A trypanosomal chancre develops ~1 week after the bite of an infected tsetse fly. A systemic febrile illness without involvement of the CNS (stage 1 disease) then evolves as the parasites disseminate through the bloodstream and lymphatics.

• Bouts of high-grade fever lasting several days are separated by afebrile periods. Malaise, headache, arthralgias, hepatosplenomegaly, and other nonspecific manifestations can develop.
• Lymphadenopathy with discrete, rubbery, nontender nodes is prominent in T. b. gambiense disease. Enlargement of nodes of the posterior cervical triangle (Winterbottom's sign) is a classic manifestation.
• With CNS invasion (stage 2 disease), pts develop progressive indifference and daytime somnolence, a state that sometimes alternates with restlessness and insomnia. Extrapyramidal signs may include choreiform movements, tremors, and fasciculations; ataxia is common.
• Disease due to T. b. rhodesiense is more acute and, if untreated, can lead to death in weeks to months; in contrast, disease due to T. b. gambiense can smolder for months or years.