Malaria is a multisystem disease with a mortality rate of 5 to 30% even with optimal treatment. Earlier studies have shown increased circulating levels of TNF in the plasma of patients as an independent predictor of severe or fatal disease. TNF has already been shown to facilitate the release of proinflammatory enzyme phospholipase A2 from various cells in vitro. Because both TNF and PLA2 are increased in patients with septicemia and because TNF levels are already shown to be increased in patients with malaria, the authors studied the relationship between TNF levels, severity of disease, and PLA2 activity.Seventy-five children (age 3 months to 10 years) with severe malaria due to Plasmodium falciparum and 34 controls (age 2 to 5 years) taking part in the malaria survey at a school in the same region in Malawi were included in the study. The children were afebrile and aparasitemic. Many of these children had cerebral malaria with coma. Twenty patients had uncomplicated falciparum malaria and 55 had cerebral malaria. Ten of them (all with cerebral malaria) died. In addition to examining the children, particularly for neurological status, laboratory studies obtained included the blood count, hematocrit, leukocyte count, thick blood smears for quantitative evaluation of parasitemia, and measurement of PLA2 activity.Mean plasma PLA2 activity in 34 healthy controls was 424 U/mL, whereas in the 75 patients with malaria the mean value was 53 804 U/mL. In the 45 children who were available for follow-up 1 month later after treatment the mean plasma PLA2 activity was 2546 U/mL. The high mean plasma level was not different between children with cerebral malaria and those with uncomplicated malaria. However the PLA2 activity in 28 children with profound coma was much higher than in other patients with malaria. The initial plasma PLA2 activity was predictive of outcome. Patients who had levels higher than 60 000 U/mL had a higher mortality rate (33%) compared with those with values less than 60 000 U at (8.3%). There was also a significant correlation between TNF and plasma PLA2 activity. Pretreatment serum PLA2 activity also correlated with the intensity of parasitemia. The cerebral spinal fluid PLA2 activity was not elevated even in those patients with severe malaria.The biological role of this observation is unclear. However, selective inhibition of PLA2 may be a new target for future therapy because PLA2 is proinflammatory enzyme.
展开▼
机译：疟疾是一种多系统疾病，即使采用最佳治疗方法，其死亡率也可达到5％至30％。较早的研究表明，患者血浆中TNF的循环水平升高是严重或致命疾病的独立预测因子。 TNF已经显示出可以促进体外各种细胞中促炎酶磷脂酶A2的释放。由于败血病患者的TNF和PLA2均升高，并且由于疟疾患者的TNF水平已显示升高，因此作者研究了TNF水平，疾病严重程度和PLA2活性之间的关系.55名儿童（3岁）该研究包括因恶性疟原虫而导致的严重疟疾和数月至10年的疟疾，并在马拉维同一地区的一所学校参加了疟疾调查的34名对照（2至5岁）。这些孩子是无发热和寄生虫的。这些儿童中许多人患有昏迷性脑疟。 20例患者未发生恶性疟疾，55例患有脑疟疾。其中十人（均患有脑疟疾）死亡。除了检查儿童，特别是神经系统状况，还进行了实验室检查，包括血细胞计数，血细胞比容，白细胞计数，浓血涂片以定量评估寄生虫病和测量PLA2活性.34名健康对照者的平均血浆PLA2活性为424。 U / mL，而在75名疟疾患者中，平均值为53804 U / mL。在治疗后1个月可进行随访的45名儿童中，平均血浆PLA2活性为2546 U / mL。患有脑疟疾的儿童和患有单纯性疟疾的儿童之间的平均血浆高水平无差异。但是，在28名严重昏迷儿童中，PLA2活性远高于其他疟疾患者。初始血浆PLA2活性可预测结果。高于60000 U / mL的患者的死亡率（33％）高于低于60000 U / mL的患者（8.3％）。 TNF与血浆PLA2活性之间也存在显着相关性。预处理血清PLA2的活性也与寄生虫病的强度有关。即使在患有严重疟疾的患者中，脑脊髓液PLA2的活性也没有升高。该观察结果的生物学作用尚不清楚。但是，由于PLA2是促炎酶，因此选择性抑制PLA2可能成为未来治疗的新目标。
展开▼
