Infectious Disease · PANCE / PANRE

Cryptosporidiosis

Apicomplexan protozoan diarrheal illness (Cryptosporidium spp.) — self-limited in healthy hosts, devastating in advanced HIV.

Also known as: cryptosporidiosis, Cryptosporidium, Crypto

Overview

Diarrheal disease caused by Cryptosporidium parvum and C. hominis, apicomplexan protozoa that infect intestinal epithelium. Chlorine-resistant oocysts are infectious immediately upon shedding.

Epidemiology

~750,000 US cases annually (CDC estimates). Leading cause of recreational water outbreaks (chlorine-resistant). Worldwide major cause of childhood diarrhea mortality in low-income settings. Children, daycare attendees, and immunocompromised most affected.

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Risk factors

  • Recreational water exposure (pools, water parks, lakes)
  • Drinking untreated surface water
  • Daycare attendance
  • Animal contact (especially calves, sheep, goats — petting zoos)
  • International travel
  • Immunocompromise: HIV with CD4 <100 — severe chronic disease
  • MSM (oral-anal contact)

Pathophysiology

Oocysts ingested → sporozoites released in small bowel → invade intestinal epithelium and develop within parasitophorous vacuoles. Cause villous blunting, secretory diarrhea, and inflammation. Cell-mediated immunity is critical for clearance — defective in advanced HIV → unrelenting chronic infection. Biliary tract, pancreas, and respiratory epithelium can be involved in immunocompromised hosts.

Clinical presentation

Symptoms

  • Incubation 2-10 days
  • Profuse watery, non-bloody diarrhea (often described as 'cholera-like')
  • Abdominal cramping, nausea, vomiting, low-grade fever
  • Self-limited in immunocompetent hosts (7-14 days)
  • AIDS (CD4 <100): chronic high-volume diarrhea (>1-25 L/day), severe wasting, dehydration, malabsorption
  • Biliary cryptosporidiosis (AIDS): right upper quadrant pain, jaundice, sclerosing cholangitis

Signs / physical exam

  • Dehydration signs (tachycardia, dry mucous membranes, decreased turgor, orthostasis)
  • Diffuse abdominal tenderness
  • Significant weight loss in chronic infection

Classic findings

Outbreak of watery diarrhea after swimming at a water park — cryptosporidium until proven otherwise. AIDS patient with CD4 <50 and chronic watery diarrhea — also high suspicion.

Differential diagnosis

  • Giardiasis — Greasy malodorous diarrhea, bloating; stool antigen
  • Cyclospora cayetanensis — Imported produce (berries, basil), prolonged diarrhea; TMP-SMX responsive
  • Microsporidiosis — AIDS-associated chronic diarrhea; modified trichrome stain
  • Isospora belli (Cystoisospora) — AIDS-associated, oocysts on acid-fast stain; TMP-SMX responsive
  • Norovirus — Acute, shorter duration, vomiting prominent
  • C. difficile — Recent antibiotic use, healthcare exposure
  • Bacterial enteritis (Salmonella, Campylobacter, Shigella) — Often bloody, fever; stool culture

Diagnostic workup

Diagnostic criteria

Detection of Cryptosporidium oocysts, antigen, or DNA in stool.

Labs

  • Stool antigen (EIA or rapid immunoassay) — sensitive and specific
  • Stool PCR (GI multiplex panels)
  • Modified acid-fast stain on stool — characteristic acid-fast oocysts (4-6 micrometer)
  • Stool O&P insensitive (oocysts small and easily missed without special stain)
  • Consider HIV testing in any adult with severe or prolonged crypto

Imaging

  • Generally not required
  • RUQ ultrasound or MRCP if biliary involvement suspected in AIDS

Diagnostic algorithm

PathogenAcid-fast stainTreatmentDistinctive
CryptosporidiumPositive (4-6 um)Nitazoxanide; ART in HIVPool/water outbreaks; chlorine-resistant
Cyclospora cayetanensisPositive (8-10 um)TMP-SMXImported berries/basil; UV autofluorescence
Cystoisospora belliPositive (large oval oocyst)TMP-SMXAIDS-associated chronic diarrhea
MicrosporidiaNegative (modified trichrome)Albendazole or fumagillinAIDS; small intracellular spores
Acid-fast intestinal protozoa: distinguishing features and treatment.

Treatment

First-line

  • Immunocompetent: supportive care — oral or IV rehydration, antimotility agents (loperamide) for symptom relief
  • Nitazoxanide 500 mg PO BID × 3 days — FDA-approved (modest benefit; better in immunocompetent than immunocompromised)
  • Pediatric nitazoxanide suspension (age-based dosing) for ages ≥1 year
  • AIDS: most important intervention is antiretroviral therapy to restore CD4 — immune restoration is the only reliable cure
  • Nitazoxanide as adjunct in HIV (limited efficacy without immune restoration)

Second-line / adjunct

  • Combination therapy (nitazoxanide + paromomycin + azithromycin) — anecdotal use in refractory AIDS-associated disease
  • Symptomatic and nutritional support
  • Avoid loperamide in severe or prolonged disease without clearance

Complications

  • Severe dehydration, electrolyte abnormalities, AKI
  • Malabsorption, wasting in chronic HIV-associated disease
  • Sclerosing cholangitis, acalculous cholecystitis (AIDS)
  • Pancreatitis (AIDS)
  • Respiratory involvement in severe immunocompromise
  • Reactive arthritis

PANCE pearls

  • Cryptosporidium oocysts are CHLORINE-RESISTANT — recreational water outbreaks remain a major source despite standard pool chlorination. Hyperchlorination or UV needed.
  • Acid-fast oocysts on stool: Cryptosporidium, Cyclospora, Cystoisospora — 'CCC' acid-fast trio.
  • AIDS-related cryptosporidiosis: ART (restoring CD4 >100) is the most effective therapy. Anti-cryptosporidial drugs alone rarely cure.
  • Suspect biliary cryptosporidiosis in HIV with RUQ pain — MRCP shows beaded bile ducts (sclerosing cholangitis pattern).
  • Public health: report outbreaks; advise infected persons not to swim for 2 weeks after symptom resolution.

References

  • CDC — Cryptosporidiosis: Diagnosis and Treatment Information for Public Health and Medical Professionals
  • DHHS OI — Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV — Cryptosporidiosis section
  • IDSA 2017 — Shane et al., Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea (Clin Infect Dis)

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Differentials & related conditions

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