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1. Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets

Author

Dooley, Nicholas L., Chabikwa, Tinashe G., Pava, Zuleima, Loughland, Jessica R., Hamelink, Julianne, Berry, Kiana, Andrew, Dean, Soon, Megan S. F., SheelaNair, Arya, Piera, Kim A., William, Timothy, Barber, Bridget E., Grigg, Matthew J., Engwerda, Christian R., Lopez, J. Alejandro, Anstey, Nicholas M., and Boyle, Michelle J.

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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4. 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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8. Malaria drives unique regulatory responses across multiple immune cell subsets

Author

Dooley, Nicholas, primary, Chabikwa, Tinashe, additional, Pava, Zuleima, additional, Loughland, Jessica, additional, Hamelink, Julianne, additional, Berry, Kiana, additional, Andrew, Dean, additional, Soon, Megan, additional, SheelaNair, Arya, additional, Piera, Kim, additional, William, Timothy, additional, Barber, Bridget, additional, Grigg, Matthew, additional, Engwerda, Christian, additional, López, J. Alejandro, additional, Anstey, Nicholas, additional, and Boyle, Michelle, additional

Published
2022
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10. Malaria drives unique regulatory responses across multiple immune cell subsets

Author

Dooley, Nicholas L., primary, Chabikwa, Tinashe G., additional, Pava, Zuleima, additional, Loughland, Jessica R., additional, Hamelink, Julianne, additional, Berry, Kiana, additional, Andrew, Dean, additional, Soon, Megan S.F., additional, SheelaNair, Arya, additional, Piera, Kim A., additional, William, Timothy, additional, Barber, Bridget E., additional, Grigg, Matthew J., additional, Engwerda, Christian R., additional, López, J. Alejandro, additional, Anstey, Nicholas M., additional, and Boyle, Michelle J., additional

Published
2022
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11. 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

12. 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

13. Safety and feasibility of apheresis to harvest and concentrate parasites from subjects with induced blood stage Plasmodium vivax infection

Author

ODEDRA, Anand, primary, Mudie, Kari, additional, Kennedy, Glen, additional, Watts, Rebecca, additional, Rossignol, Emilie, additional, Mitchell, Hayley, additional, Gower, Jeremy, additional, Rebelo, Maria, additional, Pava, Zuleima, additional, Pawliw, Rebecca, additional, Woolley, Stephen, additional, Lalloo, David, additional, Robinson, Greg, additional, Lynch, Sean, additional, Collins, Katharine, additional, Amante, Fiona, additional, and McCarthy, James, additional

Published
2021
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15. Plasmodium falciparum artemisinin-resistant K13 mutations confer a sexual-stage transmission advantage that can be overcome with atovaquone-proguanil

Author

Pava, Zuleima, primary, Mok, Sachel, additional, Collins, Katharine A., additional, Rebelo, Maria, additional, Watts, Rebecca E., additional, Robinson, Gregory J., additional, Wang, Claire Y.T., additional, Mitchell, Hayley, additional, Lynch, Sean, additional, Gower, Jeremy, additional, Webb, Lachlan, additional, McEwan, Sam, additional, Odedra, Anand, additional, Barber, Bridget, additional, Marquart, Louise, additional, Dixon, Matthew W.A., additional, Moehrle, Joerg J., additional, Fidock, David A., additional, and McCarthy, James S., additional

Published
2020
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16. Safety and parasite clearance of artemisinin-resistant Plasmodium falciparum infection: A pilot and a randomised volunteer infection study in Australia

Author

Watts, Rebecca E., primary, Odedra, Anand, additional, Marquart, Louise, additional, Webb, Lachlan, additional, Abd-Rahman, Azrin N., additional, Cascales, Laura, additional, Chalon, Stephan, additional, Rebelo, Maria, additional, Pava, Zuleima, additional, Collins, Katharine A., additional, Pasay, Cielo, additional, Chen, Nanhua, additional, Peatey, Christopher L., additional, Möhrle, Jörg J., additional, and McCarthy, James S., additional

Published
2020
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17. 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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18. 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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19. Parasite Viability as a Superior Measure of Antimalarial Drug Activity in Humans.

Author

Rebelo, Maria, Pawliw, Rebecca, Gower, Jeremy, Webb, Lachlan, Mitchell, Hayley, Pava, Zuleima, Watts, Rebecca E, Davenport, Miles P, McCarthy, James S, and Khoury, David S

Subjects
ARTEMISININ derivatives, BLOOD parasites, POLYMERASE chain reaction, PARASITES, TRYPANOSOMA cruzi, PLASMODIUM falciparum, DRUG therapy for malaria, PROTOZOA, RESEARCH, MATHEMATICAL models, RESEARCH methodology, DRUG resistance, EVALUATION research, COMPARATIVE studies, THEORY, ANTIMALARIALS
Abstract

Background: Artemisinin derivatives are the leading class of antimalarial drugs due to their rapid onset of action and rapid clearance of circulating parasites. The parasite clearance half-life measures the rate of loss of parasites from blood after treatment, and this is currently used to assess antimalarial activity of novel agents and to monitor resistance. However, a number of recent studies have challenged the use of parasite clearance to measure drug activity, arguing that many circulating parasites may be nonviable.Methods: Plasmodium falciparum-infected subjects (n = 10) in a malaria volunteer infection study were administered a single dose of artesunate (2 mg/kg). Circulating parasite concentration was assessed by means of quantitative polymerase chain reaction (qPCR). Parasite viability after artesunate administration was estimated by mathematical modeling of the ex vivo growth of parasites collected from subjects.Results: We showed that in artemisinin-sensitive infection, viable parasites declined to <0.1% of baseline within 8 hours after artesunate administration, while the total number of circulating parasites measured with quantitative polymerase chain reaction remained unchanged. In artemisinin-resistant infections over the same interval, viable parasites declined to 51.4% (standard error of the mean, 4.6%) of baseline.Conclusions: These results demonstrate that in vivo drug activity of artesunate is faster than is indicated by the parasite clearance half-life. [ABSTRACT FROM AUTHOR]

Published
2021
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20. Passively versus Actively Detected Malaria: Similar Genetic Diversity but Different Complexity of Infection

Author

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

Published
2017
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21. Genetic micro-epidemiology of malaria in Papua Indonesia: Extensive P. vivax diversity and a distinct subpopulation of asymptomatic P. falciparum infections

Author

Pava, Zuleima, primary, Noviyanti, Rintis, additional, Handayuni, Irene, additional, Trimarsanto, Hidayat, additional, Trianty, Leily, additional, Burdam, Faustina H., additional, Kenangalem, Enny, additional, Utami, Retno A. S., additional, Tirta, Yusrifar K., additional, Coutrier, Farah, additional, Poespoprodjo, Jeanne R., additional, Price, Ric N., additional, Marfurt, Jutta, additional, and Auburn, Sarah, additional

Published
2017
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22. VivaxGEN: An open access platform for comparative analysis of short tandem repeat genotyping data in Plasmodium vivax populations

Author

Trimarsanto, Hidayat, primary, Benavente, Ernest D., additional, Noviyanti, Rintis, additional, Utami, Retno Ayu Setya, additional, Trianty, Leily, additional, Pava, Zuleima, additional, Getachew, Sisay, additional, Kim, Jung-Yeon, additional, Goo, Youn-Kyoung, additional, Wangchuck, Sonam, additional, Liu, Yaobao, additional, Gao, Qi, additional, Dowd, Simone, additional, Cheng, Qin, additional, Clark, Taane G., additional, Price, Ric N., additional, and Auburn, Sarah, additional

Published
2017
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23. Submicroscopic and Asymptomatic Plasmodium Parasitaemia Associated with Significant Risk of Anaemia in Papua, Indonesia

Author

Pava, Zuleima, primary, Burdam, Faustina H., additional, Handayuni, Irene, additional, Trianty, Leily, additional, Utami, Retno A. S., additional, Tirta, Yusrifar Kharisma, additional, Kenangalem, Enny, additional, Lampah, Daniel, additional, Kusuma, Andreas, additional, Wirjanata, Grennady, additional, Kho, Steven, additional, Simpson, Julie A., additional, Auburn, Sarah, additional, Douglas, Nicholas M., additional, Noviyanti, Rintis, additional, Anstey, Nicholas M., additional, Poespoprodjo, Jeanne R., additional, Marfurt, Jutta, additional, and Price, Ric N., additional

Published
2016
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24. Characterization of blood dendritic and regulatory T cells in asymptomatic adults with sub-microscopic Plasmodium falciparum or Plasmodium vivax infection

Author

Kho, Steven, primary, Marfurt, Jutta, additional, Handayuni, Irene, additional, Pava, Zuleima, additional, Noviyanti, Rintis, additional, Kusuma, Andreas, additional, Piera, Kim A., additional, Burdam, Faustina H., additional, Kenangalem, Enny, additional, Lampah, Daniel A., additional, Engwerda, Christian R., additional, Poespoprodjo, Jeanne R., additional, Price, Ric N., additional, Anstey, Nicholas M., additional, Minigo, Gabriela, additional, and Woodberry, Tonia, additional

Published
2016
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26. Deletion of Plasmodium falciparum Histidine-Rich Protein 2 (pfhrp2) and Histidine-Rich Protein 3 (pfhrp3) Genes in Colombian Parasites

Author

Murillo Solano, Claribel, primary, Akinyi Okoth, Sheila, additional, Abdallah, Joseph F., additional, Pava, Zuleima, additional, Dorado, Erika, additional, Incardona, Sandra, additional, Huber, Curtis S., additional, Macedo de Oliveira, Alexandre, additional, Bell, David, additional, Udhayakumar, Venkatachalam, additional, and Barnwell, John W., additional

Published
2015
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27. Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Colombia: a proof of concept

Author

Aponte, Samanda L, primary, Díaz, Gustavo, additional, Pava, Zuleima, additional, Echeverry, Diego F, additional, Ibarguen, Darío, additional, Rios, Melissa, additional, Murcia, Luz M, additional, Quelal, Claudia, additional, Murillo, Claribel, additional, Gil, Pedro, additional, Björkman, Anders, additional, and Osorio, Lyda, additional

Published
2011
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29. Expression of Plasmodium vivaxcrt-oIs Related to Parasite Stage but Not Ex VivoChloroquine Susceptibility

Author

Pava, Zuleima, Handayuni, Irene, Wirjanata, Grennady, To, Sheren, Trianty, Leily, Noviyanti, Rintis, Poespoprodjo, Jeanne Rini, Auburn, Sarah, Price, Ric N., and Marfurt, Jutta

Abstract

ABSTRACTChloroquine (CQ)-resistant Plasmodium vivaxis present in most countries where P. vivaxinfection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of P. vivaxcrt-o(pvcrt-o) has been correlated with in vivoCQ resistance in an area with low-grade resistance. We assessed pvcrt-oexpression in isolates from Papua (Indonesia), where P. vivaxis highly CQ resistant. Ex vivodrug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of pvcrt-owere measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in pvcrt-oexpression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the P. vivaxβ-tubulin gene and from 0.01 to 24 relative to that seen with the P. vivaxaldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5; P< 0.001). Twenty-nine isolates fulfilled the criteria for ex vivodrug susceptibility testing and showed high variability in CQ responses (median, 107.9 [range, 6.5 to 345.7] nM). After controlling for the parasite stage, we found that pvcrt-oexpression levels did not correlate with the ex vivoresponse to CQ or with that to any of the other antimalarials tested. Our results highlight the importance of development-stage composition for measuring pvcrt-oexpression and suggest that pvcrt-otranscription is not a primary determinant of ex vivodrug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and P. vivaxdrug resistance.

Published
2015
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30. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples.

Author

Adam I, Alam MS, Alemu S, Amaratunga C, Amato R, Andrianaranjaka V, Anstey NM, Aseffa A, Ashley E, Assefa A, Auburn S, Barber BE, Barry A, Batista Pereira D, Cao J, Chau NH, Chotivanich K, Chu C, Dondorp AM, Drury E, Echeverry DF, Erko B, Espino F, Fairhurst R, Faiz A, Fernanda Villegas M, Gao Q, Golassa L, Goncalves S, Grigg MJ, Hamedi Y, Hien TT, Htut Y, Johnson KJ, Karunaweera N, Khan W, Krudsood S, Kwiatkowski DP, Lacerda M, Ley B, Lim P, Liu Y, Llanos-Cuentas A, Lon C, Lopera-Mesa T, Marfurt J, Michon P, Miotto O, Mohammed R, Mueller I, Namaik-Larp C, Newton PN, Nguyen TN, Nosten F, Noviyanti R, Pava Z, Pearson RD, Petros B, Phyo AP, Price RN, Pukrittayakamee S, Rahim AG, Randrianarivelojosia M, Rayner JC, Rumaseb A, Siegel SV, Simpson VJ, Thriemer K, Tobon-Castano A, Trimarsanto H, Urbano Ferreira M, Vélez ID, Wangchuk S, Wellems TE, White NJ, William T, Yasnot MF, and Yilma D

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., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 MalariaGEN et al.)

Published
2022
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31. Expression of Plasmodium vivax crt-o Is Related to Parasite Stage but Not Ex Vivo Chloroquine Susceptibility.

Author

Pava Z, Handayuni I, Wirjanata G, To S, Trianty L, Noviyanti R, Poespoprodjo JR, Auburn S, Price RN, and Marfurt J

Subjects
Amodiaquine pharmacology, Artemisinins pharmacology, Artesunate, Erythrocytes drug effects, Erythrocytes parasitology, Fructose-Bisphosphate Aldolase genetics, Fructose-Bisphosphate Aldolase metabolism, Gene Expression Regulation, Humans, Inhibitory Concentration 50, Life Cycle Stages genetics, Malaria, Vivax drug therapy, Malaria, Vivax parasitology, Mefloquine pharmacology, Membrane Transport Proteins metabolism, Plasmodium vivax genetics, Plasmodium vivax growth & development, Plasmodium vivax metabolism, Protozoan Proteins metabolism, Quinolines pharmacology, Transcription, Genetic, Tubulin genetics, Tubulin metabolism, Antimalarials pharmacology, Chloroquine pharmacology, Drug Resistance, Multiple genetics, Life Cycle Stages drug effects, Membrane Transport Proteins genetics, Plasmodium vivax drug effects, Protozoan Proteins genetics
Abstract

Chloroquine (CQ)-resistant Plasmodium vivax is present in most countries where P. vivax infection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of P. vivax crt-o (pvcrt-o) has been correlated with in vivo CQ resistance in an area with low-grade resistance. We assessed pvcrt-o expression in isolates from Papua (Indonesia), where P. vivax is highly CQ resistant. Ex vivo drug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of pvcrt-o were measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in pvcrt-o expression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the P. vivax β-tubulin gene and from 0.01 to 24 relative to that seen with the P. vivax aldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5; P < 0.001). Twenty-nine isolates fulfilled the criteria for ex vivo drug susceptibility testing and showed high variability in CQ responses (median, 107.9 [range, 6.5 to 345.7] nM). After controlling for the parasite stage, we found that pvcrt-o expression levels did not correlate with the ex vivo response to CQ or with that to any of the other antimalarials tested. Our results highlight the importance of development-stage composition for measuring pvcrt-o expression and suggest that pvcrt-o transcription is not a primary determinant of ex vivo drug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and P. vivax drug resistance., (Copyright © 2015 Pava et al.)

Published
2015
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