Review Drug uptake via nutrient transporters in Trypanosoma brucei

Eukaryotic micro‐organisms, including yeasts and protozoa, play important roles in the ecosystem and many are of practical importance as pathogens. African trypanosomes are parasitic protozoa which cause the disease sleeping sickness and are transmitted by tsetse flies in Sub‐Saharan Africa. Infections are maintained in the face of immune challenge because the parasites are capable of a process of antigenic variation (Rudenko 1999). Parasites move from the initial site of infection to the blood and lymphatic systems. Later they can penetrate the blood–brain barrier and invade other organs. The name sleeping sickness derives from symptoms associated with late‐stage disease where the central nervous system is involved and progressive deterioration of neuronal function leads to coma and eventually death. Drug therapy is the only viable means of controlling sleeping sickness in patients and four drugs are currently licensed to treat the parasites (Pepin and Milord 1994). Two of these, pentamidine and suramin, are useful against parasites before they invade the central nervous system while two others, melarsoprol and eflornithine, accumulate across the blood–brain barrier to levels that are high enough to also kill parasites in the cerebrospinal fluid. Problems with toxicity, resistance and lack of a guaranteed supply are seriously hindering the use of all of these drugs (Barrett, 2000). Africa is currently in the midst of a resurgent epidemic of the disease (Barrett 1999) and it is reported that a significant proportion of cases are proving refractory to treatment with melarsoprol. Novel formulations to use against sleeping sickness are urgently needed.