The 4-aminoquinolines chloroquine (CQ) and amodiaquine (AM)
were used to treat Gambian children with uncomplicated falciparum malaria
in a randomized drug trial. Blood samples were taken immediately before
treatment (day 0), and at day 7 and day 28 after treatment. Samples
from those parasitologically positive at day 7 following treatment
(‘early positives’) and those positive at day 28 but negative
at day 7 (‘late positives’) have been studied by PCR followed
by restriction enzyme digestion to determine the allelic status of the
pfmdr 1 locus at the codon-86 position (asparagine
or tyrosine), previously associated with resistance to CQ. A
significantly higher prevalence of the tyr-86 allele was observed
in samples taken immediately before treatment (day 0) in the early
positives group when compared with the late positives
group. This suggests the tyr-86 allele contributes to drug resistance
in the early positives group. This association remained
significant for both CQ and AM groups, implying a common genetic basis
of resistance. Predominance of the allele at day
7 is consistent with a strong selection in the first week following
treatment. In the late positives group, a significantly
higher prevalence of the tyr-86 allele was observed in the samples at
day 28 when compared with those at day 0, suggestive
of selection during the period day 7 to day 28. Differences were observed
in the extent of this selection in the CQ and AM
groups. The samples were genotyped at 3 unlinked polymorphic loci. These
analyses suggested that most parasites
observed at day 7 were probably recrudescences whereas most of those at
day 28 were reinfections.