Updated April 28, 2020
Infection occurs in two stages, an initial haemolymphatic stage followed by a meningoencephalitic stage after the trypanosomes invade the central nervous system (CNS). However, many of the signs and symptoms are common to both stages, making it difficult to distinguish between the two stages by clinical features alone. First-stage symptoms may be preceded by the development of a trypanosomal chancre at the site of inoculation within two days to two weeks of being bitten by an infected fly (occurs most commonly with T. b. rhodesiense, rarely with T. b. gambiense although chancres are observed with T. b. gambiense in travelers from non-endemic countries). The first stage involves nonspecific, generalized symptoms occurring 1–3 weeks after the tsetse fly bite with T. b. rhodesiense; the incubation period for T. b. gambiense is less well characterized but disease progresses more slowly than that caused by T. b. rhodesiense. First-stage symptoms for both types of sleeping sickness include headache, malaise, weakness, fatigue, pruritis, and arthralgia. First-stage signs can include hepato-splenomegaly, weight loss and intermittent fevers lasting one day to one week. The intervals between fevers can last days or months. Lymphadenopathy, mainly posterior cervical but in some cases axillary, inguinal or epitrochlear, may also occur. Posterior triangle cervical lymphadenopathy, or “Winterbottom’s sign” is commonly seen in T. b. gambiense infections.
T. b. gambiense infection progresses to the second stage after an average of 300–500 days, whereas T. b. rhodesiense infection progresses to the second stage after an estimated 21–60 days. For both types of disease, the stage is determined by examining cerebrospinal fluid (CSF) and observing trypomastigotes. In second-stage disease, invasion of the central nervous system causes a variety of neuropsychiatric manifestations to appear in addition to the first-stage signs and symptoms, with fever occurring less frequently over time. The sleep/wake cycle becomes reversed, hence the common name “African sleeping sickness”, with daytime somnolence, nocturnal insomnia, and sudden urges to sleep. The patient also experiences mental (hallucinations, delirium, anxiety, emotional lability, attention deficit, apathy, aggression, mania, confusion), motor (motor weakness, abnormal tone, gait disturbance, ataxia, tremor, speech disturbances), sensory (paraesthesia, hyperaesthesia, anaesthesia, pruritis, visual problems), and neurologic (abnormal reflexes, seizures, coma) signs and symptoms. Compared to T. b. gambiense, T. b. rhodesiense is more likely to result in endocrine abnormalities such as adrenal insufficiency, thyroid dysfunction and hypogonadism; and cardiac involvement, such as myocarditis, is more severe.