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
Fever without focus: malaria, rickettsia, dengue, leptospirosis, brucellosis, trypanosomiasis
Fever with focus: respiratory tract infection, TB, CNS infection, deep abscess/amoebic liver abscess, infectious hepatitis
Non-infective: lymphoproliferative, connective tissue disease
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
Typhoid (WHO Health Topics)
Typhoid fever (Parry, NEJM, 2002)
Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children (Patel et al, NEJM, 2021)
Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial (Shakya et al, Lancet, 2021)