Intestinal Coccidia & Microsporidia [fungi]
Intestinal Coccidia & Microsporidia
Editor: Charles Knirsch
Section Contents
- Cryptosporidium spp
- Cyclospora cayetanensis
- Cystoisospora belli (formerly known as Isospora belli)
- Microsporidia
- Assessment: Did I Get It? (DIG IT)
- Other Media Resources (Optional)
- References
Introduction
This is a long module, so please bear with us! We will cover the intestinal coccidia (Cryptosporidium, Cyclospora, Cystoisospora) and Microsporidia (although are fungi, they fit well with other coccidia and that's why we're including it here). Okay, enough of this preamble. Let's start.
Cryptosporidium spp
Background & Epidemiology
Cryptosporidium spp are a group of coccidian protozoa that cause diarrheal illness in most mammalian species (including humans). Most human infections are caused by C. hominis and C. parvum. While most patients are asymptomatic or have a self-limited diarrheal syndrome, cryptosporidiosis can be BAD, especially among immunosuppressed individuals (e.g., AIDS).
Cryptosporidium is transmitted primarily by ingesting sporulated oocysts through fecally contaminated water or food from an animal or a human source, but it can also spread from person-to-person. Oocysts are environmentally resistant, including to chlorination (therefore can spread in swimming pools).
It is found all around the world, but it’s more common in low and middle income countries. As with other diarrheal illnesses, cryptosporidiosis is more common among those who:
- Live in or travel to developing regions of the world
- Have poor hygiene practices
- Have increased oral-anal contact (e.g., men who have sex with men)
Life Cycle
The life cycle is very complicated! We outlined the basic concepts you need to know, but in case you want to dig deeper into it, you can watch the video below.
In summary, human infection starts with ingestion of sporulated oocysts mainly via fecally contaminated water or food. Only a low inoculum is needed to initiate the infection (<1000 oocysts). Sporozoites excyst in the small intestine and undergo both asexual and sexual reproduction in the enterocytes. Asexual reproduction generates merozoites which are capable of invading other enterocytes; whereas sexual reproduction generates new oocysts. Oocysts can excyst inside the same host, producing an autoinfection, while others are released with stool, capable of re-starting the life cycle.
There are two key points you should be aware of:
- Released oocysts are immediately infectious (which is different from other coccidia, like Cyclospora or Cystoisospora)
- Interestingly, both the sexual and asexual cycles in Cryptosporidium occur outside of the cytoplasm, in the extracellular membrane (quite unique, huh?)
We acknowledge this is an oversimplification. For more details, please refer back to the core lecture below.
Figure 1. Life cycle of Cryptosporidium parvum
Clinical Presentation
Incubation period is usually less than 2 weeks. Presentation largely depends on the hosts’ cellular immunity.
- Intestinal disease: in most patients, infections are either asymptomatic or present as a self-limited watery diarrhea (clinically indistinguishable from other causes). However, in immunocompromised individuals, in addition to a self-limited illness, diarrhea can be chronic/relapsing (>1-2 months) AND/OR can mimic a cholera-like illness, which can be life-threatening! This is particularly true in AIDS patients or transplant recipients
- Extraintestinal disease: among immunocompromised individuals (especially among those with AIDS), disease can also occur outside the GI tract. Patients can present with biliary involvement (e.g., sclerosing cholangitis, pancreatitis), or rarely, with respiratory involvement (e.g., pneumonia)
Diagnosis
Definitive diagnosis can be supported through different modalities:
- Stool microscopy: useful to identify oocysts in stool. Concentration methods (e.g., Kato Katz, modified ethyl acetate, Faust) and/or staining methods (Kinyoun, modified Ziehl-Neelsen) are preferred! It stains acid-fast
- Microscopy with direct fluorescent antibody (high sensitivity)
- Antigen detection kits in stool (high sensitivity): some are commercially available in conjunction with Giardia and/or Entamoeba
- PCR (high sensitivity): as part of a multiplex molecular panel in stool
Figure 2. Oocyst of Cryptosporidium spp in stool
Treatment
The most effective treatment for cryptosporidiosis is immune reconstitution with antiretroviral therapy and supportive treatment (e.g., hydration). Nitazoxanide is FDA-approved, but efficacy is variable.
Cyclospora cayetanensis
Background & Epidemiology
If you read Cryptosporidium, this will be quite easy because there are many similarities between both pathogens. Cyclospora is another coccidian protozoa, also associated with diarrheal illness, particularly bad among immunocompromised (e.g., AIDS). It’s also transmitted via fecally contaminated water and food, but has no other known routes of transmission (unlike Cryptosporidium). It’s also more common in low and middle income countries, but one distinctive feature is that it has a seasonal pattern of transmission (not transmitted year-round), but seasonality depends on the country.
Cyclospora is acquired by ingesting sporulated oocysts. However, unlike Cryptosporidium, freshly released oocysts are not immediately infectious, they require time in the environment (~1-2 weeks) to sporulate. Outbreaks have been linked to raspberries, basil, lettuce, among others products.
Life Cycle
It is similar to Cryptosporidium, with a few differences, including:
- There is NO autoinfection cycle
- Oocysts are NOT infectious upon release, need time to sporulate under appropriate conditions
- Sexual and asexual reproduction occurs within the cytoplasm (NOT outside of the cytoplasm)
Clinical Presentation
Incubation period is ~ 1 week. Most individuals will have an asymptomatic or self-limited enteropathy; but in immunocompromised individuals disease can be SEVERE. Unlike Cryptosporidium, a viral prodrome (e.g., fever) can precede the GI symptoms in cyclosporiasis and anorexia and fatigue are the most common symptoms (less so diarrhea). No extra-intestinal disease is described in cyclosporiasis.
Diagnosis
- Stool microscopy: identifying the oocysts in stool Concentration methods (e.g., Kato Katz, modified ethyl acetate, Faust) and/or staining methods (Kinyoun, modified Ziehl-Neelsen) are preferred!
- Unlike Cryptosporidium, Cyclospora variably stains acid-fast
- Microscopy with fluorescence (high sensitivity)
- PCR (high sensitivity): as part of a multiplex molecular panel in stool
Treatment
Unlike Cryptosporidium where there is not a great treatment option, in Cyclospora, most isolates respond well to trimethoprim-sulfamethoxazole. Don’t forget about antiretroviral therapy & hydration!
Prevention
Same as Cryptosporidium.
Cystoisospora belli (formerly known as Isospora belli)
Background & Epidemiology
You’re doing great! This one is a quick one. Cystoisospora is another coccidian protozoa that is associated with diarrheal illness, which is more severe among immunosuppressed individuals (e.g., AIDS). It’s also transmitted via fecally contaminated water and food, and similar to Cyclospora, has no other known routes of transmission (unlike Cryptosporidium). It’s also more common in low and middle income countries, and humans are the only reservoir.
Figure 3. Oocyst of Cystoisospora belli in wet mount of stool
Life Cycle
It is very similar to the other coccidian protozoa, but some key features include:
- There is NO autoinfection cycle
- Oocysts are NOT infectious upon release, need time to sporulate under appropriate conditions
- Sexual and asexual reproduction occurs within the cytoplasm, but out of the three is the only one that can invade beyond the epithelium and can induce peripheral eosinophilia!
Clinical Presentation
Incubation period is ~ 1 week.
- Intestinal disease: most individuals will have an asymptomatic or self-limited enteropathy; but in immunocompromised individuals disease can be SEVERE. Unlike other protozoa, cystoisosporiasis can induce peripheral eosinophilia! (controversial)
- Extraintestinal disease: among immunocompromised individuals (especially in AIDS), disease can also occur outside the GI tract. Patients can present with gallbladder involvement (e.g., cholecystitis)
Diagnosis
- Stool microscopy: identifying the oocysts in stool. Concentration methods (e.g., Kato Katz, modified ethyl acetate, Faust) and/or staining methods (Kinyoun, modified Ziehl-Neelsen) are preferred! It stains acid fast. Can see Charcot Leyden crystals from intestinal eosinophilic response
- Autofluorescence (high sensitivity)
Treatment
Unlike Cryptosporidium where there is not a great treatment option, most isolates of Cystoisospora and Cyclospora respond well to trimethoprim-sulfamethoxazole. Don’t forget about antiretroviral therapy & hydration!
Prevention
Same as Cryptosporidium & Cyclospora
Microsporidia [fungi]
Background
This is the last topic in this series, and it's probably the most difficult one! We promise we tried to simplify it… Microsporidia is not one organism, but rather a big group of many intracellular organisms (>1000 species) that affect a wide variety of hosts, including humans. They are considered closely related to fungi (NOT protozoa), but they have a lot of similarities to how coccidian protozoa behave and that’s why they are grouped together in the same module.
There are so many species, but we will concentrate only on two: Enterocytozoon bieneusi and Encephalitozoon intestinalis. Both species are more prominent in AIDS patients with CD4 <50 cell/uL. Enterocytozoon (most common) is mostly a cause of chronic diarrhea; whereas Encephalitozoon in addition to diarrhea, can disseminate and affect other organs (more on this below).
Note: For now remember:
- “Entero” = intestine (Enterocytozoon in GI tract)
- “Encephalo” = brain + “intestinalis” =intestine (Encephalitozoon intestinalis = GI tract + disseminated disease)
Epidemiology & Life Cycle
Microsporidia exists as spores and are ubiquitous in the environment (e.g., in water). Most reservoir species are animals (e.g., mammals, insects), although human transmission is thought to be possible.
Spores are believed to be mostly acquired via ingestion or inhalation of spores of fecally contaminated food or water. Spores contain a distinctive structure called polar tube, which is coiled up inside the spore. Once inside the host, the polar tube uncoils and injects its content (called sporoplasm) into the host’s cells. It undergoes a very complex asexual and sexual replication cycle which yields further spores, which can be shed into the environment or infect other cells. Some species undergo the cycle mostly in the GI tract - in which case the spores would shed in feces- while others disseminate (mostly in AIDS) to other organs (e.g., kidney, eye, lungs, CNS) - and spores would be found in urine, respiratory secretions, etc.
Clinical Presentation
Similar to the coccidian protozoa, presentation is largely dependent on the host’s cellular immunity. Most infections in immunocompetent patients are asymptomatic or self-limited. Some species can affect the eye (mostly other species that will not be discussed - Nosema spp, Vinaforma spp). In this module, we will focus on the presentation of immunocompromised (mainly described in AIDS):
- Enterocytozoon bieneusi: primarily a cause of chronic diarrhea. Rarely, can cause hepatobiliary disease (e.g., sclerosing cholangitis, acalculous cholecystitis).
- Encephalitozoon intestinalis: similarly can cause chronic diarrhea. In addition, it can disseminate and has been described as a cause of interstitial nephritis, chronic sinusitis, and keratoconjunctivitis. Other species of Encephalitozoon (cuniculi, hellem) are more associated with encephalitis, pneumonia, and ocular disease.
Diagnosis
- Identification of spores (feces, urine, sputum, CSF):
- Staining is your friend! Use modified trichrome, calcofluor white and/or chromotrope 2R.
- Send both stool and urine! Sputum and CSF if that body area is affected
- Electron microscopy is GREAT, because the spores are very small (1-4 um), but of course, not widely available
- PCR
Treatment
Species that tend NOT to disseminate (e.g., Enterocytozoon bieneusi) are better treated with Fumagilin (not available in the US, only through the companies). The species that tend to disseminate (e.g., Encephalitozoon spp) are better treated with Albendazole.
Prevention
Same as coccidian protozoa
| Cryptosporidium | Cyclospora | Cystoisospora | Microsporidia [fungi] | |
| Size | 5 um approx. | 10 um approx. | 20 um approx | 1-4 um (spores) |
| Reservoirs | Zoonosis & Anthroponosis | Unclear | Anthroponosis | Zoonosis |
| Transmission | Water- and Foodborne, Person-to-Person, ?Airbo | Water- and Foodborne | Water- and Foodborne | Water- and Foodborne, Airborne |
| Habitat | Cellular membrane | Cytoplasm | Cytoplasm | Intracellular (varies per spp) |
| Acid-Fast Staining | Yes | Variable | Yes | Yes |
| Infectivity of Freshly Released Oocysts/ Spores | Immediately infectious | Need time to sporulate | Need time to sporulate | Unclear |
| Unique features | Autoinfection | Seasonal transmission | Peripheral eosinophilia | Disseminated disease (varies per spp) |
Table 1. Comparison between intestinal coccidia and Microsporidia [fungi]
Assessment: Did I Get It? (DIG-IT)
Assessment: Did I Get It? (DIG IT)
DIG ITs are online modules designed to reinforce key learning points for you! Please choose the best answer, then check all of the answer choices for more learning pearls (Note: only available for Cryptosporidium)
Other Media Resources (Optional)
References
This was the last lesson on intestinal protozoa! It took guts to go through it...
This lesson was last updated May 21 2025