Cystoisospora belli
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# Overview
Cystoisospora belli, previously known as Isospora belli, is a parasite that causes an intestinal disease known as cystoisosporiasis. This protozoan parasite is opportunistic in immune suppressed human hosts. It primarily exists in the epithelial cells of the small intestine, and develops in the cell cytoplasm. The distribution of this coccidian parasite is cosmopolitan, but is mainly found in tropical and subtropical areas of the world such as the Caribbean, Central and S. America, India, Africa, & S.E. Asia. In the U.S., it is usually associated with HIV infection and institutional living.

# Morphology
A fully mature (sporulated) oocyst of Isospora genus is a spindle-shaped body that has two sporocysts that contain four sporozoites each. The oocysts of Cystoisospora belli are long and oval shaped. They measure between 20 and 33 micrometers in length and between 10 and 19 micrometers wide.

# Life Cycle
- An oocyst with one sporoblast is released in stool of infected person
- After the oocyst has been released, the sporoblast matures further and divides into two
- After the sporoblasts divide they create a cyst wall and become sporocysts
- The sporocysts each divide twice, resulting in four sporozoites
- Transmission occurs when these mature oocysts are ingested
- The sporocysts excyst in the small intestine where sporozoites are released
- The sporozoites then invade epithelial cells and schizogony  is initiated
- When the schizonts rupture, mereozoites are released and continue to invade more epithelial cells
- Trophozoites develop into schizonts, containing many mereozoites
- After about one week, development of male and female gametocytes begin in the mereozoites
- Fertilization results in the development of oocysts, which are released in the stool 
The sporulation time of this parasites egg is usually 14 days, and the entire life cycle takes about 910 days.

# Symptoms
Immune competent individuals are usually asymptomatic to this parasite's infection. But clinical symptoms such as mild diarrhea, abdominal discomfort, and low grade fever for approximately one week has been observed in some individuals. 
Immunocompromised people are more severely affected by Cystoisospora belli and can experience extreme diarrhea that can lead to weakness, anorexia, and weight loss. Other symptoms of cystoisosporiasis include abdominal pain, cramps, loss of appetite, nausea, vomiting, and fever, that can last from weeks to months.

# Diagnosis and Treatment
Cystoisospora belli is diagnosed by identification of the oocyst through examining a stool sample under a microscope. The diagnostic stage is the immature oocyst that contains a spherical mass of protoplasm.  In other words, the oocyst that is diagnosed in the stool sample is unsporulated, and contains only one sporoblast.  For stool diagnosis, direct smear, concentration smear, microscopic wet mount, or iodine stains of fecal smears are adequate.  But for easy screening, acid-fast stains is recommended. If stool test is negative, and biopsies of the small intestine is performed, different stages of schizogony and sporogony should exist in the epithelial cells, but the alteration of the villi is not necessarily present. Eosinophilia may also be seen unlike in the case of other protozoal infections.
This infection is easily treated with antibiotics. The most common antibiotic that is prescribed is co-trimoxazole (trimethoprimsulfamethoxazole), more commonly known as Bactrim, Septra, or Cotrim.
In AIDS patients, even though treatments can result in the disappearance of the symptoms, recurrences are common.
- 1.1 Immunocompetent hosts
- In the immunocompetent hosts, symptoms of Cystoisospora infection are usually self-limited.
- Antimicrobial therapy to immunocompetent patients may be considered if symptoms do not start to resolve spontaneously after 5 to 7 days (depending upon severity)
- Prefered regimen: Trimethoprim-sulfamethoxazole 160 mg/800 mg PO bid for 7-10 days
- Alternative regimen (1) (for patients who are allergic to or intolerant of TMP-SMX): Pyrimethamine 50-75 mg/day PO qd or divided in 2 equal doses AND Leucovorin 1025 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days (second-line alternative)
- 1.1.1 In pregnancy
- TMP-SMX should be avoided near-term because of the potential for hyperbilirubinemia and kernicterus in the newborn.
- Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- 1.1.2 During lactation
- TMP-SMX generally should be avoided by women when nursing infants who are premature, jaundiced, ill, or stressed, or who have glucose-6-phosphate dehydrogenase deficiency.
- The American Academy of Pediatrics classifies Ciprofloxacin as usually compatible with breastfeeding, whereas the World Health Organization recommends avoiding Ciprofloxacin while breastfeeding and CDC recommends Ciprofloxacin should be used during lactation only if the potential benefit justifies the potential risk to the fetus.
- 1.1.3 In pediatric patients
- The use of TMP-SMX in children less than 2 months of age generally is not recommended.
- Available evidence is conflicting regarding the potential for growth defects and arthropathies in exposed children. Use of Ciprofloxacin in children requires assessment of potential risks and benefits.
- 1.2 Immunocompromised hosts
- Preferred regimen (1): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO/IV qid for 10 days
- Preferred regimen (2): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO/IV bid for 7-10 days
- Note (1): One approach is to start with TMP-SMX (160 mg/800 mg) bid regimen first, and increase daily dose and/or duration (up to 34 weeks) if symptoms worsen or persist.
- Note (2): IV therapy is recommended for patients with potential or documented malabsorption.
- Alternative regimen (1): Pyrimethamine 5075 mg PO qd AND Leucovorin 1025 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days
- 2. Cystoisospora belli prophylaxis
- 2.1 Primary prophylaxis
- Insufficient evidence is available to support a general recommendation for primary prophylaxis for Cystoisosporiasis per se, especially for U.S. travelers in isoporiasis-endemic areas.
- 2.2 Secondary prophylaxis (preventing recurrence in patients with CD4 count < 200 cells/mm3)
- Prefered regimen: Trimethoprim-sulfamethoxazole 160 mg/800 mg PO 3 times weekly
- Alternative regimen (1): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO qd
- Alternative regimen (2): Trimethoprim-sulfamethoxazole 320 mg/1600 mg PO 3 times weekly
- Alternative regimen (3): Pyrimethamine 25 mg PO qd AND Leucovorin 510 mg PO qd
- Alternative regimen (4): Ciprofloxacin 500 mg PO 3 times weekly (second-line alternative)
- Note (1): Criteria for discontinuation of chronic maintenance therapy: sustained increase in CD4 count > 200 cells/mm3 for > 6 months in response to ART and without evidence of active Cystoisospora belli infection
- Note (2): Because of concerns about possible teratogenicity associated with first-trimester drug exposure, clinicians may withhold secondary prophylaxis during the first trimester and treat only symptomatic infection.

# Transmission and Prevention
This parasite is transmitted by ingesting food or water that has been contaminated with feces from someone who is infected. The infective stage found in stool is the mature oocyst. Washing your hands with soap and warm water after using the toilet, changing diapers, and before handling food is vital. Also, educating children the importance of hand-washing and good hygiene practice is important.
Because HIV- AIDS patients will have higher risk of symptomatic intestinal parasitic infections, and pathogenic burden can increase disease progression and contributes to early death, routine screening of parasites especially in patients with lower CD4 count should be emphasized.

# History
Isospora belli was discovered by Rudolf Virchow in 1860 and was named by Charles Morley Wenyon in 1923. The parasite is now known as Cystoisospora belli.