Kareem Walid Shehab

Interests

Research

Molecular epidemiology of Clostridium difficile infection and colonization, pediatric coccidioidomycosis. Undergraduate medical education, graduate medical education.

Teaching

Medical student education in medical microbiology, clinical problem-solving, clinical infectious diseases, and pediatrics.

Courses

Scholarly Contributions

Chapters

• Shehab, K. W., & Shehab, Z. M. (2018). Coccidioidomycosis. In Feigin and Cherry's Textbook of Pediatric Infectious Diseases. Elsevier.

Journals/Publications

• Anwar, F., Clark, M., Lindsey, J., Claus-Walker, R., Mansoor, A., Nguyen, E., Billy, J., Lainhart, W., Shehab, K., Viswanathan, V. K., & Vedantam, G. (2023). Prevalence of diagnostically-discrepant clinical specimens: insights from longitudinal surveillance. Frontiers in medicine, 10, 1238159.
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  Infection (CDI) is a healthcare-associated diarrheal disease prevalent worldwide. A common diagnostic algorithm relies on a two-step protocol that employs stool enzyme immunoassays (EIAs) to detect the pathogen, and its toxins, respectively. Active CDI is deemed less likely when the Toxin EIA result is negative, even if the pathogen-specific EIA is positive for We recently reported, however, that low-toxin-producing strains recovered from Toxin-negative ('discrepant') clinical stool specimens can be fully pathogenic, and cause lethality in a rodent CDI model. To document frequency of discrepant CDI specimens, and evaluate strain diversity, we performed longitudinal surveillance at a Southern Arizona tertiary-care hospital.
• Vedantam, G., Viswanathan, V., Shehab, K. W., Lainhart, W. D., Billy, J., Nguyen, E., Mansoor, A., Claus-Walker, R., Lindsey, J., Clark, M., & Anwar, F. (2023). Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance. Frontiers in Medicine, 10. doi:10.3398/fmed.2023.1238159
• Anwar, F., Roxas, B. A., Shehab, K. W., Ampel, N. M., Viswanathan, V. K., & Vedantam, G. (2022). Low-toxin RT027 strains exhibit robust virulence. Emerging microbes & infections, 11(1), 1982-1993.
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  is a leading cause of healthcare-associated infections worldwide. Currently, there is a lack of consensus for an optimal diagnostic method for infection (CDI). Multi-step diagnostic algorithms use enzyme immunosorbent analysis (EIA)-based detection of toxins TcdA/TcdB in stool, premised on the rationale that EIA toxin-negative (Tox) patients have less severe disease and shorter diarrhoea duration. The aim of this study was to characterize toxigenic (i.e. -positive) strains isolated from diarrheic patient stool with an EIA Tox (i.e. "discrepant") CDI diagnostic test result. Recovered strains were DNA fingerprinted (ribotyped), subjected to multiple toxin, genome and proteome evaluations, and assessed for virulence. Overall, of 1243 -positive patient stool specimens from Southern Arizona hospitals, 31% were discrepant. For RT027 (the most prevalent ribotype)-containing specimens, 34% were discrepant; the corresponding RT027 isolates were cytotoxic to cultured fibroblasts, but their total toxin levels were comparable to, or lower than, the historic low-toxin-producing strain CD630. Nevertheless, these low-toxin RT027 strains (LT-027) exhibited similar lethality to a clade-matched high-toxin RT027 strain in Golden Syrian hamsters, and heightened colonization and persistence in mice. Genomics and proteomics analyses of LT-027 strains identified unique genes and altered protein abundances, respectively, relative to high-toxin RT027 strains. Collectively, our data highlight the robust virulence of LT-027 , provide a strong argument for reconsidering the clinical significance of a Tox EIA result, and underscore the potential limitations of current diagnostic protocols.
• Roxas, B. A., Roxas, J. L., Claus-Walker, R., Harishankar, A., Mansoor, A., Anwar, F., Jillella, S., Williams, A., Lindsey, J., Elliott, S. P., Shehab, K. W., Viswanathan, V. K., & Vedantam, G. (2020). Phylogenomic analysis of Clostridioides difficile ribotype 106 strains reveals novel genetic islands and emergent phenotypes. Scientific reports, 10(1), 22135.
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  Clostridioides difficile infection (CDI) is a major healthcare-associated diarrheal disease. Consistent with trends across the United States, C. difficile RT106 was the second-most prevalent molecular type in our surveillance in Arizona from 2015 to 2018. A representative RT106 strain displayed robust virulence and 100% lethality in the hamster model of acute CDI. We identified a unique 46 KB genomic island (GI1) in all RT106 strains sequenced to date, including those in public databases. GI1 was not found in its entirety in any other C. difficile clade, or indeed, in any other microbial genome; however, smaller segments were detected in Enterococcus faecium strains. Molecular clock analyses suggested that GI1 was horizontally acquired and sequentially assembled over time. GI1 encodes homologs of VanZ and a SrtB-anchored collagen-binding adhesin, and correspondingly, all tested RT106 strains had increased teicoplanin resistance, and a majority displayed collagen-dependent biofilm formation. Two additional genomic islands (GI2 and GI3) were also present in a subset of RT106 strains. All three islands are predicted to encode mobile genetic elements as well as virulence factors. Emergent phenotypes associated with these genetic islands may have contributed to the relatively rapid expansion of RT106 in US healthcare and community settings.
• Wheat, J., Myint, T., Guo, Y., Kemmer, P., Hage, C., Terry, C., Azar, M. M., Riddell, J., Ender, P., Chen, S., Shehab, K., Cleveland, K., Esguerra, E., Johnson, J., Wright, P., Douglas, V., Vergidis, P., Ooi, W., Baddley, J., , Bamberger, D., et al. (2018). Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment. Medicine, 97(13), e0245.
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  Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.
• Katsanis, E., Shehab, K. W., Meyer, R., & Riley, G. (2017). Successful resolution of hyperammonemia following hematopoietic cell transplantation with directed treatment of Ureaplasma parvum infection. Transplant Infectious Disease.
• Larmonier, C. B., Laubitz, D., Hill, F. M., Shehab, K. W., Lipinski, L., Midura-Kiela, M. T., McFadden, R. M., Ramalingam, R., Hassan, K. A., Golebiewski, M., Besselsen, D. G., Ghishan, F. K., & Kiela, P. R. (2013). Reduced colonic microbial diversity is associated with colitis in NHE3-deficient mice. American journal of physiology. Gastrointestinal and liver physiology, 305(10), G667-77.
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  Chronic inflammation and enteric infections are frequently associated with epithelial Na(+)/H(+) exchange (NHE) inhibition. Alterations in electrolyte transport and in mucosal pH associated with inflammation may represent a key mechanism leading to changes in the intestinal microbial composition. NHE3 expression is essential for the maintenance of the epithelial barrier function. NHE3(-/-) mice develop spontaneous distal chronic colitis and are highly susceptible to dextran sulfate (DSS)-induced mucosal injury. Spontaneous colitis is reduced with broad-spectrum antibiotics treatment, thus highlighting the importance of the microbiota composition in NHE3 deficiency-mediated colitis. We herein characterized the colonic microbiome of wild-type (WT) and NHE3(-/-) mice housed in a conventional environment using 454 pyrosequencing. We demonstrated a significant decrease in the phylogenetic diversity of the luminal and mucosal microbiota of conventional NHE3(-/-) mice compared with WT. Rederivation of NHE3(-/-) mice from conventional to a barrier facility eliminated the signs of colitis and decreased DSS susceptibility. Reintroduction of the conventional microflora into WT and NHE3(-/-) mice from the barrier facility resulted in the restoration of the symptoms initially described in the conventional environment. Interestingly, qPCR analysis of the microbiota composition in mice kept in the barrier facility compared with reconventionalized mice showed a significant reduction of Clostridia classes IV and XIVa. Therefore, the gut microbiome plays a prominent role in the pathogenesis of colitis in NHE3(-/-) mice, and, reciprocally, NHE3 also plays a critical role in shaping the gut microbiota. NHE3 deficiency may be a critical contributor to dysbiosis observed in patients with inflammatory bowel disease.
• Shehab, K. W., & Banaei, N. (2012). Unexplained Fever After a Camping Trip in the American Southwest. Journal of the Pediatric Infectious Diseases Society, 1(3), 254-5.

Presentations

• Lee, J., Gronenberg, L., Weber, G., Weinberger, K., Oatman, K., Ramirez-Moreno, E., Borgstrom, M., Chen, N., & Shehab, K. W. (2022). A Jeopardy Style Review for Third Year Medical Student NBME Pediatric Subject Examination Preparation. University of Arizona Research Day. Tucson, AZ.

Poster Presentations

• Valdez, J., Yrun-Duffy, M., Lee, J., Pryor, D., Kracht, M., Gronenberg, L., Robinson, K., Borgstrom, M., Chen, N., & Shehab, K. W. (2023, February). NBME Pediatric Exam Preparation and Outcome: A Jeopardy Style Review for Third Year Medical Students. Innovations of Medical Education Virtual Conference. Virtual: USC - Keck School of Medicine.
• Shehab, K. W., Chen, N., & Maler, P. (2022, Spring). PALMS AND SOLES RASH ON THE PEDIATRIC WARDS: HORSE, ZEBRA, OR...RAT?. Society of Hospital Medicine ConvergeSociety of Hospital Medicine.
• Shehab, K. W., Chen, N., Borgstrom, M., Ramirez-Moreno, E., Oatman, K., Weinberger, K., Weber, G., Gronenberg, L., & Lee, J. (2022, July). A Jeopardy Style Review for Third Year Medical Students NBME Pediatric Subject Examination Preparation. Pediatric Hospital Medicine 2022. Lake Buena Vista, Fl.
• Cramer, N., & Shehab, K. W. (2016, October 2016). Pediatric Infectious Diseases 2 Go!. American Academy of Pediatrics National Conference and Exhibition. San Francisco, CA.
• Mansoor, A., Shehab, K. W., Anwar, F., Viswanathan, V., & Vedantam, G. (2016, July 2016). Active Clostridium difficile Infection Surveillance in a Large Tertiary Medical Center Reveals Significant Strain Variation. Anaerobe Society of the Americas Biennial Meeting. Nashville, TN.