Kabyemela Edward R, Muehlenbachs Atis, Fried Michal, Kurtis Jonathan D, Mutabingwa Theonest K, Duffy Patrick E
Mother Offspring Malaria Studies (MOMS) Project, Seattle Biomedical Research Institute, Seattle WA 98109, USA.
Malar J. 2008 Jan 29;7:26. doi: 10.1186/1475-2875-7-26.
Placental malaria (PM) is an important cause of maternal and foetal mortality in tropical areas, and severe sequelae and mortality are related to inflammation in the placenta. Diagnosis is difficult because PM is often asymptomatic, peripheral blood smear examination detects parasitemia as few as half of PM cases, and no peripheral markers have been validated for placental inflammation.
In a cohort of Tanzanian parturients, PM was determined by placental blood smears and placental inflammation was assessed by histology and TNF mRNA levels. Maternal peripheral blood levels of several immune mediators previously implicated in PM pathogenesis, as well as ferritin and leptin were measured. The relationship between the levels of these soluble factors to PM and placental inflammation was examined.
Peripheral levels of TNF, TNF-RI, TNF-RII, IL-1, IL-10, and ferritin were elevated during PM, whereas levels of IFN-gamma, IL-4, IL-5 and IL-6 were unchanged and levels of leptin were decreased. In receiver operating characteristic curve analysis, IL-10 had the greatest area under the curve, and would provide a sensitivity of 60% with a false positive rate of 10%. At a cut off level of 15 pg/mL, IL-10 would detect PM with a sensitivity of 79.5% and a specificity of 84.3%. IL-10 levels correlated with placental inflammatory cells and placental TNF mRNA levels in first time mothers.
These data suggest that IL-10 may have utility as a biomarker for inflammatory PM in research studies, but that additional biomarkers may be required to improve clinical diagnosis and management of malaria during pregnancy.
胎盘疟疾(PM)是热带地区孕产妇和胎儿死亡的重要原因,严重的后遗症和死亡率与胎盘炎症有关。诊断困难,因为PM通常无症状,外周血涂片检查仅能检测到半数PM病例的寄生虫血症,且尚无外周标志物可用于验证胎盘炎症。
在一组坦桑尼亚产妇队列中,通过胎盘血涂片确定PM,并通过组织学和TNF mRNA水平评估胎盘炎症。检测了先前与PM发病机制有关的几种免疫介质以及铁蛋白和瘦素的母体外周血水平。研究了这些可溶性因子水平与PM和胎盘炎症之间的关系。
PM期间,TNF、TNF-RI、TNF-RII、IL-1、IL-10和铁蛋白的外周水平升高,而IFN-γ、IL-4、IL-5和IL-6水平未变,瘦素水平降低。在受试者工作特征曲线分析中,IL-10的曲线下面积最大,假阳性率为10%时灵敏度为60%。在截断水平为15 pg/mL时,IL-10检测PM的灵敏度为79.5%,特异性为84.3%。初产妇的IL-10水平与胎盘炎症细胞和胎盘TNF mRNA水平相关。
这些数据表明,IL-10在研究中可能作为炎症性PM的生物标志物,但可能需要其他生物标志物来改善孕期疟疾的临床诊断和管理。