Friday, December 10, 2010

Trophozoite of Giardia Lamblia

Epidemiology of Giardia Lamblia / Giardia Intestinalis

  • It is a worldwide infection and is one of the most common intestinal infections in US
  • It has a high prevalence rate among young children in third world countries, and in places with untreated water and poor sanitation system
  • It is highly infectious, and as few as 10 cysts can cause an infection in an individual
  • Route of transmission includes waterborne transmission, ingestion of contaminated food, fecal-oral route, person-to-person contact, and sexual transmission.
  • Enhanced susceptibility to giardiasis is associated with blood group A, achlorrhydria, use of cannabis, chronic pancreatitis, malnutrition & immune defects (eg. 19A deficiency & hypogammaglobulinaemia)
  • Naturally infect cats, dogs, cattles, sheeps & many wild animals
  • Giardia species infecting birds, amphibians & mice can be differentiated from G.lamblia by morphological features

Life Cycle of Giardia Lamblia

Pathophysiology of Giardiasis  

Giardia cyst


Giardia trophozoite, after
process of Excystation
          

In the colon, Giardia cyst undergo excystation and develop into trophozoite that will develop tails called flagella. The trophozoite will then invade the enterocytes at microvillus-covered surface of the duodenum and jejunum.


When they reach the enterocytes, the trophozoite uses special disk on their ventral side to attach to enterocyte and with the help from lectin on surface of Giardia to bind with sugar found on the surface of enterocyte.


Attachment of Giardia trophozoite to enterocytes will cause changes to the architecture of the villous at jejunum and duodenum then cause malabsorption.


Trophozoite that attached at enterocyte will reproduce and multiply to produce more trophozoite at the site of attachment.


This multiplication will create physical barrier between intestinal lumen and enterocytes that will further interfere with nutrient lead to severe nutrient malabsorption.


Multiplication of trophozoites eventually lead to enterocytes damage, villi atrophy, cysts hyperplasia and intestinal hyperpermeability brush border damage that causes a reduction in disaccharidase enzyme secretion.


Besides disaccharidase, other cytopathic substances such as lectins, glycoproteins and proteinases may cause direct damage to intestinal mucosa.


Giardia trophozoites only infect intestinal lumen and not other areas such as surrounding tissue and bloodstream.


Study has shown that Giardia trophozoite can induce cell apoptosis by activating intrinsic and extrinsic pathway, down regulation of antiapoptotic protein Bcl-2 and up regulation of proapoptotic Bax that is strongly associated with induction of cell apoptosis.


REVIEW OF GIARDIASIS PATHOPHYSIOLOGY

Clinical Manifestations


·   Self-limitting
·   After an acute giardiasis, patients may heal ( with or without treatment), or become a carrier, or suffer from chronic infection and/or its complications
·   Acute giardiasis
-  Symptoms lasts for 4-5 days, flatulence, abdominal distension/cramps, nausea and anorexia, passage of foul-smelling and bulky stools and weight loss.
-  Faecal smear: watery/steatorrhoea; trophozoites seen in abundant
·   Carrier
-  Healthy
-  Faecal smear: positive for cysts with an abundant of mature cysts
·   Chronic giardiasis
-  Recurrent diarrhea and constipation, abdominal distension, malabsorption syndrome
-  Faecal smear: positive for cysts
·   Lactose intolerance
-  Symptoms: diarrhea; related to milk
-  Faecal smear: positive for cysts

Investigations

Diagnosis of Giardia Lambdia parasite
Diagnosis confirmed by presence of: 
- Cysts in patient’s stool
- Trophozoite in diarrhoeal stools, duodenal contents and jejunal biopsy.
Parasite Diagnosis:
- Cysts of G. intestinalis in the formed stool or the trophozoites by the parasite in the diarrhoeal stools,  duodenal contents and jejunal biopsy
Stool examination:
- Microscope examination of stool for trophozoites and cysts is a routine method.
- Stool specimens examined are either fresh or preserved in formalin solution.
- In acute giardiasis, wet mount preparation of:
o   Liquid stools – look for the presence of motile trophozoites.
o   Semi solid stools – Cysts are demonstrated.
- In chronic giardiasis
o   Cysts are excreted at certain time interval
*it requires examination of at least three-stool specimen for correct diagnosis.

Detection of Giardia Antigen:
Presence of Giardia antigen in the stool is detected using techniques of:
         -Counter Current Immuno-Electrophoresis (CIEP)
     -Enzyme Linked  Immunosorbent Assay (ELISA)

 Examination of Duodenal Contents:
Microscopic examination of duodenal contents is carried out when repeated stool examination is negative but giardiasis is still suspected.

The methods followed to collect the duodenal contents are:

   1.       String test/Entero test:
-   The nylon string consists of a gelatin capsule at one end. The patient swallows the capsule and the free end of the string is fixed in the mouth.
-   In the stomach, the capsule is dissolved and the string remains in the duodenum and jejunum. After overnight incubation, the string is removed and the bile stained mucus is collected on the glass slide and examined microscopically for trophozoites.

   2.       Duodenal aspiration:
-   Collected to demonstrate trophozoites

   3.       Jejunal biopsy:
-   Collected to demonstrate trophozoites but is indicated only in very serious cases.

   4.       Serological Diagnosis:
-   ELISA and Indirect Fluorescent antibody are useful in detection of Giardia antibodies in the serum, which remains elevated for longer period.
-   Axenically cultured G. intestinalis trophozoites are used as antigens in these assays.


Treatment

  • For symptomatic and supportive treatment, for patients who have severe diarrhoea, they will be given oral rehydration salt for fluid replacement and antipyretic for example paracetamol for those who are having fever.
  • Metronidazole (Flagyl) and Tinidazole are the drugs of choice. Metronidazole is given in multiple doses for 5-10 days while tinidazole is given in single dose. Metronidazole eradicates the Giardia for about 85% while tinidazole is highly effective in treating giardiasis (>90%). The side effects are nausea, dizziness and headache.
  • Furazolidone is another drug where it is slower in action but it is preferred in children because it has fewer adverse effects compared to metronidazole. Furazolidone (Furoxone) is given for 7-10 days. They are being prescribed by the doctors if only symptomatic cases have been detected.