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Team:Goettingen/project overview ZH
From 2014.igem.org
Project
背景
真菌感染——全球面临的问题
真菌是对大众健康有威胁的主要病原体之一,它们会进行大范围全球的转播。然而令人 遗憾的是这些病原体却没有引起重视。据统计,每年有 1,500,000 人死于真菌感染。并且, 人们死于前十位真菌感染疾病的数量相对于人们死于肺结核或者疟疾的数量而言只会多不会少。不仅如此,真菌感染的死亡率要比之前高了50%。
与之形成鲜明对比的是,目前用于治疗真菌感染的资金非常少,大约只占了维康基金会、 英国研究理事会以及美国国立研究院 2005~2010 年所花在医疗支出上的 1.4%~2.5%。虽然这 可能只是仅仅代表了某一地区,但是即使如此,真菌感染仍然需要资金机构和相关专家学者 们的高度注意:治疗和诊断工具的新发展应该被批判的接受,以此来改善高风险患者的处境。
最常见的真菌感染是皮肤表面感染、指甲及粘膜感染,这些病在大多数情况下都是由一 种叫做念珠菌的真菌引起的。这些感染通常不是致命的,它的临床表现往往相似，例如外阴阴道念珠菌病以及在运动员脚上的足藓。
在另一方面,具有攻击性的真菌感染却有着极高的死亡率。免疫系统的免疫能力与正常 人不同的病人如艾滋病人以及靠吃免疫抑制剂来维持自身免疫系统正常的曾接受过移植手术的病人,他们在面临这种疾病时处于一种很危险的状态——因为他们没有正常的免疫系统 去防止侵染性真菌去进攻健康的机体。
根据 Pro. Brown 的说法,在被报道的死亡中,有超过 90%的案例是由真菌引起的,这些真菌来自四个属:隐球菌属,念珠菌属,曲霉菌属,费囊虫属。但是在真菌感染这一方面流行病学上的数据很少,因为这些感染通常被误诊。所以我们极需一份对于真菌感染的准确数据。
【地方性两型真菌病】
下面的地图是由 Pro. Brown 提供的信息改编的,在这篇文章中有些作家对于这些信息的评论:
1) 这些数据可以从一些局部的小范围的研究中得出。
2) 我们缺少准确的数据,并且地图上这些数据所展现出来的信息可能并不完整。
【伺机侵入性真菌感染】
伺机侵入性真菌会感染那些免疫系统不正常的人,比如艾滋病人以及吃了免疫抑制剂的病人,尤其是那些经过皮肤移植的人。下面的地图也是由 Pro. Brown 提供的信息改编的。
从头到尾,在右上角的数据如下:1)疾病的名称 2)形成机制 3)死亡率(%在被感染 的人群中)4)世界每年估计受感染人数。
世界目前被用来检测真菌病原体感染的工具:
| 真菌感染 | 诊断技术 | |||||
|---|---|---|---|---|---|---|
| Microscopy | Agar culture | Xrays/scans | Antigen | Blood antibody | DNA detection | |
| Thrush | +++ | +++ | - | - | - | - |
| Candida bloodstream | - | +++ | + | + | + | +++ |
| Candida abdominal | + | +++ | + | - | - | - |
| Cryptococcal meningitis | ++ | +++ | + | +++ | - | - |
| Invasive aspergillosis | + | + | +++ | ++ | - | ++ |
| Chronic aspergillosis | + | + | +++ | - | +++ | ++ |
| Allergic aspergillosis | + | + | ++ | - | +++ | + |
| Coccidioidomycosis | + | ++ | ++ | - | +++ | - |
| Histoplasmosis | + | ++ | + | ++ | - | - |
| Zygomycosis | +++ | + | ++ | - | - | - |
Detection by Polymerase Chain Reaction
The table above denotes a summary of the techniques used at present to detect the leading fungal pathogens in world. Note that the column titled "DNA detection" is a term that mainly involves the use of the Polymerase Chain Reaction (PCR)to detect pathogens. Although it is touted as a reliable technique, it has several disadvantages such as high cost, requirement of laboratory settings of high standards and false positives due to detection of pathogenic DNA EVEN AFTER the resolution(clearance) of the disease. Finally, PCR amplifies the DNA in a sample and only gives qualitative results. While Real-Time PCR can give information on the initial amount of the sample, it requires RNA samples which are degraded by RNases in the body and even if it isn't, it requires a well equipped laboratory to prevent further degradation.Therefore, this method cannot be used reliably in many parts of the world (especially in the underdeveloped countries).
Another technique that can be used to detect pathogens through their DNA is DNA-hybridization, but the downside with this method is that it is labor intensive and involves the use of radio-labelled probes.
Detection by Microscopy
As mentioned before, microscopy has been the mainstay for detection of pathogenic fungi. This is primarily due to the fact that it's one of the oldest and most widely available means of detection. It only requires a microscope, a stain for contrast, the sample from a patient and a user with some experience. Furthermore, this technique requires neither the consideration of multiple parameters (such as in a PCR) nor much time (agar plate cultures need at least a day) to yield results.
Thus, we believe that improving detectability through microscopy by giving it the advantage of molecular biology (specificity and a better scope for visualization) while maintaining the advantages of conventional microscopy.
References
- 1. Brown et al., (2012), Hidden Killers: Human Fungal Infections, Sci Transl Med, Vol. 4, Issue 165.
