Mutagonda Ritah F, Kamuhabwa Appolinary A R, Minzi Omary M S, Massawe Siriel N, Maganda Betty A, Aklillu Eleni
Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P.O. BOX 65013, Dar es Salaam, Tanzania.
Department of Obstetrics and Gynaecology, School of Medicine, Muhimbili University of Allied Sciences, P.O. BOX 65013, Dar es Salaam, Tanzania.
Malar J. 2016 May 13;15(1):278. doi: 10.1186/s12936-016-1327-1.
Day 7 plasma concentrations of lumefantrine (LF) can serve as a marker to predict malaria treatment outcome in different study populations. Two main cut-off points (175 and 280 ng/ml) are used to indicate plasma concentrations of LF, below which treatment failure is anticipated. However, there is limited data on the cumulative risk of recurrent parasitaemia (RP) in relation to day 7 LF plasma concentrations in pregnant women. This study describes the prevalence, severity, factors influencing treatment outcome of malaria in pregnancy and day 7 LF plasma concentration therapeutic cut-off points that predicts treatment outcome in pregnant women.
This was a one-arm prospective cohort study whereby 89 pregnant women with uncomplicated Plasmodium falciparum malaria receiving artemether-lumefantrine (ALu) participated in pharmacokinetics and pharmacodynamics study. Blood samples were collected on days 0, 2, 7, 14, 21 and 28 for malaria parasite quantification. LF plasma concentrations were determined on day 7. The primary outcome measure was an adequate clinical and parasitological response (ACPR) after treatment with ALu.
The prevalence of malaria in pregnant women was 8.1 % (95 % CI 6.85-9.35) of whom 3.4 % (95 % CI 1.49-8.51) had severe malaria. The overall PCR-uncorrected treatment failure rate was 11.7 % (95 % CI 0.54-13.46 %). Low baseline hemoglobin (<10 g/dl) and day 7 LF concentration <600 ng/ml were significant predictors of RP. The median day 7 LF concentration was significantly lower in pregnant women with RP (270 ng/ml) than those with ACPR (705 ng/ml) (p = 0.016). The relative risk of RP was 4.8 folds higher (p = 0.034) when cut-off of <280 ng/ml was compared to ≥280 ng/ml and 7.8-folds higher (p = 0.022) when cut-off of <600 ng/ml was compared to ≥600 ng/ml. The cut-off value of 175 ng/ml was not associated with the risk of RP (p = 0.399).
Pregnant women with day 7 LF concentration <600 ng/ml are at high risk of RP than those with ≥600 ng/ml. To achieve effective therapeutic outcome, higher day 7 venous plasma LF concentration ≥600 ng/ml is required for pregnant patients than the previously suggested cut-off value of 175 or 280 ng/ml for non-pregnant adult patients.
本芴醇（LF）第7天的血浆浓度可作为预测不同研究人群疟疾治疗结果的标志物。两个主要的临界值（175和280 ng/ml）用于指示LF的血浆浓度，低于该浓度预计治疗会失败。然而，关于孕妇第7天LF血浆浓度与复发性寄生虫血症（RP）累积风险相关的数据有限。本研究描述了妊娠疟疾的患病率、严重程度、影响治疗结果的因素以及预测孕妇治疗结果的第7天LF血浆浓度治疗临界值。
这是一项单臂前瞻性队列研究，89例患有非复杂性恶性疟原虫疟疾且接受蒿甲醚-本芴醇（ALu）治疗的孕妇参与了药代动力学和药效学研究。在第0、2、7、14、21和28天采集血样进行疟原虫定量分析。在第7天测定LF血浆浓度。主要结局指标是ALu治疗后的充分临床和寄生虫学反应（ACPR）。
孕妇疟疾患病率为8.1%（95%CI 6.8５ - 9.35），其中3.4%（95%CI 1.49 - 8.51）患有严重疟疾。未经PCR校正的总体治疗失败率为11.7%（95%CI 0.54 - 13.46%）。基线血红蛋白低（<10 g/dl）和第7天LF浓度<600 ng/ml是RP的显著预测因素。发生RP的孕妇第7天LF浓度中位数（270 ng/ml）显著低于有ACPR的孕妇（705 ng/ml）（p = 0.016）。与≥280 ng/ml相比，<280 ng/ml临界值时RP的相对风险高4.8倍（p = 0.034），与≥600 ng/ml相比，<600 ng/ml临界值时RP的相对风险高7.8倍（p = 0.022）。175 ng/ml的临界值与RP风险无关（p = 0.399）。
第7天LF浓度<600 ng/ml的孕妇比≥600 ng/ml的孕妇发生RP的风险更高。为实现有效的治疗结果，与之前建议的非妊娠成年患者临界值175或280 ng/ml相比，孕妇需要第7天静脉血浆LF浓度≥600 ng/ml。
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