Trypanosomiasis encompasses two distinct entities: African trypanosomiasis and American trypanosomiasis.

African trypanosomiasis

African trypanosomiasis, or sleeping sickness, is caused by Trypanosoma brucei. The tsetse fly is the arthropod vector. CNS involvement is the principal clinical consequence.

An inflammatory nodule, a chancre, appears within several days at the site of parasite inoculation by the biting tsetse fly. Parasite replication and local tissue invasion is followed by lymphatic and bloodstream entry, causing a diffuse lymphadenopathy and parasitemia with high fever. Recurrent cycles of hemo-lymphatic parasitemia follow, with corresponding bouts of fever alternating with periods of well-being. (African trypanosomiasis and malaria are two of the few causes of true intermittent fever.155)

Trypanosomes eventually enter the CNS to cause meningoencephalitis, with a full range of neuropsychiatric signs and symptoms, including sleep-wake cycle abnormalities (e.g., daytime drowsiness and nocturnal insomnia), from which the disease derived its name. Frequent episodes of awakening during sleep, blurring of sleep stages, and irregular bursts of rapid EEG activity during stage 4 sleep occur.155 Generalized convulsions become common as the disease progresses to later stages.155 If untreated, mortality approaches 100%.

Definitive diagnosis of African trypanosomiasis depends on demonstration of the parasite in chancre fluid, lymph nodes, blood, or CSF. Lumbar puncture should be performed in all cases of suspected trypanosomiasis (after confirming absence of increased intracranial pressure risk).

Of the three drugs usually used for treatment (suramin, pentamidine, and melarsoprol), only melarsoprol penetrates the blood-brain barrier to be effective in CNS disease. Its use is complicated by an up to 18% incidence of severe, reactive arsenic encephalopathy, which can result in permanent neurologic damage or death.156,157 Consequently, melarsoprol should be used only in patients with CNS involvement.

There are three characteristic syndromes of arsenic encephalopathy:

  • status epilepticus with acute cerebral edema
  • rapidly progressive coma without seizures
  • nonfatal cognitive abnormalities without other neurologic signs.155


Steroids may help prevent or treat drug-induced encephalopathy, especially in higher-risk patients (those with trypanosomes demonstrable in CSF or greater than 100 WBC, or both).155

In a study of melarsoprol effects on patients with T. gambiense in the meningoencephalitic stage, EEG tracings before treatment showed marked abnormalities in the form of periodic delta outbursts. EEGs performed after treatment showed improvement in 56% of patients but failed to return to normal in any patient.155,158

American trypanosomiasis

American trypanosomiasis, also known as Chagas’ disease, is an acute or chronic infection caused by Trypanosoma cruzi. T. cruzi infection occurs only in the western hemisphere. Reduviid bugs of genus Triatoma are the vector.

Symptomatic CNS disease is rare in immunocompetent patients.

(Cardiac and intestinal disease are primary.) In well-described case reports of CNS involvement, seizures have occurred in both acute CNS infection and chronic Chagas’ disease.155

Immune response to American trypanosomiasis is mediated by T cells, so AIDS can alter the natural history of infection, leading to disease reactivation. A review of Chagas’ disease within the context of AIDS revealed that 87% of cases had severe, multifocal, or diffuse meningoencephalitis.159 Seizures, partial and generalized, can accompany any of these forms of CNS Chagas’ disease.

Diagnosis is via demonstration of parasites in blood, CSF, or tissue.

Treatment via trypanocides (nifurtimox) has been shown to decrease parasitemia, symptoms, and mortality. Routine anticonvulsant treatment principles apply.

Adapted from: Goldstein MA and Harden CL. Infectious states. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;83-133. 
With permission from Elsevier (

Reviewed By: 
Steven C. Schachter, MD
Monday, March 1, 2004