Wanachiwanawin Wanchai, Mendoza Leonel, Visuthisakchai Sanan, Mutsikapan Piroon, Sathapatayavongs Boonmee, Chaiprasert Angkana, Suwanagool Parvinee, Manuskiatti Worapong, Ruangsetakit Chanian, Ajello Libero
Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok, Bangkok 10700, Thailand.
Vaccine. 2004 Sep 9;22(27-28):3613-21. doi: 10.1016/j.vaccine.2004.03.031.
Human pythiosis is an emerging disease in the tropical, subtropical and temperate regions of the world. It is caused by the straminipilan, fungus-like, aquatic organism Pythium insidiosum. Pythiosis occurs in localized as well as systemic or vascular forms. Most patients with arterial pythiosis usually have underlying hematologic disorders such as thalassemia and aplastic anemia/paroxysmal nocturnal hemoglobinuria (PNH) syndrome. Vascular pythiosis is characterized by ascending blood vessel infections and thrombosis of the major arteries especially those of the lower extremities. When the infection reaches a main artery, the patient usually dies within weeks. Since this pathogen is resistant to most antifungal drugs, immunotherapy was recently used to cure humans and animals with the disease. A modified P. insidiosum-antigen (PIA) formulation had already saved a young boy with life-threatening arterial pythiosis. Here, we report the therapeutic benefits of the PIA in eight patients with vascular pythiosis. Six of them had thalassemia and the other two had PNH. All of the patients had arterial occlusion of the lower limbs. P. insidiosum was isolated and identified by culture and by histopathology. All patients had evidence of active infection when immunotherapy began. After two injections of 100-200 microl of PIA (2.0mg/ml), at a 14-day interval, four patients (50%) had dramatic and complete remission. Two patients showed partial responses to PIA while the other two did not. Clinical responses correlated with the immunological reactions at the site of injection, clearance of the arteries and cytokine production. The latter included the shifting in serum levels of IL4 and IL5 to IL2 suggesting a switching from a T helper 2 (Th2) to a T helper 1 (Th1) subset. Our findings provide further evidence that immunotherapy using PIA is a safe and effective method to treat pythiosis in humans.
人类腐皮病是一种在世界热带、亚热带和温带地区出现的疾病。它由卵菌纲、真菌样、水生生物腐皮镰刀菌引起。腐皮病以局部、全身或血管形式出现。大多数患有动脉腐皮病的患者通常有潜在的血液系统疾病，如地中海贫血和再生障碍性贫血/阵发性夜间血红蛋白尿（PNH）综合征。血管腐皮病的特征是血管感染上行以及主要动脉尤其是下肢动脉血栓形成。当感染累及主要动脉时，患者通常在数周内死亡。由于这种病原体对大多数抗真菌药物耐药，免疫疗法最近被用于治疗患有该病的人类和动物。一种改良的腐皮镰刀菌抗原（PIA）制剂已经挽救了一名患有危及生命的动脉腐皮病的小男孩。在此，我们报告PIA对8例血管腐皮病患者的治疗效果。其中6例患有地中海贫血，另外2例患有PNH。所有患者均有下肢动脉闭塞。通过培养和组织病理学分离并鉴定出腐皮镰刀菌。免疫疗法开始时，所有患者均有活动性感染的证据。在间隔14天注射两次100 - 200微升PIA（2.0mg/ml）后，4例患者（50%）出现显著且完全缓解。2例患者对PIA有部分反应，而另外2例则没有。临床反应与注射部位的免疫反应、动脉清除情况和细胞因子产生相关。后者包括血清中IL4和IL5水平向IL2的转变，提示从辅助性T细胞2（Th2）亚群向辅助性T细胞1（Th1）亚群的转变。我们的研究结果进一步证明，使用PIA的免疫疗法是治疗人类腐皮病的一种安全有效的方法。
