18 August 2012

Skinchangers: fact or fiction?

Throughout much of sub-Saharan Africa a disease called African trypanosomiasis (or sleeping sickness) is rife that affects both humans and animals alike. The main characteristic of the disease is the disruption of sleeping patterns that causes suffers to be awake at night and asleep during the day. Other symptoms of sleeping sickness include fever, sweating, headaches and the tendency to experience rapid mood swings. If the disease is left untreated, those infected with sleeping sickness could die from heart failure within 6 months of infection and, even if they get medical help in time, are likely to suffer from permanent damage to their nervous system so that their ability to live a normal life is impinged. Over 60 million people are at risk from African trypanosomiasis, which affects 50% of people in endemic areas. Furthermore, the loss of domestic cattle has had significant socio-economic consequences and the reduced ability for cattle farming has cost a staggering US$12, 000 million!

African trypanosomes are extracellular parasites, which means that they live freely in their hosts blood rather than inside of cells. Humans can be infected by two types of African trypanosome: Trypanosoma brucei gambiense and Trypanosoma brucei rhodiense, which is the most common and most deadly type, and is featured in this photo.

Sleeping sickness is spread by blood-sucking tsetse flies, which inject parasites called African trypanosomes* into their host's bloodstream along with the anticoagulants in their saliva. Once inside their host's bloodstream the parasites rapidly divide by binary fission and spread through various fluids throughout their body. What is interesting about African trypanosomes is the fact that they remain free-living in their host's body throughout their entire life cycle. This is highly unusual and most parasites (with the exception of worms), are intracellular and invade a specific type of cell to live and divide in as soon as they enter their host. The main reason many parasites do this, to put it simply, is to avoid their host's immunodefences. It is quite remarkable that African trypanosomes can manage to survive in the bloodstream,  which is a very hostile environment that is full of leukocytes (white blood cells)!

How they survive here is amazing and African trypanosomes are quite literally skinchangers! The parasites have special proteins on the surface of their 'skin' called variable surface glycoproteins (VSGs), which are encoded for by over 1, 000 different genes. The many proteins produced by these genes can be spliced together at random so that an infinite number of unique VSGs can be produced. This plays havoc for the host's defences and effectively renders the infection unclearable. This is because our immune system relies on shape: foreign invaders (or pathogens) have very specifically shaped antigens on their surfaces to which our bodies produce antibodies against in order to kill them. So, by changing the VSGs that they are displaying, African trypanosomes prevent their host's immune system from killing them off.

To explain this further, most of the parasites display the same unique VSG on their surface that their host's body cannot fight against so that they can divide unchecked. Eventually, and after a delay, the host's immune system produces new antibodies against this VSG and all of the parasites expressing that particular phenotype are killed. However a small number of the parasite population have already changed their skins by then and survive. These parasites then divide very rapidly (as they have less competition with other parasites), until the body 'learns' how to kill them and the whole cycle starts again. Eventually the parasites have done so much damage to the host, that it dies. Thus, outside medical treatment is required to kill all of the parasites at once that entails using powerful drugs such as Pentamidine or Melarsoprol.

The population of African trypanosomes in their host's bloodstream cycles depending on whether their host can kill them off or whether it is trying to produce new antibodies against them. The peaks in their population, which coincide with peaks in the symptoms of the disease, are called trypanolytic crises and were first discovered in 1910 by an Italian doctor.

So there you have it! African trypanosomes quite literally change their skin to avoid being detected and killed by their host's immune system, which allows them to persist in their host's body nearly indefinitely. 

* note that African trypanosomes are fundamentally very different to their cousins, South American trypanosomes, which cause Chagas Disease and have very different life cycles.

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