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<jats:title>ABSTRACT</jats:title><jats:p>Reports of potential drug-resistant strains of<jats:italic>Plasmodium malariae</jats:italic>in western Indonesia raise concerns that chloroquine resistance may be emerging in<jats:italic>P. malariae</jats:italic>and<jats:italic>P. ovale</jats:italic>. In order to assess this,<jats:italic>in vivo</jats:italic>and<jats:italic>in vitro</jats:italic>efficacy studies were conducted in patients with monoinfection in Papua, Indonesia. Consecutive patients with uncomplicated malaria due to<jats:italic>P. ovale</jats:italic>or<jats:italic>P. malariae</jats:italic>were enrolled in a prospective clinical trial, provided with supervised chloroquine treatment, and followed for 28 days. Blood from patients with<jats:italic>P. malariae</jats:italic>or<jats:italic>P. ovale</jats:italic>parasitemia greater than 1,000 per microliter underwent<jats:italic>in vitro</jats:italic>antimalarial drug susceptibility testing using a modified schizont maturation assay. Of the 57 evaluable patients in the clinical study (<jats:italic>P. malariae</jats:italic>,<jats:italic>n</jats:italic>= 46;<jats:italic>P. ovale</jats:italic>,<jats:italic>n</jats:italic>= 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<jats:italic>P. malariae</jats:italic>and 150 (95% CI, 54 to 245) for<jats:italic>P. ovale</jats:italic>(<jats:italic>P</jats:italic>= 0.18). One patient infected with<jats:italic>P. malariae</jats:italic>, with 93% of parasites at the trophozoite stage, was still parasitemic on day 4.<jats:italic>In vitro</jats:italic>drug susceptibility assays were carried out successfully for 40 isolates (34 infected with<jats:italic>P. malariae</jats:italic>and 6 with<jats:italic>P. ovale</jats:italic>). The<jats:italic>P. malariae</jats:italic>infections at trophozoite stages had significantly higher chloroquine 50% effective concentrations (EC<jats:sub>50</jats:sub>s) (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];<jats:italic>P</jats:italic>= 0.01). The EC<jats:sub>50</jats:sub>for chloroquine in<jats:italic>P. ovale</jats:italic>was 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<jats:italic>P. ovale</jats:italic>and<jats:italic>P. malariae</jats:italic>, but its marked stage specificity of action may account for reports of delayed parasite clearance times.</jats:p>

Original publication

DOI

10.1128/aac.01122-10

Type

Journal article

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

01/2011

Volume

55

Pages

197 - 202