Table 3.
Overview of factors involved in VL disease progression and treatment failure
Factor | References |
---|---|
Host | |
Immunological factors | (Jarvis & Lockwood, 2013; Ostyn et al. 2014) |
Pharmacokinetics | (Ostyn et al. 2014) |
Genetics | (Blackwell, 1996; Castellucci et al. 2014) |
Reinfection | (Rijal et al. 2013) |
Environment | (Perry et al. 2013) |
Drug | |
Drug quality | (Dorlo et al. 2012a, b ) |
Intrinsic drug properties (e.g. T1/2) | (Hastings et al. 2002) |
Treatment duration | (Geli et al. 2012) |
Non-compliance | (Rijal et al. 2013) |
Parasite | |
Lower intrinsic susceptibility to the drug | (Singh et al. 2006; Rijal et al. 2013) |
– gene amplification of drug target enzymes | |
– structural and functional modifications of drug target enzymes | (Mondelaers et al. 2016) |
– decrease in intracellular drug concentration due to extrusion by specific transporters | |
Higher parasite fitness | (Vanaerschot et al. 2014; Hendrickx et al. 2015b; Hendrickx et al. 2016) |