Typhoid and paratyphoid fever

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Typhoid and paratyphoid are systemic infections caused by Salmonella enterica serovars Typhi and Paratyphi A, B or C. Humans are the reservoir, and organisms spread through food or water contaminated by faeces or urine.

After intestinal entry, bacteria invade lymphoid tissue, survive in macrophages and disseminate through blood to liver, spleen, bone marrow and gallbladder. Clinical illness usually develops after travel to South Asia or another endemic region but transmission can occur through a chronic carrier.

Presentation is variable: sustained fever, headache, dry cough, malaise, abdominal discomfort, constipation or diarrhoea, hepatosplenomegaly and sometimes faint rose spots. Relative bradycardia is neither sensitive nor sufficiently specific to guide exclusion.

Antimicrobial resistance is central. Fluoroquinolone non-susceptibility is widespread and extensively drug-resistant lineages may resist ceftriaxone as well. Travel geography and isolate susceptibility must drive definitive treatment and public-health follow-up.

Key points

Suspect enteric fever in a returning traveller with sustained fever, headache, malaise and abdominal symptoms, even when diarrhoea is absent.
Ask exact countries, dates, urban or rural exposure, food and water, visiting friends and relatives, vaccination and every antibiotic taken abroad.
Obtain multiple blood-culture sets before antibiotics; blood culture is the practical first-line diagnostic test early in illness.
Send stool culture as well, but a negative early stool result does not exclude systemic enteric fever.
Bone-marrow culture is the most sensitive culture method and may remain positive after antibiotics, but its invasiveness limits routine use.
Start intravenous ceftriaxone for severe susceptible-pattern disease while seeking urgent specialist resistance advice; XDR exposure may require a carbapenem.
Azithromycin is used for selected uncomplicated susceptible disease, while ciprofloxacin is used only when the isolate is fully susceptible.
Notify suspected typhoid or paratyphoid promptly and follow health-protection instructions for contacts, exclusion and microbiological clearance.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Faecally contaminated food

Human carriers contaminate food during preparation, enabling ingestion of S Typhi or Paratyphi in areas with inadequate sanitation.

Unsafe water

Sewage contamination of drinking water and ice drives community transmission and outbreaks in endemic regions. in susceptible exposed adults.

Chronic human carriage

Persistent gallbladder colonisation permits asymptomatic faecal shedding long after clinical recovery and sustains the human reservoir.

Travel and visiting contacts

Travellers visiting friends and relatives may have prolonged local exposure and underestimate familiar food and water risks.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Intestinal invasion
Organisms cross ileal M cells and enter Peyer patches rather than remaining confined to the bowel lumen.
2
Macrophage survival
Intracellular persistence permits lymphatic and bloodstream dissemination despite early innate immune responses. during active invasive disease.
3
Reticuloendothelial replication
Bacteria multiply in liver, spleen and bone marrow before secondary sustained bacteraemia produces systemic fever. during active invasive disease.
4
Ileal ulceration
Inflammation and necrosis of Peyer patches cause gastrointestinal bleeding and perforation during established disease. during active invasive disease.
5
Biliary persistence
Gallbladder colonisation and biofilm on gallstones allow chronic carriage and intermittent faecal excretion. during active invasive disease.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Sustained febrile illness

Progressive or persistent fever with headache, profound malaise and few localising respiratory or urinary findings is typical.

Variable bowel symptoms

Abdominal pain, constipation, loose stool, nausea or anorexia occur; absence of diarrhoea does not lower systemic enteric-fever risk.

Reticuloendothelial signs

Hepatosplenomegaly, mild hepatitis, cytopenias and occasional blanching truncal rose spots reflect systemic dissemination.

Severe neurological diseaseRed flag

Delirium, encephalopathy, meningism or reduced consciousness indicates complicated illness and mandates urgent hospital treatment.

Intestinal complicationRed flag

Increasing right-lower-quadrant pain, guarding, bleeding or ileus during the second or third week suggests ileal ulceration.

Exposure and resistanceRed flag

Visiting friends and relatives, unsafe food or water and antibiotic purchase abroad define probability and likely resistance more accurately than vaccination history alone.

Red flags requiring action

Peritonism, sudden worsening abdominal pain or free air suggests ileal perforation requiring emergency surgery.
Haematemesis, melaena, haematochezia or falling haemoglobin can reflect ulceration and major intestinal bleeding.
Confusion, reduced consciousness, shock, oliguria or rising lactate marks severe systemic disease.
Travel to Pakistan or another setting with extensively drug-resistant typhoid materially changes empirical antimicrobial choice.
Persistent fever after five to seven days of active treatment suggests resistance, complication, inadequate exposure or an alternative diagnosis.
Food handling, healthcare, social care and contact with vulnerable people create immediate public-health exclusion and clearance implications.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Multiple blood-culture setsFirst step
Why
Recover S Typhi or Paratyphi and determine susceptibility before antimicrobial exposure.
Interpretation and limitations
Blood culture is the practical first-line test, especially early; sensitivity falls after antibiotics, so document every dose and repeat if fever persists.
02
Stool culture
Why
Support diagnosis, identify shedding and provide isolates for public-health typing and later clearance.
Interpretation and limitations
Early stool sensitivity is limited and a negative result does not exclude disease; follow the health-protection schedule rather than ad hoc repeat sampling.
03
Bone-marrow culture
Why
Provide the most sensitive culture method when diagnosis remains critical despite negative blood cultures.
Interpretation and limitations
It can remain positive after antimicrobial exposure but is invasive, so use only through infection or tropical-medicine specialists.
04
Full blood count, renal, liver and CRP
Why
Assess cytopenias, hepatitis, dehydration, organ dysfunction and treatment safety.
Interpretation and limitations
Leukopenia is classically described but not universal; worsening anaemia may indicate intestinal bleeding and rising transaminases can reflect severe systemic disease.
05
Antimicrobial susceptibility and reference typing
Why
Detect fluoroquinolone non-susceptibility, ceftriaxone resistance and XDR lineages and support outbreak investigation.
Interpretation and limitations
Do not infer ciprofloxacin activity from older expectations; use the reported MIC or categorical susceptibility and UKHSA reference result.
06
Abdominal radiograph or contrast CT
Why
Investigate severe pain, ileus, haemorrhage, perforation, abscess or alternative abdominal disease.
Interpretation and limitations
Free air, focal ileal inflammation or collection prompts urgent surgery; imaging is not routine for uncomplicated fever.
07
Alternative fever screen
Why
Assess malaria, dengue, viral hepatitis, rickettsial disease, leptospirosis and other travel-related causes.
Interpretation and limitations
Test urgently for malaria in any compatible traveller regardless of a plausible enteric-fever story, because coinfection and diagnostic anchoring occur.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Malaria

Any fever after endemic travel requires urgent malaria films or rapid testing, regardless of gastrointestinal symptoms or prophylaxis history.

Dengue

High fever, headache, myalgia, thrombocytopenia and travel overlap, while plasma leakage and bleeding pattern differ. on focused clinical assessment.

Viral hepatitis

Fever, anorexia and abnormal liver tests may precede jaundice and require travel- and exposure-specific serology. on focused clinical assessment.

Rickettsial infection

Sustained fever, headache, rash or eschar after vector exposure may respond to a different antimicrobial class.

Non-typhoidal Salmonella

Usually gastroenteric illness follows food or animals, while invasive bacteraemia occurs in vulnerable hosts and can seed focal sites.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01CULTURESecure diagnosis before treatmentFirst stepA traveller has sustained fever and an exposure pattern compatible with typhoid or paratyphoid.

1Use immediate travel and malaria assessment, examine for shock, encephalopathy, bleeding and peritonism and begin enteric isolation precautions.
2Obtain several blood-culture sets, stool culture, full blood count, renal and liver profile before antibiotics when this causes no dangerous delay.
3Tell microbiology the countries, dates and any overseas antibiotics so culture handling and resistance risk are interpreted correctly.
4Notify the local health-protection team on suspicion rather than waiting for final serovar confirmation.

02SEVERETreat complicated enteric feverShock, organ dysfunction, encephalopathy, significant bleeding, peritonism or inability to absorb oral treatment is present.

1Use ABCDE, cautious crystalloid resuscitation and close glucose, urine, lactate and neurological monitoring.
2Give ceftriaxone 2 g intravenously once daily when the epidemiology supports susceptibility while obtaining immediate infection-specialist advice.
3For XDR-risk exposure or ceftriaxone resistance, use the specialist-selected intravenous carbapenem regimen rather than adding ineffective empirical agents.
4Image and involve surgery immediately for increasing abdominal pain, guarding, ileus, haemorrhage or suspected perforation.

03UNCOMPLICATEDUse susceptibility-directed oral therapyThe patient is stable, can absorb tablets, has no complication and resistance risk is addressed.

1Use azithromycin 500 mg orally once daily for seven days when selected for susceptible uncomplicated infection by local or specialist guidance.
2Use ciprofloxacin only if the isolate is fully susceptible; do not rely on travel region or historical fluoroquinolone use.
3Review fever curve and clinical condition daily; fever may resolve gradually, but deterioration or persistent fever triggers repeat cultures and complication search.
4Ensure hydration, nutrition and medicine-interaction review and do not shorten treatment because temperature falls early.

04PUBLIC HEALTHPrevent onward transmissionTyphoid or paratyphoid is suspected or confirmed.

1Provide the health-protection team with occupation, household, food-handling, care and vulnerable-contact details immediately.
2Follow prescribed exclusion from food handling, healthcare, social care or nursery-related activity and reinforce meticulous hand hygiene.
3Submit clearance stool cultures at the timing and number directed by public health; antibiotics should not be prescribed simply to manipulate a result.
4Evaluate persistent carriage, particularly gallbladder disease, through infection specialists and document travel prevention and vaccination advice.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Provides parenteral treatment for systemic disease when oral absorption is unreliable or complications are present.

Ceftriaxone for severe susceptible enteric fever

Give 2 g intravenously once daily for 10 to 14 days in severe typhoid or paratyphoid when susceptibility is expected or confirmed, with exact duration set clinically.

XDR typhoid may be resistant; check travel geography and susceptibility urgently, review immediate beta-lactam allergy, biliary adverse effects and pregnancy context.

Provides an oral option active against many fluoroquinolone-non-susceptible enteric-fever isolates.

Azithromycin for uncomplicated enteric fever

Give 500 mg orally once daily for seven days when a stable adult has uncomplicated susceptible-pattern infection and the specialist pathway selects azithromycin.

Check QT interval risk, hepatic function, interactions and ability to absorb; severe disease or XDR exposure requires a different strategy.

Offers effective oral therapy for the minority of isolates proven susceptible.

Ciprofloxacin only when fully susceptible

Give 500 mg orally twice daily for seven to 10 days only when laboratory testing confirms full fluoroquinolone susceptibility and oral treatment is clinically appropriate.

Do not use empirically after typical endemic travel; review tendon, aortic, neurological and QT risks, pregnancy, interactions and resistance result.

Treats severe extensively drug-resistant typhoid when ceftriaxone and fluoroquinolones are inactive.

Carbapenem for XDR severe disease

Use the exact local intravenous meropenem regimen, commonly 1 g every eight hours with renal adjustment, only after urgent infection-specialist and microbiology review.

Obtain cultures first when safe, adjust for renal function, assess seizure risk and narrow from carbapenem as soon as susceptibility permits.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Ileal perforation

Necrotic Peyer patches rupture, causing peritonitis, septic shock and urgent need for operative source control. without timely definitive management.

Intestinal haemorrhage

Ulceration erodes bowel vessels and produces occult or major bleeding with anaemia and haemodynamic compromise. without timely definitive management.

Encephalopathy

Severe systemic inflammation causes delirium, reduced consciousness, seizures or focal neurological manifestations. without timely definitive management.

Relapse

Residual intracellular organisms cause recurrent fever and positive cultures after apparent recovery, often with milder symptoms.

Chronic carriage

Persistent gallbladder infection leads to prolonged stool shedding, occupational restrictions and ongoing transmission risk. without timely definitive management.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record temperature curve, haemodynamics, mental state, abdominal findings, stool pattern, intake and urine output each day.
Repeat blood cultures when fever or bacteraemia persists and confirm microbiological clearance in complicated disease.
Monitor full blood count, liver enzymes, creatinine, electrolytes and CRP according to severity and antimicrobial toxicity.
Examine repeatedly for ileal perforation or bleeding, especially with new localised pain, guarding, distension or falling haemoglobin.
Review susceptibility as soon as available and change therapy promptly when ceftriaxone, fluoroquinolone or azithromycin resistance is identified.
Follow public-health-directed stool clearance rather than using routine post-treatment blood tests in a clinically recovered patient.
At discharge document occupation restrictions, contact advice, relapse symptoms, antimicrobial completion and future food, water and vaccination precautions.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Diarrhoea is not required

Systemic fever and constipation can dominate, so absence of loose stool does not exclude typhoid or paratyphoid.

Blood first, stool still useful

Blood culture is more useful early for systemic diagnosis, while stool contributes to diagnosis, typing and transmission management.

Widal testing is unreliable

Background antibodies and cross-reactions limit serology; culture with susceptibility remains the microbiological basis for treatment.

Fever can settle slowly

Several days of fever after active therapy may occur, but physiological deterioration or prolonged persistence requires resistance and complication review.

Resistance is geographical

Exact travel location and antibiotics taken abroad can predict XDR risk before formal susceptibility becomes available.

The gallbladder supports carriage

Organisms can persist in biliary biofilm, especially with gallstones, producing asymptomatic shedding and rare future transmission.

11Common pitfallsFrequent interpretation and management errors.

01
Do not exclude enteric fever because diarrhoea or rose spots are absent.
02
Do not send Widal serology as a replacement for blood cultures.
03
Do not prescribe ciprofloxacin empirically without full susceptibility.
04
Do not delay malaria testing in a febrile returning traveller.
05
Do not overlook new abdominal pain or falling haemoglobin during treatment.
06
Do not return a food handler or care worker to duties without health-protection clearance.