eMedicine Specialties > Pediatrics: General Medicine > Parasitology

Isosporiasis

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Updated: Jan 22, 2009

Introduction

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

History

Typically, patients with isosporiasis 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 continue indefinitely.

• 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.

Differential Diagnoses

Other Problems to Be Considered

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

Workup

Laboratory Studies

• Stool examination for ova and parasites is the test of choice for isosporiasis.
  • 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 reveal 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

Medical Care

Although generally a self-limited infection, patients with isosporiasis 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

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

Antiprotozoal agents

Trimethoprim-sulfamethoxazole (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.

Sulfamethoxazole and trimethoprim (Bactrim, Septra, Cotrim)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. DOC and curative in the immunocompetent host. Can be used for treatment and then ongoing prophylaxis in the immunocompromised host.

Dosing

Adult

160 mg TMP/800 mg SMZ PO qid (ie, 1 double-strength [DS] tab qid) for 10 d; then bid for 21 d (2 wk may suffice in immunocompetent patient)
Posttreatment prophylaxis: 160 mg TMP/800 mg SMZ PO qd (3 times/wk may also suffice)

Pediatric

<2 months: Contraindicated
>2 months:
5 mg/kg (based on TMP component) PO tid for 10 d; then bid for 2 wk; not to exceed 160 mg TMP/800 mg SMZ (ie, 1 DS tab) per dose
Posttreatment prophylaxis: 5 mg/kg (based on TMP component) PO qd (3 times/wk may also suffice); not to exceed 1 DS tab/d

Interactions

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases prevalence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency; age <2 mo

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use near term in pregnancy because of possible kernicterus in newborns; possible blood dyscrasias, crystalluria, glossitis, renal or hepatic injury, gastrointestinal irritation, rash, Stevens-Johnson syndrome, and hemolysis with G-6-PD deficiency; reduce dose in renal impairment

Pyrimethamine (Daraprim)

The second DOC and particularly useful for those who cannot tolerate sulfonamides. It can also be used for prophylaxis, when combined with sulfadiazine or sulfadoxine. Administer with folinic acid to prevent hematologic toxicities.

Dosing

Adult

75 mg PO qd for 21 d
Posttreatment prophylaxis: 25 mg PO qd

Pediatric

Not established

Interactions

Concurrent use of antifolate medications (eg, methotrexate, pyrimethamine) may increase risk of bone marrow suppression, discontinue pyrimethamine therapy if signs of folate deficiency develop; coadministration with lorazepam may cause mild hepatotoxicity

Contraindications

Documented hypersensitivity; megaloblastic anemia resulting from a folate deficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

If signs of folate deficiency develop, reduce dose or discontinue drug, depending on patient response; caution in hepatic or renal impairment; monitor for toxoplasmosis by performing semiweekly blood counts, including platelet counts; may precipitate hemolytic anemia in G-6-PD deficiency, generally in the presence of other stressful events

Sulfadoxine and pyrimethamine (Fansidar)

Acts by reciprocal potentiation of its 2 components, achieved by a sequential blockade of 2 enzymes involved in the biosynthesis of folinic acid within the parasites. In patients not allergic to sulfonamides, can be an alternative to TMP-SMZ for long-term prophylaxis. Administer with folinic acid to prevent hematologic toxicities. Contains sulfadiazine 500 mg and pyrimethamine 25 mg per tab.

Dosing

Adult

500 mg sulfadiazine/25 mg pyrimethamine PO qwk

Pediatric

Not established

Interactions

Sulfadoxine component is highly protein bound and may displace warfarin that is protein bound, thus increasing INR; coadministration with other folic acid antagonists (eg, methotrexate, TMP-SMZ, dapsone) increases potential for hematologic toxicities

Contraindications

Documented hypersensitivity; megaloblastic anemia resulting from a folate deficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use near term in pregnancy because of risk of kernicterus in newborn; caution in premature infants and infants <2 mo (risk of hyperbilirubinemia); caution in hepatic or renal dysfunction (30-44% eliminated in urine); maintain hydration; possible fever, rash, hepatitis, systemic lupus erythematosus–like syndrome, vasculitis, bone marrow suppression, and hemolysis with G-6-PD deficiency and Stevens-Johnson syndrome; for pyrimethamine component, possible glossitis, seizures, rash, and photosensitivity

Diclazuril (Clinacox)

Investigational in the United States. This benzene acetonitrile derivative is a veterinary antiparasitic that has shown good safety and efficacy in a small number of studies involving a small number of humans. Clinical trials have been completed for use in patients with AIDS and cryptosporidial-related diarrhea. May become the DOC if further studies confirm these preliminary findings.

Dosing

Adult

300 mg PO bid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Limited data available; none reported

Vitamins

Folinic acid is a required supplement if pyrimethamine is used.

Leucovorin (Wellcovorin)

Also called folinic acid. Reduced form of folic acid that does not require enzymatic reduction reaction for activation. Allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis. Important cofactor for enzymes used in production of RBCs. Daily supplementation is required if pyrimethamine therapy is used.

Dosing

Adult

5-10 mg PO qd

Pediatric

Not established

Interactions

Decreases effect of methotrexate, phenytoin, phenobarbital, and TMP-SMZ combinations; increases toxicity of fluorouracil

Contraindications

Documented hypersensitivity; pernicious anemia; vitamin-deficient megaloblastic anemias

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Resistance to treatment may occur in patients with alcoholism and deficiencies of other vitamins

Follow-up

Further Inpatient Care

• Only patients with chronic isosporiasis 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

Medicolegal Pitfalls

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

References

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Keywords

isosporiasis, Apicomplexa coccidia protozoan, dehydration, diarrhea, foul-smelling flatus, gastrointestinal infection, GI infection, Isospora, Isospora belli, I belli, I belli disease, I belli infection, parasitic infection, steatorrhea

Contributor Information and Disclosures

Author

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Medical Editor

Glenn J Fennelly, MD, MPH, Director, Division of Pediatric Infectious Diseases, Jacobi Medical Center; Associate Professor, Department of Pediatrics, Albert Einstein College of Medicine
Glenn J Fennelly, MD, MPH is a member of the following medical societies: Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Martin Weisse, MD, Program Director, Associate Professor, Department of Pediatrics, West Virginia University
Martin Weisse, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

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