Recurrence of Plasmodium falciparum after treatment with quinine and doxycycline in the Amazon basin

Abstract

Objective: To investigate whether the recurrence of infection by Plasmodium falciparum in patients from the Brazilian Amazon was caused by an inadequate exposure to quinine. Methods: A retrospective study was carried out using blood samples from patients with slide-confirmed infection by P. falciparum, classified according to the parasitological response after 28 days of follow-up. Quinine and doxycycline were measured in plasma samples by high-performance liquid chromatography. A statistical model was used to estimate parasite clearance rates. Results: Six of 40 patients who met the criteria for inclusion in the study showed recurrence of parasitaemia within 28 days after the commencement of treatment. A group of six patients with adequate parasitological response was formed to avoid bias when the variables were compared. Parasitaemia at admission was similar in both groups. Plasma quinine concentrations were similar in both groups on days 1, 2 and 3 and ranged from 1.07 to 4.35 μg/ml in cured patients and from 1.1 to 3.2 μg/ml in patients with parasite recurrence. Concentrations of doxycycline were similar in both groups on day 3. The parasite clearance rate constant was 0.131 ± 0.16 h in the cured patients and 0.117 ± 0.02 h in those showing recurrence. The slope half-life in the cured patients was 4.8 h and 5.4 h in recurrence cases. The hillslope of the cured group (14.24) increased sharply compared to the recurrence group (4.13). Conclusion: There is evidence of a decreased in vivo sensitivity to quinine of P. falciparum strains in the Brazilian Amazon basin