In search of the hidden reservoir of Malaria

This blog was originally posted on the桑格学院blog which can be readhere

在村里的第三晚,我们被一个悲伤的父亲的哀号唤醒。他的三岁儿子在夜间刚屈服于疟疾,他无奈地寻求帮助。这发生在一个可以免费获得治疗的村庄,可悲地提醒我们,与疟疾的斗争需要社会和教育干预措施以及科学和技术性的干预措施。

The next morning over a traditional fonio breakfast, faces are groggy and still carry the night’s tragedy. Our team, composed of two clinicians, two microscopists and myself in charge of entomology, is readying for our days’ work in Faladje, a small village in central Mali.

Humans are the sole reservoir of the deadliest malaria parasitePlasmodium falciparum,正是我们的研究重点是这些寄生虫只能在蚊子里花了几个星期后感染新人。这一事实意味着,每个新病例的疟疾均起源于感染性蚊子。在里面Lawniczak实验室在我是博士后的桑格学院,我们对疟疾寄生虫和媒介蚊子之间的相互作用感兴趣。我的项目尤其关注寄生虫如何在人们内部表现出来,以增加他们在蚊子内部最终登上内部的机会,从而最终是一个新人。

Humans are the sole reservoir of the deadliest malaria parasitePlasmodium falciparum.

人类红细胞内有几种不同的寄生虫“阶段”。引起发烧和死亡的阶段在红细胞内复制,然后破裂并感染新的红细胞。其他被称为配子细胞的阶段,正在等待被蚊子占领,在接下来的十天左右的时间里,他们将交配并发展。我要在马里执行的项目的重点是配子细胞。

A paradox lies in the fact that some people can transmit parasites to mosquitoes even when none can be seen in their blood. We are researching whether gametocytes are at higher densities in the skin where mosquitoes actually get their bloodmeals from, than in the freely circulating blood. To do this, we compare gametocytes inside mosquitoes that have fed on blood naturally versus artificially. Natural feeding is the kind that is making you itchy right now…a mosquito lands on you, inserts her proboscis, and finds a capillary to puncture and drink from. Artificial feeding is where we take blood from the vein and feed it to mosquitoes through an artificial membrane, visible in the photo below.

蚊子在人造膜喂食器上取血。
蚊子在人造膜喂食器上取血。

这项工作需要使用很少的生物材料。尽管蚊子可以喝血液的体重,但与之一起工作仍然很少(血餐约为两个微量液体)。我已经在桑格学院(Sanger Institute)建立了能够检测性阶段的配子细胞并用很少的材料来表征其遗传学的分子测定法。

Malaria rapid diagnostic tests (RDT) on a random morning, the ones with two bands are positive.
Malaria rapid diagnostic tests (RDT) on a random morning, the ones with two bands are positive.

进行这项研究提出了一些道德问题。虽然无害,但幼稚的蚊子叮咬还是不舒服的,有时甚至很痛苦。我们已经获得了内部审查委员会的道德批准,并已与村庄的当地公证人进行了全面的社区同意程序,并制定了一些非常严格的纳入标准和个人同意程序。该村庄将在我们在那里的时间里受益,并为任何疾病提供免费治疗,所有含有的患者将纳入全面的随访中28天。在我的第一个纳入中,我仍然很紧张。我以前从事实地考察,但这是我第一次领导它,也是我们第一次直接在这个村庄的孩子身上喂蚊子。

M. is the first patient included in our study, his blood is positive forP. falciparum根据快速诊断测试(见上文),并包含配子细胞传输阶段。他是一个安静的11岁男孩。我首先和他的母亲一起将他带到昆虫上,并用简化的法语解释该程序。然后,我对自己进行蚊子饲料,以证明该过程对他们俩的简单程度。在诊所服用血液样本后,我将他带回蚊子饲料。

M.现在没有疟疾,正在开玩笑,并很好奇地了解昆虫中每件设备的功能。

We place two pots of mosquitoes on M.’s calves, the five-minute feed seems endless in spite of the microscopist’s and my efforts to distract M. from the itch. M. comes back the next day and I realise I had been wrong, far from quiet, M., now free of malaria, is joking around and curious to understand the function of literally every piece of equipment in the insectary. M. now frequently visits us at the insectary with a few of his friends. On their last visit I was transferring samples to the liquid nitrogen tank and they were observing the fog bubbling out of the container from a distance. Although this will need replication, I think I made an initial discovery: liquid nitrogen has a universal appeal.

M.在昆虫外面。
M.在昆虫外面。

Since M.’s first visit, we have treated 800 patients and included more than 20 in the study and the protocol has become a lot smoother. We hope to get some indication as to the hidden biology of the sexual stages of malaria within the next six months.

As malaria biologists, we sometimes get lost in the fascination of studying biological problems, and lose touch with real world issues caused by these deadly parasites. Coming to work every morning for the past weeks to witness dozens of febrile children waiting for treatment has served a powerful reminder of the real burden of malaria and the importance of ridding the world of this affliction.


出版物:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031309/pdf/12936_2016_Article_1538.pdf

其他链接:

亚瑟Talman的页面:https://www.sanger.ac.uk/people/directory/talman-arthur-m

Mara Lawniczak的个人页面:https://www.sanger.ac.uk/people/directory/lawniczak-mara-k-n

向量寄生虫互动组页面:https://www.sanger.ac.uk/science/groups/lawniczak-group

Yourgenome Malaria lifecycle:https://www.yourgenome.org/facts/what-is-malaria

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