Extra-intestinal and long term consequences of Giardia duodenalis infections

Table 1 Main pathophysiological effects of Giardia duodenalis and their mechanisms

Giardia-induced pathophysiological responses	Mechanisms involved or hypothesized to be involved	Selected references
Intestinal epithelial cell apoptosis	Induction of pro-apoptotic factors: Caspase-3, 8 and 9, Inhibition of anti-apoptotic factors: poly (ADP-ribose) polymerase (PARP) cleavage	[10,18,19,21,23]
Halt of enterocyte cell-cycle progression	Nutrient competition (arginine), up-regulation of cell-cycle genes	[25]
Intestinal barrier dysfunction	Disruption of claudin-1 and alpha-actinin by unknown mechanisms, caspase-3 mediated disruption of zonula-occludens (ZO)-1, myosin light chain kinase-mediated disruption of F-actin, and ZO-1	[10,17,19,21,26,27,29,30]
Small intestinal hypermotility	Adaptive immunity, neuronal nitric oxide, mast cell degranulation	[118-120]
Diffuse shortening of brush border microvilli	CD8+ lymphocytes - mediated via parasite secretory/excretory products	[13,16,21,31]
Crypt hyperplasia	Alteration villus/crypt ratio	[21,62,99]
Microbiota composition	Microbiota from infected host may become pathogenic	[14,33]
Increased mucus production	Increased mucus secretion in response to the parasite	[66]
Brush border enzyme activity deficiencies	Loss of surface area (microvilli and villi)	[16,21,98,121,122]
Disaccharidases deficiencies	Loss of surface area (microvilli and villi)	[10,16,99,122]
Electrolyte/nutrient/water malabsorption	Loss of surface area (microvilli and villi)	[10,19,21,62,99,123]
Anion hypersecretion	Unknown mechanisms	[10,19,99]

PARP : Poly adenosine diphosphate ribose polymerase.

Table 2 International reports of post-giardiasis metabolic consequences

Post-giardiasis effects	Country	Selected references
Lower cognitive function	India, Peru, Turkey	[40,67,68,76,77]
Lower intellectual quotient
Lower social quotient
Lower weight	Brazil, Columbia, Ecuadora, Guatemala, Iran, Israel, Mexico, Rwanda, Turkey, United States	[37-39,63,64,66-68,72,77,78,124-129]
Lower height
Stunting
Failure to Thrive	Columbia, Ecuadora, United States	[64,66,127]
Nutrient deficiencies	Iran, Mexico, Tanzania	[38,69,78,81]

Table 3 Extra-intestinal and long-term consequences of giardiasis

Post-infectious consequences	Speculated mechanisms involved	References
Ocular pathologies	Speculated involvement of toxic metabolites produced by the parasite	[47-49]
Arthritis	Bacterial antigens in synovial fluids possibly due to increased intestinal permeability	[50-52]
Allergies	Alteration in antigen uptakeDysfunction of the intestinal barrier	[54-57]
Hypokalemic myopathy	Loss of potassium related to diarrhea, impaired nutrient and electrolyte absorption	[59-62]
Failure to thrive	Inadequate food intake, Reduced nutrients absorption, excessive utilisation of energy, Steatorrhea, maldigestion, malabsorption	[38,39,63-65,69,71,118]
Stunting	Nutritional status, sanitary, socio-economic conditions, loss of intestinal surface area, maldigestion, malabsorption	[37,63,64,67,77,121]
Impaired cognitive functions	Chronic malnutrition and stunting following G. duodenalis infectionNutrient malabsorption and micronutrient deficiencies	[40,41,63,64,68,76-78]
Chronic fatigue syndrome	Altered natural killer-cell levelsLower ratio CD4:CD8	[15,82-87,89]
Post-infectious irritable bowel syndrome	Microscopic duodenal inflammationInteraction host - gastrointestinal microbiotaIncreased T-cells and Mast-cells	[14,84,93,100-105]
Cancer	No cause-to-effect established	[113-116]