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If left untreated, African trypanosomiasis will invariably kill the patient. The human immune system is unable to clear the infection.

I am aware of a few other infectious diseases with this property and I have a rudimentary understanding of the reason why. For example, I'm told that rabies has evolved to be uniquely good at attacking the brain because that's the only way it can spread to other hosts, and the neuroimmune system, being quite different from the peripheral immune system, is not capable of dealing with a virus that has this property.

I do not understand why the human immune system is ineffective against trypanosomiasis. One explanation I was offered is that the human immune system is just not very good at fighting parasitic infections (compared to viral and bacterial infections). However, this can't be the full answer, because there are other parasitic infections that may go away on their own without treatment.

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    $\begingroup$ Welcome to SE Biology. As a veteran contributor to StackOverflow you will know how important it is to follow the guidelines of a SE community. Our guidelines, like most, specify the audience (biology researchers, academics, and students) which is important in that answers will assume a certain level of knowledge, just as on SO) and that posters are expected to show that they have researched a question before asking it. If you search for "trypanosome immune evasion" you will find many articles on a very broad field. $\endgroup$
    – David
    Apr 16, 2020 at 10:28

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African trypanosomiasis, or sleeping sickness, is caused by the protozoan Trypanosoma brucei, a single-celled eukaryote. Being eukaryotic, it has a cell nucleus and a larger genome than most bacteria; it also has a flagellum with which it can propel itself. Infection with T. brucei occurs via the bite of a blood-sucking fly, one of several species of tsetse fly.

The mammalian immune system has a difficult time with T. brucei because of an effective set of adaptations. The protozoan's surface maintains a dense coat of a particular glycoprotein on its surface which generally hide other necessary surface features such as chemical receptors and ion channels. Since it is this glycoprotein that the adaptive immune system will encounter, that molecule is the one which it will develop antibodies to recognize.

Within a few days the protozoans would be recognized and soon eliminated by the immune system except that T. brucei at random times changes the glycoprotein used as its surface coat. The mechanism that does this is called a variant surface glycoprotein (VSG) expression system. The organism has a repertoire of about 1500 different proteins to select from to use for a new glycoprotein coat. The overall effect is that by the time the immune system is able to flood the body with the antibody type it has developed, most of the T. brucei population is not recognizable by those antibodies. T. brucei devotes a significant portion of its genome and its protein production to this immune evasion system.

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    $\begingroup$ good answer!, also, the trypanosome gets through the blood-brain barrier where immune system options are fewer, and fewer chemicals can get there. $\endgroup$
    – Polypipe Wrangler
    Apr 16, 2020 at 11:14
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    $\begingroup$ This makes sense. I wonder if you have an opinion as to why a VSG-like mechanism hasn't evolved in other kinds of infectious parasites, though? It seems that it the trade-off involved would be similar for them (i.e. the benefit of being more effective at infection versus the cost of the additional genome size and protein production) $\endgroup$
    – Brian
    Apr 16, 2020 at 14:56
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    $\begingroup$ @Brian That's probably wide enough topic for a separate question, but I think the fly-mammal-fly lifecycle might have something to do with it. Malaria has a somewhat similar, but apparently separately evolved, mechanism of varying its surface characteristics. More here: en.wikipedia.org/wiki/Antigenic_variation $\endgroup$
    – jpa
    Apr 16, 2020 at 15:46
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    $\begingroup$ I hope you're not trying to give a new idea to our newest coronavirus, @brian! $\endgroup$
    – John Dvorak
    Apr 17, 2020 at 16:15
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    $\begingroup$ @Brian Evolution isn't forward-looking. It doesn't seek out adaptations which would be useful; it merely preserves any adaptations which it happens to come across which turn out to be useful. (Of course, there isn't really any "force of evolution" which causes these things to occur. Evolution is merely the name we give to the self-evident fact that adaptations which propagate themselves propagate themselves.) $\endgroup$
    – Tanner Swett
    Apr 18, 2020 at 16:24

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