الفهرس 
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Abstract
Microsporidia are obligate intracellular pathogens that were previously considered as
protozoa belonging to the phylum microsporidia, however recently, they have been related
to fungi. Microsporidiosis is an emerging infectious disease primarily found in patients
with compromised immune systems, however, they have also been known to parasitize
those with competent immune systems. Enterocytozoon bieneusi (E. bieneusi) and the
Encephalitozoon intestinalis (E. intestinalis) are the most predominant species of
microsporidia recognized in humans causing intestinal microsporidiosis and manifested by
malabsorption, chronic diarrhea and wasting.
Treatment of microsporidiosis is still a challenge since the used drugs do not fully
eradicate the pathogens. Promising drugs for microsporidiosis are scarce and still being
tested. Orlistat (tetrahydrolipstatin) is a safe and efficient inhibitor of pancreatic and gastric
lipases inside the gastrointestinal tract, and it was approved by a US Food and Drug
Administration (FDA) as anti-obesity drug. Furthermore, orlistat has been reported to
prevent the in vitro growth of cancer cells, and recently, it has been also revealed to inhibit
the in vitro growth of several pathogens. Orlistat may affect the pathogens directly by
inhibiting the parasite’s own lipid metabolizing enzymes and indirectly by preventing the
lipid supply through inhibition of host enzymes.
Lipids orchestrates the processes of infection, development, and cell division in
microsporidia. Analysis of microsporidia genomes reveal that they have lost many genes
needed for making lipids, moreover, they have also shown reduction of the mitochondria.
Amitochondriate protozoa are unable to synthesize the majority of their own lipids; rather,
they depend mostly on supplies from their host.
The relevant importance of lipids in microsporidia and its inability to synthesize
most of its own lipids renders the drugs targeting the enzymes involved in lipid metabolism
a promising strategy. Because of the great need to develop a new anti-microsporidial agent,
trials was designed in the present study to evaluate the potency of orlistat against intestinal
microsporidiosis caused by both E. bieneusi and E. intestinalis in mice.
Thirty two stool samples were collected from immuno-compromised patients during
the hot season suffering from GIT problems, mainly diarrhea. Each sample was divided
into two parts; the first was preserved in potassium dichromate for parasitological
examination and were stained and examined for microsporidial spores. The second part
was freshly frozen to be used for the real-time PCR and DNA melting curve analysis for
the confirmation of the diagnosis and identification of the microsporidial species.
The preserved stool samples proven to be E. bieneusi and E. intestinalis were pooled
separately and filtered to remove excess debris before animal infection. Spores of each
species were counted in 0.01ml of stained stool sample and the dose of infection was
calculated to be 104 / mouse.
Three drugs were administered orally for the microsporidia-infected mice; orlistat in
a dose of 2.5 mg /kg/ mouse, fumagillin as a control drug for E. bieneusi and was given in
a dose of 22 μg/mouse/day, and albendazole as a control drug for E. intestinalis and was
given at a corresponding human dose of 400 mg twice daily for two to four weeks. All