typhoid (enteric) fever

^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11]^[12]

Etiology

Epidemiology

most cases can be traced to a human carrier
- food or water contaminated by human carrier
- chronic carriers
  - generally > 50 years of age
  - more commonly women
  - often have gallstones (Salmonella resides in bile)
- Salmonella excreted in feces of carrier
- transmitted via fecal oral route in areas with poor sanitation^[10]
500 cases annually
median age of patients 24 years
Mexico is primary reservoir for USA
risk of clinical typhoid increased 25-fold in HIV patients
1 in 3000 unimmunized travelers to developing countries infected
infectivity may persist for 15 years^[9]
travelers returning for Southeast Asia^[10]
extensively drug-resistant Salmonella typhi among travelers to or from Pakistan 2016-2018^[11]
from February 2018 to November 2020, 71 cases of extensively drug-resistant Salmoniella typhi infection were reported in the U.S
- 87% reported travel in Pakistan within 30 days prior to symptom onset
- 13% denied a travel history^[12]

Pathology

infection is initiated by oral ingestion of the organisms
bacteria that successfully evade 'acid death' in the stomach penetrate the mucosal barrier in the distal ileum & colon
initial bacterial invasion results in transient asymptomatic bacteremia, with organisms ingested by monocytes within which they survive & multiply
antibody-opsonized bacteria are lysed by neutrophils
when intracellular multiplication of bacteria has progressed enough to permit persistent bacteremia, the clinical phase of typhoid fever begins
invasion of gall bladder & Peyer's patches of the intestine
bacteremia is responsible for persistent fever
inflammatory response to tissue invasion determine other signs/symptoms
- cholecystitis
- necrotizing lymphadenitis with intestinal hemorrhage or intestinal perforation^[10]
with invasion of gallbladder & Peyer's patches, bacteria regain entry to the bowel lumen & may be recovered in the feces
seeding of the kidney may lead to positive urine cultures

Clinical manifestations

incubation period variable: 3-60 days (1-4 weeks)^[4]^[5] (8-14 days)^[4] depending upon inoculum
presentation with fever, headache, arthralgias, myalgias, pharyngitis, anorexia, abdominal pain & tenderness^[4]
step-like daily increase in temperature with headache, malaise & chills
persistent, prolonged fever (up to 4-8 weeks in untreated patients)
- pulse-temperature dissociation, relative bradycardia, prostration
GI manifestations
- constipation more common than diarrhea initially
- diarrhea more often occurs as the disease progresses
  - diarrhea early^[4]
- abdominal pain, tenderness
- anorexia
- mild hepatosplenomegaly
- intestinal bleeding or perforation (3rd of 4th week)
- necrotizing cholecystitis (3rd of 4th week)
- diagnosis is unlikely without GI symptoms
non-productive cough^[4]^[10]
in severe disease, DIC may occur
small pale red, blanching, slightly raised macules 'rose spots' on chest & abdomen during 1st week (1/3 of patients)^[4]^[5]
changes in sensorium (encephalopathy)

Laboratory

complete blood count (CBC)
- neutropenia in 25%
- thrombocytopenia
serum chemistries
- serum bilirubin & serum transaminases may be elevated
- serum sodium: hyponatremia common
blood cultures (rate of recovery highest in 1st week)
- sensitivity may be <= 40%
bone marrow cultures frequently positive even when patient is taking antibiotics
stool cultures are often negative in 1st week, generally become positive by 3rd week
agglutinating antibodies to O & H antigens (Widal test)
- may represent prior infection in endemic areas^[10]
Latex agglutination test for antibody to Vi antigen
- more sensitive & specific than Widal test
- diagnostic in patients already started on antibiotics
- not commercially available or in widespread use

Complications

Differential diagnosis

rickettsial infection, brucellosis, tularemia, leptospirosis, miliary tuberculosis, viral hepatitis, infectious mononucleosis, cytomegalovirus, malaria, lymphoma
dengue:
- petchechial rash, leukopenia, thrombocytopenia, myalgia, arthralgia, leukopenia, thrombocytopenia, elevated LFTs, hepatomegaly, no GI symptoms, negative blood cultures

Management

antibiotics
- 3rd generation cephalosporin for severe infection^[10]
  - ceftriaxone is as effective as chloramphenicol
- fluoroquinolone, resistance is increasing^[4]
  - 70% of Salmonella typhi isolates resistant to fluoroquinolones^[7]
- azithromycin
- chloramphenicol was gold standard for treatment
  - adults: 2-4 g/day PO for 2 weeks
  - children: 50-75 mg/kg/day
  - may reduce dose to 2 g/day or 30 mg/kg after 5 days if afebrile
  - clinical response is generally apparent within 24-48 hours
- extensively drug-resistant Salmonella typhi
  - carbapenem & azithromycin are effective^[12]
  - resistant to ampicillin, ceftriaxone, chloramphenicol, ciprofloxacin, & TMP-SMX^[12]
intravenous dexamethasone + antibiotics decreases mortality in severe disease^[4]
- 3 mg/kg loading dose over 30 min
- 1 mg/kg every 6 hours for 24-48 hours
other antibiotics
- high dose ampicillin
- amoxicillin 4-6 g/day PO divided QID
- aztreonam
- Bactrim 640 mg/day divided BID (based on trimethoprim)
multidrug-resistant Salmonella typhi
- ceftriaxone (drug of choice for children)
- fluoroquinolone
avoid salicylates to diminish risk of intestinal hemorrhage
relapse rate 20% in treated patients, 5-10% in untreated patients
eradication of carrier state
- difficult, especially in presence of gallstones
- traditional therapy for 6 weeks
  - ampicillin or amoxicillin 100 mg/kg/day plus probenecid 30 mg/kg/day
  - Bactrim 160 mg/day based on trimethoprim plus rifampin 600 mg QD
- fluoroquinolone for 4 weeks is probably better
prevention
- 2 vaccines are available
  - typhoid live virus vaccine (oral)
  - typhoid polysaccharide vaccine (IM)
- neither vaccine is 100% effective^[4]^[5]

More general terms

Additional terms

References

↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 672
↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 951-54
↑ Prescriber's Letter 9(7):40 2002
↑ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 ^4.7 ^4.8 ^4.9 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2021.
↑ ^5.0 ^5.1 ^5.2 ^5.3 Meltzer E, Schwartz E. Enteric fever: a travel medicine oriented view. Curr Opin Infect Dis. 2010 Oct;23(5):432-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20613510
↑ Steinberg EB, Bishop R, Haber P et al Typhoid fever in travelers: who should be targeted for prevention? Clin Infect Dis. 2004 Jul 15;39(2):186-91. Epub 2004 Jul 1. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15307027
↑ ^7.0 ^7.1 National Antimicrobial Resistance Monitoring System The 2012 NARMS Annual Human Isolates Report CDC NARMS tracks antimicrobial resistance in Salmonella and other enteric (intestinal) bacteria that may cause mild or severe diarrhea or bloodstream infection. http://www.cdc.gov/narms/reports/annual-human-isolates-report-2012.html
↑ Waddington CS, Darton TC, Pollard AJ. The challenge of enteric fever. J Infect. 2014 Jan;68 Suppl 1:S38-50. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24119827
↑ ^9.0 ^9.1 Hancock-Allen J, Cronquist AB, Peden J et al Notes from the Field: Typhoid Fever Outbreak Associated with an Asymptomatic Carrier at a Restaurant - Weld County, Colorado, 2015. MMWR Morb Mortal Wkly Rep 2016;65:606-607 http://www.cdc.gov/mmwr/volumes/65/wr/mm6523a4.htm
↑ ^10.0 ^10.1 ^10.2 ^10.3 ^10.4 ^10.5 ^10.6 Rothaus C Home Sweet Home. NEJM Resident 360. Jan 31, 2018 https://resident360.nejm.org/content_items/home-sweet-home
↑ ^11.0 ^11.1 Chatham-Stephens K, Medalla F, Hughes M, et al. Emergence of Extensively Drug-Resistant Salmonella Typhi Infections Among Travelers to or from Pakistan - United States, 2016-2018. MMWR Morb Mortal Wkly Rep 2019;68:11-13 https://www.cdc.gov/mmwr/volumes/68/wr/mm6801a3.htm
↑ ^12.0 ^12.1 ^12.2 ^12.3 Harrison L CDC Warns of Drug-Resistant Typhoid Fever Outbreak Medscape - Feb 17, 2021. https://www.medscape.com/viewarticle/945986
Centers for Disease Control & Prevention (CDC) Extensively Drug-Resistant Salmonella Typhi Infections Among U.S. Residents Without International Travel. CDC Health Alert Network. Feb 12, 2021 https://emergency.cdc.gov/han/2021/han00439.asp

[ref1-1] Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 672

[ref2-2] Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 951-54

[ref3-3] Prescriber's Letter 9(7):40 2002

[ref4-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 ^4.7 ^4.8 ^4.9 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2021.

[ref5-5] 5.0 ^5.1 ^5.2 ^5.3 Meltzer E, Schwartz E. Enteric fever: a travel medicine oriented view. Curr Opin Infect Dis. 2010 Oct;23(5):432-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20613510

[ref6-6] Steinberg EB, Bishop R, Haber P et al Typhoid fever in travelers: who should be targeted for prevention? Clin Infect Dis. 2004 Jul 15;39(2):186-91. Epub 2004 Jul 1. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15307027

[ref7-7] 7.0 ^7.1 National Antimicrobial Resistance Monitoring System The 2012 NARMS Annual Human Isolates Report CDC NARMS tracks antimicrobial resistance in Salmonella and other enteric (intestinal) bacteria that may cause mild or severe diarrhea or bloodstream infection. http://www.cdc.gov/narms/reports/annual-human-isolates-report-2012.html

[ref8-8] Waddington CS, Darton TC, Pollard AJ. The challenge of enteric fever. J Infect. 2014 Jan;68 Suppl 1:S38-50. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24119827

[ref9-9] 9.0 ^9.1 Hancock-Allen J, Cronquist AB, Peden J et al Notes from the Field: Typhoid Fever Outbreak Associated with an Asymptomatic Carrier at a Restaurant - Weld County, Colorado, 2015. MMWR Morb Mortal Wkly Rep 2016;65:606-607 http://www.cdc.gov/mmwr/volumes/65/wr/mm6523a4.htm

[ref10-10] 10.0 ^10.1 ^10.2 ^10.3 ^10.4 ^10.5 ^10.6 Rothaus C Home Sweet Home. NEJM Resident 360. Jan 31, 2018 https://resident360.nejm.org/content_items/home-sweet-home

[ref11-11] 11.0 ^11.1 Chatham-Stephens K, Medalla F, Hughes M, et al. Emergence of Extensively Drug-Resistant Salmonella Typhi Infections Among Travelers to or from Pakistan - United States, 2016-2018. MMWR Morb Mortal Wkly Rep 2019;68:11-13 https://www.cdc.gov/mmwr/volumes/68/wr/mm6801a3.htm

[ref12-12] 12.0 ^12.1 ^12.2 ^12.3 Harrison L CDC Warns of Drug-Resistant Typhoid Fever Outbreak Medscape - Feb 17, 2021. https://www.medscape.com/viewarticle/945986
Centers for Disease Control & Prevention (CDC) Extensively Drug-Resistant Salmonella Typhi Infections Among U.S. Residents Without International Travel. CDC Health Alert Network. Feb 12, 2021 https://emergency.cdc.gov/han/2021/han00439.asp

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typhoid (enteric) fever

Contents

Etiology

Epidemiology

Pathology

Clinical manifestations

Laboratory

Complications

Differential diagnosis

Management

More general terms

Additional terms

References

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typhoid (enteric) fever

Etiology

Epidemiology

Pathology

Clinical manifestations

Laboratory

Complications

Differential diagnosis

Management

More general terms

Additional terms

References

Navigation menu

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