Cystoisosporiasis, formerly known by the more common name isosporiasis, is an infectious small intestine disease. It is caused by a single-celled, microscopic protozoan parasite called Cystoisospora belli. This parasite belongs to a group of organisms known as coccidia, making it a relative of other intestinal parasites like Cryptosporidium and Cyclospora.

The disease occurs when a person ingests the parasite in its dormant, egg-like form (an oocyst). Once inside the small intestine, the oocyst “hatches” and releases active parasites that invade the epithelial cells that line the intestinal wall. This invasion causes direct damage to these cells, disrupting the intestine’s ability to absorb water and nutrients and triggering an inflammatory response.

A helpful analogy is to think of the lining of your small intestine as a lush, velvety carpet.

• This carpet is made of billions of tiny, finger-like projections called villi, which are responsible for absorbing all the nutrients from your food.
• When a person ingests the Cystoisospora parasite, it is like tiny, invasive seeds landing on this carpet.
• The seeds hatch, and their “roots” (the parasites) burrow directly into the individual fronds of the carpet, damaging and destroying the cells.
• This widespread damage to the carpet prevents it from doing its primary job of absorbing water and nutrients, which leads to profuse, watery diarrhea and malabsorption. The body’s inflammatory response to this invasion is what causes the associated abdominal cramping and discomfort.

In my experience, most patients with cystoisosporiasis present with unexplained, persistent diarrhea particularly those who are immunocompromised or recently traveled to tropical regions.

Cystoisosporiasis is caused by infection with the parasite Cystoisospora belli. Humans are the only known host for this parasite, meaning it completes its life cycle in humans and is not carried by animals.

The life cycle is important for understanding how the disease spreads.

1. An infected person passes immature, non-infectious oocysts in their stool.
2. For these oocysts to become infectious, they must mature, or sporulate, in the environment. This process requires warmth, moisture, and time, typically taking one to two days outside the body.
3. A new person becomes infected by ingesting these mature, sporulated oocysts.
4. Once in the new host’s intestine, the oocysts release parasites that invade the intestinal cells, undergo both asexual and sexual reproduction, and eventually produce new, immature oocysts that are passed in the stool, continuing the cycle.

Because the oocysts require time to mature outside the body, direct person-to-person transmission is unlikely. The infection is almost always acquired from an environmentally contaminated source.

Clinically, infection occurs when someone accidentally ingests mature oocysts from contaminated hands, food, or surfaces especially in warm, humid environments with poor hygiene practices.

Cystoisosporiasis is transmitted via the fecal-oral route. This means a person gets the infection by ingesting something food, water, or soil that has been contaminated with human feces containing the mature parasite. The infection is intrinsically linked to areas with poor sanitation and contaminated water supplies.

The primary modes of transmission include:

• Drinking contaminated water: This is a major source of infection and outbreaks.
• Eating contaminated food: Eating raw fruits or vegetables that were grown in contaminated soil, washed with contaminated water, or handled by an infected person who did not practice good hand hygiene.
• Contact with contaminated soil or surfaces.

While the disease is found worldwide, it is most common in tropical and subtropical regions, including parts of Latin America, Africa, and Southeast Asia. It is a well-known cause of “traveler’s diarrhea” in people who visit these endemic areas. In developed countries, outbreaks have been linked to contaminated imported produce.

In my experience, I’ve often seen it in patients with HIV/AIDS or those on immunosuppressive therapy, where their compromised immunity allows the parasite to cause more severe and prolonged illness.

The clinical presentation of cystoisosporiasis depends almost entirely on the immune status of the host.

In Immunocompetent Individuals (People with a Healthy Immune System)

For most healthy children and adults, the infection is either asymptomatic or causes a mild to moderate, self-limiting illness. After an incubation period of about one week, symptoms may include:

• The Hallmark Symptom: The sudden onset of profuse, watery, non-bloody diarrhea.
• Abdominal pain and cramping.
• Nausea.
• Loss of appetite.
• A low-grade fever.
• General feelings of malaise and fatigue.

In healthy individuals, the illness typically resolves on its own within two to three weeks, although a milder diarrhea may linger for longer.

In Immunocompromised Individuals

In people with severely weakened immune systems, the clinical picture is dramatically different and much more serious. The most at-risk group is individuals with advanced HIV/AIDS, particularly those with a low CD4 count.

• Chronic, Debilitating Diarrhea: The diarrhea is much more severe and does not resolve. It becomes a chronic condition that can last for months or even years.
• Severe Malabsorption and Weight Loss: The persistent diarrhea and damage to the intestine lead to a severe inability to absorb nutrients, resulting in significant and sometimes profound weight loss, a condition known as “wasting syndrome.”
• Dehydration and Electrolyte Imbalance: The massive fluid loss from the chronic diarrhea can lead to severe dehydration and dangerous electrolyte abnormalities.
• Extraintestinal Disease: In very rare cases in severely immunocompromised individuals, the parasite can spread outside of the intestines to affect other organs, such as the liver and biliary tree.

Clinically, I pay close attention to persistent symptoms beyond 7–10 days, especially in HIV-positive patients, where the infection can become chronic or even disseminate.

A diagnosis of cystoisosporiasis is suspected in any person with profuse watery diarrhea, particularly a traveler returning from an endemic region or an immunocompromised individual.

• Stool Ova and Parasite (O&P) Exam: The gold standard for diagnosis is the identification of the characteristic Cystoisospora belli oocysts in a stool sample examined under a microscope.
  • The oocysts are large and oval-shaped.
  • A doctor may need to order multiple stool samples to be collected on different days, as the oocysts may not be shed continuously, and a single negative sample does not rule out the infection.
  • The laboratory may use a specific technique, such as a modified acid-fast stain, to make the oocysts easier to see.
• Other Tests:
  • Blood Tests: A complete blood count may show eosinophilia, which is an elevated level of a type of white blood cell called an eosinophil. This is a common finding with many parasitic infections.
  • Endoscopy: In difficult cases where stool tests are negative but suspicion is high, a doctor may perform an upper endoscopy with a biopsy of the small intestine. Pathologists can see the parasite directly within the intestinal tissue.

In my experience, multiple stool samples are sometimes needed due to intermittent shedding of the parasite. PCR testing can also help confirm the diagnosis.

Unlike many causes of traveler’s diarrhea, cystoisosporiasis responds very well to treatment with specific antibiotics. The goals of treatment are to eradicate the parasite, resolve the diarrhea, and, in immunocompromised patients, to prevent relapses.

1. Antibiotic Therapy

• The Treatment of Choice: The cornerstone of treatment is the antibiotic combination trimethoprim-sulfamethoxazole (TMP-SMX), known commonly by brand names like Bactrim, Septra, or Cotrim.
• Course: In an immunocompetent person, a course of TMP-SMX for 7 to 10 days is typically sufficient to cure the infection.
• Alternatives: For individuals with an allergy to sulfa drugs, other antibiotics such as ciprofloxacin may be used, though they may be less effective.

2. Treatment in Immunocompromised Patients

• Initial Treatment: Individuals with weakened immune systems often require a longer and sometimes higher-dose course of TMP-SMX to clear the initial, severe infection.
• Maintenance Therapy (Prophylaxis): Because the infection is very likely to relapse once treatment is stopped in a person with a persistently weak immune system, they are often placed on long-term maintenance therapy. This involves taking a lower daily dose of TMP-SMX to suppress the parasite and prevent future episodes of diarrhea.

3. Supportive Care

• Rehydration: This is a crucial part of management. Replacing the fluids and electrolytes lost through diarrhea is essential to prevent dehydration. This can often be done with oral rehydration solutions (ORS).
• Hospitalization: In cases of severe dehydration or in very ill patients, hospitalization for intravenous (IV) fluids may be necessary.

Prevention

Prevention is focused on public health measures and safe practices in endemic areas.

• Improving sanitation and ensuring access to clean, safe drinking water.
• For travelers, avoid tap water, ice, and uncooked foods like salads or unpeeled fruits that may have been washed in contaminated water.

I typically treat with trimethoprim-sulfamethoxazole (TMP-SMX), which is highly effective, patients with HIV may need prolonged or even maintenance therapy.

Cystoisosporiasis is an important and treatable cause of parasitic diarrheal disease worldwide. While it is often a temporary inconvenience for healthy travelers, it can transform into a severe, chronic, and debilitating disease for individuals with compromised immune systems. Its diagnosis rests on a simple stool examination, and its treatment is highly effective with a course of common and accessible antibiotics. Awareness of this infection is key for both travelers to endemic regions and for healthcare providers caring for immunocompromised patients with chronic diarrhea. In my experience, prompt diagnosis and treatment of cystoisosporiasis significantly improve outcomes especially in immunosuppressed patients, where early therapy can prevent serious complications.

Centers for Disease Control and Prevention (CDC). (2021). Parasites – Cystoisosporiasis (formerly known as Isosporiasis). Retrieved from https://www.cdc.gov/parasites/cystoisosporiasis/index.html

The Merck Manual Professional Version. (2022). Cystoisosporiasis. Retrieved from https://www.merckmanuals.com/professional/infectious-diseases/intestinal-protozoa-and-microsporidia/cystoisosporiasis

National Institutes of Health, MedlinePlus. (2023). Isosporiasis. Retrieved from https://medlineplus.gov/ency/article/000639.htm