الفهرس 
Giardia LambliaOnly 14 pages are availabe for public view
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Abstract
Giardia lamblia is one of the most prevalent enteric protozoan parasites worldwide, with prevalence rates ranging from 2-5% in the developed countries and 20-30% in the developing countries. The parasite life cycle alternates between active vegetating parasitic trophozoites and environment-resistant infective cysts. Human infections are initiated by the ingestion of quadrinucleate cysts in contaminated food or water or directly from person to person through fecal-oral transmission by contaminated hands.
Most cases of giardiasis in immunocompetent people are self-limiting and resolve spontaneously within weeks of exposure. Clinical presentation of infection varies between asymptomatic carrier state to a severe disease associated with acute or chronic diarrhea alternating with constipation, abdominal cramps, flatulence, fat malabsorption and lactose intolerance due to disaccharidase deficiency.
Post-infection complications may arise after Giardia elimination in the form of stunting, failure to thrive, chronic fatigue syndrome, irritable bowel syndrome, allergies, and arthritis.
Pathophysiology in the acute phase of giardiasis occurs in the absence of trophozoites invading of the intestinal tissues and in the absence of any overt inflammatory cell infiltration. It includes increased rates of enterocyte apoptosis, disrupted intestinal barrier function, diffuse shortening of small intestinal brush border microvilli and disaccharidase deficiency.
Both innate and adaptive immune system components play a role in the immune system to giardiasis. TNF-α was found to play a vital role in protection against G. lamblia infection.
TNF-α antagonists had been used in the past few years to treat many inflammatory diseases as RA, ankylosing spondylitis, and Crohn’s disease. Although their great effect in controlling inflammatory diseases, the risk of infection associated with their use has been an issue.
The present study was conducted to investigate the effect of TNF-α antagonist (ADA) on the pathology and the infection outcome of giardiasis in mice.
The study was conducted on 45 Swiss albino male mice. They were classified into two main groups of mice: control and test groups. Control mice were distributed into two main subgroups, normal and infected mice subgroups. Test group was experimentally infected with Giardia and receiving anti-TNF-α (ADA) in three different doses: subgroups Ia, receiving 1.5 mg/Kg BW, subgroup Ib, receiving 3mg/Kg BW and subgroup Ic, receiving 6mg/kg BW.
Monitoring the serum TNF-α level in all mice was done on two occasions (day 16 and 28 post infection) by ELISA to follow variation in its level in mice with and without administration of the drug. Infection outcome was assessed by counting cysts shed in stools of infected mice on intermittent days, counting trophozoites in intestinal wash, registering weight of animals, and studying histopathological changes in the small intestine.
The results of the present study showed the following:
Highly significant increase in serum TNF-α was recorded in infected control group on day 16 post-infection than in normal control group. Similarly, a significant increase in serum TNF-α level in the 3 test subgroups that received ADA but in lower levels than attained in infection control group. On day 28 post infection, serum TNF-α level decreased in all infected mice with no significant differences, being higher in infected control group than in non-infected control group.
As regard cyst shedding in stools, peak cyst counts in all subgroups were reached on day 15 p.i. Cyst shedding was higher in test subgroups than in control infected group. The significantly highest counts were recorded in test subgroup (Ib) that received 3 mg/kg BW compared to infection control subgroup and to test subgroups Ia and Ic in most days,
Trophozoite count in intestinal wash of all test subgroups was significantly higher than count in infected control group on day 28 p.i. Subgroup (Ib) showed the highest trophozoite count compared to other test subgroups (Ia) and (Ic).
On day 28 p.i, the mean weight of mice in infected control subgroup was highly significantly lower than in healthy control subgroup. Moreover, mean weights of mice in test subgroups were significantly lower than mean weights of mice in normal control group and in infection control group.
Histopathological studies of intestine of healthy control group showed preserved architecture with normal appearance of villi. Histopathological studies in infection control subgroup on day 16 p.i. showed significant inflammatory changes in the form of villous shorting and core widening.
The intestinal sections of Giardia-infected ADA-treated mice groups on day 16 p.i. showed moderate to severe inflammatory reaction with more inflammatory cellular infiltration in the lamina propria causing villous shortening and blunting more than that observed in Giardia-infected control mice. Moreover, lymphoid aggregation and follicles were only present in mice of test group Ib. Sloughing of mucosa was recorded in all the infected test mice groups.
While on day 28 p.i., pathological changes decreased from what was observed on day 16p.i. This high degree of inflammation and intestinal pathological changes in ADA treated mice subgroups implied the crucial role of TNF-α in protection against pathological changes caused by G. lamblia infection.
Conclusion
from the results of the present study, it was concluded that the administration of TNF-a antagonist (ADA) to mice infected with Giardia lamblia infection led to exacerbation of infection as proven by the increased cyst shedding, increased trophozoite count and decrease weight gains, and more histopathological changes. The effect was more pronounced in mice receiving a dose of 3 mg/ Kg BW of the drug.
from the result of the present study, it’s concluded that, patients who are on regular ADA therapy for inflammatory diseases may be at increased risk of flourishing G.lamblia infection.
Recommendations
from the present work, the following are suggested recommendations:
• Screening of intestinal parasitic infections, particularly G. lamblia in patients diagnosed with inflammatory diseases before administration of TNF-α antagonist treatment.
• Early diagnosis and treatment of G. lamblia should be considered in patients receiving TNF-α antagonist as ADA to avoid clinical and intestinal complications of giardiasis.
• Patients receiving TNF- α antagonist must be advised to follow strict sanitary measures to protect themselves from getting infected by the parasite.
• Further research should be encouraged on the use of biological drugs in treatment of inflammatory diseases and the related risk of flaring up of existing parasitic infection.
• Further studies are required to develop planned guidelines for the use of TNF-α antagonists in patients with systemic inflammatory diseases.
• Advanced molecular and immunological research is needed to relate different Giardia genotypes with infection outcome in patients treated with TNF-α antagonist drugs