Overview
Recognise typhoid and paratyphoid after travel or food exposure, secure cultures before treatment when safe, manage severity and resistance intelligently, and complete exclusion, clearance and notification duties.
S. Typhi and S. Paratyphi are human-restricted pathogens. After surviving gastric acid they invade ileal lymphoid tissue, multiply within macrophages and disseminate through the reticuloendothelial system. A secondary bacteraemia produces sustained fever and multisystem illness. Necrosis of Peyer patches can cause lower gastrointestinal bleeding or perforation, commonly in the second or third week if effective treatment is delayed.
Risk assessment should record exact countries and dates, visiting-friends-and-relatives travel, food and water exposures, typhoid vaccination, previous antibiotics, hospital attendance overseas and household illness. Vaccination reduces but does not eliminate typhoid risk and does not provide dependable protection against paratyphoid. Previous antimicrobial exposure can suppress cultures without excluding infection.
Antimicrobial resistance is central rather than incidental. Fluoroquinolone non-susceptibility is widespread, extended-spectrum beta-lactamase-producing and extensively drug-resistant Typhi occur, and susceptibility may change the definitive agent. Empirical selection therefore depends on severity, place of acquisition, recent antibiotics and local or national surveillance, with microbiology or infection ownership.
Key points
Aetiology
Human-restricted Salmonella
S. enterica serovars Typhi and Paratyphi circulate only through infected people or carriers, reaching new hosts by faecally contaminated food or water.
Travel exposure
Most UK cases follow travel to endemic regions, especially South Asia, with greater risk during visits to friends and relatives and prolonged local food exposure.
Chronic carriage
A minority continue shedding after illness, often from gallbladder colonisation associated with gallstones, creating an asymptomatic reservoir for later transmission.
Pathophysiology
- 1Mucosal invasion
Organisms survive gastric acid, cross ileal M cells and enter Peyer patches, where uptake by macrophages permits intracellular persistence.
- 2Reticuloendothelial spread
Infected macrophages transport bacteria to mesenteric nodes, liver, spleen and marrow before secondary bacteraemia produces sustained systemic inflammation.
- 3Ileal ulceration
Hyperplasia and necrosis of Peyer patches create longitudinal terminal-ileal ulcers that may erode vessels or perforate the bowel wall.
- 4Biliary persistence
Survival in bile and gallbladder biofilm allows intermittent faecal shedding after symptoms resolve and explains some chronic carrier states.
Clinical features and red flags
Fever usually rises over several days with headache, marked malaise, anorexia, dry cough or myalgia; the patient may look disproportionately unwell despite few focal signs.
Diffuse discomfort, right iliac fossa pain, diarrhoea, constipation, nausea, vomiting or abdominal distension can occur, and bowel habit alone cannot distinguish typhoid from paratyphoid.
Hepatosplenomegaly, coated tongue, faint truncal rose spots and pulse-temperature dissociation are recognised clues but are insensitive; their absence should never reassure.
Confusion, delirium, reduced consciousness, seizure or focal neurology may accompany severe disease and should prompt glucose measurement, sepsis care and assessment for meningitis or cerebral malaria.
New bleeding, abrupt severe pain, involuntary guarding or septic deterioration after a longer febrile course suggests ileal ulcer haemorrhage or perforation.
Investigations
- 01
First-line blood culturesFirst stepFirst line - Why
- Confirm bacteraemia, identify Typhi or Paratyphi and generate the susceptibility profile that controls definitive therapy.
- Interpretation and limitations
- Take at least two appropriately filled sets before antimicrobials when safe and state travel details. Sensitivity falls after antibiotics; a negative result does not end investigation when the syndrome fits.
- 02
Stool culture - Why
- Provide additional organism recovery during acute illness and support later public-health clearance where directed.
- Interpretation and limitations
- Yield varies with illness stage and intermittent shedding. A positive result supports diagnosis, but acute blood culture remains more useful and clearance sampling must follow the health protection schedule.
- 03
Susceptibility and reference testing - Why
- Determine fluoroquinolone, azithromycin, ceftriaxone and carbapenem activity and identify resistant phenotypes.
- Interpretation and limitations
- Act on the reported MIC or category rather than assumed geographic susceptibility. Discuss resistant, discordant or clinically failing isolates with microbiology and the relevant reference laboratory.
- 04
Severity and complication panel
Differential diagnosis
Malaria
Fever, headache, cytopenias and gastrointestinal symptoms overlap; urgent serial parasite testing remains mandatory whenever geographic exposure is plausible.
Dengue
Fever, headache, thrombocytopenia and abdominal warning symptoms may mimic enteric fever, but exposure, rash, capillary leak and virology help distinguish it.
Leptospirosis
Freshwater or animal-urine exposure, conjunctival suffusion, myalgia, jaundice and renal injury suggest leptospirosis, confirmed with appropriately timed molecular or serological testing.
Rickettsial infection
An eschar, rash or arthropod exposure supports rickettsiosis, but these clues may be absent and specialist empirical treatment may be time critical.
Non-travel sepsis
Pyelonephritis, pneumonia, intra-abdominal infection, endocarditis and viral illness can produce sustained fever and must be investigated in parallel.
Management
01SAMPLE FIRSTInvestigate suspected enteric feverFirst stepSustained fever or compatible systemic illness follows residence in or travel to an endemic setting.+
- 1Perform ABCDE, establish dates and exact locations, review antibiotics and vaccination, and assess for bleeding, peritonism, encephalopathy and shock.
- 2Take blood-culture sets before antimicrobials if this can be done immediately; add stool culture, severity bloods and urgent malaria testing without allowing sampling to delay resuscitation.
- 3Notify suspected typhoid or paratyphoid according to national arrangements and contact the health protection team early for risk-group, household and occupational advice.
- 4Ask microbiology or infection specialists to select empirical treatment from severity, likely geography and current resistance data, then narrow when organism and susceptibility are known.
02UNCOMPLICATEDTreat stable oral diseaseThe patient has no shock, organ dysfunction, gastrointestinal complication or absorption problem and reliable follow-up is possible.
Complications
Intestinal haemorrhage
Peyer-patch ulceration can erode mesenteric vessels, causing occult blood loss, melaena, major lower gastrointestinal bleeding and haemodynamic collapse.
Ileal perforation
Transmural ulceration causes peritonitis, polymicrobial secondary sepsis and shock, requiring urgent surgery alongside broad antimicrobial treatment.
Neurological dysfunction
Severe systemic infection may cause delirium, encephalopathy, seizures or reduced consciousness and is associated with a worse prognosis.
Focal seeding
Bacteraemia can seed bone, joints, endovascular structures, gallbladder or other sites, particularly with haemoglobinopathy, prosthetic material or immunosuppression.
Relapse and carriage
Incomplete clearance may produce recurrent fever after apparent recovery or prolonged asymptomatic shedding with ongoing public-health implications.
Monitoring and follow-up
- Record temperature, haemodynamics, mental state, abdominal findings, oral intake, urine output and stool frequency daily; deterioration matters more than delayed defervescence alone.
- Trend FBC, renal and liver profiles and CRP; repeat haemoglobin and coagulation urgently when gastrointestinal bleeding is suspected.
- Review culture identification and susceptibility every day, confirm an active regimen and document why broad or combination therapy remains necessary.
- Repeat blood cultures for persistent sepsis, recurrent fever after initial improvement or suspected endovascular infection rather than as a routine ritual in every improving case.
- Arrange clear review for relapse during the weeks after treatment and ensure the health protection team controls any faecal clearance schedule.
- Before discharge, reconcile occupational or school exclusion, contact advice, hand hygiene, treatment completion and the named team responsible for outstanding results.
Special situations
Fever can resolve slowly
A stable patient may remain febrile for several days after active therapy begins; worsening physiology, persistent bacteraemia or a focal complication is more concerning than temperature alone.
Stool culture has two roles
During illness it can support diagnosis, while after treatment specifically timed specimens assess clearance in selected risk groups; the purposes and timing should not be confused.
Vaccination is incomplete protection
Available vaccines reduce typhoid risk but do not eliminate it and provide no reliable paratyphoid protection, so compatible post-travel fever still needs cultures.
Carriage is a public-health problem
Persistent biliary or intestinal shedding may be asymptomatic, particularly with gallbladder disease; eradication and any further investigation require specialist and health-protection coordination.
Resistance follows geography
The country and sometimes region of acquisition can change empirical therapy, but only isolate susceptibility can safely determine definitive narrowing.
Common pitfalls
- 01
Do not dismiss enteric fever because the patient has constipation rather than diarrhoea, lacks rose spots or does not show relative bradycardia.
- 02
Do not wait for stool culture when blood cultures can be obtained promptly, and do not use Widal serology to establish acute infection.
- 03
Do not start empirical ciprofloxacin simply because it was historically standard; contemporary resistance makes susceptibility essential.
- 04
Do not allow cultures to postpone antimicrobials in shock, perforation or another time-critical severe presentation.
- 05
Do not assume antimicrobial completion automatically ends exclusion from food handling, healthcare, nursery work or attendance; health protection decides clearance requirements.
- 06
Do not overlook malaria, viral haemorrhagic fever risk assessment or another concurrent imported infection because one test has returned positive.