Studies of neurocysticercosis and animal cestode infections

神经囊尾蚴病和动物绦虫感染的研究

• 批准号: 8336135
• 负责人: THEODORE NASH
• 金额: $ 10.4万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336135
• 关键词: Adrenal Cortex Hormones; Adult; Albendazole; Alkaline Phosphatase; Animals; Anthelmintics; Anti-Inflammatory Agents; Anti-inflammatory; Antigens; Astrocytosis; Biochemical; Blood; Blood Vessels; Brain; Calcified; Cerebrospinal Fluid; Cestoda; Cestode Infections; Clinical; Clinical Research; Combined Modality Therapy; Cyst; Cysticercosis; Cysticercus; Cytotoxic agent; Data; Disease; Edema; Epilepsy; Family suidae; Feces; Functional disorder; Goals; Granuloma; Human; Immune response; Immunosuppression; In Vitro; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Ingestion; Laboratories; Laboratory Study; Larva; Measures; Methods; Mononuclear; Muscle; Nature; Nervous system structure; Neurocysticercosis; Organ; Ovum; Parasites; Parasitic infection; Patients; Peru; Pharmaceutical Preparations; Praziquantel; Recurrence; Resources; Rural; Safety; Seizures; Site; Small Intestines; Sulfoxide; Supporting Cell; Taenia solium; Time; Tissues; United States National Institutes of Health; burden of illness; capsule; cooking; hatching; in vivo; prevent; programs; relating to nervous system

Neurocysticercosis resulting from Taenia solium infections is a major cause of adult-acquired seizures worldwide. Disease is caused by larval cysts, and treatment consists of the anthelmintic drugs albendazole or praziquantel. There are no standard methods to assess drug activity to T. solium cysts in vitro.Morphological, functional, and biochemical changes that might reflect damaging (inhibiting, cytotoxic)drug effects were analyzed after exposure of cysts to albendazole sulfoxide (ABZ-SO), the major active metabolite of the drug in vivo, praziquantel (PZQ), or combinations of both. PZQ exposure led to a decrease in cyst size and inhibition of evagination, whereas ABZ-SO exposure resulted in minimal changes. Alkaline phosphatase (AP) is normally secreted by cysts, and both drugs inhibited AP secretion at concentrations of 5 and 50 ng/ml for PZQ and ABZ-SO, respectively. Some combinations of both drugs resulted in additive and/or synergistic activities. Parasite-specific antigen, detected in the cerebrospinal fluid and blood of infected patients, is also normally secreted by T. solium cysts. Antigen secretion was similarly inhibited by ABZ-SO and PZQ and a combination of both drugs, suggesting that inhibition of secretion is a common downstream consequence of the activities of both drugs. These studies establish quantitative methods to measure in vitro anthelmintic activity and suggest combination therapy with ABZ-SO and PZQ may have clinical benefit. We described the first detailed histological description of an excised calcified Taenia solium granuloma from a patient who developed recurrent seizures associated with perilesional edema surrounding a calcified cysticercus (PEC). The capsule, around a degenerated cysticercus, contained marked mononuclear infiltrates that extended to adjacent brain, which showed marked astrocytosis, microgliosis, and inflammatory perivascular infiltrates. The presence of large numbers of mononuclear cells supports an inflammatory cause of PEC. Immunosuppression or anti-inflammatory measures may be able to treat and prevent PEC and recurrent seizures. The cystic larvae of Taenia solium commonly infect the human nervous system resulting in neurocysticercosis, a major contributor to seizure disorders in most of the world. Inflammation around the parasites is a hallmark of neurocysticercosis pathophisiology. Although mechanisms regulating this inflammation are poorly understood, anti‐inflammatory drugs and particularly corticosteroids have been long used alone or concomitant to anthelmintics to manage disease and limit damage to neural tissues. Only scarce controlled data exists to guide the selection of particular drug or treatment regime. This review revisits the mechanisms of action, rationale, evidence of benefit, safety and problems of corticosteroids in the context of NCC as well as alternative anti-inflammatory strategies to limit the damage caused by inflammation in the CNS.

taenia ilium感染引起的神经囊肿是全球成人获得性癫痫发作的主要原因。疾病是由幼虫囊肿引起的，治疗由驱虫药物阿替唑或普拉齐甘特尔组成。 There are no standard methods to assess drug activity to T. solium cysts in vitro.Morphological, functional, and biochemical changes that might reflect damaging (inhibiting, cytotoxic)drug effects were analyzed after exposure of cysts to albendazole sulfoxide (ABZ-SO), the major active metabolite of the drug in vivo, praziquantel (PZQ), or combinations of both. PZQ暴露导致囊肿大小的减小和驱逐的抑制作用，而ABZ-SO暴露会导致最小的变化。碱性磷酸酶（AP）通常由囊肿分泌，两种药物分别以PZQ和ABZ-SO分别抑制5和50 ng/ml的AP分泌。两种药物的某些组合都产生了添加剂和/或协同活动。在脑脊液和感染患者的血液中检测到的寄生虫特异性抗原通常也被T. silium囊肿分泌。 ABZ-SO和PZQ类似地抑制了抗原分泌，并且两种药物的组合都表明抑制分泌是两种药物活性的常见下游结果。这些研究建立了测量体外驱虫活性的定量方法，并建议与ABZ-SO和PZQ结合疗法可能具有临床益处。 我们描述了从 围绕钙化囊肿（PEC）的周围水肿相关的复发性癫痫发作的患者。 胶囊在变成囊肿的囊肿附近，包含明显的单核浸润，延伸至相邻大脑， 显示出明显的星形细胞增多症，小胶质细胞增多症和炎症周围的浸润。大量存在 单核细胞的炎症原因。可以采取免疫抑制或抗炎措施 能够治疗并预防PEC和复发性癫痫发作。 Taenia ilium的囊性幼虫通常会感染人类神经系统，导致神经囊虫病，这是世界上大多数地区癫痫发作疾病的主要因素。寄生虫周围的炎症是神经囊肿病理学的标志。尽管调节这种炎症的机制知之甚少，但长期以来，抗炎药，尤其是皮质类固醇的抗炎药已被单独使用或与Anthelmintics一起使用，以管理疾病并限制对神经组织的损害。仅存在稀缺的受控数据，以指导特定药物或治疗方案的选择。这篇综述重新审查了在NCC背景下的作用，理由，福利证据和皮质类固醇问题的机制，以及替代性抗炎策略，以限制CNS炎症造成的损害。