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.
sources
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.
host risk factors
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)
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
if outpatient Mx is appropriate and fever < 7 days duration, oral azithromycin 20mg/kg up to 1g 1st dose then daily for 10mg/kg up to 500mg daily for further 6 days 1)
for more unwell patients needing hospital care:
if from pakistan:
iv meropenem 1 g (child: 20 mg/kg up to 1 g) 8-hourly (adjust dose for renal function)
or, iv azithromycin 1 g (child: 20 mg/kg up to 1 g) as a single dose on day 1, followed by 500 mg (child: 10 mg/kg up to 500 mg) intravenously, daily
otherwise from other countries:
iv ceftriaxone 2g daily until clinical response adequate then change to oral azithromycin for a further 6 days
or, iv azithromycin 1 g (child: 20 mg/kg up to 1 g) as a single dose on day 1, followed by 500 mg (child: 10 mg/kg up to 500 mg) intravenously, daily
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
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.