Combination therapy for sleeping sickness: a wake-up call.

Ours is a smaller world than that of previous generations. Given humankind's insatiable desire to change places for all kinds of reasons and through all kinds of routes, clinicians in developed countries are increasingly exposed to diseases that used to be considered " exotic. " Cases of African trypanosomiasis, the archetype of such diseases ever since Joseph Conrad's Heart of Darkness, are now seen in the Western world—albeit rarely—in tourists who have visited the game parks of East and southern Africa [1], where they acquired Trypanosoma brucei rhodesiense infection , and in asylum seekers or long-term expatriates from Central Africa, where T. brucei gambiense sleeping sickness reemerged 10 years ago [2]. T. brucei rhodesiense trypanosomiasis is a zoonosis, with cattle being the main reservoir , and humans are occasionally infected through an animal-fly-human cycle ; interhuman transmission is rare, except during epidemics, such as in the Busoga focus of Uganda 20 years ago [3]. The disease is characterized by a short incubation period, a high degree of parasi-temia (which facilitates parasitological diagnosis by use of blood smears), early complications, and rapid progression (within weeks) to central nervous system infection. Thus, this subspecies kills its human hosts too rapidly for its own interest, but cattle and game animals, which tolerate it fairly well, allow it to prosper [4]. T. brucei rhodesiense trypanosomiasis is found only in East and southern Africa, and !1000 cases are reported each year to the World Health Organization (WHO) [5]. In recent years, most cases among tourists were acquired in Serengeti Park [1]. In contrast, T. brucei gambiense shares with HIV a key epidemiological parameter: a very long duration of infection, which explains its ability to cause dramatic epidemics [4]. Most humans are infected through a human-fly-human cycle, and animals (mostly pigs) probably contribute to the dynamics of sleeping sickness only at the very end of an epidemic, when the human reservoir has dwindled. After a long (months or years) asymptomatic period , patients initially develop intermittent fevers (corresponding to successive waves of parasites expressing new variant surface glycoproteins, a process known as " anti-genic variation ") and then slowly develop classical sleeping sickness, which is characterized by somnolence, persistent headaches , occasional psychiatric symptoms, and a chronic lymphocytic meningoen-cephalitis. Because the parasitemia is low grade and intermittent, it may be difficult to document trypanosomes in blood smears, but cervical lymph-node aspirates and the cerebrospinal fluid (CSF) …