Delayed anemia assessment in patients treated with oral artemisinin derivatives for uncomplicated malaria: a pooled analysis of clinical trials data from Mali

Malaria Journal

Research

Renaud Piarroux¹  Abdoulaye Djimde²  Kassoum Kayentao²  Ogobara K Doumbo²  Issaka Sagara³  Jean Gaudart⁴  Roch Giorgi⁴ 

[1] Aix-Marseille University, UMR MD3, 13005, Marseille, France;Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odonto-Stomatogy, University of Sciences, Techniques and Technologies of Bamako, BP 1805, Point G Bamako, Mali;Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odonto-Stomatogy, University of Sciences, Techniques and Technologies of Bamako, BP 1805, Point G Bamako, Mali;UMR912 SESSTIM (INSERM, IRD, AMU), Aix-Marseille University, 13005, Marseille, France;UMR912 SESSTIM (INSERM, IRD, AMU), Aix-Marseille University, 13005, Marseille, France;

关键词: Uncomplicated;    Plasmodium falciparum;    Malaria;    Delayed anaemia;    Artemisinin;    Clinical trials;   

DOI  :  10.1186/1475-2875-13-358

 received in 2014-05-07, accepted in 2014-09-02,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundIn sub-Saharan Africa, artemisinin-based combination therapy (ACT) and injectable artesunate are the first-line treatments for uncomplicated and severe Plasmodium falciparum malaria, respectively. However, recent studies suggest that delayed anaemia is associated with these treatments in non-immune travellers. This paper aimed to assess the risk factors associated with delayed anaemia after falciparum malaria treatment with artemisinin-containing drugs in malaria-endemic populations.MethodsPooled, individual malaria patient data were extracted from 13 clinical trials performed from 2002 to 2011 in various settings of Mali. Treatment regimens were artemether-lumefantrine, artesunate plus amodiaquine, artesunate plus sulphadoxine-pyrimethamine, artesunate plus sulphamethoxypyrazine-pyrimethamine, artesunate plus mefloquine, artesunate-pyronaridine, artesunate monotherapy, chloroquine, sulphadoxine-pyrimethamine, amodiaquine and sulphadoxine-pyrimethamine plus amodiaquine. Univariate and multivariate analyses were performed using the generalized linear and latent mixed model procedures to assess risk factors associated with haemoglobin concentration evolution and anaemia during the treatment follow-up.ResultsA total of 5,990 participants were recruited and followed from day 0 to day 28. The participants’ median age was five years, ranging from three months to 70 years. There was a decrease in haemoglobin level on day 7 in all treatment arms, but the magnitude varied across treatments. There was a significant risk of haemoglobin level decrease on day 7 in the artemisinin-based therapy compared to the non-artemisinin treatments. The risk of haemoglobin concentration drop was associated with age group < five years old (0.61 g/dL 95% CI (0.71 to 0.51), p < 0.001), baseline high parasite density (0.43 g/dL 95% CI (0.51 to 0.35), p < 0.001) and treatment failure (0.40 g/dL 95% CI (0.59 to 0.20), p = 0.018), while high haemoglobin level at baseline was a protective factor (0.53 to 0.59) p < 0.001). No association was found between artemisinin-based therapy and severe delayed anaemia.ConclusionsOral artemisinin derivative treatments for uncomplicated P. falciparum malaria are associated with a transient and clinically moderate haemoglobin decrease by day 7 but not associated with a delayed severe anaemia.

【 授权许可】

CC BY   
© Sagara et al.; licensee BioMed Central Ltd. 2014