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LF223: Microbial Pathogens > Lecture 8. Apicomplexan parasites: Cryptosporidiosis and Toxoplasmosis > Flashcards

Lecture 8. Apicomplexan parasites: Cryptosporidiosis and Toxoplasmosis Flashcards

1
Q

What are Cryptosporidium parvum and Cryptosporidium hominis?

A

Waterborne pathogens
Cause cryptosporidiosis (“Crypto” for short)
Diarrhoea and flu-like symptoms

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2
Q

What is cryptosporidiosis?

A

Quite serious and potentially life-threatening in immunodeficient patients (especially AIDS), characterised by a profuse watery diarrhoea - community outbreaks can occur

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3
Q

What is cryptosporidium the second leading cause of and a major contributor of?

A

Diarrhoea in young children and a major contributor for diarrheal deaths in LMICs (low or middle income country)

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4
Q

What is required for cryptosporidium to replicate?

A

One host required
For C. hominis host is a human
For C. parvum host is either human or animal (e.g cattle)

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5
Q

What is the cryptosporidium life cycle?

A
  1. Thick-walled oocyte (sporulated) exits host (focused in the gut)
  2. Contamination of water and food with oocytes
  3. Thick-walled oocyst ingested by host
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6
Q

What occurs in the sexual part of the cryptosporidium life cycle?

A

Merozoites differentiate into the gamonts (male and female versions) which fuse to form zygote
Thin-walled oocysts proceed to infect more gut cells within the host, thick-walled oocysts exit the host to infect new host

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7
Q

What occurs in the asexual part of the cryptosporidium life cycle?

A

Thin-walled oocytes bind onto the cell wall of the gut and undergo asexual cycles
Oocytes differentiate into merozoites that undergo multiple cycles within the gut

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8
Q

What is the main transmission routes of Cryptosporidium?

A

Swallowing water or beverages contaminated by stool from infected humans or animals
Swallowing recreational water contaminated with Cryptosporidium
Eating contaminated uncooked food
Touching your mouth with contaminated hands

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9
Q

What are the risk factors of cryptosporidiosis?

A

Small size of oocysts
Wide range of host specificity
Monoxenous development (only 1 host needed)
Close associations between human and animal hosts
Large number of oocysts excreted (up to 100 billion per calf)
Low infective dose
Robust oocysts which are resistant to chlorine
A complex protective barrier consisting of a double layer of a protein-lipid-carbohydrate matrix

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10
Q

What are examples of occupationally acquired cryptosporidiosis?

A

Workers in sewage and waste water
Workers in outdoor leisure industries in contact with water
Farm workers
Abattoir workers, meat processing plant workers and butchers
Veterinary surgeons
Healthcare and care workers
Construction/demolition/building renovation workers eg where there is stagnant water

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11
Q

What is the distribution of cryptosporidium within the UK?

A

The number of reported cases in England and Wales around 4000 annually
As many cases are thought to be unreported, the actual number of cases is probably several times higher

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12
Q

When do symptoms of cryptosporidiosis infection show?

A

2-10 days after infection
Some infections are asymptomatic

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13
Q

What are the main symptoms of cryptosporidiosis in immuno-competent people?

A

Main symptoms water diarrhoea for 1-2 week
Stomach camps or pain
Nausea or vomiting
Weight loss
Dehydration
Fever

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14
Q

What are the main symptoms of cryptosporidiosis in immuno-suppressed people?

A

Disease in immuno-suppressed people can become more serious, chronic and life-threatening
Children under 5 at more risk, especially where malnourished. Even a single episode of cryptosporidiosis can result in growth
deficits especially during the first 2y of life, and impact growth long-term

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15
Q

What are the exact mechanisms of cryptosporidiosis?

A

Exact mechanisms still unclear
Invasion of parasites in gut epithelial trigger disease and malabsorption of nutrients

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16
Q

How is cryptosporidiosis diagnosed?

A

Microscopic examination of stool samples for presence of oocysts
Immunoassay
Molecular methods: PCR, Real-time PCR

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17
Q

What are the treatment recommendations for cryptosporidiosis?

A

Since cryptosporidiosis is a self-limiting illness in immuno-competent individuals, general, supportive care is the only
treatment for the illness
Oral or intravenous rehydration and replacement of electrolytes may be necessary for particularly voluminous, watery diarrhoea
Nitoxazonide is partially effective in immuno-competent patients but works no better than a placebo in immuno-suppressed patients
Patients with HIV/AIDS are advised to take anti retrovirals to improve immune response

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18
Q

How is cryptosporidiosis controlled?

A

Remove contamination at source (Water supply, Swimming pool)
Monitoring
Hygiene measures as for prevention of all faecal-oral diseases especially for at risk professions (nursery staff, agricultural workers etc)

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19
Q

Does cryptosporidiosis have any vaccines?

A

No vaccines on horizon currently
Knowledge and understanding being gained in anti-malarial vaccines beneficial

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20
Q

What is an example of an outbreak of cryptosporidiosis?

A

Outbreak in Milwaukee during the spring of 1993 in which an estimated 400,000 people developed symptomatic cryptosporidiosis with 50 deaths, 93% deaths are people with HIV

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21
Q

What are the future directions?

A

Development of an effective drug (children, immunosuppressed people)

22
Q

What does Toxoplasma gondii cause?

A

Chronic infections in up to one-third of the human population and in animals

23
Q

In healthy individuals, what symptoms does a primary infection with Toxoplasma result in?

A

Relatively mild symptoms

24
Q

In immunocompromised patients or in the developing foetus, what symptoms does a primary infection with Toxoplasma result in?

A

It can cause life-threatening infections with severe neurological and ocular manifestations

25
Q

What is the definitive host of Toxoplasma?

A

Felines

26
Q

What does the life cycle of toxoplasma consist of?

A

Intestinal and tissue phases

27
Q

What occurs in the intestinal phase of toxoplasma infection?

A

The intestinal phase of the infection occurs only in felines and exhibits a typical intestinal life cycle consisting of merogony and gametogony

28
Q

What occurs in the sexual cycle of toxoplasma infection?

A

The sexual cycle produces oocysts which are excreted in the faeces

29
Q

What happens in the cat stage in the life cycle of toxoplasma?

A
  1. Infected cat sheds faecal oocysts
  2. Faecal oocyst eaten by bird/rodent
  3. T. gondii forms cysts within the tissues of the bird/rodent
  4. Cat eats the infected bird/rodent, T. gondii reproduces in the cat’s gut
30
Q

How can infected faecal oocysts containing T. gondii end up in humans?

A

Ingestion of contaminated food or water
Coming into contact with contaminated litter tray
Ingestion of livestock that have tissue cysts
Contaminated blood transfusion

31
Q

What happens in the cat stage of the toxoplasma life cycle (more detail)?

A

Intermediate hosts - ingestion of sporulated oocysts
Sporozoites are released, penetrate the intestinal epithelium, and invade macrophages and other types of cells
The parasite undergoes binary fission (i.e., merogony) to form tachyzoites (Tachy means rapid.)
The host cell will rupture and release the tachyzoites which will invade new host cells and repeat the replicative cycle
Infected macrophages will disseminate the tachyzoites throughout the host during this acute infection

32
Q

What is the distribution of toxoplasma within the UK?

A

In the UK about 30% of people will be infected by the age of 30

33
Q

What is the distribution of toxoplasma within the US?

A

About 30-35% have antibodies

34
Q

What is the distribution of toxoplasma within France?

A

More than 65% of women tested for antibodies had toxoplasmosis

35
Q

What is the transmission routes of T. gondii?

A

Ingestion of material contaminated with sporulated oocysts, cat faeces
Ingestion of undercooked meat containing tissue cysts or tachyzoites, particularly lamb and pork
Infection rates of 50% or higher in domestic chickens, geese, cattle, goats, pigs, and sheep
38% of meat samples in UK positive

36
Q

How many women each year catch toxoplasmosis during pregnancy?

A

2 in 1000 women, about 1400 each year in the UK

37
Q

How likely is it that a women who catches toxoplasmosis during pregnancy will pass it on to the unborn baby?

A

In only about 30-40% of women who catch toxoplasmosis during pregnancy, does the infection pass to the unborn baby. Risk is greatest in the third trimester at 70%, whereas in early pregnancy only 15% of infants will become infected

38
Q

What are the symptoms of acute toxoplasmosis (in immunocompetent people)?

A

Does not normally cause symptoms
Can cause flu-like symptoms
Typically self-resolving within 6 weeks

39
Q

Who is more at risk of acquiring acute toxoplasmosis?

A

Pregnant women and their unborn children
Those with weakened immune systems

40
Q

What can acute toxoplasmosis cause in those most vulnerable to it?

A

Miscarriage, stillbirth or survival with growth problems, blindness, water on the brain (hydrocephalus), brain damage, epilepsy, or deafness. This often develops after birth, so even normally born infants of women with known infection should be kept under observation for some time

41
Q

What can chronic toxoplasmosis cause?

A

The effects of congenital toxoplasmosis can be life long
Ocular disease (eye disease) – can reactivate causing more damage each time
Reactivation of dormant tissue cysts can occur
In immuno-compromised people leading to fever, confusion, headache, seizures, nausea, and poor coordination
Can lead to toxoplasmic encephalitis
In immuno-compromised pregnant women leading to congenital toxoplasmosis
Possible chronic psychological and neurological effects

42
Q

What happens in the dormant or resting stage of toxoplasmosis infection?

A

As the host develops immunity the replication rate will slow and the infected host cells will become encapsulated (ie, tissue cysts)
These slowly replicating forms are called bradyzoites (brady means slow) and represent a dormant or resting stage
Bradyzoites secrete chitin and other components to form a cyst wall

43
Q

How can a dormant toxoplasmosis infection be reactivated?

A

The reactivation of an infection associated with waning immunity (malignancies, transplantation, AIDS)
Results from the release of the encysted organisms and the initiation of the tachyzoite stage of the infection – followed by local tissue damage and inflammation

44
Q

During the 1980’s toxoplasmic encephalitis emerged as a common complication associated with what?

A

AIDS
Headache, fever, lethargy, altered mental state
Progress to neurological deficits and convulsions
Dementia in late stage AIDS is associated with Toxoplasma

45
Q

What causes ocular toxoplasmosis?

A

Ocular toxoplasmosis occurs from activation of cysts deposited in or near the retina

46
Q

How is toxoplasmosis diagnosed?

A

Serologic testing IgG or IgM
Molecular testing eg PCR
Can detect parasite in biopsies
Ocular disease by case history and serologic testing

47
Q

How is toxoplasmosis treated?

A

The recommended treatment is the synergistic combination of pyrimethamine plus sulfadiazine
Spiramycin for prophylactic use during pregnancy

48
Q

How is toxoplasmosis controlled?

A

Cooking meat to safe temperatures
Wash fruit and vegetables
Avoid drinking untreated water
Wear gloves for gardening and wash hands afterwards
Clean cat litter trays immediately (avoid if possible if pregnant)

49
Q

What vaccines are being developed and validated for toxoplasmosis?

A

One of the most effective vaccines against any protozoal disease, Toxovax is intended for the prevention of toxoplasmosis abortion in ewes (may revert to pathogenic strain so not suitable for humans)
Another type of vaccine that would be of great importance would be one administered to cats that could prevent or reduce the shedding of oocysts (an effective oral vaccine was developed and validated for cats, but unprofitable for the manafaturer as could only be grown in mice)

50
Q

What are the chronic effects of latent toxoplasmosis on rodent psychology?

A

Host behavioural changes could benefit parasite
Infected rodents are more likely to investigate novel stimuli and appear less cautious when presented with signs of cats
Hypothesised to increase the susceptibility of infected rodents to predation by cats, and therefore to increase the odds of completing the T. gondii life cycle

51
Q

What are the chronic effects of latent toxoplasmosis on human psychology?

A

No adaptive benefit to parasite
Case-control studies show interesting correlations with human behaviours, mental health disorders and toxoplasma seropositivity
Schizophrenia, autism, risk-taking eg risk of traffic accident

LF223: Microbial Pathogens (15 decks)

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