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
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TLDR
An assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies is developed and validated by evaluating mixtures of laboratory parasite strains, and used to screen P. falciparum parasites from >1100 African infections collected since 2002.Abstract:
Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance.read more
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Falciparum malaria molecular drug resistance in the Democratic Republic of Congo: a systematic review
Dieudonné Makaba Mvumbi,Jean Marie Kayembe,Hippolyte Situakibanza,Thierry Lengu Bobanga,Célestin N. Nsibu,Georges Lelo Mvumbi,Pierrette Melin,Patrick De Mol,Marie-Pierre Hayette +8 more
TL;DR: A systematic review demonstrates the lack of molecular resistance studies in DRC and the MOH must implement a national surveillance system for monitoring malaria drug resistance.
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
Polymorphisms in K13, pfcrt, pfmdr1, pfdhfr, and pfdhps in parasites isolated from symptomatic malaria patients in Burkina Faso.
Anyirékun Fabrice Somé,Hermann Sorgho,Issaka Zongo,Thomas Bazié,Frederic Nikiema,Amadé Sawadogo,Moussa Zongo,Yves Daniel Compaoré,Jean-Bosco Ouédraogo +8 more
TL;DR: The results provide baseline prevalence of known drug resistance polymorphisms and suggest that artemisinin combination therapies may retain good efficacy in the treatment of uncomplicated malaria in Burkina Faso.
Journal ArticleDOI
K13-Mediated Reduced Susceptibility to Artemisinin in Plasmodium falciparum Is Overlaid on a Trait of Enhanced DNA Damage Repair.
Aoli Xiong,Aoli Xiong,Prem Prakash,Xiaohong Gao,Marvin Chew,Marvin Chew,Ian Jun Jie Tay,Charles J. Woodrow,Bevin P. Engelward,Jongyoon Han,Peter R. Preiser,Peter R. Preiser +11 more
TL;DR: A quantitative analysis of DNA damage and repair in the malaria parasite Plasmodium falciparum is performed and finds a strong link between enhanced DNA damage repair and artemisinin resistance.
Journal ArticleDOI
Impact of Daily Cotrimoxazole on Clinical Malaria and Asymptomatic Parasitemias in HIV-Exposed, Uninfected Infants
Nicole L. Davis,Eric J. Barnett,William C. Miller,Anna Dow,Charles Chasela,Michael G. Hudgens,Dumbani Kayira,Gerald Tegha,Sascha R. Ellington,Athena P. Kourtis,Charles van der Horst,Denise J. Jamieson,Jonathan J. Juliano +12 more
TL;DR: CPT appears to reduce overall malaria infections, with more prolonged impacts on asymptomatic infections, therefore, CPT prophylaxis may have important individual and public health benefits.
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