AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

First recognized as a human pathogen among military personnel during World War I, Isospora belli is an Apicomplexa coccidia protozoan that causes a self-limited diarrheal illness in immunocompetent hosts. In individuals with immunocompromise, it may cause chronic life-threatening diarrhea and dehydration.

Pathophysiology

I belli is ingested in contaminated food or water and its life cycle requires a stage outside the host. Oocysts liberate sporozoites (possibly in response to bile in the small intestine), which invade the enterocytes of the proximal small intestine. Here, they become trophozoites, and asexual multiplication (schizogony) produces merozoites that invade previously uninfected cells. Shortly thereafter, a sexual multiplication cycle (sporogony) begins, generating oocysts that may pass into the environment. Outside the host, oocysts mature and become infectious 2-3 days later. Oocysts may persist for months in the environment.

Frequency

United States

I belli infection is distinctly rare among immunocompetent individuals. Among patients with acquired immunodeficiency syndrome (AIDS), 0.2-3% have stools positive for Isospora. In Los Angeles from 1985-92, 1% of patients with AIDS had stools positive for Isospora.¹ Infection was more common in foreign-born and Hispanic residents with AIDS (eg, those from El Salvador [7.4%] or Mexico [5.4%]) and less common in those receiving trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis for Pneumocystis infection.¹

International

Infection with Isospora is endemic in tropical regions, particularly of Central and South America, Africa, and Southeast Asia. One study found positive examination findings in up to 15% of Haitians infected with AIDS.² In developing countries, 8-40% of patients with AIDS are infected.

Mortality/Morbidity

Generally a self-limited disease in immunocompetent hosts, I belli can cause chronic life-threatening diarrhea and dehydration, particularly in persons with AIDS.

Race

No racial predilection for isosporiasis has been reported, other than the racial distribution of people with AIDS. In the United States, Hispanics appear to be more at risk, likely secondary to importation.

Sex

No sex predilection for infection has been noted, aside from the sex distribution of people with AIDS, the risk factor most commonly associated with this disease.

Age

People of all ages are susceptible to this infection, although it tends to be more serious in infants and young children, possibly as a result of the risk of dehydration in this population.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Typically, patients present with mild crampy abdominal pain and profuse, watery, extremely foul-smelling diarrhea. I belli is most commonly observed in immunocompromised individuals or in individuals who have recently traveled to tropical areas, in people who are institutionalized, or in persons who live in poor sanitary conditions. Symptoms begin approximately 1 week after ingesting the oocysts and last 2-3 weeks, with gradual improvement. Infection in people who are immunocompromised may indefinitely last.

• Foul-smelling flatus may be reported.
• Anorexia is sometimes reported.
• Low-grade fever may be present.
• Steatorrhea may occur.
• Nausea and vomiting are uncommon.
• Myalgias are rarely noted.
• Headache is a rare symptom.

Physical

In immunocompromised individuals with severe or long-lasting disease, dehydration may be evident. Otherwise, minimal abdominal tenderness may be present.

Causes

Exposure to contaminated food or water predisposes to this infection. Because an external stage in the environment is required for the oocysts to mature, direct person-to-person transmission is unlikely.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Aeromonas infection
Clostridium difficile infection
Celiac disease
Kaposi sarcoma
Lymphoma
Microsporidiosis
Sarcocystis infection

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Stool examination for ova and parasites is the test of choice.
• • Mature oocysts measure 30 X 12 µm and have a thin translucent wall and 2 round sporocysts, each of which has 4 crescentic sporozoites.
  • Auramine-rhodamine fluorescent, modified Kinyoun acid-fast, hematoxylin/eosin, Giemsa, and/or carbol fuchsin staining may be helpful in identifying the translucent oocysts.
  • Oocysts autofluoresce under ultraviolet epifluorescence illumination using a 450- to 490-nm excitation filter.
  • Charcot-Leyden crystals and high fat content are often observed.
• CBC count may demonstrate mild peripheral eosinophilia in one half of patients.
• Serologic testing is not available.
• Electron microscopy may be helpful, but it is labor intensive and lacks specificity.

Imaging Studies

Double contrast barium upper GI series with small-bowel follow-through may be helpful.

• The severity of radiographic findings seems to depend on duration of illness and to correlate with the degree of villous atrophy noted on biopsy findings.
• Short-term disease (<1 y) seems to result in minimal or irregular thickening of mucosal folds.
• Long-term disease seems to correlate with markedly granular mucosal appearance with effacement of the folds.

Other Tests

• The Entero-Test (swallowed string test to provide a duodenal sample) may yield a positive specimen, if stool study results are negative.

Procedures

Upper GI endoscopy may provide useful specimens for examination, if the following test results are negative:

• Duodenal aspirate for ova and parasite examination
• Small bowel biopsy for histopathology

Histologic Findings

Histologic findings appear to correlate with the severity of the symptoms observed. Focal-to-widespread mucosal changes are associated with severe symptoms. In mild cases, the only findings may range from flattened villi to mild, nonspecific alterations and increased inflammatory cells in the lamina propria.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Although generally a self-limited infection, patients who are treated tend to improve in 2-3 days, whereas those who are not treated remain sick considerably longer. Immunocompetent hosts generally respond very rapidly to antiparasitic therapy, with symptomatic improvement within 5 days. The immunocompromised host also responds well, although less rapidly. However, these individuals relapse at a high rate (50% in 2 mo) once therapy is stopped. Thus, indefinite prophylaxis following therapy is recommended in this population. Therapy for dehydration may be the most urgent intervention required.

Consultations

Consultation with an infectious diseases specialist, a gastroenterologist, or both may be appropriate.

Diet

A standard diarrhea diet may be appropriate, until symptoms resolve.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Unlike many of the protozoal infections that cause similar diseases, effective therapies are available for isosporiasis.

Drug Category: Antiprotozoal agents

TMP-SMZ is the drug of choice because it is the best-studied and most readily available agent. Many patients with AIDS are already taking this agent as prophylaxis for Pneumocystis infection. An alternative for long-term prophylaxis is pyrimethamine with sulfadiazine or sulfadoxine (either of which should be accompanied by folinic acid). For patients who cannot tolerate sulfonamides, ciprofloxacin or pyrimethamine plus folinic acid may be nearly as effective for both acute treatment and prophylaxis. The US Food and Drug Administration considers all of these regimens investigational for this infection. Studies have proposed the veterinary agent diclazuril as a possible drug of choice if further studies confirm its use and safety.³ Doxycycline, roxithromycin, and nitazoxanide^{4, 5} are reported to have some efficacy, but only a few of these reports are available; thus, recommending these drugs is premature at present.

Drug Category: Vitamins

Folinic acid is a required supplement if pyrimethamine is used.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Only patients with chronic infection associated with severe dehydration should require continued inpatient care.

Transfer

• Transfer patients only if the required specialists and/or therapeutic measures are not available at the institution.

Deterrence/Prevention

• Emphasize avoidance of potentially contaminated food and water.
• Use appropriate isolation measures because shedding of oocysts may last for weeks.

Complications

• Severe dehydration is the most common complication and almost always occurs in patients who are very young or immunocompromised.
• Acalculous cholecystitis has been reported in patients with AIDS.
• Tissue invasion and dissemination has been reported on autopsy findings in a few patients with AIDS.
• Colitis in patients with AIDS has been rarely reported.
• Reactive arthritis is very unusual in the immunocompromised patient.

Prognosis

• Prognosis is excellent with therapy (and prophylaxis, if appropriate).

Patient Education

• Emphasize good hygiene and careful attention to possible exposure to contaminated food and water.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider the diagnosis in the appropriate setting
• Failure to explain the possibility of serious reactions to the medications used to treat the infection

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Feb 6, 2008