Isospora Belli

Gastrointestinal Pathology Evening Specialty Conference March 17, 2016 Laura W. Lamps, MD Professor and Vice Chair of Academic Affairs University of Arkansas for Medical Sciences Little Rock, AR Clinical Summary • 40 year old woman with HIV – Undetectable viral loads for more than 15 years • 15 month history of episodic nausea, vomiting, diarrhea – Some episodes resolved spontaneously – Others severe, requiring hospitalization for dehydration Clinical Summary • Patient originally from Ethiopia, occasionally traveled there – Lived in Western US for many years – Symptoms do not correlate with travel • Previous EGD/colonoscopy normal x2; normal capsule endoscopy Clinical Summary Laboratory Data • Peripheral eosinophilia • Stool O&P repeatedly negative • Positive Strongyloides antibody; all other infectious disease serologies negative Diagnosis: Cystoisosporiasis Cystoisosporiasis • Cystoisospora belli (formerly Isospora belli) • Obligate intracellular coccidian parasite with worldwide distribution – Especially common in tropical/subtropical climates – Ubiquitous in animal kingdom – Transmission through food, water Cystoisosporiasis • Originally described in soldiers during WWI and WWII • Rare in USA prior to AIDS epidemic – Prevalence in Western countries ~ 5% – Prevalence in developing countries ~10‐15% Cystoisosporiasis Life cycle • Complex to say the least – Ingestion, followed by excystation and invasion – Asexual division produces more organisms that infect more cells – Some enter the sexual phase, develop male and female gametes, fertilization occurs, oocysts released into the lumen – Sexual forms can autoinfect or pass in the stool to continue the cycle Cystoisospora Life Cycle http://www.cdc.gov/dpdx/cystoisosporiasis/ Cystoisosporiasis Clinical • Immunocompetent patients – Typically asymptomatic diarrheal infections • Immune compromised patients – Watery nonbloody diarrhea, dehydration – Abdominal pain – Nausea, vomiting – Fever, malaise Cystoisosporiasis Clinical • Infection more severe in immunocompromised patients – Severe malabsorption, dehydration, cachexia, dissemination – Many cases respond to antiobiotics (Bactrim), so important to recognize infection Cystoisosporiasis Clinical • Peripheral eosinophilia common – Charcot‐Leyden crystals may be seen in stool • EGD/colonoscopy usually normal – Occasionally mild erythema • Stool studies – Usually not helpful unless special stains requested Variably present villous blunting, surface disarray, increased IELs Eosinophils usually prominent in GI specimens but not biliary Parasitophorous vacuole is characteristic PAS Giemsa Cystoisospora Biliary infection • Symptomatic cholangitis, typically in AIDS patients • Reported in gallbladders from liver donors, cholecystectomy for biliary dyskinesia in otherwise healthy patients – Often minimal tissue reaction Courtesy Dr. Keith Lai Diagnosis • Light microscopy • Stool O&P – Sensitivity/specificity variable depending on technique (40‐100%; 88‐100%) • Acid fast stains, antigen detection techniques • PCR from stool – 87‐100% sensitivity; 88‐100% specificity Differential Diagnosis • Other things that cause villous blunting +/‐ eosinophils – Celiac disease – Idiopathic eosinophilic enteritis – Adverse drug effect – Food allergy Idiopathic eosinophilic enteritis Olmesartan toxicity Differential Diagnosis • Other coccidians • Other intracellular organisms – Will almost always be within macrophages, and not at the luminal surface of the epithelium • Leishmania • Toxoplasmosis • Fungi (Histoplasmosis, P. marneffei) Comparison of Enteric “Coccidians*” Feature Microsporidia Cryptosporidia Cyclospora Cystoisospora Size 2‐3µ (smallest) 2‐5 µ 2‐3µ schizonts 15‐20µ (largest) 5‐6µ merozoites Location Epithelial cells Apical surface Upper epithelium Epithelium Macrophages Staining Mod trichrome Giemsa Acid fast Giemsa Giemsa Gram Auramine Gram Gram PAS W‐S GMS PAS Other Birefringent under Bulges out of Parasitophorous Parasitophorous polarized light luminal apex of vacuole vacuole enterocyte Eosinophils *Microsporidia are now classified as fungi *Cryptosporidia are still parasites, but Gregorines, not coccidia Cryptosporidium Microsporidia Modified trichrome stain highlights organisms Cyclospora: surface epithelial cell disarray Case and pictures courtesy of Dr Rhonda Yantiss Round schizonts and banana shaped merozoites in parasitophorous vacuoles Differential Diagnosis • Other coccidians • Other intracellular organisms – Will almost always be within macrophages, and not at the luminal surface of the epithelium • Leishmania • Toxoplasmosis • Fungi (Histoplasmosis, P. marneffei) P. marneffei Histoplasmosis Summary/Take Home • Cystoisospora is the largest coccidian, but easily missed – Associated histologic findings may be subtle, so remember to look for them • They are treatable with antibiotics • Not limited to immunocompromised patients • Stool studies can be helpful .

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