Potential new drugs for human African trypanosomiasis: some progress at last

Abstract

The new developments in trypanocidal drug discovery mean that new compounds could become available within the next 5 years to support the WHO declared campaign to eliminate HAT.

Deoxyhypusine Modification of Eukaryotic Translation Initiation Factor 5A (eIF5A) Is Essential for Trypanosoma brucei Growth and for Expression of Polyprolyl-containing Proteins

“…Log phase cells were cultured in media supplemented with 50 M [1, [4][5][6][7][8][9][10][11][12][13][14] C]putrescine dihydrochloride (114 mCi/mmol; Amersham Biosciences) for 6 -12 h before cells (BSF, 10 6 ; PF, 10 7 ) were pelleted and washed with PBS (1 ml) three times. Cells were resuspended in 100 l of Tryp Lysis Buffer (defined above) and lysed by three cycles of successive free/thaw.…”

“…Human African trypanosomiasis, also known as sleeping sickness, is a fatal vector-borne disease caused by the single celled parasitic protozoan Trypanosoma brucei (1)(2)(3)(4). Although the disease reached epidemic levels in the 1990s, the World Health Organization now reports fewer than 10,000 cases, although millions in sub-Saharan Africa remain at risk (5).…”

Inhibition of Isoleucyl-tRNA Synthetase as a Potential Treatment for Human African Trypanosomiasis

“…Current drug treatments for stage 1 HAT include pentamidine and suramin (for T. brucei gambiense and T. brucei rhodesiense, respectively), whereas those for stage 2 HAT include melarsoprol and eflornithine (for T. brucei rhodesiense and T. brucei gambiense, respectively). More recently, nifurtimox and eflornithine in combination have also been used as a treatment for chronic disease (4,5). These treatments are highly toxic, require complicated dosing, and must also contend with increasing parasite drug resistance (5)(6)(7)(8).…”

Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei

“…The Z 1 factor for the controls was calculated to be 0.64 using the equation defined as Z 1 = 1´3(σ C + + σ C´) /|µ C +´µ C´| where σ C + /σ C´a re the standard deviation (SD) of the positive/negative controls and µ C + /µ C´a re the mean values, indicating that the assay was performed with a sufficient window between the two controls ( Figure 1). [9,10]. Current clinical treatment relies on very few drugs, namely, suramin, pentamidine, melarsoprol and eflornithine (the latter now also in combination with nifurtimox) [11].…”

“…T. b. gambiense HAT takes a chronic course usually lasting for years, while T. b. rhodesiense HAT causes an acute course usually taking only months. Both forms inevitably lead to death if untreated [9,10]. Current clinical treatment relies on very few drugs, namely, suramin, pentamidine, melarsoprol and eflornithine (the latter now also in combination with nifurtimox) [11].…”