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

摘要

Background In 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. Methods Pooled, 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. Results A 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?