Application of a multi-faceted approach for the assessment of treatment response in falciparum malaria: a study from Malaysian Borneo.
Thirty-two patients reporting to the Lundu District Hospital, Sarawak, Malaysian Borneo, with uncomplicated falciparum malaria were recruited into a multifaceted study to assess treatment response. Following combined chloroquine and sulphadoxine/pyrimethamine treatment the patients were followed for 28 days according to the World Health Organisation in vivo drug response protocol. The in vivo study revealed that 13 (41%) of the patients had a sensitive response to treatment, five (16%) cleared asexual stage parasites but had persistent gametocytes, 11 (34%) had RI type resistance and three (9%) had RII type resistance requiring quinine intervention before day 7 for parasite clearance. Although clinically insignificant, patients with persistent gametocytes, surviving chloroquine and sulphadoxine/pyrimethamine treatment during maturation, were placed in the reduced response to treatment group for analysis. Allelic typing detected 100% prevalence of the pfcrt K76T marker associated with chloroquine resistance and 78% prevalence of the pfdhfr NRNL haplotype associated with sulphadoxine/pyrimethamine treatment failure. High serum chloroquine levels and pfdhfr haplotypes with <or=2 point mutations were independently associated with a sensitive response to treatment. However four patients in the sensitive response group had both low serum chloroquine levels and the pfdhfr NRNL haplotype. A degree of immunity, consistent with malaria endemicity, may account for the apparently paradoxical presence of markers of drug resistance in the sensitive group.
Cox-Singh
J
J
Faculty of Medicine and Health Sciences, University Malaysia Sarawak, 93150, Sarawak, Malaysian Borneo, Kuching, Malaysia. cox@tm.net.my
Lu
H Y
HY
Davis
T M E
TM
Ilett
K F
KF
Hackett
L P
LP
Matusop
A
A
Singh
B
B
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D001893:Borneo; D002738:Chloroquine / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019450:Genes, MDR; D017125:Genes, Protozoan; D005819:Genetic Markers; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000235:genetics; D017354:Point Mutation; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D016896:Treatment Outcome
D000962:Antimalarials; D005819:Genetic Markers; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine