Department of Pathology, Aga Khan University, Nairobi, Kenya.
Department of Medicine, Aga Khan University, Nairobi, Kenya.
Clin Microbiol Rev. 2021 Dec 15;34(4):e0002419. doi: 10.1128/CMR.00024-19. Epub 2021 Aug 11.
Giardia duodenalis captured the attention of Leeuwenhoek in 1681 while he was examining his own diarrheal stool, but, ironically, it did not really gain attention as a human pathogen until the 1960s, when outbreaks were reported. Key technological advances, including cultivation, genomic and proteomic databases, and advances in microscopic and molecular approaches, have led to an understanding that this is a eukaryotic organism with a reduced genome rather than a truly premitochondriate eukaryote. This has included the discovery of mitosomes (vestiges of mitochondria), a transport system with many of the features of the Golgi apparatus, and even evidence for a sexual or parasexual cycle. Cell biology approaches have led to a better understanding of how Giardia survives with two nuclei and how it goes through its life cycle as a noninvasive organism in the hostile environment of the lumen of the host intestine. Studies of its immunology and pathogenesis have moved past the general understanding of the importance of the antibody response in controlling infection to determining the key role of the Th17 response. This work has led to understanding of the requirement for a balanced host immune response that avoids the extremes of an excessive response with collateral damage or one that is unable to clear the organism. This understanding is especially important in view of the remarkable ranges of early manifestations, which range from asymptomatic to persistent diarrhea and weight loss, and longer-term sequelae that include growth stunting in children who had no obvious symptoms and a high frequency of postinfectious irritable bowel syndrome (IBS).
十二指肠贾第鞭毛虫在 1681 年引起了列文虎克的注意，当时他正在检查自己的腹泻粪便，但具有讽刺意味的是，直到 20 世纪 60 年代爆发疫情时，它才真正被视为人类病原体。关键技术的进步，包括培养、基因组和蛋白质组数据库，以及显微镜和分子方法的进步，使人们了解到这是一种具有简化基因组的真核生物，而不是真正的前线粒体真核生物。这包括发现了 mitosomes（线粒体的遗迹）、具有高尔基体许多特征的运输系统，甚至有证据表明存在有性或准性生殖周期。细胞生物学方法使人们更好地了解贾第鞭毛虫如何在两个核的情况下生存，以及它如何在宿主肠道腔这个恶劣环境中作为一种非侵入性生物经历其生命周期。对其免疫学和发病机制的研究已经超越了对抗体反应在控制感染中的重要性的普遍理解，而进入了确定 Th17 反应关键作用的阶段。这项工作使人们了解到需要宿主免疫反应达到平衡，以避免因过度反应导致的附带损害或无法清除病原体的反应。鉴于早期表现的显著范围，包括无症状到持续性腹泻和体重减轻，以及包括没有明显症状的儿童生长发育迟缓以及感染后肠易激综合征（IBS）的高频率在内的长期后果，这一点尤其重要。
