An adult patient with no significant past medical history presented to the emergency room one day after arriving from a one-month stay outside of the United States. They had a fever for approximately 10 days. At the ER, their temperature measured over 102 degrees Fahrenheit. They also complained of nausea, cough, and headache. However, they denied abdominal pain, vomiting, neck pain, diarrhea, constipation, or urinary symptoms. The attending physician ordered a urinalysis, viral panel, dengue serology, malarial blood smear, urine culture, and blood culture. The urinalysis was consistent with a UTI and the patient was discharged with ceftriaxone.
The respiratory viral panel (RSV, Influenza A/B, SARS-CoV-2), malarial blood smear, urine culture, and dengue fever serology came back negative the next day. However, the Gram stain from the blood showed gram negative rods (Image 1) with concurrent bacterial growth on the blood, chocolate, and MacConkey agars. No growth was present on the CNA agar (Image 2).
Multiplex PCR from positive blood culture and later MALDI of the pure isolate confirmed the Salmonella organism, which was later serotyped via a Salmonella Rapid Latex Agglutination Test Kit as Salmonella typhi. Susceptibility testing revealed that the organism was susceptible to Ceftriaxone and the patient was treated accordingly.
The Salmonella genus is divided into two species: Salmonella bongori and Salmonella enterica. The Salmonella species can be further divided into the following subspecies: enterica (group I), salamae (group II), arizonae (group IIIa), diarizonae (group IIIb), houtenae (group IV), indica (group VI). To complicate matters more, these subspecies may be further classified based on their serotype.1 Salmonella can be serotyped based on their O, H, and Vi antigens.2 As a whole, the Salmonella enterica sub enterica (group I) are gram negative rods that belong to the Enterobacteriales family. They are highly motile, facultative anaerobes that produce H2S and do not ferment lactose. We will be primarily focusing on the non-typhoidal Salmonella and typhoidal Salmonella subspecies.
The non-typhoidal Salmonella organism resides within the enteric tracts of humans and animals. They primarily cause infection via the feco-oral route via contaminated poultry, eggs, and meat products. These organisms are very sensitive to stomach acid; therefore, an abundant inoculation must take place within the gastrointestinal tract. The mucosa is invaded and becomes inflamed. The subsequent increase in prostaglandins and cAMP cause the patient to experience loose diarrhea.2 Shallow ulcerations may be present on histology. Non-typhoidal Salmonella most commonly causes gastroenteritis consisting of bloody diarrhea, fever, vomiting, and abdominal pain. Bacteremia may occur in approximately 5% of patients. In addition, sickle cell patients are at risk of developing osteomyelitis. The diagnosis is made through a stool culture and most patients can be treated symptomatically, as this is a self-limiting infection.3
On the other hand, typhoidal Salmonella may have a more serious presentation. The typhoidal Salmonella infections are caused by the Typhi and Paratyphi (A, B, or C) serotypes, with the former causing more severe illness. These serotypes reside in humans and are also transmitted via the feco-oral route. The organism reaches the basolateral side of the M cells and spread to the mesenteric lymph nodes and the blood. They also replicate within macrophages and are able to inhibit the fusion of lysosomes with phagosomes.2 Clinically, the patients present with fevers due to the bacteremia, followed by abdominal pain and the characteristic “rose spots” on the second week of infection. If not treated, patients may develop complications such as septic shock, hepatosplenomegaly, or abdominal perforations secondary to necrosis of Peyer’s patches within the GI tract. The infection is diagnosed with blood (40-80%) and stool (30-40%) cultures and must be reported to the state. Patients are parenterally treated with ceftriaxone and may be changed to other susceptible antibiotics if clinically indicated.3
There are two typhoid vaccines available: a live oral vaccine and an inactivated injection. The typhoid vaccine is recommended for certain high risk populations including travelers, those with known contact with typhoid carrier, and some laboratory workers who work routinely with this organism. The vaccine, while beneficial, does not replace proper hand and food hygiene in prevention of typhoid fever.4
- Achtman, M., Wain, J., Weill, F.-X., Nair, S., Zhou, Z., Sangal, V., Krauland, M. G., Hale, J. L., Harbottle, H., Uesbeck, A., Dougan, G., Harrison, L. H., & Brisse, S. (2012). Multilocus Sequence Typing as a Replacement for Serotyping in Salmonella enterica. PLoS Pathogens, 8(6), e1002776. https://doi.org/10.1371/journal.ppat.1002776
- Kaplan Medical. (2017). USMLE step 1 lecture notes 2017: Immunology and microbiology. Simon and Schuster.
- Spec, A., Escota, G. V., & Chrisler, C. (2019). Comprehensive review of infectious diseases. Elsevier.
- Typhoid VIS. (2019, October 30). CDC. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/typhoid.html
-Ximena Wise, MD is an AP/CP pathology resident at the University of Chicago (NorthShore). She is interested in pursuing fellowships in Surgical Pathology and Gynecologic Pathology after completing her residency training.
-Paige M.K. Larkin, PhD, D(ABMM), M(ASCP)CM is the Director of Molecular Microbiology and Associate Director of Clinical Microbiology at NorthShore University HealthSystem in Evanston, IL. Her interests include mycology, mycobacteriology, point-of-care testing, and molecular diagnostics, especially next generation sequencing.