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
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
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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
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Journal ArticleDOI
Efficacy, Safety, and Selection of Molecular Markers of Drug Resistance by Two ACTs in Mali
Abdoulaye Djimde,Bakary Fofana,Issaka Sagara,Bakary Sidibe,Sekou Toure,Demba Dembele,Souleymane Dama,Dinkorma T. Ouologuem,Alassane Dicko,Ogobara K. Doumbo +9 more
TL;DR: The ACTs were efficacious and safe, but the selection of markers for resistance to the partner drugs raises concerns over their lifespan in areas of intense malaria transmission.
Journal ArticleDOI
Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria
Jean Louis Ndiaye,Milijaona Randrianarivelojosia,Issaka Sagara,Philippe Brasseur,Ibrahima Ndiaye,Babacar Faye,Laurence Randrianasolo,Arsène Ratsimbasoa,Doris Forlemu,Vicky Jocelyne Ama Moor,Aminata Traore,Yahia Dicko,Niawanlou Dara,Valerie Lameyre,Mouctar Diallo,Abdoulaye Djimde,Albert Same-Ekobo,Oumar Gaye +17 more
TL;DR: The non-inferiority of ASAQ compared with AL was demonstrated and the fixed-dose combination artesunate + amodiaquine (ASAQ) is safe and efficacious even in young children under 5 years of age.
Journal ArticleDOI
Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis
Julien Zwang,Piero Olliaro,Hubert Barennes,Maryline Bonnet,Philippe Brasseur,Hasifa Bukirwa,Sandra Cohuet,Umberto D'Alessandro,Abdulaye Djimdé,Corine Karema,Jean-Paul Guthmann,Sally Hamour,Jean Louis Ndiaye,Andreas Mårtensson,Claude Rwagacondo,Issaka Sagara,Albert Same-Ekobo,Sodiomon B. Sirima,Ingrid van den Broek,Adoke Yeka,Walter Rj Taylor,Grant Dorsey,Milijaona Randrianarivelojosia +22 more
TL;DR: AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied.
Journal ArticleDOI
Efficacy of three artemisinin combination therapies for the treatmentof uncomplicated Plasmodium falciparum malaria in the Republic of Congo
Ingrid van den Broek,Christa Kitz,Sarwatt Al Attas,François Libama,Manica Balasegaram,Jean-Paul Guthmann +5 more
TL;DR: Considering the higher efficacy of AL as compared to AS+SP and the relatively high proportion of cases with re-infections in the AS+AQ group, it is concluded that AL is clinically more effective than AS+ SP and AS-AQ in this area of the Republic of Congo.
Journal ArticleDOI
No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali
Amelia Walling Maiga,Bakary Fofana,Issaka Sagara,Demba Dembele,Antoine Dara,Oumar B Traore,Sekou Toure,Kassim Sanogo,Souleymane Dama,Bakary Sidibe,Aminatou Kone,Mahamadou A. Thera,Christopher V. Plowe,Ogobara K. Doumbo,Abdoulaye Djimde +14 more
TL;DR: Artesunate was highly efficacious, with no evidence of delayed parasite clearance, and baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa is provided.
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