In Vivoand In VitroEfficacy of Chloroquine against Plasmodium malariaeand P. ovalein Papua, Indonesia

ABSTRACTReports of potential drug-resistant strains of Plasmodium malariaein western Indonesia raise concerns that chloroquine resistance may be emerging in P. malariaeand P. ovale. In order to assess this, in vivoand in vitroefficacy studies were conducted in patients with monoinfection in Papua, Indonesia. Consecutive patients with uncomplicated malaria due to P. ovaleor P. malariaewere enrolled in a prospective clinical trial, provided with supervised chloroquine treatment, and followed for 28 days. Blood from patients with P. malariaeor P. ovaleparasitemia greater than 1,000 per microliter underwent in vitroantimalarial drug susceptibility testing using a modified schizont maturation assay. Of the 57 evaluable patients in the clinical study (P. malariae, n= 46; P. ovale, n= 11), none had recurrence with the same species during follow-up. The mean parasite reduction ratio at 48 h was 86 (95% confidence interval [CI], 57 to 114) for P. malariaeand 150 (95% CI, 54 to 245) for P. ovale(P= 0.18). One patient infected with P. malariae, with 93% of parasites at the trophozoite stage, was still parasitemic on day 4. In vitrodrug susceptibility assays were carried out successfully for 40 isolates (34 infected with P. malariaeand 6 with P. ovale). The P. malariaeinfections at trophozoite stages had significantly higher chloroquine 50% effective concentrations (EC50s) (median, 127.9 nM [range, 7.9 to 2,980]) than those initially exposed at the ring stage (median, 14.0 nM [range, 3.5 to 27.0]; P= 0.01). The EC50for chloroquine in P. ovalewas also higher in an isolate initially at the trophozoite stage (23.2 nM) than in the three isolates predominantly at ring stage (7.8 nM). Chloroquine retains adequate efficacy against P. ovaleand P. malariae, but its marked stage specificity of action may account for reports of delayed parasite clearance times.