African trypanosomes are kinetoplastid parasites that proliferate as extracellular forms in the blood and cause sustained or intermittent fevers, lymphadenopathy, splenomegaly, progressive brain dysfunction (sleeping sickness), cachexia, and death.
Trypanosoma brucei rhodesiense infections, which occur in East Africa, are often acute and virulent. Trypanosoma brucei gambiense infection tends to be chronic and occurs most frequently in the West African bush.
Tsetse flies (genus Glossina) transmit African Trypanosoma to humans either from the reservoir of parasites found in wild and domestic animals (T. brucei rhodesiense) or from other humans (T. brucei gambiense). Within the fly, the parasites multiply in the stomach and then in the salivary glands before developing into nondividing trypomastigotes, which are transmitted to humans and animals.
Pathogenesis
African trypanosomes are covered by a single, abundant, glycolipid-anchored protein called the variant surface glycoprotein (VSG). As parasites proliferate in the bloodstream, the host produces antibodies to the VSG, which, in association with phagocytes, kill most of the organisms, causing a spike of fever. A small number of parasites, however, undergo a genetic rearrangement and produce a different VSG on their surface and so escape the host immune response. These successor trypanosomes multiply until the host mounts an antibody response against their VSG and kills them, allowing another clone with a new VSG to take over. In this way, African trypanosomes escape the immune response to cause waves of fever before they finally invade the central nervous system.
Trypanosomes have about 1000 VSG genes, only one of which is expressed at a time. The parasite uses an elegant mechanism to turn VSG genes on and off.
Although VSG genes are scattered throughout the trypanosome genome, only VSG genes found within chromosomal regions called bloodstream expression sites, located in telomeres (the ends of chromosomes), can be expressed. New VSG genes are moved into the bloodstream expression sites mainly by homologous recombination.
A poorly understood transcription apparatus, which includes the RNA polymerase that transcribes VSG genes, associates with a single bloodstream expression site to limit expression to a single VSG gene.
Morphology
A large, red, rubbery chancre forms at the site of the insect bite, where large numbers of parasites are surrounded by a dense, largely mononuclear, inflammatory infiltrate.
With chronicity, the lymph nodes and spleen enlarge owing to hyperplasia and infiltration by lymphocytes, plasma cells, and macrophages, which are filled with dead parasites.
Trypanosomes, which are small and difficult to visualize, concentrate in capillary loops, such as the choroid plexus and glomeruli. When parasites breach the blood-brain barrier and invade the central nervous system, a leptomeningitis extends into the perivascular Virchow-Robin spaces, and eventually a demyelinating panencephalitis occurs.
Plasma cells containing glycoprotein globules are frequent and are referred to as flame cells or Mott cells. Chronic disease leads to progressive cachexia, and patients, devoid of energy and normal mentation, waste away.