Giardia duodenalis: New Research Developments in Pathophysiology, Pathogenesis, and Virulence Factors

Abstract

Giardia duodenalis is a very common, ubiquitous, intestinal protozoan parasite infecting animals and humans. Of the eight distinct genetic assemblages known to date, assemblages A and B are infectious to humans. Giardia is the most commonly recognized cause of traveller's diarrhea. Giardiasis impairs weight gain and is responsible for a variety of extraintestinal and post-infectious complications, including postinfectious irritable bowel syndrome, chronic fatigue, failure to thrive, and cognitive impairment. Giardiasis occurs in the absence of invasion of the intestinal tissues by the trophozoites and in the absence of any overt inflammatory cell infiltration, with the exception of a modest increase in intraepithelial lymphocytes and mast cells. In endemic parts of the World where the infection is often concurrent with bacterial enteritis causing inflammation-driven diarrheal disease, giardiasis appears to be protective against diarrhea. Recent observations have demonstrated that this effect may be due to a direct immuno-modulating effect of the parasite via its cathepsin B cysteine protease which cleaves pro-inflammatory CXCL8. No known toxin has yet been directly implicated in the pathophysiology of giardiasis. Diarrhea in giardiasis is mostly malabsorptive in nature, rather than hypersecretory. Findings from ongoing research indicate that the post-infectious effects of giardiasis may be due to microbiota dysbiosis induced by the parasite during the acute phase of infection.

Disruptions of Host Immunity and Inflammation by Giardia Duodenalis: Potential Consequences for Co-Infections in the Gastro-Intestinal Tract

“…Our understanding of the pathophysiology and immunity in giardiasis is drastically improving, yet discrepancies in study results persist and much remains to be learned [ 23 , 24 , 25 , 26 ]. Several parasites are known to affect various aspects of their host’s pro-inflammatory responses [ 27 , 28 ], and recent findings indicate that Giardia actively modulates host inflammatory responses (as referenced below).…”

Effect of probiotics on giardiasis. Where are we?

“…The pathophysiology of acute diarrhea in giardiasis implicates increased rates of enterocyte apoptosis, disruption of the intestinal barrier function, activation of host lymphocytes, CD8 + lymphocyte-mediated shortening of brush border microvilli with or without coinciding villous atrophy, crypt hyperplasia, deficiency of disaccharidases, intestinal malabsorption, anion hypersecretion, and increased intestinal transit (Müller, von Allmen, 2005;Buret et al, 2015).…”

“…It has been suggested that the intestinal microbiota composition can potentially interfere in the process of G. lamblia infection. Findings from ongoing research indicate that the post-infectious effects of giardiasis may be due to microbiota dysbiosis induced by the parasite during the acute phase of infection (Buret et al, 2015). Keselman et al (2016) found that the disruption of the intestinal microbiota through antibiotic treatment for G. lamblia limited the disaccharidase deficiency, prevented pathological CD8 + T cell activation, and also did not change the numbers of CD4 + T cells in the lamina propria and the activation of T cell receptor-expressing intraepithelial lymphocytes (IEL) found in giardiasis.…”

Control of Giardiasis by Interleukin-17 in Humans and Mice—Are the Questions All Answered?

“…Infections can result in subclinical disease with patients exhibiting little, if any, sign of the infection or can produce severe cramps, nausea, and diarrhea. Nutrient malabsorption can occur in patients with subclinical disease, as well as those experiencing acute symptoms, and Giardia infection has been correlated to physical and cognitive developmental defects in children in several studies (5,6). The mechanisms involved in both control of the infection and the production of symptoms are not well understood, although immune responses are considered important for both.…”