Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria.
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.
Djimdé
Abdoulaye A
AA
Bandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali.
Doumbo
Ogobara K
OK
Traore
Ousmane
O
Guindo
Ando B
AB
Kayentao
Kassoum
K
Diourte
Yacouba
Y
Niare-Doumbo
Safiatou
S
Coulibaly
Drissa
D
Kone
Abdoulaye K
AK
Cissoko
Yacouba
Y
Tekete
Mamadou
M
Fofana
Bakary
B
Dicko
Alassane
A
Diallo
Dapa A
DA
Wellems
Thomas E
TE
Kwiatkowski
Dominic
D
Plowe
Christopher V
CV
D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology* / Q000469:parasitology; D008297:Male; D008302:Mali / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000235:genetics*; D017354:Point Mutation
D000962:Antimalarials; D002738:Chloroquine