**3. Symptoms and sign of chronic infection with giardiasis**

Chronic infection is particularly important in children as it may cause malabsorption leading to growth retardation. There are reports of small intestinal villous atrophy especially in children. It is important at this stage to exclude coeliac sprue on gastrointestinal immunodeficiency syndrome for the correct diagnosis to be made [25].

Other symptoms include:

#### **3.1. Chronic diarrhoea**

is Caspase 3, Caspase 9 dependent [20]. The reasons behind the activations of these proteins, which play crucial roles in apoptosis, still have not been fully understood. However, it is believed that both host and parasite factors modulate the activation of these proteins, although the exact mechanism is still not known. Interestingly, Giardia's trophozoites may halt enterocytes cell-cycle progression by consumption of arginine and upregulation of cell-cycle inhibitory genes [21].

**Table 1.** The major virulence factors of *Giardia* spp. *Giardia* is a complex organism; they produce complex enterotoxin and

Attachment Colonisation and attachment to intestinal endothelium is by the ventral adhesive disc and surface lecithin

Antigenic variation *Giardia* is cleared from the body by IgA directed clearance. This is protected

Alteration of host innate defences Down regulate epithelial production of nitric oxide by releasing arginine

luminal proteases

Anti-inflammatory modifications Unknown trophozoite products have anti-inflammatory roles

Differentiation into cysts

by VSP

deaminase

Re-localization by flagellar motility allows further colonisation. Protective factors such as variant-specific surface protein (VSP) protect *Giardia* from

Other possible key pathophysiology of giardiasis is *Giardia*-induced epithelial bush boarder microvilli shortening. This leads to symptoms of maldigestion and malabsorption such as diarrhoea. The factor contribute to microvilli shortening is still not fully validated; however, it was postulated that parasite's toxins may play a key role in the development of this abnormality. This is very similar to "protease" which was released in patients with bacterial over-

*Giardia* infections tend to be self-limiting in immune-competent patient. A recent study in Brazilian children suggests that symptoms are less severe during re-infection. This supports the previous hypothesis that, during the primary infection, the immunity develops leading to less severe symptoms [23]. Patients who are immunodeficiency or have common variable immune deficiency such as Bruton's X-linked agammaglobulinema are prone to chronic giar-

Chronic infection is particularly important in children as it may cause malabsorption leading to growth retardation. There are reports of small intestinal villous atrophy especially in

diasis. This finding confirms the importance of immune system in giardiasis [24].

**3. Symptoms and sign of chronic infection with giardiasis**

growth causing villi shortening and malabsorption syndrome [22].

**Function Virulence factor**

IgA, immunoglobulin A; VSP, variant-specific surface protein.

Circumvention of the natural factors

Survival in stomach acid and the

proteinase causing epithelial cell damage.

external environment

of the intestinal lumen

28 Current Topics in Giardiasis

A small number of people develop acute explosive watery diarrhoea, foul flatus, abdominal cramps and vomiting. These symptoms usually last 3–4 days before subacute symptoms develop. Symptoms of chronic infection including chronic diarrhoea, anorexia and weight loss occur as much as 66% of the infected individuals [1]. Chronic sporadic diarrhoea may continue for months, and post-infected lactase deficiency also presented in 5–40% of cases [1].

Stools of the infected individuals become more mushy, malodourous and greasy. Watery diarrhoea may alternate with soft stools or even constipation. Steatorrhea is a common finding in patients who have malabsorption syndrome.

#### **3.2. Function gastrointestinal disorder**

FGID represents a group of disorders characterised by recurring gastrointestinal symptoms. IBS and functional dyspepsia are best describing FGID. There are multiple reports of postinfectious IBS following salmonella, campylobacter infections. These usually follow episodes of acute gastroenteritis. Interestingly, recent reports suggest that individuals who are infected with *Giardia duodenalis* develop post-infectious IBS symptoms without parasitic load [26]. Irritable bowel syndrome (IBS) characterised by abdominal discomfort associated with altered bowel habit with no abnormality in routine diagnostic test. One common theory that has been postulated is that these symptoms develop following episodes of acute gastroenteritis. This explains the persisting symptoms of chronic diarrhoea and abdominal pain despite parasite clearance [27]. The risk of developing IBS increases six-fold after gastrointestinal infection as shown from multiple recent meta-analyses. This is interesting because these risks could remain elevated for at least 2–3 years post-infection. Moreover, it is estimated that 7–31% of patients with gastroenteritis go on to develop post-infectious IBS [27, 28]. Risk factors of developing IBS in this situation include longer duration of symptoms, younger age and female gender. The exact mechanisms of post-infectious IBS is still not known; however, there are reports that suggest that it associates with increase intestinal permeability, increase gut motility and increase number of enterochromaffin cells leading to persistent intestinal inflammation, which is characterised by increase T lymphocytes, mask cells and inflammatory cytokines [29, 30].

#### **3.3. Other gastrointestinal symptoms**

Report suggests that symptoms of lactase intolerance such as excessive flatus, abdominal bloating and diarrhoea can occur as a consequence of giardiasis. These patients will not be able to take milk, cheese or any products that contain lactose. It may take up to 1 month following the clearance of the parasite until the body return to normal state.
