Giardia is the commonest parasitic diarrheal pathogen affecting humans and a frequent cause of waterborne/foodborne parasitic diseases worldwide. Prevalence of giardiasis is higher in children, living in poor, low hygiene settings in developing countries, and in travelers returning from highly endemic areas. The clinical picture of giardiasis is heterogeneous, with high variability in severity of clinical disease. It can become chronic or be followed by post-infectious sequelae. An alarming increase in cases refractory to the conventional treatment with nitroimidazoles (ie, metronidazole) has been reported in low prevalence settings, such as European Union countries, especially in patients returning from Asia. In view of its relevance, we aim in this review to recapitulate present clinical knowledge about Giardia, with a special focus on the challenge of treatment-refractory giardiasis. We propose a working definition of clinically drug-resistant giardiasis, summarize knowledge regarding resistance mechanisms, and discuss its clinical management according to research-based evidence and medical practice. Advances in development and identification of novel drugs and potential non-pharmacological alternatives are also reviewed with the overall aim to define knowledge gaps and suggest future directions for research.

Cysts of Giardia duodenalis were collected in Mexico from symptomatic children (n = 9) and from pet dogs (n = 5), and they were directly characterized by nested polymerase chain reaction (PCR) amplification of the beta-giardin gene. Eight isolates of human origin established as in vitro cultures and 2 reference strains, representing assemblages A and B of G. duodenalis, were also analyzed. PCR-restriction fragment length polymorphism showed that all isolates belonged to assemblage A. Sequence analyses indicated that the large majority of isolates were of the A1 genotype; interestingly, 2 human isolates displayed the A3 genotype, which has been previously identified in human isolates from Italy. The presence of cysts of the A1 and A3 genotypes in isolates from pet dogs is consistent with their role as reservoirs for human infection, although further studies are needed to confirm the occurrence of zoonotic transmission. Remarkably, cysts of assemblage B have not been found in any of the Mexican isolates studied to date.