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Multisystems > Micro- Diarrheal Diseases in AIDS > Flashcards

Micro- Diarrheal Diseases in AIDS Flashcards

1
Q

How do the organisms that cause diarrhea in an immunocompetent host compare to those that cause diarrhea in a patient with AIDS?

A

They may be the same organism, however in the AIDS patient, they tend to produce:

  1. more virulent
  2. protracted clinical course
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2
Q

Why is cryptosporidium one of the most frequent diarrheal pathogens in patients with AIDS?

A

in part because it is refratory to treatment.

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3
Q

How can the majority of enteric infections be identified?

A

Stool studies of:

  1. bacterial cultures [shigella, salmonella, campy]
  2. ova and parasite with modified acid fast [cryptosporidium, cyclospora]
  3. C. difficile toxin assay

If stool studies are not diagnostic–>

  1. colonoscopy
  2. upper endoscopy [aspirates, biopsy from small bowel for protozoa]
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4
Q

A patient presents with new onset, watery diarrhea with fever, leukocytosis and cramps. What should definitely be part of the workup?

A

C. difficile Toxin assay

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5
Q

What are upper endoscopies needed for when trying to identify the cause of enteric infection?

A

If stool studies do not provide definitive diagnosis, you do upper endoscopy [aspirate/biopsy] of small bowel to detect protozoa, especially:

  1. cryptosporidia
  2. microsporidia
  3. giardia
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6
Q

What species of cryptosporidium is the most prevalent causing disease in humans?
Where does it reside?
What is the structure? [size, contents]
How can it be identified?

A

Cryptosporidium parvum

  • intracellular coccidian protozoa
  • exist in the environment as small 5 micron oocyst containing 4 sporozoites

It is acid fast, staining red

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7
Q

What cells do cryptosporidium parvum infect?
How does this contribute to the clinical presentation?
How long does diarrhea last in an immunocompetent patient?

A

They infect epithelial cells of the GI, biliary, and respiratory tracts.

Clinical presentation:

  • watery diarrhea
  • anorexia, vomiting, abdominal pain
  • NO FEVER or MALAISE

Self-limited and lasts less than 2 weeks

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8
Q

At what CD4 count does chronic infection by cryptosporidium lead to dehydration, malnutrition and wasting?

A

<100

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9
Q

What are the 4 general clinical-categories of AIDS related cryptosporidiosis?

A
  1. cholera-like illness requiring IV rehydration [1/3]
  2. chronic diarrheal illness [1/3]
  3. intermittent diarrheal illness [1/6]
  4. transient diarrheal illness [1/6]
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10
Q

What are large outbreaks of diarrhea caused by cryptosporidium attributed to?

A

inadequate purification of drinking water

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11
Q

What is the reservoir of cryptosporidium?

A

humans, cattle, domestic animals

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12
Q

What is the mode of transmission of cryptosporidium?

A

Fecal-oral and mainly occurs via:

  1. contaminated water
    - waterparks, community pools, day care
    - drinking water
  2. food sources
    - chicken salad
  3. exposure to infected animals
  4. MSM sexual activity
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13
Q

What are the major risks of getting a severe form of cryptosporidium?

A
  1. AIDS

2. renal or bone marrow transplant

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14
Q

Describe the pathogenesis of cryptosporidium starting with infection.

A
  1. infected by ingesting oocysts [that contain 4 sporozoites]
  2. travel through gut lumen to small intestine
  3. rupture and release sporozoites [10 is min. infectious #]
  4. Sporozoites adhere and invade epithelial cells along the small intestine [mostly jejunum]
  5. carry out their life cycle among the microvilli of the small intestine
  6. impairs absorption and enhances secretion –> diarrhea
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15
Q

How does it differ for immunocompetent and immunocompromised hosts?

A

Immunocompetent
- life cycle takes place once or twice resulting in a single episode of diarrhea lasting less than 14 days.

Immunocompromised

  • life cycle is repeated many times, resulting in persistent watery diarrhea.
  • merozoites differentiate to gamonts which undergo sexual reproduction regenerating oocysts that are excreted in feces

NEITHER HAS INVASION INTO BLOOD STREAM

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16
Q

What are the 2 key immune components necessary for prevention and resolution of cryptosporidosis?

A

CD4+ lymphocytes

IFNg

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17
Q

How is the lab diagnosis of cryptosporidium made?

A
  1. biopsy of human GI mucosa or ova in stool
    - intracellular
    - 5 micrometer [smaller than cyclospora]
    - spherical
    - sporozoites are visible in the oocyst indicating sporulation has occurred
  2. acid fast stain
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18
Q

How can cryptosporidium and cyclospora be differentiated on wet mount, differential interference contrast microscopy?

A

Crypto

  • 5micrometers
  • visible sporozoites in oocyst showing sporulation has occurred

Cyclospora

  • 10micrometers
  • upon excretion are NOT sporulated [get sporulated in the environment]
19
Q

What is treatment for cryptosporidium for:

  1. immunocompetent
  2. immunocompromised [what CD4 count would have severe crypto]
A

Immunocompetent:

  1. fluid and electrolyte replacement
  2. self-limited infection so give it 2 wks

If AIDS CD4+ less than 100:

  1. fluid and electrolyte replacement
  2. partial restoration of immune function via HAART
20
Q

How is cryptosporidium infection prevented?

A
  1. routine testing of drinking water

2. maintain immune system with HAART

21
Q

For primary disease with cyclospora cayetanensis, what is the incubation period?
How does symptomatic infections manifest?
How long do untreated infections last?

What CD4 count puts someone at increased risk?

A

Incubation of the 8-10micron “coccidia-like” parasite is one week.

Symptoms include:

  1. watery diarrhea
  2. anorexia, weight loss [diff from crypto]
  3. abdominal pain, nausea, vomiting
  4. myalgia, fatigue, fever [dff from crypto]

Untreated infections last 10-12 weeks and follow a relapsing course

CD4 less than 100 is increased risk

22
Q

An AIDS patient with a CD4+ count of 90 presents with watery diarrhea, anorexia, myalgias, fever, vomiting. He admits to eating raspberries last week. What is the likely pathogen?

A

cyclospora

23
Q

What is the mode of transmission of cyclospora?

A

Fecal-Oral

  1. swallowing oocysts found in contaminated water and food
  2. drinking or swimming in contaminated water
24
Q

How do the cysts of cyclospora differ from entamoeba/giardia when they are excreted in human feces?

A

Cyclospora oocysts are NOT infectious when they are excreted.
The parasite become infectious when they sporulate after they incubate for days/weeks in warm/high humidity environments

25
Q

What are the risks for a person to get diarrhea from cyclospora?

A
  1. spring/summer with warmth/high humidity

2. immunocompromised have more severe/longer course of diarrhea

26
Q

Describe pathogenesis for cyclospora beginning with sporulation.

A
  1. In the environment after days/weeks at high temps, sporont divides into 2 sporocysts [each containing 2 sporozoites]
  2. sporulated oocyst is ingested in contaminated food/water
  3. in GI tract, oocyst excysts and releases sporozoites
  4. sporozoites invade epithelial cells of the small intestine [mostly jejunum]
  5. in the cell they undergo asexual multiplication and sexual development
27
Q

How is lab diagnosis of cyclospora made?

A
  1. Direct microscopy of stool specimen
    - 8-9mm “wrinkled spheres” on wet mount
  2. Modified acid fast of stool
    - oocyst stains light pink to dark red [VARIABLY acid-fast]
    - some oocysts have granules and a bubbly appearance
28
Q

What is recommended treatment for cyclosporiasis?

A
  1. Trimethaprim-sulfamethoxazole
  2. fluid electrolyte balance
  3. rest
29
Q

What are the 3 coccidian parasites that infect epithelial cells of the small intestine?
Which is the LEAST common?
All can stain with acid fast, and can be visualized on wet mount with DIC, but which ONE cannot autofluoresce?
Which one is NOT treated with TMP/SMX?

A
  1. cryptosporidium - cannot autofluoresce, not treated with TMP/SMX
  2. cyclosporidia
  3. isospora belli - least common
30
Q

Describe the primary disease presentation of isosporiasis.
Isospora causes severe disease in HIV patients with what CD4 count?
What would you see on histology that would differentiate it from the other protozoan infections?

A
  1. acute non-bloody diarrhea
  2. crampy abdominal pain lasting for weeks
  3. malabsorption and weight loss

Severe disease if CD4+ count is below 100 [same for all coccidia]

On histology you would see eosinophilia [different from other protozoan infections]

31
Q

What is the mode of transmission and major risk factors for isosporidia infection?

A

Mode of Transmission:
1. contaminated water [drinking only]

Risks:
1. AIDS

32
Q

Describe the pathogenesis of isospora starting at excretion.

A
  1. at excretion the immature oocyst had one sporoblast
  2. maturation in the environment has the sporoblast divide into 2
  3. sporoblasts secrete cyst walls and become sporocysts
  4. sporocysts divide 2x to make 4 sporozoites each
  5. ingestion of sporocyst-containing oocyst
  6. sporocysts excyst in the small intestine releasing sporozoites which invade epithelial cells
  7. asexual multiplication for minimum one week
  8. sexual stage begins to form oocysts
33
Q

How is the lab diagnosis of isospora belli made?

A
  1. Wet mount microscopy with bright field differential interference contrast
    - large [25-30 microns]
    - ellipsoidal shape
  2. epifluorescence
  3. acid fast
34
Q

What is treatment for isospora belli?

A

TMP/SMX

35
Q

What infectious agent do the following describe:

  1. obligate intracellular protozoan
  2. produces resistant spores
  3. possess polar tubule/filament coiled inside the spore
  4. is 1-4 microns
A

microsporidia

36
Q

What CD4+ count makes an AIDS patient susceptible to microsporidia?

A

less than 50

37
Q

How is the lab diagnosis of microsporidia made?

A
  1. light microscopy to examine stained clinical smears [especially from fecal samples] can tell you if it is microsporidia, but cannot tell you the species
  2. PCR can diagnose specific species of microsporidia
38
Q

What is treatment for microsporidia?

A

albendazole

39
Q

Describe the pathogenesis of microsporidia.

A
  1. exists in the environment for a long time as a resistant spore
  2. spore extrudes polar filament and infects the cell by injecting infective sporoplasm into the eukaryotic cell
  3. sporoplasm multiplies in the cytoplasm OR inside a vacuole
    - merogeny [binary fission]
    - schizogeny [multiple fission]
  4. develop to mature spores by forming a thick wall around the spores making them resistant to environment
  5. rupture the cell and release into the surroundings
40
Q

MAC is a common infection in patients with AIDS and a CD4 count below ________.

A

50

41
Q

An AIDS patient with a CD4 count of 45 presents with fever, weight loss, anorexia, and night sweats. He also has watery diarrhea without leukocytes.
On small bowel biopsy, you see macrophages filled with acid-fast bacilli.

What is it likely he has?
What is treatment?

A

MAC [mycobacteria avium complex]

Treat with:

  1. macrolide and ethambutol
  2. HAART
42
Q 
What virus accounts for 20% of diarrhea in AIDS patients?
How does it present?
What do you see on colonoscopy?
What do you see on biopsy?
What is treatment?
A

CMV

  • colitis
  • fever
  • small volume, bloody diarrhea with leukocytes

Colonoscopy shows punctuate hemorrhages with ulcerations

Biopsy shows intranuclear inclusions

Treatment: ganciclovir, foscarnet

43
Q

What is the suggested mechanism by which the HIV virus itself causes enteropathy/diarrhea?

A

Opening of tight junctions between epithelial cells by HIV-stimulated cytokines [IFNg, TNF]

44
Q

Diarrhea is the most common adverse effect of HAART. Which drugs cause it?

A
  1. protease inhibitors [NAVIRS]
    - nelfinavir, ritonovir/liponavir
  2. nucleoside analogues [VUDINES]
    - didanosine, lamivudine

Multisystems (29 decks)

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