II. History

  1. Typhoid Mary was a cook who infected 51 patients
    1. Brooks (1996) CMAJ 154:915-6 [PubMed]

III. Epidemiology: Incidence

  1. World: 13-17 million cases per year
    1. Most cases occur in Asia (13 Million)
    2. Worldwide annual deaths approach 600,000
  2. U.S.: 400 cases per year (70% in travelers)
    1. Decreased from nearly 36,000 cases in 1920

IV. Pathophysiology

  1. Salmonella Characteristics (same as non-typhoid Salmonella)
    1. Facultative Anaerobic Gram Negative Rod in Enterobacteriaceae family
      1. Grouped with SS Gram Negative Bacteria (Salmonella, Shigella)
    2. Salmonella is distinguished from other Enterobacteriaceae
      1. Motile with flagella (unlike Shigella)
      2. Does not ferment lactose (unlike E. coli)
      3. Produces Hydrogen Sulfide or H2S (unlike Shigella)
  2. Salmonellosis Pathogenesis
    1. Vi Antigen (Virulence Antigen)
      1. Also present in Non-Typhoid Salmonella
      2. Surrounds the SalmonellaBacterial cell surface
      3. Protects surface Antigen O from immune response (Opsonization, Phagocytosis)
    2. Salmonella invades intestinal epithelial cells
      1. Cellular invasion is similar to non-typhoid Salmonella
      2. However, typhoid Salmonella results in systemic infection
        1. Invades regional Lymph Nodes and then spreads to other organ systems
        2. Salmonella typhi can also survive within Phagocytes (Macrophages)
  3. Systemic Bacterial Infection (Enteric Fever)
    1. Salmonella typhi (Typhoid Fever)
      1. Most common and more severe form
    2. Salmonella paratyphi (Paratyphoid Fever)
      1. Much more mild than Typhoid Fever
    3. SalmonellaCholeraesuis
  4. Transmission
    1. Humans are only hosts of Salmonella typhi and Salmonella paratyphi
    2. Asymptomatic chronic carriers can shed Bacteria in the stool
    3. Ingestion of contaminated food or water (via feces or urine) is primary source
      1. Raw fruits and vegetables (grown in fields fertilized by sewage)
      2. Street vendor food and drink
      3. Contaminated water or ice ingestion
      4. Flooding
      5. Poor Hand Washing practices
    4. Other sources
      1. May also be transmitted by patient contact in healthcare workers
      2. Male sexual partners may also transmit to each other

V. Risk factors

  1. Highly dense living conditions (e.g. Refugee camp)
  2. Travel to developing country
    1. Highest risk in Southeast Asia
    2. Also high risk in Africa, West Asia, Central and South America
    3. High risk countries: Mexico, India, Pakistan, Philippines, El Salvador and Haiti

VI. Symptoms

  1. Incubation (first 5-21 days after ingestion depending on inoculum load, may be up to 60 days)
    1. Usually asymptomatic in Incubation Period
    2. Diarrhea may occur during Incubation Period
  2. Active infection
    1. Malaise
    2. Fever (75% of cases)
      1. Intermittent Fever initially
      2. Sustained Fever to high Temperatures later
      3. See Pulse-Temperature Dissociation described below
    3. Associated symptoms
      1. Severe Headache
      2. Myalgia
      3. Anorexia
      4. Nausea or Vomiting
      5. Generalized Abdominal Pain or right lower quadrant (may mimic Appendicitis)
      6. Change in stool consistency (<50% of cases)
        1. Child: Diarrhea most common
        2. Adult: Constipation most common

VII. Signs

  1. Pulse-Temperature Dissociation (Faget Sign, uncommon)
    1. Paradoxical and Relative Bradycardia with fever spikes
  2. Rose Spots (Pathognomonic, present in up to 30% of cases)
    1. Groups of blanching, faint pink Macular and papular spots 2-3 mm over trunk
    2. Onset at end of first week or into second week of infection
    3. Represent Bacterial emboli to the skin
  3. Other findings
    1. Hepatosplenomegaly
    2. Epistaxis
  4. Severe Infection
    1. Gastrointestinal Bleeding
    2. Bowel perforation and peritonitis
    3. Septic Shock
    4. Altered Level of Consciousness

VIII. Labs

  1. Complete Blood Count
    1. Leukopenia
    2. Thrombocytopenia
    3. Increased liver transaminases
    4. Increased acute phase reactants (CRP, ESR)
  2. Cultures
    1. Blood Culture
      1. Best Test Sensitivity in first week (up to 40-60% Test Sensitivity)
    2. Bone Marrow culture (rarely used in clinical practice)
      1. Higher sensitivity than Blood Culture
    3. Fecal culture
      1. Low Test Sensitivity (~33%)
      2. Better Test Sensitivity after the first week
  3. Salmonella Serology (Widal's Test)
    1. Poor Test Specificity
    2. Low Test Sensitivity (70%)

X. Management: Antibiotics

  1. Antibiotic Resistance is increasing (esp. in Asia to Fluoroquinolones)
  2. Severe or complicated infection
    1. Ceftriaxone 2 g IV/IM every 24 hours for 7-14 days OR
  3. Infection acquired outside Asia
    1. Ciprofloxacin 400 mg IV (or 500 mg orally) every 12 hours for 7-10 days OR
    2. Levofloxacin 750 mg IV (or 750 mg orally) every 24 hours for 7-10 days
  4. Infection acquired in Asia
    1. Ceftriaxone 2 g IV/IM every 24 hours for 7-14 days OR
    2. Azithromycin 1 g orally day 1, then 500 mg orally daily for 5-7 days
      1. Consider using Azithromycin combined WITH Ceftriaxone in ill hospitalized patients
  5. Alternative Antibiotics (resistance is common)
    1. Chloramphenicol 500 mg IV or oral every 6 hours for 14 days
  6. Additional measures
    1. Consider adding Dexamethasone in seriously ill patients

XI. Complications (occurs in 10-15% of cases)

  1. Typhoid encephalopathy
  2. Peyer patch necrosis (sites of Salmonella infiltration at Small Intestine lymphoid Nodules)
    1. Gastrointestinal Bleeding (2-10% of cases)
    2. Bowel perforation and peritonitis
  3. Mycotic aneurysm (10% of patients over age 50 years old)
  4. Septic Arthritis or Osteomyelitis
  5. Pneumonia
  6. Chronic Carrier state
    1. Affects 2-5% of Typhoid Fever survivors after acute infection
    2. Salmonella typhi may continue to survive chronically in the gallbladder
    3. May continue to spread Salmonella to others
    4. Gunn (2014) Trends Microbiol 22(11):648-55 +PMID: 25065707 [PubMed]

XII. Prognosis

  1. Mortality in untreated, prolonged cases is 12-60%

XIII. Prevention

  1. See Foodborne Illness Prevention
  2. See Water Disinfection
  3. Typhoid Vaccine
    1. Adjunctive, but not complete protection, and non-compliance with the oral Vaccine is common)
    2. Even when taken properly, still <75% effective
  4. Steam or boil shellfish at least 10 minutes
  5. All milk and dairy products should be pasteurized
  6. Control fly populations

XIV. References

  1. Anderson (2014) Crit Dec Emerg Med 28(7):11-9
  2. Black, Martin, DeVos (2018) Crit Dec Emerg Med 32(8): 3-12
  3. Butler in Goldman (2000) Cecil Medicine, p. 1681-3
  4. Nordurft-Froman and DeVos (2022) Crit Dec Emerg Med 36(4): 4-15
  5. Pearson in Mandell (2000) Infectious Disease, p. 1136
  6. Feder (2013) Am Fam Physician 88(8): 524-30 [PubMed]
  7. Maskalyk (2003) CMAJ 169:132 [PubMed]
  8. Wain (2015) Lancet 385(9973): 1136-45 [PubMed]

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Related Studies

Ontology: Paratyphoid Fever (C0030528)

Definition (MSHCZE) Dlouhodobé horečnaté onemocnění obvykle způsobené několika paratyfovými sérotypy SALMONELLA ENTERICA. Podobné břišnímu tyfu, ale méně závažné.
Definition (MSH) A prolonged febrile illness commonly caused by several Paratyphi serotypes of SALMONELLA ENTERICA. It is similar to TYPHOID FEVER but less severe.
Concepts Disease or Syndrome (T047)
MSH D010284
ICD9 002.9
ICD10 A01.4
SnomedCT 187268002, 186092009, 266174006, 154270009, 85904008
English Fevers, Paratyphoid, Paratyphoid Fever, Paratyphoid Fevers, Fever, Paratyphoid, Paratyphoid fever, unspecified, Paratyphoid fever,unspecifd, [X]Paratyphoid fever, unspecified, [X]Paratyphoid fever,unspecifd, paratyphoid fever, paratyphoid fever (diagnosis), Salmonella paratyphi infection, Paratyphoid, Paratyphoid fever NOS, Paratyphoid Fever [Disease/Finding], paratyphoid, Paratyphoid fever NOS (disorder), [X]Paratyphoid fever, unspecified (disorder), Paratyphoid fever, Paratyphoid fever (disorder), Salmonella; infection, paratyphi, Salmonella; paratyphoid fever, infection; Salmonella, paratyphi, Paratyphoid fever, NOS
Dutch Salmonella paratyphi-infectie, paratyfus, niet-gespecificeerd, Salmonella; infectie, paratyphi, Salmonella; paratyfus, infectie; Salmonella, paratyphi, Paratyfus, niet gespecificeerd, paratyfus, Paratyfus, Tyfus, para-
French Infection à Salmonella paratyphi, Fièvre paratyphoïde, non précisée, Fièvre paratyphoïde, Paratyphoïde
German Salmonella paratyphi-Infektion, paratyphoid, Paratyphusfieber, unspezifisch, Paratyphus, nicht naeher bezeichnet, Paratyphusfieber, Paratyphus
Italian Infezione da Salmonella paratyphi, Paratifo, Paratifo non specificato, Febbre paratifoide
Portuguese Paratifóide, Febre paratifóide NE, Infecção por Salmonella paratyphi, Febre Paratifoide, Febre paratifóide
Spanish Infección por Salmonella paratyphi, Fiebre paratifoidea no especificada, Paratifoidea, fiebre paratifoidea, SAI (trastorno), [X]fiebre paratofoidea, no especificada (trastorno), [X]fiebre paratofoidea, no especificada, fiebre paratifoidea, SAI, enfermedad de Schottmuller, fiebre paratifoidea (trastorno), fiebre paratifoidea, Fiebre paratifoidea, Fiebre Paratifoidea
Japanese パラチフス、詳細不明, パラチフス菌感染, パラチフス, パラチフスショウサイフメイ, パラチフスキンカンセン, パラチフス
Swedish Paratyfus
Czech paratyfus, Paratyfus, Paratyfus, blíže neurčený, Infekce Salmonella paratyphi, paratyfoidní horečka
Finnish Pikkulavantauti
Russian PARATIF, ПАРАТИФ
Korean 상세불명의 파라티푸스
Polish Paradury, Dury rzekome, Zakażenie Salmonella paratyphi A, Zakażenie Salmonella shottmuelleri, Paratyfus, Zakażenie Salmonella hirschfeldi
Hungarian paratyphus, Paratyphus, nem meghatározott, paratífusz, Salmonella paratyphi fertőzés
Norwegian Paratyfoidfeber

Ontology: Salmonella typhi (C0036125)

Definition (CSP) serotype of the species, Salmonella enterica, and is the etiologic agent of typhoid fever.
Definition (MSH) A serotype of SALMONELLA ENTERICA which is the etiologic agent of TYPHOID FEVER.
Concepts Bacterium (T007)
MSH D012485
SnomedCT 5595000
LNC LP20802-2, MTHU030267
English Salmonella typhosa, Salmonella 9,12,Vi;d;-, S. typhi, s typhi, s. typhi, salmonella typhi, typhi salmonella, salmonella typhi organism, typhoid bacillus, salmonella typhosa, Salmonella enterica serovar Typhi, Eberthella typhi, Typhoid bacillus, Salmonella typhi, Salmonella typhi (organism), Salmonella 9,12, [Vi]:d:-, Salmonella 9,12,Vi:d:-, Salmonella Typhi (organism), Salmonella Typhi, Salmonella enterica subsp. enterica ser. Typhi
French Salmonella enterica sérotype Typhi, Salmonella typhosa, Salmonella enterica serovar Typhi, Salmonella typhi
Swedish Salmonella typhi
Spanish Salmonella typhi (organismo), Salmonella 9,12, [Vi]:d:-, Salmonella typhosa, Salmonella typhi, Salmonella 9,12,Vi:d:-, Eberthella typhi, Salmonella Typhi, bacilo tifoideo, Salmonella Typhi (organismo), Salmonella enterica subesp. enterica ser. Typhi
Czech Salmonella typhi
Finnish Salmonella typhi
Russian BRIUSHNOTIFOZNAIA PALOCHKA, BRIUSHNOI TIF, VOZBUDITEL', БРЮШНОЙ ТИФ, ВОЗБУДИТЕЛЬ, БРЮШНОТИФОЗНАЯ ПАЛОЧКА
Japanese サルモネラ・ティフィ, チフス菌, サルモネラチフィ, 腸チフス菌
Italian Salmonella typhosa, Salmonella enterica serovar Typhi, Salmonella typhi
Croatian SALMONELLA TYPHI
Polish Pałeczki duru brzusznego, Salmonella typhi
German Salmonella typhi, Salmonella typhosa
Dutch Salmonella typhi
Portuguese Salmonella typhi

Ontology: Typhoid Fever (C0041466)

Definition (MSHCZE) Akutní systémová horečnatá infekce způsobená (bakterií) SALMONELLA TYPHI, sérotypem SALMONELLA ENTERICA.
Definition (NCI) A bacterial infectious disorder contracted by consumption of food or drink contaminated with Salmonella typhi. This disorder is common in developing countries and can be treated with antibiotics.
Definition (CSP) acute systemic febrile infection caused by Salmonella typhi.
Definition (MSH) An acute systemic febrile infection caused by SALMONELLA TYPHI, a serotype of SALMONELLA ENTERICA.
Concepts Disease or Syndrome (T047)
MSH D014435
ICD9 002.0
ICD10 A01.0 , A01.00
SnomedCT 186091002, 266174006, 154270009, 4834000
LNC LA16615-9
English Abdominal Typhus, Enteric Fever, Enteric Fevers, Fevers, Enteric, Typhoid, Typhoids, Typhus, Abdominal, Fever, Enteric, TYPHOID FEVER, Enteric fever, typhoid fever (diagnosis), typhoid fever, Salmonella typhi infection, Typhoid fever, unspecified, Typhoid Fever [Disease/Finding], enteric fever, Typhoid Fevers, Fever, Typhoid, Fevers, Typhoid, Fever: [typhoid] or [enteric] (disorder), Fever: [typhoid] or [enteric], Typhoid fever, Infection by Salmonella typhi, Typhoid fever (disorder), typhoid, Salmonella; infection, typhi, Salmonella; typhoid fever, ileotyphus, infection; Salmonella, typhi, infection; typhoid, typhoid; infection, Typhoid fever any site, Typhoid infection any site, Typhoid any site, Typhoid infection, Typhoid Fever
Dutch tyfoïde, Salmonella typhi-infectie, enterische koorts, Salmonella; infectie, typhi, Salmonella; typhus abdominalis, infectie; Salmonella, typhi, infectie; tyfus, tyfus; infectie, buiktyfus, Buiktyfus, Tyfus, Typhus abdominalis
German enterisches Fieber, Bauchtyphus, Salmonella typhi-Infektion, Typhusfieber, Febris thyphoides, Typhus abdominalis, Typhus
Italian Tifoide, Infezione da Salmonella typhi, Tifo addominale, Febbre enterica, Febbre tifoide
Portuguese Infecção por Salmonella typhi, Tifóide, Febre entérica, Febre Tifoide, Febre tifóide, Febre Entérica, Tifo Abdominal
Spanish Tifoideas, Infección por Salmonella typhi, Fiebre entérica, fiebre entérica, fiebre tifoidea (trastorno), fiebre tifoidea, infección por Salmonella typhi, tifoide, Fiebre tifoidea, Fiebre Entérica, Fiebre Tifoidea, Tifus Abdominal
Japanese 腸チフス熱, チフス菌感染, チョウチフス, チョウチフスネツ, チフスキンカンセン, チョウネツ, 腸チフス, 腸熱
Swedish Tyfoidfeber
Finnish Lavantauti
Russian TIFOIDNAIA LIKHORADKA, BRIUSHNOI TIF, БРЮШНОЙ ТИФ, ТИФОИДНАЯ ЛИХОРАДКА
Czech Břišní tyfus, Infekce Salmonella typhi, abdominální tyfus, tyfoidní horečka, enterická horečka, břišní tyfus, tyfus břišní
Korean 장티푸스
Polish Gorączka durowa, Dur brzuszny, Gorączka brzuszna
Hungarian Typhoid, Enteralis láz, hastífusz, Salmonella typhi fertőzés
Norwegian Tyfoidfeber
Croatian TRBUŠNI TIFUS
French Fièvre typhoïde, Typhoïde, Typhus abdominal, Fièvre entérique, Infection à Salmonella typhi

Ontology: rose spot (C0240915)

Concepts Finding (T033)
English rose spot, rose spots