Priya Sivan Padma, Sakinah S, Sharmilah K, Hamat Rukman A, Sekawi Zamberi, Higuchi Akon, Ling Mok Pooi, Nordin Syafinaz Amin, Benelli Giovanni, Kumar S Suresh
Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, 43400 UPM Serdang Selangor, Malaysia.
Department of Chemical and Materials Engineering, National Central University, Jhong-li, Taoyuan, Taiwan; Department of Botany and Microbiology, King Saud University, Riyadh, Saudi Arabia; Department of Reproduction, National Research Institute for Child Health and Development, Tokyo, Japan.
Acta Trop. 2017 Dec;176:206-223. doi: 10.1016/j.actatropica.2017.08.007. Epub 2017 Aug 16.
Immuno-pathogenesis of leptospirosis can be recounted well by following its trail path from entry to exit, while inducing disastrous damages in various tissues of the host. Dysregulated, inappropriate and excessive immune responses are unanimously blamed in fatal leptospirosis. The inherent abilities of the pathogen and inabilities of the host were debated targeting the severity of the disease. Hemorrhagic manifestation through various mechanisms leading to a fatal end is observed when this disease is unattended. The similar vascular destructions and hemorrhage manifestations are noted in infections with different microbes in endemic areas. The simultaneous infection in a host with more than one pathogen or parasite is referred as the coinfection. Notably, common endemic infections such as leptospirosis, dengue, chikungunya, and malaria, harbor favorable environments to flourish in similar climates, which is aggregated with stagnated water and aggravated with the poor personal and environmental hygiene of the inhabitants. These factors aid the spread of pathogens and parasites to humans and potential vectors, eventually leading to outbreaks of public health relevance. Malaria, dengue and chikungunya need mosquitoes as vectors, in contrast with leptospirosis, which directly invades human, although the environmental bacterial load is maintained through other mammals, such as rodents. The more complicating issue is that infections by different pathogens exhibiting similar symptoms but require different treatment management. The current review explores different pathogens expressing specific surface proteins and their ability to bind with array of host proteins with or without immune response to enter into the host tissues and their ability to evade the host immune responses to invade and their affinity to certain tissues leading to the common squeal of hemorrhage. Furthermore, at the host level, the increased susceptibility and inability of the host to arrest the pathogens' and parasites' spread in different tissues, various cytokines accumulated to eradicate the microorganisms and their cellular interactions, the antibody dependent defense and the susceptibility of individual organs bringing the manifestation of the diseases were explored. Lastly, we provided a discussion on the immune trail path of pathogenesis from entry to exit to narrate the similarities and dissimilarities among various hemorrhagic fevers mentioned above, in order to outline future possibilities of prevention, diagnosis, and treatment of coinfections, with special reference to endemic areas.
钩端螺旋体病的免疫发病机制可以通过追踪其从进入到离开的路径来很好地描述,同时它会在宿主的各种组织中造成灾难性损害。致命性钩端螺旋体病一致被归咎于失调、不适当和过度的免疫反应。针对疾病的严重程度,人们对病原体的内在能力和宿主的无能进行了争论。当这种疾病未得到治疗时,会观察到通过各种机制导致致命结局的出血表现。在流行地区,不同微生物感染中也会出现类似的血管破坏和出血表现。宿主同时感染一种以上病原体或寄生虫被称为合并感染。值得注意的是,钩端螺旋体病、登革热、基孔肯雅热和疟疾等常见的地方感染,在类似气候下拥有有利于繁殖的环境,这些环境因积水而加剧,居民个人和环境卫生差又使其恶化。这些因素有助于病原体和寄生虫传播给人类和潜在的病媒,最终导致具有公共卫生意义的疫情爆发。疟疾、登革热和基孔肯雅热需要蚊子作为病媒,与钩端螺旋体病不同,钩端螺旋体病直接侵入人体,尽管环境细菌负荷通过其他哺乳动物(如啮齿动物)得以维持。更复杂的问题是,不同病原体感染表现出相似症状,但需要不同的治疗管理。本综述探讨了表达特定表面蛋白的不同病原体,以及它们与一系列宿主蛋白结合的能力,无论是否有免疫反应以进入宿主组织,它们逃避宿主免疫反应以进行侵袭的能力,以及它们对某些组织的亲和力导致常见的出血症状。此外,在宿主层面,探讨了宿主易感性增加以及无法阻止病原体和寄生虫在不同组织中传播的情况,为根除微生物而积累的各种细胞因子及其细胞相互作用、抗体依赖性防御以及各个器官的易感性导致疾病表现。最后,我们讨论了发病机制从进入到离开的免疫路径,以阐述上述各种出血热之间的异同,从而概述合并感染预防、诊断和治疗的未来可能性,特别提及流行地区。