Case study 1 - Giardiasis Flashcards
What is Giardiasis also known as?
bever fever
backpackers diarrhoea
wilderness diarrhoea
backcountry diarrhoea
many different names depending on where you pick it p from
Why is Giardiasis also known as bever fever?
It was one believed that people could pick up the infection from bevers
What is the best way to figure out which disease this was?
the symptoms are similar to many other symptoms, the morphology of the disease provides the most evidence. The cysts are indicative of Giardiasis especially since they were excreted inonly 1 of 3 stools
What are the 2 different stages of infection?
acute
chronic
where is giardiasis the leading parasitic infection?
US
how many people are symptomatic with this disease?
280 million
WHere is it distributed?
worldwide but more prevalent in developing countries
how many adults and children in percent have the disease?
2% adults
6% children
how many people in the US are symptomatic?
2.5 million people
which communities are at most risk?
homosexual communities, nursing homes, babies
what are the disease symptoms? (5)
Appears usually in first week of travelling
3 or more unformed stools within 24hrs
nausea, vomitting
rapid weakness, bloating, cramps, fever, loss of appetite
if you are lactose intolerant what can happen when you get giardiasis?
rashes
what is the causative agent of Giardiasis?
Giardia lamblia
Giardia lamblia is also known as….
Giardia intestinalis
Giardia duodenalis
What has genotyping shown about Giardia lamblia?
there are 5 different sub groups of which the sub groups A and B infect humans. C,D,E will infect other animals as will A and B.
There are other species of Giardia that infect what?
birds
reptiles
amphibians
What are the 2 forms of the protozoan giardia lamblia?
trophozoite
cyst
which form of the protozoan is infective?
cyst
Describe the morphology of the trophozoite
motile form leaf shaped flattened 10-12micro m long 4 pairs of flagella 2 nucleis median body claw hammer shaped ventral adhesive disk lack golgi apparatus lack perioxsomes
How does the trophozoite generate energy?
glycolysis
Is the trophozoite anaerobic or aerobic?
anaerobic
adapted to life in the gut
What is the ventral disk used for?
adhesive disk used for attachment - myosin rich structure that anchors this parasite onto the brush boarder of the digestive tract
Are both nucelis in the trophozoite active?
both are transcriptionally active
What is the surface of the cell of the trophozoite coated with?
VSP
variant surface protein
antigenic variation
changes every 10 generations
Describe the morphology of the cyst
4 nuclei
resistant to UV, freezing and chlorine due to its protective wall structure
flagella is internalised
what causes the cyst to release the trophozoite?
stomach acid
change in pH
When the cysts undergo excystation one cyst will give rise to how many trophozoites?
2
trophozoites divide how?
by binary fission
what is the minimum number of cysts required for infection?
10
how many cysts can be produced by one person?
10 billion
how does Giardia lamblia eter the body?
contaminated water is responsible for transmission.
can be direct through water or indirect through food
also sexual behaviour, direct contact with faecal matter
Where is the optimal environment for G.lamblia?
the GI tract is the optimal environment
how do disease symptoms relate to pathogenesis?
Damage surface area over which nutrients can be taken up
parasites sitting on the surface is just a physical barrier over the surface
cell to cell junctions you have gap junctions that put the cells together, as a result of the inflammatory responses it could weaken the gap junctions so material is not released / taken up into the lumen – affecting the permeability of the layer itself
What is the host response to the infection?
C4 T cells
shedding of the gut lining of the parasites every 2-3 days
bacterial micro flora is competition with the pathogen
mucous produced in the gut prevents it binding
respond in an innate way - AMPs defensis and lactoferin
in vitro what has been found to kill giardia?
macrophages
How is the disease diagnosed?
immunofluorescence enterotest stool sample small bowel biopsy immunogenic test
what is the enterotest?
string test
swallow gelatin capsule attached to string
attach string to face
leave gelatin there and then pull back after 2 hours
analyse under microscope
what is the most common drug prescribed?
metronidazole
how does metronidazole stop infection?
• Metronidazole utilizes the anaerobic metabolic pathways present in Giardia. The drug enters the trophozoite, and once it is within the cell, electron transport protein ferredoxins from the parasite donate electrons to the nitro group of the drug. The drug becomes “activated” by reduction of this nitro group and a gradient favoring the intracellular transport of metronidazole is established by this reduction reaction. Reduced metronidazole serves as a terminal electron acceptor which binds covalently to DNA macromolecules. This results in DNA damage in the form of loss of helical structure, impaired template function, and strand breakage, with subsequent trophozoite death. In addition to this effect, metronidazole inhibits trophozoite respiration. The reductive activation of metronidazole may also lead to toxic radicals, which react with essential cellular components
what is the problem with metronidazole?
tastes metallic
7% react to drug
no alcohol
simple way the prodrug metronidazole works?
• essentialy the activation pathway is the same as described this morning - nitro group undergoes one electron reduction, nitroanion radical formed, these interact with each other and one of the nitroanion radical becomes a nitroso form which breaks down further and all of the derivatives can bind to DNA and prevent DNA being produced killing the cell
what are 4 other drugs used to treat giardiasis?
Quinacrine
Furazolidine
albendazole
paromomycin
mebendazole
what preventative steps can be taken against the disease?
drink bottled water
boil water
avoid street food
wash hands with soap
what other microorganisms cause travellers diarrhoea?
bacteria - 80%
viruses and protozoans - 20%
what is the causative agent of amoebic dysentery?
Entamoeba histolytica
what is the life cycle of entamoeba histolytica?
Cysts and trophozoites are passed in faeces
Cysts are typically found in formed stool, whereas trophozoites are typically found in diarrheal stool.
Infection by Entamoeba histolytica occurs by ingestion of mature cysts in faecally contaminated food, water, or hands.
Excystation occurs in the small intestine and trophozoites are released, which migrate to the large intestine.
The trophozoites multiply by binary fission and produce cysts and both stages are passed in the feces
Because of the protection conferred by their walls, the cysts can survive days to weeks in the external environment and are responsible for transmission. Trophozoites passed in the stool are rapidly destroyed once outside the body, and if ingested would not survive exposure to the gastric environment.
In many cases, the trophozoites remain confined to the intestinal lumen of individuals who are asymptomatic carriers, passing cysts in their stool. In some patients the trophozoites invade the intestinal mucosa, or, through the bloodstream, extraintestinal sites such as the liver, brain, and lungs with resultant pathologic manifestations.
What is the life cycle of giardia lamblia?
Cysts are resistant forms and are responsible for transmission of giardiasis.
Both cysts and trophozoites can be found in the feces (diagnostic stages)
The cysts are hardy and can survive several months in cold water.
Infection occurs by the ingestion of cysts in contaminated water, food, or by the fecal-oral route (hands or fomites)
In the small intestine, excystation releases trophozoites (each cyst produces two trophozoites).
Trophozoites multiply by binary fission, remaining in the lumen of the proximal small bowel where they can be free or attached to the mucosa by a ventral sucking disk
Encystation occurs as the parasites transit toward the colon. The cyst is the stage found most commonly in nondiarrheal feces.
Because the cysts are infectious when passed in the stool or shortly afterward, person-to-person transmission is possible. While animals are infected with Giardia, their importance as a reservoir is unclear
