This patient had multiple possible parasitic organisms that could have been considered as a possible cause for his symptoms, considering his history of travel to Africa and South America. On the list of possibilities would certainly be malaria. There are rapid immunochromatographic assays available now that can help to rule out malaria. The BinaxNOW™ is an example of such a rapid immunochromatographic assay that has been found to have a 84.2% senistivity and 99.8% specificity with a result in 15 minutes with minimal temperature requirements and no instrumentation. However the peripheral smear of this patient was diagnostic. In conjunction with the clinical presentation and travel history, this patient is diagnosed with having a trypanosome infection based on the presence of the hemoflagellate in the peripheral smear.
But which trypanosome? We can exclude South American trypanosomiasis by carefully looking at the organism in the peripheral smear. Even with the history of travel to South America and potential exposure, the morphologic characteristics are not consistent with South American trypanosomiasis caused by Trypanosoma cruzi. Typically African trypanosomes will have a kinetoplast that is significantly less prominent than the kinetoplast present in Trypanosoma cruzi. The trypanosome seen in the patient’s peripheral smear do not have a prominent kinetoplast. The morphologic differences can be seen in the comparison photos shown below.
The patient’s history of travel to Eastern Africa, and the development of cervical lymphadenopathy shortly upon arriving at Manaus/Brazil, point that the exposure was most likely in Eastern Africa. The cervical lymphoid involvement is classic of African trypanosomiasis and is called Winterbottom’s Sign. Additionally, central nervous system involvement is apparent by the abnormal chemistries for the cerebral spinal fluid tests (increased protein, presence of white blood cells with a lymphoid differential), positive Kernigs Sign, and the patient’s irrational agitated state.
So we can deduce that the trypanosome suspected is an African trypanosome. But which one? There are two trypanosomes that are endemic in Africa, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. Both are found in differing geographic areas, though some overlap can occur, and both differ in disease progression. The acute presentation, presence of trypanosome in the peripheral blood, and the history of travel to Eastern/Southern Africa point to East African Sleeping Sickness caused by Trypanosoma brucei rhodesiense. The other sleeping sickness, West African Sleeping Sickness, is caused by Trypanosoma brucei gambiense. Both are virtually indistinguishable on the peripheral smear. Trypanosoma brucei gambiense is a less aggressive form of African Sleeping Sickness and geographically it is endemic in Western/Central Africa. As mentioned previously there is some geographic overlap of both trypanosomes. Both are transmitted by the bite of the Tsetse fly. A highly aggressive biting fly found in 36 African countries.
Initial bites of the Tsetse fly will produce skin lesions or the development of a bite chancre in 48 hours. These chancre are usually 2 to 5 cm in diameter and red to purple in color. The bite is itchy and can be painful. With the development of a chancre, there is the enlargement of lymph nodes (Winter Bottom’s Sign) most commonly in the posterior cervical area. Generally there are three stages described upon being infected. There is an initial cutaneous stage as described previously; there is a hemolymphatic stage where the organisms can be found in the lymphatics and peripheral blood; and finally a central nervous system stage where the trypanosomes invade the central nervous system to produce the characteristic symptoms of African Sleeping Sickness (headache, progressive confusion, lack of energy, weakness, arthralgia, personality changes, longer sleeping periods, and eventual fatal meningoencephalitis). In this central nervous system stage you can find tryponsomes in the CNS fluid. In the central nervous system the organism will target circumventricular organs in the brain resulting in the inflammatory responses of hypothalamic structures that lead to dysfunctions in the circadian-timing and sleep-regulatory systems. Thus the name “sleeping sickness”.
As stated previously Trypanosoma brucei rhodesiense is a more aggressive form of African Sleeping Sickness. The reservoir of the organism for the Tsetse fly are the wild game or cattle in the environment such as African antelopes and other such grazing wild animals. The reservoir for Trypanosoma brucei gambiense is thought to be primates and humans. Trypanosoma brucei rhodesiense is considered not as adapted to having humans as hosts and therefore the disease will present in an aggressive manner. Death of the host is more rapid and therefore it can be said that the infection in the human host is not an advantage to the parasite. This may be the reason that sleeping sickness due to Trypanosoma brucei rhodesiense is less common.
The organism is treatable when caught early in order to prevent central nervous system involvement and morbidity/mortality. Without treatment death occurs within a few months. Treatment with Melarsopol had been the go-to-compound for African Sleeping Sickness at one time. The compound was introduced in the 1940s. However the compound is derived from arsenic and had been found difficult to tolerate with one in twenty patients treated killed. In 2009 another compound was introduced called NECT. NECT was a combination of pills and 14 intravenous infusions. This was not practical however as the administration of NECT required trained personnel. Recent advances in the treatment of trypanosomiasis center around the development of a compound called fexinidazole. In 2023, the European Medicines Agency adopted a positive opinion on the use of fexinidazole for the treatment of Trypanosoma brucei rhodesiense. An orally administered compound. Generally the patients should be followed up closely for 24 m onths after treatment and monitored for any relapse.
African trypanosomiasis can be detected by testing for the presence of trypanosomes in the peripheral blood; fluid aspirated from enlarged lymph nodes; chancre fluid; and the CSF in advanced stages. The material can be stained with Geimsa stain and observed under the microscope for the presence of trypanosomes.