Open AccessArtemisinin resistance phenotypes and K13 inheritance in a Plasmodium falciparum cross and Aotus model
Author(s) -
Juliana M. Sá,
Sarah R. Kaslow,
Michael Krause,
Viviana A. Melendez-Muniz,
Rebecca E. Salzman,
Whitney A. Kite,
Min Zhang,
Roberto R. Moraes Barros,
Jianbing Mu,
Paul K. Han,
J. Patrick Mershon,
Christine E. Figan,
Ramoncito L. Caleon,
Rifat Rahman,
Tyler J. Gibson,
Chanaki Amaratunga,
Erika P. Nishiguchi,
Kimberly F. Breglio,
Theresa Engels,
Vel Murugan,
Stacy Ricklefs,
Judith Straimer,
Nina F. Gnädig,
Bingbing Deng,
Anna Liu,
Ababacar Diouf,
Kazutoyo Miura,
Gregory Tullo,
Richard T. Eastman,
Sumana Chakravarty,
Eric R. James,
Kenneth Udenze,
Suzanne Li,
Daniel E. Sturdevant,
Robert W. Gwadz,
Stephen F. Porcella,
Carole A. Long,
David A. Fidock,
Marvin L. Thomas,
Michael P. Fay,
B. Kim Lee Sim,
Stephen L. Hoffman,
John H. Adams,
Rick M. Fairhurst,
Xinzhuan Su,
Thomas E. Wellems
Publication year - 2018
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1813386115
Subject(s) - artemisinin , plasmodium falciparum , malaria , biology , clearance , drug resistance , mutation , chloroquine , artesunate , virology , plasmodium (life cycle) , genetics , parasite hosting , immunology , gene , medicine , urology , computer science , world wide web
Significance Artemisinin-based combination therapies (ACTs) are first-line antimalarial therapies used worldwide. The artemisinin drug (ART) component clears the bulk of infection rapidly, but small numbers of persistent parasites must be removed by the partner drug. Longer parasite clearancet 1/2 values have been associated with a Kelch-propeller mutation (K13 C580Y), raising concerns of increased ART resistance. We investigated effects of C580Y by using aPlasmodium falciparum cross and a monkey malaria model. Following three standard doses of ART, infections with or without the C580Y mutation cleared to microscopically undetectable levels, as in humans; however, frequent recrudescences occurred with both types of infection. These results emphasize the importance of effective partner drugs to kill the parasites that persist through the ART component of ACT.
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