Part I – Sub-Saharan Safari
A 51-year-old man named Robert Bragg reported to a hospital in the United Kingdom complaining of general malaise
(discomfort), myalgia (muscle pain), fevers, headache, vomiting, and diarrhea. He complained that during the day he
felt weak and tired; he was unsure if this was because his symptoms kept him awake at night, or if something else was
causing his fatigue.
Robert had recently returned from a two-week safari in central Africa. He said that he felt fi ne during the entire
trip, but reported that he had received numerous bug bites while on safari. He also said that while he was in Africa
he routinely ate unfamiliar foods, including meats, which may have been prepared and stored under conditions that
would not be considered sanitary practices in the United Kingdom.
Doctors suspected Robert’s symptoms were caused by an infection he developed while on safari.
Questions
1. Make a list of human pathogens that are endemic to sub-Saharan Africa and can be transmitted through bug
bites or consumption of contaminated foods. Looking over your list, what do you think is the most likely
cause(s) of Robert’s illness?
2. What tests should doctors conduct to confi rm this diagnosis?
Because Robert had spent much of his time outdoors in an area of the world where the Anopheles mosquitoes that
transmit malaria are common, the doctors immediately suspected he had contracted malaria. His symptoms matched
those generally expected of people with malaria, but to confi rm the diagnosis doctors collected a blood sample from
Robert to analyze for the presence of the Plasmodium falciparum parasites that cause the disease.
When doctors looked at Robert’s blood smear under a
light microscope, they did not see any malaria parasites.
However, they did make a startling discovery.
“I found Trypanosoma brucei parasites in the patient’s
blood,” one of the doctors remarked.
“What is Trypanosoma brucei? ” asked a nurse. “Is it a
type of malaria?”
“Trypanosoma brucei is a protozoan parasite. It is not
closely related to Plasmodium falciparum genetically,
but there are many similarities in the way it infects
people and in the symptoms it causes. Th e disease
caused by Trypanosoma brucei, called African
trypanosomiasis, is also known as African sleeping
sickness. All of the patient’s symptoms are explained
by this diagnosis.”
Questions
1. What is a protozoan? How is a protozoan parasite diff erent from bacteria and multi-celled parasites such
as intestinal worms? How does T. brucei diff er from the closely related American trypanosome T. cruzi, the
causative agent of Chagas disease, and from the P. falciparum parasite that causes malaria? Describe notable
diff erences in morphology, life cycle, infectivity, transmission, geographical range, disease presentation, and
treatment.
2. How do people become infected with T. brucei? What are the risk factors as far as behavior, lifestyle, and
geographic location?
3. What are the clinical manifestations and symptoms of African trypanosomiasis? Compare and contrast these
with the symptoms of malaria.
4. Why does T. brucei infection cause the symptoms that led to the term “African Sleeping Sickness”?
5. How is T. brucei infection diagnosed? What factors often make diagnosis diffi cult?
Part III – Symptoms and Treatment
Th e 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?”
“Th ere is medication to treat this disease, Mr. Bragg,” said the doctor. “It’s called suramin. It is very eff ective at killing
Trypanosoma brucei when given early enough in the disease process, but it can also cause severe side eff ects, including
joint pain, severe weakness, light sensitivity and even loss of consciousness. We need to start your treatment at once
despite these side eff ects 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 fi rst examine your
central nervous system (CNS) fl uid for the presence of parasites to confi rm 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 eff ects 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, then
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. Th is trend would continue until you were given
medication to clear the parasites, and would look like
this if graphed.”
“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?”
Th e 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 variant 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. Th e 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 eff ective at recognizing one particular variant of VSG.”
Th e 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
1. Investigate the diff erent 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.
2. What would happen if T. brucei suddenly loss the ability to undergo antigenic variation?
3. 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?
4. Based on the similarities and diff erences you identifi ed earlier between T. brucei, P. falciparum, and T. cruzi, do
you predict that P. falciparum and T. cruzi undergo similar antigenic variation? Why or why not?
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