FC27.

Published
2022
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31. 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

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. 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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38. 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

39. Diagnostic Practices and Treatment for P. vivax in the InterEthnic Therapeutic Encounter of South-Central Vietnam: A Mixed-Methods Study

Author

Nguyen, Thuan Thi, primary, Nguyen, Xa Xuan, additional, Ronse, Maya, additional, Nguyen, Quynh Truc, additional, Ho, Phuc Quang, additional, Tran, Duong Thanh, additional, Gerrets, Rene, additional, Thriemer, Kamala, additional, Ley, Benedikt, additional, Marfurt, Jutta, additional, Price, Ric N., additional, Grietens, Koen Peeters, additional, and Gryseels, Charlotte, additional

Published
2020
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40. 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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41. 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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43. 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

44. 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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45. 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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47. Therapeutic response to Dihydroartemisinin-Piperaquine for P. falciparum and P. vivax nine years after its introduction in Southern Papua, Indonesia

Author

Poespoprodjo, Jeanne Rini, Kenangalem, Enny, Wafom, Johny, Chandrawati, Freis, Puspitasari, Agatha M., Ley, Benedikt, Trianty, Leily, Korten, Zoé, Surya, Asik, Syafruddin, Din, Anstey, Nicholas M., Marfurt, Jutta, Noviyanti, Rintis, and Price, Ric N.

Subjects
Adult, Adolescent, Infant, Articles, Middle Aged, Parasitemia, Artemisinins, Antimalarials, Drug Combinations, Young Adult, Child, Preschool, parasitic diseases, Malaria, Vivax, Quinolines, Humans, Prospective Studies, Treatment Failure, Malaria, Falciparum, Child
Abstract

Dihydroartemisinin–piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days. Clinical and laboratory data were collected daily until parasite clearance and then weekly for 6 weeks. Molecular analysis was undertaken for all patients with recurrent parasitemia. A total of 129 study patients were enrolled in the study. At day 42, the polymerase chain reaction-adjusted efficacy was 97.7% (95% confidence intervals [CI]: 87.4–99.9) in the 61 patients with P. falciparum malaria, and 98.2% [95% CI: 90.3–100] in the 56 patients with P. vivax malaria. By day 2, 98% (56/57) of patients with P. falciparum and 96.9% (63/65) of those with P. vivax had cleared their peripheral parasitemia; none of the patients were still parasitaemic on day 3. Molecular analysis of P. falciparum parasites showed that none (0/61) had K13 mutations associated previously with artemisinin resistance or increased copy number of plasmepsin 2–3 (0/61). In the absence of artemisinin resistance, DHP has retained high efficacy for the treatment of uncomplicated malaria despite extensive drug pressure over a 9-year period.

Published
2018

49. 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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50. Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial

Author

Taylor, Walter R J, primary, Thriemer, Kamala, additional, von Seidlein, Lorenz, additional, Yuentrakul, Prayoon, additional, Assawariyathipat, Thanawat, additional, Assefa, Ashenafi, additional, Auburn, Sarah, additional, Chand, Krisin, additional, Chau, Nguyen Hoang, additional, Cheah, Phaik Yeong, additional, Dong, Le Thanh, additional, Dhorda, Mehul, additional, Degaga, Tamiru Shibru, additional, Devine, Angela, additional, Ekawati, Lenny L, additional, Fahmi, Fahmi, additional, Hailu, Asrat, additional, Hasanzai, Mohammad Anwar, additional, Hien, Tran Tinh, additional, Khu, Htee, additional, Ley, Benedikt, additional, Lubell, Yoel, additional, Marfurt, Jutta, additional, Mohammad, Hussein, additional, Moore, Kerryn A, additional, Naddim, Mohammad Nader, additional, Pasaribu, Ayodhia Pitaloka, additional, Pasaribu, Syahril, additional, Promnarate, Cholrawee, additional, Rahim, Awab Ghulam, additional, Sirithiranont, Pasathron, additional, Solomon, Hiwot, additional, Sudoyo, Herawati, additional, Sutanto, Inge, additional, Thanh, Ngo Viet, additional, Tuyet-Trinh, Nguyen Thi, additional, Waithira, Naomi, additional, Woyessa, Adugna, additional, Yamin, Fazal Yamin, additional, Dondorp, Arjen, additional, Simpson, Julie A, additional, Baird, J Kevin, additional, White, Nicholas J, additional, Day, Nicholas P, additional, and Price, Ric N, additional

Published
2019
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