Enteric Fever (Typhoid and Paratyphoid): Complete Clinical Diagnosis and Management

Clinical Medicine Year 3 • systemic Salmonella infection, complications and prevention

Clinical safety note: Use current Uganda Clinical Guidelines, the local antibiogram and culture susceptibility results when selecting antibiotics. Resistance patterns change; the antibiotic examples below are teaching principles and must not replace a current prescription protocol.

Why enteric fever deserves more than a “typhoid” summary

Enteric fever is a bloodstream and reticuloendothelial infection caused by human-adapted Salmonella. It can begin as an apparently mild prolonged fever, then produce intestinal ulceration, gastrointestinal haemorrhage, ileal perforation, encephalopathy, myocarditis, hepatitis, shock or chronic gallbladder carriage. The clinical pattern is modified by early antibiotics, malnutrition, HIV, age and antimicrobial resistance.

The doctor’s task is to combine a careful exposure history, repeated examination, appropriate cultures, malaria and sepsis assessment, early fluids, resistance-aware antimicrobial treatment and surveillance for complications—especially after the first week of illness.

Learning outcomes

Define typhoid and paratyphoid fever and distinguish enteric fever from acute gastroenteritis.
Describe Salmonella antigens, reservoirs, faecal–oral transmission and the pathogenesis of bacteraemia.
Explain the clinical evolution through incubation, week one, week two, week three, relapse and carrier state.
Take a relevant history and identify dehydration, sepsis, intestinal bleeding, perforation and encephalopathy.
Interpret blood/stool/urine culture, susceptibility, full blood count, imaging and the limitations of Widal testing.
Manage uncomplicated, severe, resistant, paediatric and pregnancy-associated disease and arrange surgical review when needed.
Prevent outbreaks through water, sanitation, food safety, vaccination, case notification and carrier control.

1. Definition and terminology

Enteric fever is a systemic febrile illness caused by Salmonella enterica serovar Typhi (typhoid fever) or serovars Paratyphi A, B or C (paratyphoid fever). It is different from non-typhoidal Salmonella gastroenteritis, which usually causes acute diarrhoea after contaminated food and does not follow the same prolonged bacteraemic course.

Typhoid means disease caused by S. Typhi; paratyphoid is caused by S. Paratyphi. Clinically they overlap, and laboratory identification is needed to distinguish them. Humans are the major reservoir for both.

2. Organism and microbiology

Salmonella enterica is a motile, facultative anaerobic, gram-negative bacillus in the Enterobacterales. Important surface structures include:

O (somatic) antigen: part of the lipopolysaccharide cell wall; contributes to endotoxin activity and serological reactions.
H (flagellar) antigen: associated with motility and antibody responses.
Vi capsular antigen: particularly associated with S. Typhi, helping evade phagocytosis and complement. The Vi antigen is also the basis of typhoid conjugate vaccines.
Intracellular survival: organisms can persist in macrophages and the gallbladder, allowing relapse and chronic carriage.

Antimicrobial resistance may involve multidrug resistance, reduced fluoroquinolone susceptibility, extended-spectrum beta-lactamase production and extensively drug-resistant strains. Therefore, a historical “typhoid drug” is not automatically an appropriate modern treatment.

3. Epidemiology and transmission

The supplied teaching deck emphasises contaminated water and food, houseflies, overcrowding, poor personal hygiene, poverty, inadequate sanitation and open defecation. Enteric fever spreads by the faecal–oral route when organisms from an infected person or carrier reach another person’s food or water.

Risk setting/exposure	Why risk rises	Questions to ask
Unsafe water	Human sewage contaminates wells, springs, taps or storage containers	Source, boiling/chlorination, recent water interruption
Street/uncooked food	Food handled after cooking or washed with contaminated water	Raw vegetables, ice, milk, shellfish, vendors
Household case	Shared toilets, hands, food and towels	Anyone with prolonged fever/diarrhoea or recent treatment?
Institutional outbreak	Schools, barracks, prisons, hospitals and crowded settlements amplify exposure	Other students/workers affected?
Chronic carrier	Gallbladder colonisation causes intermittent stool shedding	Food-handler occupation, recurrent family clusters
Travel and resistance	Imported strains may have different resistance patterns	Recent travel, treatment abroad or previous antibiotics

4. Pathogenesis: why fever becomes systemic

4.1 Ingestion and intestinal invasion

After ingestion, organisms must survive gastric acid. They reach the terminal ileum, attach to M cells over Peyer patches and cross the intestinal epithelium. Macrophages ingest them, but the bacteria survive and replicate inside the mononuclear phagocyte system.

4.2 Lymphatic and primary bacteraemia

Organisms pass through mesenteric lymphatics to regional nodes and then the bloodstream. The early bacteraemia may be clinically silent and blood cultures can be negative. The liver, spleen, bone marrow and gallbladder become important sites of intracellular multiplication.

4.3 Secondary bacteraemia and clinical illness

After replication in reticuloendothelial organs, organisms re-enter the bloodstream in larger numbers. Endotoxin and inflammatory mediators produce sustained fever, malaise, relative bradycardia in some patients and organ dysfunction. Organisms return to the intestine through bile, where Peyer patches become swollen, necrotic and ulcerated.

4.4 The ileal ulcer

Longitudinal ulcers in the terminal ileum can erode vessels and cause haemorrhage. Full-thickness necrosis can perforate the bowel, releasing intestinal contents and causing peritonitis, sepsis and shock. The risk rises in untreated or late-presenting disease, often during the second or third week.

4.5 Relapse and carrier state

Relapse may occur after apparent recovery, usually within weeks, and is often shorter and milder. Persistent organisms in the gallbladder—especially with gallstones—can lead to chronic carriage and faecal shedding without symptoms.

5. Incubation and clinical evolution

Incubation is commonly 6–30 days but varies with inoculum, gastric acidity, immunity and previous vaccination. Antibiotics can blur the classical sequence.

Week one: insidious onset

Gradually increasing fever, malaise, headache, anorexia, dry cough and vague abdominal discomfort.
Weakness, myalgia, sore throat or constipation may precede diarrhoea.
The “step-ladder” fever pattern is a teaching classic, not a requirement.

Week two: established systemic disease

Persistent high fever, toxic appearance, coated tongue with a relatively clean tip, abdominal tenderness, diarrhoea or constipation.
Relative bradycardia can occur but is neither sensitive nor specific.
Hepatosplenomegaly and faint salmon-coloured rose spots on the trunk may appear; absence does not exclude disease.
Apathy, confusion, delirium or a “typhoid state” suggests encephalopathy and severe illness.

Week three: complications

Untreated patients may develop intestinal bleeding, perforation, peritonitis, encephalopathy, myocarditis, hepatitis, pneumonia, renal injury, shock or disseminated intravascular coagulation.

Recovery, relapse and prolonged fatigue

Fever and systemic symptoms may abate over two to four weeks after effective therapy, but lethargy, weight loss and reduced concentration can persist. Relapse resembles the original illness but is commonly shorter. Persistent fever must trigger a search for resistance, a complication or an alternative diagnosis.

Urgent danger signs: new severe abdominal pain or guarding, abdominal distension, melena/haematemesis, hypotension, cold extremities, oliguria, repeated vomiting, confusion, seizures, respiratory distress, jaundice or persistent fever despite treatment require admission and senior review.

6. History and examination

6.1 Focused history

Onset, fever pattern, headache, cough, abdominal pain, bowel frequency, constipation/diarrhoea, blood or black stool, vomiting and urine output.
Water source, sanitation, food vendor meals, raw vegetables, ice, unpasteurised milk, shellfish, household cases and institutional exposure.
Previous antibiotics, antimalarials, vaccination, previous enteric fever, travel and resistance history.
Pregnancy, HIV, malnutrition, diabetes, sickle cell disease, immunosuppression and gallbladder disease.
Occupation—food handler, health worker, teacher or caregiver—and ability to isolate from food preparation.

6.2 Examination

Measure temperature, pulse, blood pressure, respiratory rate, oxygen saturation, capillary refill, weight and mental state. Assess hydration, pallor, jaundice, rash and lymph nodes. Examine the mouth/tongue, chest, heart, abdomen for tenderness/distension/guarding, bowel sounds, hepatosplenomegaly and signs of peritonitis. Perform neurological examination for delirium, meningism or focal signs, and rectal examination when bleeding is suspected.

7. Investigations

7.1 Blood culture: the key test

Obtain blood cultures before antibiotics whenever this will not delay resuscitation. Sensitivity is affected by prior treatment, illness stage, blood volume and laboratory quality. In severe disease, more than one set may improve yield. Tell the laboratory that enteric fever is suspected and request susceptibility testing.

7.2 Stool and urine culture

Stool culture is less sensitive early but becomes useful later and is important when investigating a carrier or outbreak. Urine culture is occasionally positive. A positive stool result after treatment may represent carriage rather than acute invasive disease, so interpret it with symptoms and blood-culture history.

7.3 Full blood count and severity tests

Leukopenia can occur; a normal white count does not exclude enteric fever.
Eosinopenia is a classic but non-specific teaching finding.
Severe anaemia should prompt a search for intestinal haemorrhage, malnutrition or another disease.
Thrombocytopenia may accompany severe disease, DIC, bleeding or marrow involvement.
Electrolytes, urea/creatinine, glucose, liver enzymes, bilirubin, coagulation and lactate assess organ dysfunction.

7.4 Widal test: why it misleads

Widal detects agglutinating antibodies against Salmonella antigens. A single titre is unreliable where background antibodies, prior infection, vaccination and cross-reacting infections are common. False positives occur with other Salmonella serotypes, other Enterobacterales, malaria, typhus, cirrhosis and previous whole-cell vaccination; false negatives occur early and in some culture-proven cases. If used at all, paired titres showing a significant rise are more informative, but culture remains preferable.

7.5 Imaging and special tests

Ultrasound can assess hepatosplenomegaly, gallbladder disease, ascites, bowel thickening, abscess or free fluid.
Erect abdominal radiograph may show free sub-diaphragmatic air, but a normal film does not exclude perforation.
CT is useful for uncertain perforation, abscess, pancreatitis or focal complications where available.
Malaria testing, HIV testing, chest imaging, dengue/rickettsial tests and other cultures are guided by local epidemiology and syndrome.

8. Differential diagnosis

Condition	Overlapping features	Helpful distinctions/tests
Malaria	Fever, headache, weakness, splenomegaly	Blood film/RDT; cycles, travel and anaemia; co-infection is possible
Brucellosis	Prolonged fever, sweats, hepatosplenomegaly	Raw dairy/animal exposure, serology/culture, focal osteoarticular disease
Rickettsial/leptospiral disease	Fever, headache, myalgia, rash	Vector/water exposure, conjunctival suffusion, renal/liver pattern and specialised testing
TB/HIV infection	Weight loss, fever, night sweats	Chronic cough/contact, molecular TB test, HIV testing and imaging
Viral hepatitis	Fever, malaise, abdominal symptoms	Marked transaminases, jaundice and viral markers
Endocarditis	Prolonged fever, weight loss, splenomegaly	Murmur, embolic signs and multiple blood cultures
Appendicitis/IBD/amoebiasis	Abdominal pain, diarrhoea or fever	Focal peritonism, stool studies and imaging

9. Management on arrival

9.1 Resuscitation and admission

Assess airway, breathing, circulation, disability and exposure; check glucose and sepsis physiology.
Give oxygen for hypoxia, obtain IV access, take cultures and start appropriate fluids for shock or clinically significant dehydration.
Monitor urine output, mental state, perfusion, electrolytes, lactate and repeat abdominal examinations.
Admit severe disease, pregnancy with systemic toxicity, children with danger signs, immunocompromised patients and anyone unable to drink or adhere safely.

9.2 Fluids and nutrition

Use oral rehydration for stable patients who can drink. Use isotonic IV fluid for shock or severe dehydration, reassessing frequently to avoid pulmonary oedema. Treat hypoglycaemia, correct electrolyte disturbances, continue enteral nutrition when safe and replace ongoing diarrhoeal losses. Avoid NSAIDs when bleeding, renal injury or dehydration is possible.

9.3 Antimicrobial principles

Choose the regimen according to severity, pregnancy, age, site, resistance and culture. Ceftriaxone or azithromycin are common empiric options in many settings, but local guidance may differ. Fluoroquinolones should not be used empirically where reduced susceptibility is common. Severe sepsis, suspected XDR disease, meningitis, treatment failure or an ESBL-producing isolate requires infectious-disease/microbiology advice and often a broader or intravenous regimen.

Uncomplicated disease

Use the national first-line oral option when the patient is stable, can absorb medicines and resistance risk is acceptable. Explain the full course, review culture results and narrow treatment when possible.

Severe disease

Admit, use an appropriate parenteral regimen, monitor perfusion and organ function, then step down to oral therapy after clinical improvement and susceptibility review.

Pregnancy/children

Use age- and pregnancy-compatible therapy from the current guideline; calculate weight-band doses and involve paediatrics/obstetrics for severe disease.

Resistance or treatment failure

Do not simply extend the same antibiotic. Re-culture, check adherence/absorption, image for a complication, assess alternative diagnoses and refer urgently.

10. Managing major complications

10.1 Intestinal haemorrhage

Look for melena, fresh blood, tachycardia, postural symptoms, pallor, falling haemoglobin or shock. Stop NSAIDs, resuscitate with isotonic fluid and blood products as indicated, cross-match, correct coagulopathy, continue appropriate antimicrobial therapy and involve surgery/gastroenterology. Repeated haemoglobin and vital-sign monitoring is essential.

10.2 Ileal perforation and peritonitis

Sudden worsening abdominal pain, guarding, rigidity, rebound, distension, absent bowel sounds, fever or shock is an emergency. Keep the patient nil by mouth, give IV fluids, analgesia and broad-spectrum antibiotics covering enteric organisms, correct electrolytes, insert a nasogastric tube when indicated, obtain imaging without delaying surgery and involve a surgeon for source control.

10.3 Encephalopathy, seizures and meningitis

Check glucose, oxygenation, electrolytes, malaria and meningism. Protect the airway, treat seizures, avoid sedating drugs where possible, assess for cerebral oedema and seek high-dependency/neurological care. Do not label confusion as “typhoid state” until hypoglycaemia, sepsis, meningitis, drug toxicity and other causes have been assessed.

10.4 Shock and organ failure

Use sepsis principles: cultures, cautious fluid resuscitation, lactate, urine-output monitoring, vasopressor support when indicated, renal/liver support and repeated examination. Search for perforation, bleeding, myocarditis and co-infection.

10.5 Hepatitis, myocarditis and pancreatitis

Jaundice, tender hepatomegaly, arrhythmia, heart failure, chest pain or persistent vomiting warrants ECG, troponin/echo when available, liver tests, pancreatic enzymes and specialist care. Distinguish infection-related organ injury from antibiotic toxicity.

11. Follow-up, relapse and chronic carriage

Review fever, hydration, bowel function, abdominal signs, weight, appetite, adherence and adverse effects.
Fever can take several days to settle; worsening after initial improvement suggests resistance, a complication, poor absorption, non-adherence or a new diagnosis.
Relapse commonly occurs after fever subsides or treatment stops and is often milder. Re-culture and review susceptibility rather than repeating an unverified prescription.
Persistent stool shedding may indicate a chronic carrier, especially with gallbladder disease or stones. Food handlers require public-health and occupational assessment, repeat cultures and specialist eradication planning.

12. Prevention, vaccination and outbreak control

12.1 The four prevention pillars

Safe water: protect wells, chlorinate/boil water, use covered containers and safe household storage.
Sanitation: toilets, safe sewage disposal, no open defecation and functioning drainage.
Food hygiene: handwashing, thorough cooking, safe refrigeration and exclusion of symptomatic food handlers.
Vaccination: typhoid conjugate vaccine according to Uganda’s programme and outbreak policy; it complements, not replaces, sanitation.

12.2 Outbreak response

Notify public health, define and line-list cases, collect cultures, map common water/food exposures, inspect sanitation, provide safe water, communicate risk clearly and monitor contacts. Do not use mass antibiotics as a substitute for source control.

13. Clinical reasoning examples

Example A: prolonged fever with a negative Widal

A young adult has 12 days of fever, headache, constipation and abdominal discomfort. The Widal test is negative. This does not exclude enteric fever. Obtain blood cultures if possible, test for malaria and assess hydration, abdominal tenderness and alternative infections. Treat according to syndrome and local guidance if severely ill while awaiting results.

Example B: fever followed by melena

A patient treated for presumed typhoid develops black stool and tachycardia in week three. Manage as gastrointestinal bleeding: resuscitate, cross-match, repeat haemoglobin, perform serial abdominal examinations and involve surgery/gastroenterology. Do not simply add another oral antibiotic.

Example C: persistent fever after ceftriaxone

Reassess the diagnosis, culture and susceptibility, adherence, dosing, absorption, abscess/perforation, malaria/TB/brucellosis and drug fever. Persistent fever alone is not proof that the organism is resistant, but it is a reason for structured reassessment.

14. Examination pearls

Enteric fever is systemic Salmonella infection; watery diarrhoea alone is not enough to diagnose it.
The step-ladder fever, rose spots and relative bradycardia are useful teaching clues but are not required.
Blood culture is more valuable than a single Widal titre.
Leukopenia, eosinopenia or normal haemoglobin may occur; laboratory patterns are supportive, not diagnostic.
Always reassess for perforation and bleeding after the first week.
Antibiotic resistance and local susceptibility should guide therapy.
Chronic carriers are a public-health risk even when asymptomatic.

15. References

SlideShare: Enteric Fever teaching deck — epidemiology, pathogenesis, clinical course, investigations, complications, management, prevention and vaccination.
Uganda Clinical Guidelines and current Ministry of Health antimicrobial guidance.
WHO typhoid conjugate-vaccine and enteric-fever prevention guidance.
Current local laboratory susceptibility reports and outbreak-control protocols.