Risk factors for treatment failure after melarsoprol for Trypanosoma brucei gambiense trypanosomiasis in Uganda

Characterization of the OSSN Microbiome in HIV-1 Infected Patients

“…It is possible that before ART era AIDS patients died before the appearance of HPV and other HIV associated lesions, and that the prolongation of life now allows the development of these benign and neoplastic lesions (Meys, Gotch, & Bunker, 2010). There are studies that show that the success of ARTs lowering HIV-1 viral load leads to increased opportunistic infections, some of which are drug resistant (Palefsky, 2009;Croft, Sundar, & Fairlamb, 2006;Legros, Evans, Maiso, Enyaru, & Mbulamberi, 1999). …”

Future treatment options for human African trypanosomiasis

“…The drug is extremely toxic with up to 10% of all patients developing a post-treatment reactive encephalopathy (PTRE) that leads to death in 50% of cases [13]. Furthermore, pyrexia, headache and general malaise occur in nearly all patients and resistance has reached 30% in some regions [14]. An alternative to melarsoprol, eflornithine was introduced in 1990 for the treatment of CNS stage T.b.…”

Antiprotozoal glutathione derivatives with flagellar membrane binding activity against T. brucei rhodesiense

“…Chemotherapy of trypanosomiasis and leishmaniasis is inadequate as many treatments have poor clinical efficacy, with patients suffering side effects or are toxic at the high dosage regimes, used especially in the late chronic stages. This situation has been further aggravated by the emergence of resistance to some of the first line drugs, 6 or the increasing incidence of treatment failure 7 . Genetic approaches have identified some key gene products responsible for resistance 8 in trypanosomes these include the trypanosome P2 adenosine transporter, AT1 9 , responsible for the uptake of the front-line drugs melarsoprol and pentamidine used to treat HAT, which was found to be mutated or absent in a number of drug resistant strains 10 .…”

“…The trypanothione cycle maintains the hexapeptide, trypanothione (N 1 , N 8 -bis (glutathionyl)spermidine) (T(SH) 2 ), an antioxidant replacing glutathione (GSH) via trypanothione reductase (TR), in its reduced form and so decreases the cell's sensitivity to oxidative stress; which is a consequence of rapid growth. 7 A variety of trypanothione reductase inhibitors have been reported to date of both natural and synthetic origin which include peptides, polyamines, 15,16 tricyclics, 17 2-aminodiphenyl sulfides, 18 2-and 3-substituted 1,4-naphthoquinone derivatives as subversive substrates 19 and organometallic compounds. 20 Only a few compounds achieve activities in the nanomolar range (100 nM) required to overcome the induced phenotypic changes in TR and a 90% level of inhibition.…”