Abstract
BackgroundAnaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity.MethodsIndividual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models.ResultsEight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5’s had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence.Hb began to fall after treatment start. In under 5’s the estimated nadir was ~35 h (range 29–48), with a drop of −12.8% from baseline (from 9.8 g/dl to 8.7 g/dl, p = 0.001); in under 15’s, the mean Hb decline between day 0–3 was −4.7% (from 9.4 to 9.0 g/dl, p = 0.001). The degree of Hb loss was greater in patients with high pre-treatment Hb and parasitaemia and with slower parasite reduction rates, and was unrelated to age. Subsequently, Hb increased linearly (+0.6%/day) until day 28, to reach +13.8% compared to baseline.Severe anaemia (<5 g/dl, 2 per 1000 patients) was transient and all patients recovered after day 14, except one case of very severe anaemia associated with parasite recurrence at day 28.There was no systematic difference in Hb concentrations between treatments and no case of delayed anaemia.ConclusionOn presentation with acute malaria young children with high parasitaemia have the highest risk of anaemia. The majority of patients experience a drop in Hb while on treatment as early as day 1–2, followed by a linear increase through follow-up. The degree of the early Hb dip is determined by pre-treatment parasitaemia and parasite clearance rates. Hb trends and rick of anaemia are independent of treatment.
Highlights
IntroductionIt is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity
Analyses were based on 8897 patients, 89.6% treated with an Artemisinin-based Combination Therapy (ACT) and 10.4% with non-ACTs (Additional file 2: Table S2, Additional file 3: Fig. S1), providing 38,864 Hb measurements (93% and 7% for ACT and non-ACT, respectively)
While anaemia is a common feature of uncomplicated falciparum malaria, studying anaemia during and after malaria treatment is challenging because it is difficult to disentangle the contributions of the infection itself, the process of recovering from the disease, and drug-induced adverse events
Summary
It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. As anaemia is a common occurrence in malaria, it is often difficult, in treated patients, to disentangle disease from drug effects. Malaria anaemia has both central (decreased red cell production) and peripheral causes (haemolysis, phagocytosis of infected and uninfected erythrocytes) [1, 2]. Artemisinin-based Combination Therapy (ACT) the treatment of choice for uncomplicated Plasmodium falciparum malaria [3] - is generally safe and well-tolerated, but anaemia remains a potential concern, in particular for artemisinin derivatives. Even when monitored, is variably reported as a continuous variable (haemoglobin concentration) or categorical variable (using different thresholds and severity classes)
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