Clinical Illness and Outcomes in Nigerian Children with Persistent Early Appearing Anaemia Following Initiation of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria.
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Date
2019
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Publisher
Parasite
Abstract
In non-anaemic children with malaria, early-appearing anaemia (EAA) is common following artemisininbased combination treatments (ACTs) and it may become persistent (PEAA). The factors contributing to and kinetics
of resolution of the deficit in haematocrit from baseline (DIHFB) characteristic of ACTs-related PEAA were evaluated
in 540 consecutive children with malaria treated with artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine. Asymptomatic PEAA occurred in 62 children. In a multiple logistic regression model, a
duration of illness 3 days before presentation, haematocrit <35% before and <25% one day after treatment initiation,
drug attributable fall in haematocrit 6%, and treatment with dihydroartemisinin-piperaquine independently predicted
PEAA. Overall, mean DIHFB was 5.7% (95% CI 4.8–6.6) 7 days after treatment initiation and was similar for all treatments. Time to 90% reduction in DIHFB was significantly longer in artemether-lumefantrine-treated children compared with other treatments. In a one compartment model, declines in DIHFB were monoexponential with overall
mean estimated half-time of 3.9 days (95% CI 2.6–5.1), Cmax of 7.6% (95% CI 6.7–8.4), and Vd of 0.17 L/kg
(95% CI 0.04–0.95). In Bland-Altman analyses, overall mean anaemia recovery time (AnRT) of 17.4 days (95% CI
15.5–19.4) showed insignificant bias with 4, 5 or 6 multiples of half-time of DIHFB. Ten children after recovery from
PEAA progressed to late-appearing anaemia (LAA). Progression was associated with female gender and artesunateamodiaquine treatment. Asymptomatic PEAA is common following ACTs. PEAA or its progression to LAA may have
implications for case and community management of anaemia and for anaemia control efforts in sub-Saharan Africa
where ACTs have become first-line antimalarials