Salmonella typhi (typhoid enteric fever)

see also:

• clinically important bacteria
• antibiotics
• shigella
• paratyphoid enteric fever
• gastroenteritis
• the febrile returned traveller
• traveller's diarrhoea

• Salmonella are Gram negative anaerobe clinically important bacteria
• certain host factors make humans particularly susceptible to infection, contracted by ingesting contaminated food or water
• travellers to Asia and other regions are at risk of enteric fever, often with constipation rather than diarrhoeal illness:
  • typhoid
  • paratyphoid enteric fever
• after crossing the intestinal epithelial layer, the bacteria replicate in macrophages in Peyer’s patches, mesenteric lymph nodes, and the spleen. The bacteria may then potentially disseminate to the lungs, gallbladder, kidneys, spleen, testes, bone, joints or central nervous system.
• the bacteria predominantly reside in phagolysosomes within phagocytic cells and thus in vitro antibacterial responses do not necessarily equate with in vivo responses - hence aminoglycosides are generally not useful, furthermore, as S. typhi and S. paratyphi are obligate infections of man, there are no appropriate animal models in which to test treatment regimens.

• humans are the only known carriers of Salmonella typhi
  • 10% of patients recovering from typhoid fever excrete S. typhi in the stool for three months while 2-3% become chronic carriers
• faecal-oral transmission from person to person in areas with poor sanitation
• contaminated or nonchlorinated water
• most US cases are from travel to Peru, India (30%), Pakistan (13%), Mexico (12%), Bangladesh (8%), Philippines (8%), and Haiti (5%).(Emedicine)), with risk much higher in those visiting friends or family than just being tourists.

• extremes of age
  • neonates have highest risk
  • those under 20 years and those over 70 years also have high risk (particularly if from nursing homes)
  • case fatality rate for nontyphoid is 1.3% for those over age 50 years
• immunocompromised states
• prior antibiotic use (alters faecal flora and increases Salmonella invasion risk)
• achlorhydria (eg. neonates, proton pump inhibitors (PPIs), antacids) allows more bacteria to survive the gastric juices and enter the intestine
• recent bowel surgery
• malnutrition
• other infections such as schistosomiasis, malaria, histoplasmosis and bartonellosis increase risk

• incubation period 5-21 days

• 7-10 day prodrome of headache, cough, sweating, anorexia, weakness, sore throat, malaise, abdominal pain (20-40%) and constipation (10-40%) or pea-soup diarrhoea
• diarrhoea is particularly likely in neonates or the immunocompromised
• prodromal symptoms plateau as fever increases in stepwise manner peaking by week 2 of illness at 39-40degC

• may include:
  • high fevers (39-40 degC)
    • typically, fever rises gradually in 1st week, reaching a high plateau during the 2nd week, often associated with mental confusion, lethargy, insomnia
  • abdominal pain (often RIF pain)
  • hepatosplenomegaly (in 50%)
  • rose spot rash on trunk - faint 2-3mm salmon colored papules in 2nd week
  • meningism
  • relative bradycardia (in 50%)
  • thrombocytopaenia may occur
  • dissemination to lungs, gallbladder, kidneys or CNS may occur
  • rarely, may present as fulminant septic shock
• untreated patients experience either resolution or potentially serious complications by the 4th week:
  • intestinal perforation in 3-10%
  • endocarditis
  • pericarditis
  • pneumonitis
  • orchitis
  • localised abscess
  • chronic carrier states (stool carriage > 1 year) occurs in 1-4% of untreated typhoid cases

• institute isolation procedures to prevent transmission to staff and patients
• iv access
• FBE
• U&E
• LFT's
• look for other common differentials:
  • malaria screen if returning from endemic region
  • infectious mononucleosis screen (eg. Monospot)
• 2 x blood cultures PRIOR to starting antibiotics (positive in 50-70%)
  • note: PCR on blood has sensitivity of 85-95% when performed in 1st 5 days
• stool culture
  • but only +ve in 60% children and 25% of adults
• consult with infectious diseases team early
• antibiotic Rx:
  • reduced susceptibility to fluoroquinolones is common in infections acquired in the Indian subcontinent and South-East Asia. Initial therapy for infections from these regions should be with o azithromycin or iv ceftriaxone
  • iv ceftriaxone 1g bd until clinical response adequate then change to oral azithromycin or ciprofloxacin for a further 7 days¹⁾
  • or, if outpatient Mx is appropriate and fever < 7 days duration, o azithromycin 20mg/kg up to 1g daily for 7 days
• iv fluids if dehydrated
• admit to inpatient unit, single room
• watch for and Ix and Mx complications as indicated
• fever may continue for another 4-6 days despite antibiotic Rx

• exclusion from work and social activities should be considered for symptomatic, and asymptomatic, people who are:
  • food handlers
  • healthcare/daycare staff who are involved in patient care and/or child care
  • children attending unsanitary daycare centers
  • older children who are unable to implement good standards of personal hygiene.
• the exclusion applies until two consecutive stool specimens are taken from the infected patient and are reported negative.