The doctors informed Robert of the diagnosis. After they explained the cause of his illness, Robert asked "Will I be ok?  Do you have a medication to kill Trypanosoma brucei?"

"There is medication to treat this disease, Mr. Bragg," said the doctor. "It's called suramin. It is very effective at killing Trypanosoma brucei when given early enough in the disease process, but it can also cause severe side effects, including joint pain, severe weakness, light sensitivity and even loss of consciousness.  We need to start your treatment at once despite these side effects because the disease has a high fatality rate if left untreated.  Fortunately, you are not exhibiting signs of severe damage to your central nervous system, such as violent behavior, convulsions, or coma, so I think that we have caught the disease at an early enough stage for treatment to be successful.  However, we will first examine your central nervous system (CNS) fluid for the presence of parasites to confirm that the disease has not progressed."

"All right, doctor.  Do what you have to... but is there any chance that I can recover from this parasite on my own, without risking the side effects of that medication?"

A second doctor interjected: "Actually, the human immune system is somewhat capable of killing Trypanosoma brucei and lowering the parasitemia (number of parasites in the blood); however, the parasite has adapted a way to continually evade the immune system so that it can continue replicating."

"If we were to count the number of parasites in your blood every day," explained the doctor, "we would likely notice that the parasitemia level would steadily increase for a period of time, perhaps one week, the the parasitemia level would fall drastically over one or two days as large numbers of parasites were killed by your immune system, only to rise again the following week. This trend would continue until you were given medication to clear the parasites, and would look like this if graphed." The doctor then pointed to a graph in a paper he was holding:

http://tryps.rockefeller.edu/trypsru2_avariation_intro.html (look at the graph on the left side of the page)

"I don't understand," said Robert. "If my immune system is capable of killing the parasites, why would the number of parasites in my blood repeatedly rebound in that way?"

The doctor explained that in order for African trypanosomes to become successful extracellular parasites and survive in the bloodstream of their human hosts, they had evolved a mechanism to evade the host's immune response.

"African trypanosomes are covered by a protective coat containing proteins called varian surface glycoprotein (VSG). Although VSG helps protect the parasite, it's also an antigen, which means it triggers the immune system to respond by making antibodies against it, which can lead to the destruction of the parasite.  The genome of African trypanosomes contains many variations, or alleles, of the gene that encodes VSG.  Only one allele is expressed at a time, but the parasite can vary which allele is expressed, allowing it to change its VSG coating as soon as the host's immune system becomes effective at recognizing one particular variant of VSG."

The doctor continued: "Every spike in parasitemia levels in the graph represents a switch in VSG expression.  It takes time for the immune system to adapt to each new VSG.  Once it does, parasites are rapidly killed and parasitemia levels drop sharply, only to increase again after another round of VSG switching."

QUESTIONS

Q1: Investigate the different parts of the human immune system and explain which cells/products of innate and adaptive immunity are responsible for recognizing antigens on the surface of T. brucei and clearing the parasite.

Q2: If researchers developed a drug that could prevent T. brucei from undergoing antigenic variation, do you think it could be successful in eradicating African Sleeping Sickness?  Would the drug have to be administered at a certain point before or after infection in order to be helpful?