Original case by Brandon Fainstad, MD.
Edits, updates on fever in a traveler and graphics by Yilin Zhang, MD.
- Pathogenesis and clinical presentation of typhoid fever (S. typhi infection)
- Evaluation and empiric management of a patient with suspected typhoid fever
A 36 year old previously healthy woman from El Salvador presents with 10 days of fevers and headache. Her fevers come and go, and range up to 40C. Her headache is mild without associated photophobia, vision changes or neck pain/stiffness. She otherwise denies sinus pain, congestion, cough, SOB, abdominal pain, diarrhea, dysuria or skin changes. She initially started taking some left over ciprofloxacin for the first 4 days but stopped at the recommendation of her PCP who felt it was likely viral. After arriving in the US to visit friends, she presented to the ED on day 9 of her fevers. She was discharged from the ED last night and called back for blood cultures positive for GNRs.
She is otherwise healthy except for occasional UTIs. She is on no chronic medications but has been taking APAP as needed for fever and headache. She lives in El Salvador and recently traveled to Guatemala. She denies an substance use.
VS: 39.2C, HR 72, BP 105/65, SaO2 100% on RA
Neck: supple, full range of motion
CV: 2/6 systolic murmur best at RUSB
Abd: soft, no hepatosplenomegaly
MSK: no CVA tenderness
Skin: warm, no rashes
- Na 133, K 3.4, Cl 98, CO2 27, BUN 12, Cr 0.6, Glu 100, Ca 8.8
- WBC 3.7k, Hct 35%, Plt 150
- AST 300, ALT 300, tbili 0.5, alk phos 300, albumin 3.2, total protein 6.0
- INR 1.0
- UA: no bact / no WBC
- CXR: normal
Give a one liner for this patient.
A one liner should include important PMH, symptoms, physical exam signs and laboratory abnormalities. The notable points from this case are:
- A patient from Central America
- Fever and headache
- Elevated LFTs – acute liver injury
Example: This is a 36 yo otherwise healthy F from Central America who presents with 9 days of fevers and headaches, found to have acute liver injury.
What is your differential diagnosis and what additional work-up do you want?
Fever in a patient with a travel history should take into account potential travel related infections. The CDC contains a list of endemic infections to each region. Since some tropical infections can be life threatening, its important to consider them in the differential.
With concurrent hepatitis but no other symptoms, differential could include:
- Hepatitis A/B/C/D/E
- EBV or CMV
- Travel related infections
- Severe malaria
- Typhoid fever
- Pyogenic liver abscess from amebiasis (typically associated with diarrhea)
FINAL DIAGNOSIS AND OUTCOME:
Typhoid Fever – Patient was treated with ceftriaxone for presumptive typhoid fever. Blood cultures later speciated to pan-sensitive Salmonella typhi. Her fever curve and headaches improved over but did not resolve over the next few days. She was discharged with azithromycin to complete a 7 day course. She followed up in clinic 3 days after discharge with ongoing fevers that were milder than before along with new mild, intermittent, central abdominal cramping without changes in her bowel movements that seemed to follow her doses of azithromycin. This was thought to be related to her azithromycin or resolving infection. She did not return before going back home to El Salvador
Salmonella Hepatitis – Elevated LFTs with hepatocellular profile likely due to salmonella hepatitis given time course. She was not taking excessive doses of APAP. Hep A/B/C negative.
Typhoid fever or enteric fever is rare in the US (~300 cases/year). Roughly 85% of these cases are related to travel from endemic areas – south Asia, SE Asia, Africa, South America and the Caribbean.
Transmission and Pathogenesis:
The incubation period if typicaly 6-30 d with gradually increasing fever.
Headache, malaise and anorexia are seen in almost all patients. Rose spots are a transient, macular rash typically seen on the trunk.
Blood cultures should be drawn in all patients with suspected typhoid fever, though they only turn positive in a single culture ~ 50% of the time. Reoeat cultures improve diagnostic yield.
IV 3rd generation cephalosporins are the empiric drug of choice. There is high fluoroquinolone resistance in some S. typhi species, though fluoroquinolones can used for outpatient treatment.
TAKE HOME POINTS:
- Pulse-temperature dissociation is seen in patients with typhoid fever.
- Salmonella hepatitis and hepatomegaly are common complications in the second weeks of typhoid infection.
- Blood cultures should be drawn in everyone with suspected typhoid fever and these patients should be empirically treated with IV ceftriaxone.
- Untreated typhoid has a 15% mortality and risk of chronic carrier state.
- Thwaites, GE & Day, NPJ. Approach to Fever in the Returning Traveler. NEJM. 2017; 376: 548-60.
- “Typhoid Fever.” VisualDx. Web. 02 Jan. 2016.
- United States. Centers for Disease Control and Prevention. Typhoid and Paratyroid Fever. By Michael Judd and Eric Mintz. Atlanta, GA: CDC, 2013. Accessed at: https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/typhoid-paratyphoid-fever
- Pramoolsinsap, C & Vikit Viranuvatti. “Salmonella Hepatitis.” J Gastroenterol Hepatol Journal of Gastroenterology and Hepatology 13.7 (1998): 745-50.