Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)

Summary

Human African trypanosomiasis, or sleeping sickness, is caused by infection with parasites of the genus Trypanosoma, transmitted by the tsetse fly. The disease has two forms, Trypanosoma brucei (T b) rhodesiense and T b gambiense; and is almost always fatal if untreated. Despite a recent reduction in the number of reported cases, patients with African trypanosomiasis continue to present major challenges to clinicians. Because treatment for CNS-stage disease can be very toxic, diagnostic staging to distinguish early-stage from late-stage disease when the CNS in invaded is crucial but remains problematic. Melarsoprol is the only available treatment for late-stage T b rhodesiense infection, but can be lethal to 5% of patients owing to post-treatment reactive encephalopathy. Eflornithine combined with nifurtimox is the first-line treatment for late-stage T b gambiense. New drugs are in the pipeline for treatment of CNS human African trypanosomiasis, giving rise to cautious optimism.

Introduction

Human African trypanosomiasis (HAT), which is also known as sleeping sickness, is one of the world's neglected diseases. Caused by protozoan parasites of the genus Trypanosoma and transmitted by the bite of the blood-sucking tsetse fly of the genus Glossina, about 60 million people are estimated to be at risk of the disease between latitudes 14° north and 29° south throughout many countries in sub-Saharan Africa.1, 2, 3 HAT is almost always fatal if untreated or inadequately treated and is a substantial cause of both mortality and morbidity in affected regions, where it also has a substantial effect on livestock production. The problem of the disease is compounded by the extent of tsetse fly infestation, which covers about 10 million km² of the landmass of Africa.²

There are two forms of HAT, the more common west African disease caused by Trypanosoma brucei gambiense (T b gambiense) and the less common east African disease caused by T b rhodesiense.1, 2 Although about 97% of cases of HAT are due to the T b gambiense variant, the T b rhodesiense variant, which is responsible for only about 3% of cases,⁴ causes a more acute and severe illness, and it can be a substantial hazard in travellers from Europe and the USA returning from visits to east African game parks.5, 6

For centuries there had been a general awareness of the existence of a severe wasting disease called nagana occurring in cattle in sub-Saharan latitudes and also of a fatal sleep disorder of human beings occurring in those areas.7, 8 The cause of nagana was finally identified in 1899 by David Bruce, who showed that the disease was caused by a trypanosome that became known eponymously as Trypanosoma brucei, with his subsequent studies proving that it was the tsetse fly that transmitted the disease from wild to domestic animals.7, 8 During the following decade, several other discoveries were made, including the identification by Dutton of a subspecies in a European individual, which was termed T b gambiense; the first identification by Castellani of trypanosomes in the blood and CSF in a patient with HAT; and the identification by Stephens and Fantham of a subspecies called T b rhodesiense.7, 8, 9 Although animals such as cattle are the main reservoirs of trypanosomes causing T b rhodesiense disease, human beings are the main reservoir for trypanosomes causing T b gambiense HAT.3, 10 Figure 1 shows the distribution of these two HAT variants. In Uganda, both types of HAT exist, raising the possibility that some patients can become co-infected with both T b gambiense and T b rhodesiense.8, 12 The existence of these two variants in the same region raises the problematic issue of patient treatment, which would be different for both diseases, especially because microscopy alone is not sufficient to distinguish between the two subspecies.