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5/27/2017 Disclosure Emerging Infections: historical perspectives, precipitating factors, and pathologic diagnosis I have nothing to disclose. Except that my silly dogs will Laura W. Lamps M.D. feature prominently Godfrey D. Stobbe


  1. 5/27/2017 Disclosure Emerging Infections: historical perspectives, precipitating factors, and pathologic diagnosis • I have nothing to disclose. Except that my silly dogs will Laura W. Lamps M.D. feature prominently Godfrey D. Stobbe Professor of Gastrointestinal Pathology in this lecture. University of Michigan Department of Pathology Patient Safety Officer, Michigan Medicine What we are going to do today What is an “emerging” infectious disease? • Introduction • (1) A totally new or previously unrecognized – What is an emerging infectious disease? organism: – Risk/probability matrix in pathology – HIV • Case examples – Probably crossed species in 1920s • Revisit risk/probability in pathology and why – Virus characterized in 1980s – Hepatitis C (1988) we should study rare things – Hantavirus (1993) – SARS (2003) 1

  2. 5/27/2017 What is an “emerging” infectious disease? What is an “emerging” infectious disease? • (3) A known pathogen that has undergone changes such that it is • (2) A previously recognized organism that has increasing in incidence or geographic been recently identified as a true pathogen: range: – H. pylori – Basidiobolomycosis (unknown) – Aeromonas spp – Schistosomiasis (dam building) – Lyme disease (reforestation favoring ticks and deer near homes) – Cryptosporidium (contaminated surface water, faulty water purification) Factors that contribute to “emerging” Vulnerable Host Populations infectious diseases Who is immunocompromised? • Antibiotic resistance • AIDS • New (permissive) environment • Chemotherapy – Transportation, travel, migration • Solid organ and bone marrow – Urbanization with new exposure to pathogens transplants or vectors – Food/water contamination • New (vulnerable) host population – Immune deficiency 2

  3. 5/27/2017 Vulnerable Host Populations Vulnerable Host Populations Who is immunocompromised? Who is immunocompromised? • Elderly patients • Diabetics • Young children • Patients without spleens • Patients with CIIBD, autoimmune • Chronic alcoholism disease on chronic immunomodulator • Malnutrition therapy • Any chronic debilitating disease • Corticosteroid use My Favorite Question Risk/Probability Matrix • Why should I study infectious diseases? We • Probabilistic risk assessment (PRA) is a tool never see them. used to define the potential impact of an – A. So you only study the things you might see occurrence, activity or action. Risk is regularly? Like hernia sacs? characterized by two things: – B. Either that, or you do see them but you don’t – Likelihood ( probability ) each consequence recognize them. actually happening – C. I guess I’ll just go home then. – Magnitude (severity) of the possible adverse – D. All of the above. consequence(s) 3

  4. 5/27/2017 Heart Minor attack drug reaction Lung SCC in a H. pylori smoker infection Viral pandemic Many of the cases for Risk impact/probability chart Risk impact/probability chart discussion today Give us the Case Example #1 chicken. We’ll check it for Salmonella. • A 45 year old migrant worker, currently employed in Arizona, presented with severe abdominal pain. Imaging studies showed a large near-obstructing colonic/pericolonic mass that was suspicious for malignancy. A segmental resection was performed. 4

  5. 5/27/2017 Prominent eosinophils Extensive necrosis Granulomas 5

  6. 5/27/2017 Organisms are rare, not angioinvasive, and associated with Splendore-Hoeppli material 6

  7. 5/27/2017 Emerging Infection: Basidiobolomycosis Gastrointestinal Basidiobolomycosis • Basidiobolus ranarum , closely related to • GI cases can mimic malignancy, Mucormycosis (Entomophthorales) idiopathic inflammatory bowel disease • Worldwide soil saprophyte – Until recently, primarily considered a • Most cases respond to long-term subcutaneous infection (site changing) antifungal therapy, but colonic – Most cases reported in Saudi Arabia, Africa, perforation, dissemination, and death South America; current cohort of cases in are well-documented Arizona (geography changing) Basidiobolomycosis Low probability, high impact event • We report here the case of a 55-year-old man from Mali, who • Vulnerable populations: presented with abdominal pain. Radiological exploration revealed an ileo-colonic mass surrounding the appendix. A biopsy was taken – Children and on histology, transmural granulomatous inflammation of numerous eosinophils, lymphocytes, plasmocytes and giant cells – Peptic ulcer disease was seen. Tuberculosis was suspected clinically and an antibiotic treatment was initiated. Two months later, the patient died of – Diabetes septic complications. Basidiobolus ranarum was identified by PCR. Pathogens were retrospectively highlighted on biopsies. Gastro- – Pica intestinal basidiobolomycosis is rare and presents considerable diagnostic difficulty. This infection needs to be diagnosed because – Ranitidine use surgical resection and prolonged antifungal treatment are curable in most cases. – Living in an endemic area Cazorla et al. Ann Pathol 2014;34:228-32 7

  8. 5/27/2017 Mucor vs. Basidiobolomycosis GI Mucormycosis Mucor Basidiobolomycosis • Often caused by colonization of ulcers • Angioinvasive • Not angioinvasive • Abundant organisms • Fewer organisms • Stomach and colon are most frequently • No Splendore-Hoeppli • Splendore-Hoeppli involved sites • Necrosis • Necrosis and granulomas • Ulcers often have heaped-up, rolled • Not eosinophilic • Markedly eosinophilic edges that mimic malignancy grossly • Diabetics, ketoacidosis • Farm workers, desert dwellers • Pathologic features very similar to aspergillosis 8

  9. 5/27/2017 Summary • Basidiobolomycosis resembles mucormycosis, but is not angioinvasive and has a different tissue reaction • Suspect in patients from endemic areas with paracolonic masses • Patients often not immunocompromised • Mucor in the sinonasal tract is a medical emergency 9

  10. 5/27/2017 Alys searches for soil saprophytes . Case Example #2 • A 25 year old Chinese exchange student presented with diarrhea and lower GI bleeding. CT scan showed a thickened colon and liver lesions. Colonoscopy showed areas of friable mucosa. Biopsies were obtained. 10

  11. 5/27/2017 Emerging Infection : Penicillium marneffei • Dimorphic fungus • Endemic in Southeast Asia and Far Eastern Asia • Most commonly involves lungs and liver, followed by GI tract 11

  12. 5/27/2017 Emerging Infection : Penicillium P. marneffei marneffei • Inflammatory response is • Yeast forms are septate ( “ pill capsule ” ) • Now one of the most common granulomatous, suppurative, or mixed opportunistic infections in Asian patients with AIDS and similar to histoplasmosis, but they – Occasional elongated “ sausage ” forms – Travel/immigration do not bud – Immunocompromise with prominent septum • Require months of antifungal therapy, and dissemination can be rapidly fatal Low probability, high impact event • Results: A total of 47 AIDS-associated penicilliosis were confirmed by fungal culture, which accounted for 4.8% of 981 AIDS-related admissions. Two independent predictors for early mortality (death within 12 weeks) of the patients (21.3%, 10/47) were a delayed diagnosis and no treatment with antifungal therapy. Zheng et al. A clinical study of AIDS-associated Penicillium marneffei infection from a non-endemic area in China. PLoS One June 17 2015 Courtesy Dr. David Walker 12

  13. 5/27/2017 Characteristics of Yeast in Tissue Sections Fungus Exposure Histology Stains Histoplasma Ohio/MS river Uniformly small oval pointed pole; “ Halo ” in GMS capsulatum valleys yeast with buds at PAS tissue Usually in macrophages P. marnefeii Asia Small nonbudding GMS septated yeast PAS Cryptococcus Worldwide Variably sized yeast GMS, PAS neoformans with narrow based Melanin buds Mucicarmine Blastomyces Ohio and MS river Large yeast with broad GMS dermatitidis valleys based buds PAS Great Lakes Gram negative NW Ontario Candida torulopsis Worldwide Small budding yeast GMS, PAS Often extracellular No hyphae Courtesy Dr. Rodger Haggitt 13

  14. 5/27/2017 Courtesy Dr. Brian West 14

  15. 5/27/2017 Summary • P. marneffei is now one of the most common infectious diseases among Asian AIDS patients • Given travel and immigration, seen more and more in the USA • Must be distinguished from other small intracellular fungi We see you have bacon. We also enjoy bacon. Case Example #3 • A 46 year old HIV-positive man presented with fever and weight loss. • CT scan showed mesenteric lymphadenopathy. A mesenteric lymph node biopsy was performed. 15

  16. 5/27/2017 Mycobacteria-associated (MAI) spindle cell nodule Emerging Infection: Atypical (non- Atypical (non-Tubercular) Mycobacteria Tubercular) Mycobacteria • Tremendous geographic variability • Ubiquitous soil, milk, food, and water • Increasing in patients without AIDS inhabitants • Increasing in patient populations with • Four major groups that cause infections chronic pulmonary disease, all over the body immunosuppressive medications and • MAI is most commonly encountered comorbid diseases – 25% of patients in one large study had no known risk factors 16

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