We evaluated gametocyte carriage and intensities of gametocytaemia in 710 children presenting with acute, symptomatic, uncomplicated
Plasmodium falciparum malaria who were treated with various
antimalarial drug regimens:
chloroquine (CQ);
chloroquine plus
chlorpheniramine, a
histamine H1 receptor antagonist that reverses CQ resistance in P. falciparum in vitro and in vivo (CQCP);
chloroquine plus
ketotifen, a
histamine H1 receptor antagonist that reverses CQ resistance in P. falciparum in vitro but not in vivo in the present study (CQK);
chloroquine plus
pyrimethamine-sulphadoxine (CQPS);
amodiaquine (AQ);
amodiaquine plus
pyrimethamine-sulphadoxine (AQPS); and
pyrimethamine-sulphadoxine (PS). On presentation, gametocyte carriage was significantly higher in CQ-resistant (CQ-R) than in CQ-sensitive (CQ-S)
infections. Following CQ treatment, gametocyte carriage was significantly higher at all times
after treatment and gametocyte density significantly higher on day 7 of follow-up in children with CQ-R than CQ-S
infections. CQ treatment of CQ-R
infections resulted in significantly higher density of gametocytaemia on day 7 compared with pre-treatment (day 0), but similar treatment of CQ-S
infections resulted in significantly lower density of gametocytaemia on day 14 compared with day 0. Among children with CQ-R
infections, those with mild (RI) resistance carried gametocytes significantly more often than those with moderate (RII) resistance on days 5 and 7 of follow-up (P = 0.04 and 0.01, respectively). Disposition kinetics of gametocytaemia using a non-compartmental method showed that the half life of gametocytaemia was longer and the clearance slower in children with CQ-R than in those with CQ-S
infections. PS treatment was associated with significantly higher gametocyte carriage at all times between days 1 and 14, and significantly higher gametocytaemias on days 7 and 14 than in the other treatment regimens. Combination of AQ with PS significantly decreased gametocyte carriage at all times between days 1 and 14 of follow-up. Continuing use of CQ in CQ-R
infections may encourage transmission of CQ-R
infections; SP monotherapy is associated with significant gametocyte carriage and gametocytaemia and may encourage transmission of SP resistant
infections as resistance to the
drug increases.