Plasmodium falciparum clearance in clinical studies of artesunate-amodiaquine and comparator treatments in sub-Saharan Africa, 1999–2009
Julien Zwang,Grant Dorsey,Andreas Mårtensson,Umberto D'Alessandro,Jean Louis Ndiaye,Corine Karema,Abdoulaye Djimde,Philippe Brasseur,Sodiomon B. Sirima,Piero Olliaro +9 more
Reads0
Chats0
TLDR
Within the period covered by these studies, rapid Plasmodium falciparum clearance continues to be achieved in Sub-Saharan African patients treated with ACT, and in particular with ASAQ, and the prediction formula for parasite clearance time could be a pragmatic tool for studies with binary outcomes and once-daily sampling.Abstract:
Artemisinin-based combination therapy (ACT) is the recommended first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide but decreased artemisinin susceptibility, phenotypically characterized as slow parasite clearance time (PCT), has now been reported in Southeast Asia. This makes it all too important to measure the dynamics of parasite clearance in African patients treated with ACT over time, to understand trends and detect changes early enough to intervene Individual patient data from 27 clinical trials of artesunate-amodiaquine (ASAQ) vs comparators conducted between 1999 and 2009 were analysed for parasite clearance on modified intent-to-treat (ITT) basis. Overall 15,017 patients treated for uncomplicated P. falciparum malaria at 44 sites in 20 sub-Saharan African countries were included in the analysis; 51% (n=7,660) vs 49% (n=7,357) were treated with ASAQ and comparator treatments, respectively. Seventy-seven per cent (77%) were children under six years of age. The proportion of the patients treated with ASAQ with persistent parasitaemia on Day 2 was 8.6%, and 1.5% on Day 3. Risk factor for not clearing parasites on Day 2 and Day 3 calculated by multivariate logistic regression with random effect on site and controlling for treatment were: high parasitaemia before treatment was (adjusted risk ratios (AOR) 2.12, 95% CI 1.91-2.35, AOR 2.43, 95% CI 1.98-3.00, respectively); non-ACT treatment (p=0.001, for all comparisons). Anaemia (p=0.001) was an additional factor for Day 2 and young age (p=0.005) for Day 3. In patients treated with ASAQ in studies who had complete parasitaemia data every 24 hours up to Day 3 and additionally Day 7, the parasite reduction ratio was 93.9% by Day 1 and 99.9% by Day 2. Using the median parasitaemia before treatment (p0=27,125 μL) and a fitted model, the predicted PCT (pPCT = 3.614*ln (p0) – 6.135, r² = 0.94) in ASAQ recipients was 31 hours. Within the period covered by these studies, rapid Plasmodium falciparum clearance continues to be achieved in Sub-Saharan African patients treated with ACT, and in particular with ASAQ. The prediction formula for parasite clearance time could be a pragmatic tool for studies with binary outcomes and once-daily sampling, both for research and monitoring purposes.read more
Citations
More filters
Journal ArticleDOI
Polymorphisms in K13 and Falcipain-2 Associated with Artemisinin Resistance Are Not Prevalent in Plasmodium falciparum Isolated from Ugandan Children
Melissa D. Conrad,Victor Bigira,James Kapisi,Mary K. Muhindo,Moses R. Kamya,Diane V. Havlir,Grant Dorsey,Philip J. Rosenthal +7 more
TL;DR: The prevalence of K13-propeller and FP2 polymorphisms did not increase over time, and was not associated with either time since prior receipt of an ACT or the persistence of parasites ≥2 days following treatment with an ACT, indicating that artemisinin resistance is not prevalent in Uganda.
Journal ArticleDOI
Temporal trends in prevalence of Plasmodium falciparum molecular markers selected for by artemether–lumefantrine treatment in pre-ACT and post-ACT parasites in western Kenya
Angela O. Achieng,Peninah Muiruri,Luicer A. Ingasia,Benjamin Opot,Dennis W. Juma,Redemptah Yeda,Bidii S. Ngalah,Bernhards Ogutu,Ben Andagalu,Hoseah M. Akala,Edwin Kamau +10 more
TL;DR: There is a significant change in parasite genotype, with key molecular determinants of AL selection almost reaching saturation, and there is need to closely monitor parasite genotypic, phenotypic and clinical dynamics in response to continued use of AL in western Kenya.
Journal ArticleDOI
Insight into k13-propeller gene polymorphism and ex vivo DHA-response profiles from Cameroonian isolates.
Sandie Menard,Joëlle Njila Tchoufack,Christelle Ngou Maffo,Sandrine E. Nsango,Xavier Iriart,Luc Abate,Majoline Tchioffo Tsapi,Parfait Awono-Ambene,Francis A. Abega Mekongo,Isabelle Morlais,Antoine Berry +10 more
TL;DR: This study demonstrated the absence of k13-resistant genotypes in P. falciparum isolates from Cameroon, giving a baseline for the long-term monitoring of artemisinin derivative efficacy in Africa.
Journal ArticleDOI
Antileukemic activity and cellular effects of the antimalarial agent artesunate in acute myeloid leukemia.
Bijender Kumar,Arjun Kalvala,Su Chu,Steven D. Rosen,Stephen J. Forman,Guido Marcucci,Ching-Cheng Chen,Vinod Pullarkat +7 more
TL;DR: The results demonstrate the potent preclinical antileukemic activity of ARTS as well as its potential for a rapid transition to a clinical trial either alone or in combination with conventional chemotherapy or BCL-2 inhibitor, for treatment of AML.
Journal ArticleDOI
Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy.
Mónica Guerra,Rita Neres,Patrícia Salgueiro,Cristina Mendes,Nicolas Ndong-Mabale,Pedro Berzosa,Bruno de Sousa,Ana Paula Arez +7 more
TL;DR: An analysis of P. falciparum genetic diversity, focusing on antimalarial resistance-associated molecular markers in two socioeconomically different villages in mainland Equatorial Guinea, suggests that closer monitoring should be maintained to prevent the possible spread of artemisinin resistance in Africa.
References
More filters
Journal ArticleDOI
Reduced artemisinin susceptibility of Plasmodium falciparum ring stages in western Cambodia
Benoit Witkowski,Nimol Khim,Pheaktra Chim,Saorin Kim,Sopheakvatey Ke,Nimol Kloeung,Sophie Chy,Socheat Duong,Rithea Leang,Pascal Ringwald,Arjen M. Dondorp,Rupam Tripura,Françoise Benoit-Vical,Antoine Berry,Olivier Gorgette,Frédéric Ariey,Jean-Christophe Barale,Odile Mercereau-Puijalon,Didier Menard +18 more
TL;DR: The reduced susceptibility to artemisinin in Pailin appears to be associated with an altered in vitro phenotype of ring stages from Pailsin in the RSA, which is associated with a clear-cut geographic dichotomy.
Journal ArticleDOI
Efficacy of Artesunate Plus Amodiaquine versus That of Artemether-Lumefantrine for the Treatment of Uncomplicated Childhood Plasmodium falciparum Malaria in Zanzibar, Tanzania
Andreas Mårtensson,Johan Strömberg,Christin Sisowath,Mwinyi I. Msellem,J. Pedro Gil,Scott Montgomery,Scott Montgomery,Piero Olliaro,Abdullah S. Ali,Anders Björkman +9 more
TL;DR: Both treatments were highly efficacious, but AL provided stronger prevention against reinfection and the genetic selection by the long-acting partner drug underlines the importance of long follow-up periods in clinical trials.
Journal ArticleDOI
Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial.
Grant Dorsey,Sarah G. Staedke,Tamara D. Clark,Denise Njama-Meya,Bridget Nzarubara,Catherine Maiteki-Sebuguzi,Christian Dokomajilar,Moses R. Kamya,Philip J. Rosenthal +8 more
TL;DR: A single-blind randomized clinical trial, conducted between November 2004 and June 2006, of treatment for all episodes of uncomplicated malaria in children in an urban community in Kampala, Uganda, was conducted as mentioned in this paper.
Journal ArticleDOI
The parasite clearance curve.
TL;DR: The slope of the log-linear segment in the middle of the parasite clearance curve has the least inter-individual variance and is the focus of therapeutic assessment.
Journal ArticleDOI
In vivo parasitological measures of artemisinin susceptibility.
Kasia Stepniewska,Kasia Stepniewska,Elizabeth A. Ashley,Elizabeth A. Ashley,Sue J. Lee,Sue J. Lee,Nicholas M. Anstey,Karen I. Barnes,Tran Quang Binh,Umberto D'Alessandro,Nicholas P. J. Day,Nicholas P. J. Day,Peter J. de Vries,Grant Dorsey,Jean-Paul Guthmann,Mayfong Mayxay,Paul N. Newton,Piero Olliaro,Piero Olliaro,Lyda Osorio,Ric N. Price,Mark Rowland,Frank Smithuis,Walter R. J. Taylor,François Nosten,François Nosten,Nicholas J. White,Nicholas J. White +27 more
TL;DR: In this article, the authors analyzed data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low, moderate and high levels of malaria transmission across the world and identified a simple in vivo screening measure for Artemisinin resistance.
Related Papers (5)
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
Frédéric Ariey,Benoit Witkowski,Chanaki Amaratunga,Johann Beghain,Anne-Claire Langlois,Nimol Khim,Saorin Kim,Valentine Duru,Christiane Bouchier,Laurence Ma,Pharath Lim,Rithea Leang,Socheat Duong,Sokunthea Sreng,Seila Suon,Char Meng Chuor,Denis Mey Bout,Sandie Menard,William O. Rogers,Blaise Genton,Thierry Fandeur,Olivo Miotto,Pascal Ringwald,Jacques Le Bras,Antoine Berry,Jean Christophe Barale,Rick M. Fairhurst,Françoise Benoit-Vical,Odile Mercereau-Puijalon,Didier Menard +29 more
Spread of Artemisinin Resistance in Plasmodium falciparum Malaria
Elizabeth A. Ashley,Mehul Dhorda,Rick M. Fairhurst,Chanaki Amaratunga,Pharath Lim,Seila Suon,Sokunthea Sreng,Jennifer M. Anderson,Mao S,Sam B,Chantha Sopha,Char Meng Chuor,Chea Nguon,Siv Sovannaroth,Sasithon Pukrittayakamee,Podjanee Jittamala,Kesinee Chotivanich,K Chutasmit,C Suchatsoonthorn,R Runcharoen,Tran Tinh Hien,Nguyen Thuy-Nhien,Thanh Nv,Nguyen Hoan Phu,Ye Htut,Han Kt,Kyin Hla Aye,Olugbenga A. Mokuolu,Rasaq Olaosebikan,Olaleke Oluwasegun Folaranmi,Mayfong Mayxay,Maniphone Khanthavong,Bouasy Hongvanthong,Paul N. Newton,M A Onyamboko,Caterina I. Fanello,Antoinette Tshefu,Neelima Mishra,Neena Valecha,Aung Pyae Phyo,François Nosten,Yi P,Rupam Tripura,Steffen Borrmann,Mahfudh Bashraheil,Judy Peshu,M A Faiz,Aniruddha Ghose,M A Hossain,Rasheda Samad,M. R. Rahman,Manal Hasan,Ashraful Islam,Olivo Miotto,Roberto Amato,Bronwyn MacInnis,Jim Stalker,Dominic P. Kwiatkowski,Zbynek Bozdech,Atthanee Jeeyapant,Phaik Yeong Cheah,Tharisara Sakulthaew,Jeremy Chalk,Benjamas Intharabut,Kamolrat Silamut,Lee Sj,Benchawan Vihokhern,Chanon Kunasol,Mallika Imwong,Joel Tarning,Taylor Wj,Shunmay Yeung,Charles J. Woodrow,Jennifer A. Flegg,Debashish Das,Jennifer L. Smith,Meera Venkatesan,Christopher V. Plowe,Kasia Stepniewska,Philippe J Guerin,Arjen M. Dondorp,Nicholas P. J. Day,Nicholas J. White +82 more
Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study
Steve M. Taylor,Steve M. Taylor,Christian M. Parobek,Derrick K. DeConti,Kassoum Kayentao,Sheick Oumar Coulibaly,Brian Greenwood,Harry Tagbor,John V. Williams,Kalifa Bojang,Fanta Njie,Meghna Desai,Simon Kariuki,Julie Gutman,Don P. Mathanga,Andreas Mårtensson,Billy Ngasala,Melissa D. Conrad,Philip J. Rosenthal,Antoinette Tshefu,Ann M. Moormann,John M. Vulule,Ogobara K. Doumbo,Feiko O. ter Kuile,Feiko O. ter Kuile,Steven R. Meshnick,Jeffrey A. Bailey,Jonathan J. Juliano +27 more
Artemisinin Resistance in Plasmodium falciparum Malaria
Arjen M. Dondorp,François Nosten,Poravuth Yi,Debashish Das,Aung Phae Phyo,Joel Tarning,Khin Maung Lwin,Frédéric Ariey,Warunee Hanpithakpong,Sue J. Lee,Pascal Ringwald,Kamolrat Silamut,Mallika Imwong,Kesinee Chotivanich,Pharath Lim,Trent Herdman,Sen Sam An,Shunmay Yeung,Pratap Singhasivanon,Nicholas P. J. Day,Niklas Lindegardh,Duong Socheat,Nicholas J. White +22 more