Table 1.

Current drugs – their application, and resistance mechanisms identified by low throughput analysis of laboratory-derived and clinical resistant isolates

Drug	Stage/Trypanosome	Resistance determinant(s) laboratory	Clinical
Berenil	T. congolense, T. vivax, T. b. brucei	•adenosine transporter 1 (AT1)	AT1
Isometamidium		•nda	nd
Homidium		•nd	nd
Suramin	Stage 1 T. b. rhodesiense	•bloodstream form-specific factorb	ndc
Pentamidine	Stage 1 T. b. gambiense	•AT1 •high & low affinity pentamidine transporters(HAPT & LAPT)	ndd
Melarsoprol	Stage 2 T. brucei spp.	•AT1 •multidrug resistance protein A (MRPA)	AT1e
Eflornithine	Stage 2 T. b. gambiense	•amino acid transporter 6 (AAT6)	ndf
Nifurtimox	T. cruzi, stage 2 T. b. gambiense	•nitroreductase (NTR)	NTR
Benznidazole	T. cruzi	•NTR	NTR

Notes

^aNot determined.

^bFollowing selection, a suramin-resistant phenotype was expressed in bloodstream but not insect stage parasites (Scott et al. 1996).

^cTreatment failures reported in west Africa in the 1950s (Pepin and Milord, 1994).

^dPentamidine resistant T. brucei can be generated in the laboratory, but they have not been reported in the field (Barrett et al. 2011).

^eMutation or loss of AT1 renders T. brucei less sensitive to melarsoprol, however not all resistant clinical isolates have modified this locus (Matovu et al. 2001).

^fEflornithine monotherapy treatment failures reported in some foci (Barrett et al. 2011), as well as a limited number of NECT relapses (Franco et al. 2012).