Case of the Week 683

Answer to Case 683: Cryptosporidium sp. oocysts

The following OUTSTANDING discussion is from our guest author, Hadel Go, a third year medical student with a strong interest in clinical parasitology.

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We received some excellent feedback! Thank you all for leaving comments on the blog, on Twitter, and on LinkedIn.

Yes, these are Cryptosporidium oocysts. These protozoans can be identified by their size and consistent red color on modified acid-fast staining of stool samples. They can also be diagnosed from H&E stained tissue biopsies (see images here: Cryptosporidium, parasitewonders.com), but nucleic acid amplification tests (NAATs) and immunofluorescence microscopy have the greatest sensitivity and specificity. The two main species that cause infection in humans are C. parvum and C. hominis, although several others are also capable. Species identification requires molecular methods like NAAT and/or sequencing.

Transmission is fecal-oral through food and water contaminated by stool from an infected person or animal. Some examples include swallowing pool water, eating unwashed fruits/vegetables from unsafe farms where produce is contaminated with feces containing oocysts (@StephenTristam on Twitter noted a strong association with farming communities), handling infected farm animals especially calves (@KevKeel brought up infections among vet students!), caring for an infected person, engaging in anal sexual contact (as mentioned by @RA_MLS), and touching your mouth with contaminated hands.

Cryptosporidiosis will present with explosive watery diarrhea, stomach pain, nausea, vomiting and fever 2-10 days after acquiring the parasite as seen in our 4-year-old case patient. These are self-limiting in most immunocompetent individuals. Replenishing fluids and electrolytes to prevent dehydration is usually sufficient. The infection is mainly concentrated in the small intestine, but complications can lead to malnutrition and wasting due to malabsorption or severe dehydration especially in babies.

Immunocompromised patients such as people with HIV/AIDS, inherited immune diseases, or on immunosuppressive drugs can progress to severe chronic infection which may become fatal. The respiratory tract can also be affected (respiratory cryptosporidiosis) resulting in a persistent cough.

Nitazoxanide is the FDA approved treatment for diarrhea caused by Cryptosporidium in immunocompetent patients ≥ 1 year of age. However, as Idzi P. mentioned in the comments, “efficacy in immunocompromised patients is not yet clear… for patients with HIV, anti-retroviral therapy (to improve immune status) could resolve the symptoms.”

Prevention is essential: practice good hygiene, wash hands often, do not swallow water when swimming, only drink filtered or treated water/ice especially when traveling or camping, practice safe sex, do not consume undercooked meat or unpasteurized milk/apple cider, wash your fruits and veggies. To avoid recurrent outbreaks, please do not go swimming if you have diarrhea or within two weeks of resolution of symptoms.

The differential diagnosis is a protozoa in the same family - Cyclospora cayetanensis (discussed in Case 457). It causes cyclosporiasis which presents similarly and can be differentiated from Cryptosporidium species by measuring the oocysts. Their location within enterocytes also varies; see photos from Case 343. The table below compares the two:

	Cryptosporidium parvum	Cyclospora cayetanensis
Oocyst size	4-6 μm	7.5-10 μm
Acid-fast staining	Red staining (can be variable)	Often variable staining
Autofluorescence under UV	No (as pointed out by Idzi P.)	Yes
Location in enterocyte	Replicates outside the cytoplasm just below the cell membrane	Replicates within the cytoplasm
Transmission	Oocysts are immediately infectious leading to massive outbreaks	Person-person transmission unlikely because sporulation can take weeks and occurs in the soil.

DID YOU KNOW?
- Each sporulated oocysts contains 4 sporozoites.
- Cryptosporidium is resistant to chlorine treatments alone due to their protective outer shell.
- Ultraviolet light and boiling are effective ways to inactivate this protozoan.
- Cryptosporidium parvum oocysts are commonly found in young calves 1-4 weeks old.
- Cryptosporidium zoonotic infection can occur from sheep, cows, pigs, rodents and other animals.

LIFE CYCLE (3 developmental stages in bold)

1.      Oocysts (thick-walled spore, infective form) are shed in stool and ingested by host

2.      Excystation releases sporozoites which parasitize epithelial cells of the GI tract

3.      Meronts undergo asexual multiplication within the brush border

4.      Gamonts are produced from sexual multiplication

a.      Microgamonts = male; these rupture releasing microgametes

b.      Macrogamonts = female

5.      Microgametes fertilize macrogamonts forming a zygote

6.      Zygotes give rise to two types of oocysts

a.      Thin-walled oocysts cause autoinfection

b.      Thick-walled oocysts are excreted into the environment

TAXONOMY
Domain: Eukaryota
Clade: SAR
Infrakingdom: Alveolata
Phylum: Apicomplexa
Order: Eucoccidiorida
Family: Cryptosporidiidae

More information:
1. Parasites - Cryptosporidium (also known as "Crypto") | Cryptosporidium | Parasites | CDC
2. CDC - DPDx - Cryptosporidiosis Life Cycle

Thanks to Idzi P. for sharing the following articles about the 1993 outbreak in Milwaukee, WI (the largest known outbreak affecting ~400,000 people):
1. A Massive Outbreak in Milwaukee of Cryptosporidium Infection Transmitted through the Public Water Supply | NEJM
2. Costs of Illness in the 1993 Waterborne Cryptosporidium Outbreak, Milwaukee, Wisconsin