Challenges during Treatment of Microbial Infections: Sanctuary Niches, Persistence and Relapse

Many infectious diseases suffer from post-treatment clinical reactivation. The ontogenyof such treatment failure may relate to features of the pathogen, host and drug. Besides drug resistance,tissues or cellular niches that escape drug activity have gained increasing awareness for the last coupleof years. Evidence has also emerged for pathogen dormancy and persistence in combination with hidingin such sanctuary niches. Protozoans such as Trypanosoma, Toxoplasma and Plasmodium are liable totreatment failure resulting from infection of tissues such as the adipose, central nervous system and liverrespectively. Several bacteria, most notably Mycobacterium, Staphylococcus and Salmonella, are knownto form persisters that are drug tolerant and that can reside in multiple sanctuary niches. This reviewwill focus on the tissues and host cells reported to provide sanctuary underlying treatment failure andsubsequent relapse, whereby visceral leishmaniasis will be elaborated as a disease that is prone torelapse of multifactorial origin.