Enteric fever

Background

Microbiology

• Caused by Salmonella enterica subspecies enterica serotypes Typhi and Paratyphi
• Virulence is related to Vi antigen and invasin protein

Epidemiology

• Fecal-oral transmission acquired from contaminated food, milk, or water
• Less than 5% of infected people become chronic carriers, with bacteria remaining in the gallbladder despite adequate antibiotic treatment

Pathophysiology

• Induction of pH-shock proteins and other adaptions allow ingested bacteria to pass through the stomach and into the small intestine
• There, they penetrate the intestinal mucosa followed by mononuclear cells, which transport them to lymph nodes
• They multiple within the reticuloendothelial system during the incubation period
• After a threshold is reached, they disseminate to blood

Clinical Manifestations

• Most commonly presents as fever in the returned traveller
• Incubation period 5 to 21 days
• Symptoms progress over weeks
  • First week: fever, chills, bacteremia, relative bradycardia, headache
  • Second week: abdominal pain, and a blanchable papular rash ("rose spots") may appear
  • Third week: can progress to gastrointestinal perforation, hepatosplenomegaly, GI bleed, secondary bacteremia
• Constipation is more common in adults, while diarrhea is more common in children and people with HIV
• CBC shows leukopenia and anemia
• Extraintestinal manifestations are myriad
  • Myelitis, psychosis, ataxia, parkinsonism
  • Meningoencephalopathy
  • Abscess or empyema
  • Endocarditis, myocarditis, and pericarditis
  • Pneumonia
  • Hepatitis, cholestasis, liver abscess
  • Osteomyelitis, rarely

Diagnosis

• Blood cultures (large volume, like x4), stool cultures, bone marrow biopsy (most sensitive)

Management

• Treatment with third-generation cephalosporins like ceftriaxone, stepped down to oral when improving and susceptibility data are available
  • Alternatives are azithromycin, followed by ampicillin, TMP-SMX, chloramphenicol
  • Avoid fluoroquinolones due to high resistance rate
• Duration 10 to 14 days
  • Can take 4 to 6 days to defervesce, even with treatment
• Monitor for relapse 2 to 3 weeks after treatment ends

Antibiotic	Dose	Duration
azithromycin	1 g p.o. once followed by 500 mg p.o. daily, or 1 g p.o. daily	5 to 7 days
ciprofloxacin	500 mg p.o. twice daily	7 to 10 days
ofloxacin	400 mg p.o. twice daily
ceftriaxone	2 g IV daily	10 to 14 days
cefotaxime	1 to 2 g IV every 6 to 8 hours
cefixime	200 mg p.o. twice daily
meropenem	1 to 2 IV every 8 hours
TMP-SMX	1 DS tablet p.o. twice daily
amoxicillin	1 g p.o. three times daily
chlormaphenicol	500 tp 750 mg p.o. four times daily	14 to 21 days