**4. Extraintestinal manifestation of giardiasis and long-term consequences**

#### **4.1. Nutritional consequences**

In combination with diarrhoea, giardiasis leads to iron deficiency anaemia, micronutrient deficiencies, protein-energy malnutrition, growth and cognitive retardation and malabsorption [31]. Studies from Peru and Brazil found that diarrhoea disease occurring in the first 2 years of life negatively correlates with verbal fluency, cognitive function and may lead to long-term growth failure [32]. Growth failure is assessed by anthropometric indices such as height for weight, height for age and weight for age. Interestingly, the prevalence of giardiasis is higher among children between 6 months and 5 years in developing country as compare to industrialised country [33]. Therefore, it has long been linked optimum health of children, socio-economic status, socio-cultural and environmental factors (**Table 2**).

#### **4.2. Failure to thrive**

Failure to thrive (FTT) is the term used when a child present with a rate of weight gain that is significantly below the expected weight from children of the same age, sex and ethnicity [34]. Common causes of FTT are inadequate food intake, inadequate food absorption, or maldigestion of nutrients and excessive loss of nutrient [34]. There is a strong association between *Giardia* infection and malnutrition, wasting and stunting [31–33]. Malabsorption, maldigestion and malnutrition due to giardiasis have been shown to affect anthropomorphic factors as well as calories intake during childhood especially in the second year of life [31]. Researchers now


**Table 2.** Extraintestinal and long-term complication of giardiasis.

develop key predictors of FTT and growth disturbance such as severity of diarrhoea diseases and duration of infection episodes [35]. Of note, vitamin deficiencies such as vitamin A, B1, B3, B6 and B12 are common reasons behind grown stunt in children infected with giardiasis.

#### **4.3. Cancer**

**4. Extraintestinal manifestation of giardiasis and long-term** 

socio-economic status, socio-cultural and environmental factors (**Table 2**).

Post-infectious consequence Speculated mechanism involved

Cancer Still need further research

**Table 2.** Extraintestinal and long-term complication of giardiasis.

absorption

Impaired cognitive function Chronic malnutrition and stunting following G. duodenalis

Increased T-cells and Mast-cells

In combination with diarrhoea, giardiasis leads to iron deficiency anaemia, micronutrient deficiencies, protein-energy malnutrition, growth and cognitive retardation and malabsorption [31]. Studies from Peru and Brazil found that diarrhoea disease occurring in the first 2 years of life negatively correlates with verbal fluency, cognitive function and may lead to long-term growth failure [32]. Growth failure is assessed by anthropometric indices such as height for weight, height for age and weight for age. Interestingly, the prevalence of giardiasis is higher among children between 6 months and 5 years in developing country as compare to industrialised country [33]. Therefore, it has long been linked optimum health of children,

Failure to thrive (FTT) is the term used when a child present with a rate of weight gain that is significantly below the expected weight from children of the same age, sex and ethnicity [34]. Common causes of FTT are inadequate food intake, inadequate food absorption, or maldigestion of nutrients and excessive loss of nutrient [34]. There is a strong association between *Giardia* infection and malnutrition, wasting and stunting [31–33]. Malabsorption, maldigestion and malnutrition due to giardiasis have been shown to affect anthropomorphic factors as well as calories intake during childhood especially in the second year of life [31]. Researchers now

Ocular pathologies Speculated involvement of toxic metabolite produced by the parasite.

Allergy Alteration of antigen uptake due to dysfunction of the intestinal barrier. Hypokalemic myopathy Loss of potassium related to diarrhoea, impaired nutrient and electrolyte

Arthritis Increase intestinal permeability leads to increase bacteria in synovial fluid joint.

Failure to thrive Inadequate food intake, reduced nutrients absorption, excessive utilisation of energy, steatorrhea, maldigestion, malabsorption Stunting Nutritional status, sanitary, socio-economic conditions, loss of intestinal surface area, maldigestion, malabsorption

Microscopic duodenal inflammation. Interaction host-gastrointestinal microbiota.

**consequences**

30 Current Topics in Giardiasis

**4.2. Failure to thrive**

Post infectious irritable bowel

syndrome

**4.1. Nutritional consequences**

Multiple reports have described pancreatic cancer with pancreatic giardiasis. However, the relationship of these remains unknown. The coexistence of these two diseases may prompt further research into mechanism of carcinogenesis in giardiasis [36]. Interestingly, *Giardia's* trophozoite is usually found in proximal small intestine, but they can be identified in stomach, distal small bowel, and caecum, and there are reports of pancreatic infection with giardiasis [37].

#### **4.4. Impair cognitive function**

Cognitive functions are important especially in the first 2 years of life, as there is rapid brain growth and maturation. Nutrition, infection and other environmental factors have been found to affect neuroplasticity and have long-lasting effect in developing children [38]. One of the most important causes of brain development abnormality is malnutrition. Micronutrients deficiencies (such as iodine) and iron deficiency have been found to cause impairment in cognitive function in children [38]. The complex interaction among malnutrition, diarrheal disease and environmental factors such as low socioeconomic status and education makes it extremely difficult to determine the exact reason for cognitive impairment [39, 40]. However, chronic malnutrition and stunting during infancy secondary to giardiasis have been associated with poor cognitive functions [39–41]. Furthermore, diarrheal disease during early childhood was found to impair visual-motor co-ordination, auditory, short-term memory and cortical cognitive functions [40].

There are studies that associate *Giardia* with poor language cognition and impair psychomotor development [31]. These studies also demonstrate a role for nutrient malabsorption and micronutrient deficiencies such as zinc, iron, or vitamin (A and B12) in human and in animals [40–42]. It was widely known that significantly lower serum ferritin and iron affect psychomotor development, and this has been detected in patients with giardiasis [38]. Similarly, diarrheal disease due to giardiasis was linked to poor cognitive function by causing zinc and iron micronutrient deficiency, as well as defects in anti-oxidant system which can affect neuroplasticity [38]. Zinc supplements were found to decrease the rate of diarrhoea caused by giardiasis [43]. This issue remains complicated, and further investigation is needed to the reversal of cognitive impairment following micronutrient supplement or *giardia* clearance.

#### **4.5. Muscular complications**

Hypokalaemia myopathy has long been associated with coeliac disease, radiation enteritis and infections. Several cases of myopathy following hypokalaemia induced by giardiasis have been reported with both immunocompromised and immunocompetent patients [44]. This suggests that *giardia* can trigger muscular manifestations independently to the immune status of the host. During infection, potassium loss is related to number of bout of diarrhoea per day [44]. Hypokalaemia following bouts of diarrhoea is the trigger of transient myopathy. In fact, after the resolve of diarrhoea, myopathy also improves. Main symptoms of these patients are proximal myopathy which is transient, but patients may have other co-morbid symptoms associated with hypokalaemia.
