Giardiasis in the Post Genomic Era: Treatment, Drug Resistance and Novel Therapeutic Perspectives

Abstract

Giardia duodenalis (syn. G. lamblia, G. intestinalis) is a flagellated protozoan, member of the order Diplomonadidae, that parasitizes the upper part of the small intestine of mammals, including human, pets and livestock. G. duodenalis is the causative agent of giardiasis, the most common non-bacterial and non-viral diarrheal diseases affecting humans worldwide. Recently, giardiasis was included in the 'Neglected Disease Initiative', estimating that 280 million people are infected each year with G. duodenalis. Transmission occurs via the faecal-oral route by ingestion of cysts, the infective stage of the parasite, either by direct person-to-person transmission or indirectly through water and food. There are several effective drugs that have been approved for the treatment of giardiasis. The 5-nitroimidazole and benzimidazole derivatives, quinacrine, furazolidone, paromomycin, nitazoxanide are the most commonly used, however some of these compounds have sometimes relevant side effects. Single- and multi-drug resistance to some of these compounds, including metronidazole (MTZ), has been reported in human patients and can be induced in vitro. The aims of this review are (i) to provide a bird's eye view on the current knowledge of the mechanisms of action, including resistance mechanisms, of the most commonly used anti-giardial compounds, and (ii) to summarize recent findings on novel promising drugs targeting unique proteins and metabolic pathways of G. duodenalis.