Journal ArticleDOI
Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria.
Abdoulaye A. Djimde,Ogobara K. Doumbo,Ousmane Traore,Ando B. Guindo,Kassoum Kayentao,Yacouba Diourte,Safiatou Niaré-Doumbo,Drissa Coulibaly,Abdoulaye K. Kone,Yacouba Cissoko,Mamadou Tekete,Bakary Fofana,Alassane Dicko,Dapa A. Diallo,Thomas E. Wellems,Dominic P. Kwiatkowski,Christopher V. Plowe +16 more
TLDR
Age-adjusted comparison of subjects able to clear resistant parasites and those unable to do so provides a new phenotype for identifying host immune and genetic factors responsible for protective immunity against malaria.Abstract:
Residents of malaria-endemic areas sometimes spontaneously clear Plasmodium falciparum infection without drug treatment, implying an important role for host factors such as immunity in this clearance. Host factors may also contribute to clearance of parasites resistant to a treatment drug. Chloroquine resistance is caused by point mutations in P. falciparum chloroquine resistance transporter (pfcrt) gene. We investigated the clearance of malaria parasites carrying the key chloroquine resistance-conferring PfCRT mutation K76T in patients treated with chloroquine. We found that the ability to clear these resistant parasites is strongly dependent on age (the best surrogate for protective immunity in endemic areas), suggesting that host immunity plays a critical role in the clearance of resistant P. falciparum infections. Age-adjusted comparison of subjects able to clear resistant parasites and those unable to do so provides a new phenotype for identifying host immune and genetic factors responsible for protective immunity against malaria.read more
Citations
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Journal ArticleDOI
Effectiveness of antimalarial drugs.
TL;DR: A global resurgence of malaria has taken place as a result of a lapse in preventive efforts and the emergence of resistance to standard antimalarial drugs.
Journal ArticleDOI
Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic.
TL;DR: Recent advances in understanding how antimalarials act and how resistance develops are reviewed, and new strategies for effectively combatting resistance, optimizing treatment and advancing the global campaign to eliminate malaria are discussed.
Journal ArticleDOI
The complexities of malaria disease manifestations with a focus on asymptomatic malaria.
Dolie D Laishram,Dolie D Laishram,Patrick L. Sutton,Nutan Nanda,Vijay Lakshmi Sharma,Ranbir Chander Sobti,Jane M. Carlton,Hema Joshi +7 more
TL;DR: The problems and obstacles to the study and control of asymptomatic malaria are discussed, the human and parasite factors associated with differential clinical outcomes are described, and the management and treatment strategies for the control of the disease are outlined.
Journal ArticleDOI
PfCRT and its role in antimalarial drug resistance
TL;DR: The results highlight the need to be vigilant in screening for the appearance of novel pfcrt alleles that could contribute to new multi-drug resistance phenotypes.
Journal ArticleDOI
A critical role for PfCRT K76T in Plasmodium falciparum verapamil-reversible chloroquine resistance
Viswanathan Lakshmanan,Patrick G. Bray,Dominik Verdier-Pinard,David J. Johnson,Paul Horrocks,Rebecca A. Muhle,George E Alakpa,Ruth H Hughes,Steve A. Ward,Donald J. Krogstad,Amar Bir Singh Sidhu,David A. Fidock +11 more
TL;DR: Findings establish PfCRT K76T as a critical component of CQR and suggest that CQ access to ferriprotoporphyrin IX is determined by drug–protein interactions involving this mutant residue.
References
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Journal ArticleDOI
Mutations in the P. falciparum Digestive Vacuole Transmembrane Protein PfCRT and Evidence for Their Role in Chloroquine Resistance
David A. Fidock,Takashi Nomura,Angela K. Talley,Roland A. Cooper,Sergey M. Dzekunov,Michael T. Ferdig,Lyann M. B. Ursos,Amar Bir Singh Sidhu,Bronwen Naudé,Kirk W. Deitsch,Xin-zhuan Su,John C. Wootton,Paul D. Roepe,Thomas E. Wellems +13 more
TL;DR: The determinant of verapamil-reversible chloroquine resistance (CQR) in a Plasmodium falciparum genetic cross maps to a 36 kb segment of chromosome 7 that harbors a 13-exon gene, pfcrt, having point mutations that associate completely with CQR in parasite lines from Asia, Africa, and South America.
Journal ArticleDOI
A molecular marker for chloroquine-resistant falciparum malaria.
Abdoulaye A. Djimde,Ogobara K. Doumbo,Joseph F. Cortese,Kassoum Kayentao,Safi N. Doumbo,Yacouba Diourte,Drissa Coulibaly,Alassane Dicko,Xin-zhuan Su,Takashi Nomura,David A. Fidock,Thomas E. Wellems,Christopher V. Plowe +12 more
TL;DR: This study shows an association between the pfcrt T76 mutation in P. falciparum and the development of chloroquine resistance during the treatment of malaria, and this mutation can be used as a marker in surveillance forchloroquine-resistant falcIParum malaria.
Journal ArticleDOI
Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum.
TL;DR: Direct proof that mutations in Pgh1 can confer resistance to mefloquine, quinine and halofantrine is provided, which has important implications for the development and efficacy of future antimalarial agents.
Journal ArticleDOI
Chloroquine-Resistant Malaria
TL;DR: Recent field studies suggest chloroquine resistance arose in > or = 4 distinct geographic foci and substantiate an important role of immunity in the outcomes of resistant infections after chlorquine treatment.
Journal ArticleDOI
Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria
Peter C. Bull,Brett Lowe,Brett Lowe,Moses Kortok,Catherine Molyneux,Chris I. Newbold,Chris I. Newbold,Kevin Marsh,Kevin Marsh +8 more
TL;DR: It is shown that the PfEMPI variants expressed during episodes of clinical malaria were less likely to be recognized by the corresponding child's own preexisting antibody response than by that of children of the same age from the same community.