Typhoid

Pathogen

Salmonella enterica

  • Typhoidal salmonella/enteric fever: Salmonella typhi (typhoid fever), paratyphi (paratyphoid fever)

Epidemiology

  • 21 million cases, 200,00 deaths WW per year. 40-80% children, 5-40% < 5 years. 10-33% admitted to hospital

Transmission/pathogenesis

  • Faecal-oral transmission: Ingestion (water, food, hot season or flooding) - water contaminated by human faeces (infectious dose e.g. swallow 10,000-100,000 bacteria vs. 100 with shigella)

  • No animal reservoir

  • Bacteria passes through M cells over Peyer's patch (1st exposure) and enters macrophage (therefore intracellular bacteria), mesenteric LN, spleen, liver, gallbladder, re-enters GI tract (2nd exposure to Peyer's patch, ulcer), bone marrow

Clinical

  • Incubation period 7-14 days

  • Prolonged febrile illness with bacteraemia: 90% uncomplicated. Often something pointing to the abdomen (discomfort, nausea...)

  • 1st week: prodromal symptoms (like URTI, cough, headache, malaise), remittent or step ladder fever, relative bradycardia, abdominal pain, vomiting

  • 2nd week: high-grade fever, maculo-papular 'rose spot' rash, abdominal symptoms (pea soup stool or constipation, hepato-splenomegaly)

  • 3rd week: complications: (10-15%) haemolytic anaemia, cholecystitis, UTI, intestinal perforation & haemorrhage, typhoid facies, agitated delirium/meningitis

  • 4th week: convalescence

  • 10%+ mortality with no treatment (cause of death … septicaemia, DIC, meningitis, myocarditis); <1% mortality if adequate treatment

  • Relapse

  • Early convalescent and chronic faecal carriage (gall bladder) e.g. "typhoid Mary"

Diagnosis

  • Clinical (e.g. fever lasting more than a few days, absence of viral URTI sx, some abdominal localisation), simple blood tests (CRP usually elevated)

  • Blood /bone marrow culture

  • Nucleic acid detection

Serology:

  • Widal test: agglutinating antibodies against antigen (O lipopolysaccharide, H flagellar, VI capsular) but could be false positives in endemic populations; tube or slide format

  • Rapid diagnostic tests (RDTs): Cochrane review found limited sensitivity/specificity

Differential diagnosis

Management

  • 70-90% managed as outpatient: general supportive, oral rehydration, antibiotics (fluoroquinolones [ciprofloxacin, levofloxacin...], cephalosporins [ceftriaxone, cefixime..], azithromycin)... resistance increasing

  • Inpatient: oral/IV rehydration, antibiotics +/- intensive care, pressure area care, surgery, blood transfusion, steroids e.g. dexamethasone from one trial (severe complicated disease, altered conscious...)

  • Chronic carriage: prolonged antibiotics

Immunity

  • Antibodies produced after infection but repeat infection possible???

Vaccination

  • Ty21a oral live attenuated

  • Vi polysaccharide IM: WHO approved for use in endemic settings (no paratyphoid vaccine);

  • Vi conjugate?

Could typhoid ever be eradicated?

References