Early Rising Asexual Parasitemia in Nigerian Children Following a First Dose of Artemisinin-Based Combination Treatments of Falciparum Malaria.
Loading...
Date
2017
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
BMC Infectious Diseases
Abstract
Background: Early rising asexual parasitaemia (ERAP), initially defined as ‘an increase in the parasite count over the
baseline pre-treatment level during the first 24 h of treatment’ of falciparum malaria with artemisinin derivatives is
well documented, but there is no characterization of its risk factors, kinetics, molecular features or relationship to
late-appearing anaemia (LAA) in acute falciparum malaria in African children following oral artemisinin-based
combination therapies (ACTs).
Methods: ERAP was defined as ≥5% increase in pre-treatment parasitaemia within 8 h of initiating treatment.
Parasitaemia was quantified pre-treatment and 1–2 hourly for 8 h, and less frequently thereafter for 6 weeks
following randomized treatment of acutely malarious children with artesunate-amodiaquine, artemetherlumefantrine or dihydroartemisinin-piperaquine. Risk factors were determined by stepwise multiple logistic
regression model. Kinetics of release into and of elimination of asexual parasites and DNA clones from peripheral
blood were evaluated by method of residuals and non-compartment model, respectively. Parasite population
changes were evaluated morphologically and by molecular genotyping.
Results: ERAP occurred in 205 of 416 children. A parasitaemia <100,000/μL and parasitaemia 1 day post-treatment
initiation were independent predictors of ERAP. In children with ERAP: mean and peak time of increase in
parasitaemia were 105.6% (95% CI 81–130.1) and 2.5 h (95% CI 2.2–2.7), respectively. Mean lag time, half-time and
rate constant of release were 0.2 h (95% CI 0.2–0.3), 1 h (95% CI 0.9–1.1), and 0.9 h−1 (95% CI 0.8–1), respectively.
Schizonts and young gametocytes were seen only in peripheral blood of few children with ERAP. In age-, gender-,
baseline parasitaemia- and treatment-matched children with and without ERAP, parasite DNA clearance time and
area under curve of number of DNA clones versus time were significantly higher in children with ERAP indicating
peripheral retention of released parasites followed by elimination. DNA clone elimination was monoexponential.
Conclusion: ERAP is common, occurs rapidly as first order process and may be due to mobilization of parasites
from deep tissue following a first dose of ACTs of acute childhood falciparum malaria.