Ruizendaal E, Schallig H D F H, Bradley J, Traore-Coulibaly M, Lompo P, d'Alessandro U, Scott S, Njie F, Zango S H, Sawadogo O, de Jong M D, Tinto H, Mens P F
Department of Medical Microbiology, Academic Medical Centre, Amsterdam, The Netherlands.
Medical Research Council (MRC) Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK.
Biomark Res. 2017 Dec 13;5:34. doi: 10.1186/s40364-017-0114-7. eCollection 2017.
Diagnosis of malaria in pregnancy is problematic due to the low sensitivity of conventional diagnostic tests (rapid diagnostic test and microscopy), which is exacerbated due to low peripheral parasite densities, and lack of clinical symptoms. In this study, six potential biomarkers to support malaria diagnosis in pregnancy were evaluated.
Blood samples were collected from pregnant women at antenatal clinic visits and at delivery. Microscopy and real-time PCR were performed for malaria diagnosis and biomarker analyses were performed by ELISA (interleukin 10, IL-10; tumor necrosis factor-α, TNF-α; soluble tumor necrosis factor receptor II, sTNF-RII; soluble fms-like tyrosine kinase 1, sFlt-1; leptin and apolipoprotein B, Apo-B). A placental biopsy was collected at delivery to determine placental malaria.
IL-10 and sTNF-RII were significantly higher at all time-points in malaria-infected women ( < 0.001). Both markers were also positively associated with parasite density ( < 0.001 and = 0.003 for IL-10 and sTNF-RII respectively). IL-10 levels at delivery, but not during pregnancy, were negatively associated with birth weight. A prediction model was created using IL-10 and sTNF-RII cut-off points. For primigravidae the model had a sensitivity of 88.9% (95%CI 45.7-98.7%) and specificity of 83.3% (95% CI 57.1-94.9%) for diagnosing malaria during pregnancy. For secundi- and multigravidae the sensitivity (81.8% and 56.5% respectively) was lower, while specificity (100.0% and 94.3% respectively) was relatively high. Sub-microscopic infections were detected in 2 out of 3 secundi- and 5 out of 12 multigravidae.
The combination of biomarkers IL-10 and sTNF-RII have the potential to support malaria diagnosis in pregnancy. Additional markers may be needed to increase sensitivity and specificity, this is of particular importance in populations with sub-microscopic infections or in whom other inflammatory diseases are prevalent.
由于传统诊断测试（快速诊断测试和显微镜检查）的敏感性较低，妊娠疟疾的诊断存在问题，而外周血寄生虫密度低和缺乏临床症状会使这一问题更加严重。在本研究中，评估了六种支持妊娠疟疾诊断的潜在生物标志物。
在产前检查和分娩时收集孕妇的血样。进行显微镜检查和实时聚合酶链反应以诊断疟疾，并通过酶联免疫吸附测定法（白细胞介素10，IL-10；肿瘤坏死因子-α，TNF-α；可溶性肿瘤坏死因子受体II，sTNF-RII；可溶性fms样酪氨酸激酶1，sFlt-1；瘦素和载脂蛋白B，Apo-B）进行生物标志物分析。在分娩时采集胎盘活检样本以确定胎盘疟疾。
在感染疟疾的女性中，IL-10和sTNF-RII在所有时间点均显著升高（<0.001）。这两种标志物也均与寄生虫密度呈正相关（IL-10和sTNF-RII分别为<0.001和=0.003）。分娩时而非孕期的IL-10水平与出生体重呈负相关。使用IL-10和sTNF-RII的临界值创建了一个预测模型。对于初产妇，该模型在诊断孕期疟疾时的敏感性为88.9%（95%置信区间45.7 - 98.7%），特异性为83.3%（95%置信区间57.1 - 94.9%）。对于经产妇和多产妇，敏感性较低（分别为81.8%和56.5%），而特异性相对较高（分别为100.0%和94.3%）。在3名经产妇中有2名以及12名多产妇中有5名检测到亚显微镜感染。
生物标志物IL-10和sTNF-RII的组合有潜力支持妊娠疟疾的诊断。可能需要额外的标志物来提高敏感性和特异性，这在存在亚显微镜感染或其他炎症性疾病普遍流行的人群中尤为重要。
