CLEARANCE OF DRUG-RESISTANT PARASITES AS A MODEL FOR PROTECTIVE IMMUNITY IN PLASMODIUM FALCIPARUM MALARIA

• Published in: The American journal of tropical medicine and hygiene Vol. 69; no. 5; pp. 558 - 563
• Main Authors: DJIMDE, ABDOULAYE A, DOUMBO, OGOBARA K, TRAORE, OUSMANE, GUINDO, ANDO B, KAYENTAO, KASSOUM, DIOURTE, YACOUBA, NIARE-DOUMBO, SAFIATOU, COULIBALY, DRISSA, KONE, ABDOULAYE K, CISSOKO, YACOUBA, TEKETE, MAMADOU, FOFANA, BAKARY, DICKO, ALASSANE, DIALLO, DAPA A, WELLEMS, THOMAS E, KWIATKOWSKI, DOMINIC, PLOWE, CHRISTOPHER V
• Format: Journal Article
• Language: English
• Published: Lawrence, KS ASTMH 01.11.2003; Allen Press
• Subjects: Adolescent; Animals; Antimalarials - therapeutic use; Biological and medical sciences; Child; Child, Preschool; Chloroquine - therapeutic use; Drug Resistance - genetics; Female; Human protozoal diseases; Humans; Infant; Infectious diseases; Malaria; Malaria, Falciparum - blood; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Male; Mali - epidemiology; Medical sciences; Parasitic diseases; Plasmodium falciparum; Plasmodium falciparum - genetics; Point Mutation; Protozoal diseases; Mali; Africa; Human; Protozoa; Antimalarial; Apicomplexa; Protozoal disease; Malaria; Parasitosis; Immunity; Blood; Infection; Resistance; Plasmodium falciparum; Tropical medicine; Models
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.2003.69.558

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.