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.
Faculty of Medicine and Health Sciences, University Malaysia Sarawak, 93150, Sarawak, Malaysian Borneo, Kuching, Malaysia. cox@tm.net.my
J
J
Cox-Singh
H Y
HY
Lu
T M E
TM
Davis
K F
KF
Ilett
L P
LP
Hackett
A
A
Matusop
B
B
Singh
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