Zwang Julien, D'Alessandro Umberto, Ndiaye Jean-Louis, Djimdé Abdoulaye A, Dorsey Grant, Mårtensson Andreas A, Karema Corine, Olliaro Piero L
Independent Researcher, Mae Sot, Thailand.
Medical Research Council Unit, Fajara, Banjul, The Gambia.
BMC Infect Dis. 2017 Jun 23;17(1):443. doi: 10.1186/s12879-017-2530-6.
Anaemia 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.
Individual-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.
Eight 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.
On 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.
贫血在疟疾中很常见。量化贫血风险并区分与疾病自然史相关的因素和潜在药物毒性很重要。
基于来自撒哈拉以南非洲13个国家的9项单纯性恶性疟治疗随机对照试验的个体患者数据分析。使用混合效应模型分析就诊时和治疗后血红蛋白（Hb）浓度降低及贫血的危险因素。
8897例患者（77.0%年龄<5岁）接受青蒿素联合疗法（ACT，90%，n = 7968）或非ACT治疗并随访28天。基线时，5岁以下儿童贫血风险最高（77.6%对32.8%），寄生虫血症水平（43,938个/微升）高于年龄较大者（2784个/微升）。基线贫血增加寄生虫学复发风险。治疗开始后Hb开始下降。5岁以下儿童估计最低点约在35小时（范围29 - 48小时），较基线下降-12.8%（从9.8克/分升降至8.7克/分升，p = 0.001）；15岁以下儿童，第0 - 3天Hb平均下降-4.7%（从9.4降至9.0克/分升，p = 0.001）。治疗前Hb和寄生虫血症水平高以及寄生虫减少率较慢的患者Hb丢失程度更大，且与年龄无关。随后，Hb直到第28天呈线性增加（+0.6%/天），较基线增加+13.8%。严重贫血（<5克/分升，每1000例患者中有2例）是短暂性的，除1例在第28天因寄生虫复发出现极严重贫血外，所有患者在第14天后康复。治疗之间Hb浓度无系统性差异，也无迟发性贫血病例。
急性疟疾就诊时，寄生虫血症水平高的幼儿贫血风险最高。大多数患者在治疗第1 - 2天就出现Hb下降，随后随访期间呈线性增加。早期Hb下降程度由治疗前寄生虫血症水平和寄生虫清除率决定。Hb趋势和贫血风险与治疗无关。
