Enteric Fever

Dr. Parag Chauhan

Introduction

Enteric fever is a systemic infectious disease primarily affecting the gastrointestinal tract and reticuloendothelial system.

  • It is caused by:

    • Salmonella enterica serovar Typhi (Typhoid fever)

    • Salmonella enterica serovar Paratyphi (Paratyphoid fever)

  • The disease is transmitted through the fecal–oral route, mainly by ingestion of:

    • Contaminated food

    • Contaminated water

  • It is closely associated with:

    • Poor sanitation

    • Unsafe drinking water

    • Inadequate sewage disposal

    • Poor personal hygiene

  • Enteric fever is more common in:

    • Developing countries

    • Overcrowded communities

    • Areas with limited access to clean water

  • After ingestion, the organism:

    • Invades intestinal mucosa

    • Multiplies in Peyer’s patches

    • Enters bloodstream (bacteremia)

    • Spreads to liver, spleen, and bone marrow

  • Clinically characterized by:

    • Prolonged high-grade fever

    • Headache

    • Abdominal pain

    • Weakness

    • Rose spots (in some patients)

 

Etiological Agent

  • Enteric fever is caused by Gram-negative bacilli belonging to the family Enterobacteriaceae.

  • The main causative organisms are:

    • Salmonella enterica serovar Typhi

    • Salmonella enterica serovar Paratyphi (A, B, C)

  • S. Typhi causes classical and more severe typhoid fever.

  • S. Paratyphi usually causes a milder form of the disease.

Morphological Characteristics

  • Gram-negative rods

  • Motile (peritrichous flagella)

  • Non-spore forming

  • Facultative anaerobes

Important Antigens

  • O antigen – Somatic antigen (heat stable)

  • H antigen – Flagellar antigen (heat labile)

  • Vi antigen – Capsular antigen (important virulence factor in S. Typhi)

Virulence Factors

  • Ability to survive within macrophages

  • Endotoxin (LPS) causing systemic symptoms

  • Vi antigen helps in immune evasion

 

Epidemiology

  • Enteric fever is a waterborne and foodborne disease.

  • It is endemic in:

    • South Asia

    • Southeast Asia

    • Sub-Saharan Africa

    • Parts of Latin America

  • High incidence in countries with:

    • Poor sanitation

    • Inadequate sewage disposal

    • Unsafe drinking water

  • Commonly affects:

    • Children and young adults

    • Low socioeconomic populations

  • Transmission occurs through:

    • Contaminated water

    • Contaminated food

    • Food handlers who are chronic carriers

  • Chronic carriers harbor bacteria in the gallbladder and shed organisms in stool.

    • Classic example: Mary Mallon

  • Incidence increases during:

    • Rainy seasons

    • Floods

    • Natural disasters

  • Global burden remains significant despite availability of vaccines.

 

Mode of Transmission

https://www.newsclick.in/sites/default/files/2023-05/bundelkhand%20water%20crisis.jpeg

  • Enteric fever is transmitted mainly by the fecal–oral route.

  • Infection occurs through ingestion of:

    • Contaminated drinking water

    • Contaminated food

    • Raw vegetables washed with unsafe water

    • Street food prepared under unhygienic conditions

  • Sources of infection:

    • Patients in acute stage

    • Chronic carriers (organism persists in gallbladder)

  • Chronic carrier example:

    • Mary Mallon

  • Flies may act as mechanical vectors, carrying organisms from feces to food.

  • Person-to-person transmission may occur in areas with poor hygiene.

 

Pathogenesis

Step-wise Mechanism:

  1. Ingestion of contaminated food/water.

  2. Organisms survive gastric acid (especially when gastric acidity is low).

  3. Reach small intestine → invade Peyer’s patches (lymphoid tissue of ileum).

  4. Taken up by macrophages and multiply intracellularly.

  5. Enter bloodstream → Primary bacteremia (often asymptomatic).

  6. Localize in reticuloendothelial system:

    • Liver

    • Spleen

    • Bone marrow

  7. Multiply further → Secondary bacteremia → Clinical symptoms appear.

  8. Reinvasion of intestine → Inflammation, necrosis, and ulceration of Peyer’s patches.

  9. Severe cases may lead to intestinal hemorrhage or perforation.

 

Clinical Features

  • Incubation period: 7–14 days (range 3–60 days).

General Symptoms

  • Prolonged high-grade fever (step-ladder pattern)

  • Headache

  • Malaise and weakness

  • Loss of appetite

  • Body ache

Gastrointestinal Symptoms

  • Abdominal pain

  • Constipation (early stage)

  • Diarrhea (later stage)

  • Coated tongue

Physical Signs

  • Relative bradycardia (Faget sign)

  • Hepatosplenomegaly

  • Abdominal tenderness

Characteristic Sign

  • Rose spots:

    • Faint salmon-colored maculopapular rash

    • Seen on trunk

    • Usually appears in 2nd week

Severe Cases

  • Delirium (“Typhoid state”)

  • Encephalopathy

 

Complications

Complications usually occur in 3rd week if untreated.

Intestinal Complications

  • Intestinal hemorrhage

  • Intestinal perforation (most serious)

  • Peritonitis

Systemic Complications

  • Septic shock

  • Encephalopathy

  • Myocarditis

  • Pneumonia

  • Hepatitis

Chronic Complication

  • Chronic carrier state

 Mortality increases significantly if complications are not managed promptly.

Laboratory Diagnosis

Laboratory diagnosis depends on the stage of disease and aims to detect either the organism or antibodies.

A. Specimen Collection (According to Week of Illness)

  • 1st week → Blood culture (best method)

  • 2nd week → Widal test, blood culture

  • 3rd week onward → Stool and urine culture

  • Bone marrow → Any stage (highest sensitivity)

B. Direct Detection of Organism (Culture Methods)

1. Blood Culture (Gold Standard in 1st Week)

  • Most reliable early diagnostic method

  • 5–10 mL blood collected before antibiotics

  • Culture media:

    • Bile broth

    • Automated blood culture systems

  • Positive in 60–80% cases (early stage)

Advantages:

  • Confirms diagnosis

  • Allows antibiotic sensitivity testing

2. Bone Marrow Culture

  • Most sensitive method (up to 90–95%)

  • Remains positive even after antibiotic therapy

  • Useful in complicated or treated cases

3. Stool Culture

  • Positive from 2nd–3rd week

  • Useful for detecting carriers

  • Selective media:

    • MacConkey agar

    • XLD agar

    • DCA agar

4. Urine Culture

  • May be positive in later stages

  • Less sensitive than blood culture

C. Identification of Isolate

  • Gram-negative bacilli on Gram staining

  • Biochemical tests:

    • Non-lactose fermenter

    • TSI: Alkaline slant / Acid butt with H₂S

  • Serotyping with O, H, and Vi antisera

Causative organisms:

  • Salmonella enterica serovar Typhi

  • Salmonella enterica serovar Paratyphi

D. Serological Tests

1. Widal Test

  • Detects antibodies against:

    • O antigen

    • H antigen

  • Becomes positive after 7–10 days

Interpretation:

  • Significant rise in antibody titer

  • Single high titer in endemic areas may be misleading

Limitations:

  • False positives

  • False negatives

  • Baseline titers vary in endemic regions

2. Rapid Tests

  • TyphiDot

  • IgM/IgG ELISA

  • Tubex test

Advantages:

  • Quick results

  • Useful in resource-limited settings

Limitations:

  • Variable sensitivity and specificity

E. Molecular Methods

  • PCR (Polymerase Chain Reaction)

  • High sensitivity

  • Useful in early diagnosis

  • Expensive and not widely available

F. Hematological Findings (Supportive)

  • Leukopenia

  • Relative lymphocytosis

  • Mild anemia

  • Elevated ESR

  • Thrombocytopenia (in severe cases)

 

Prevention & Control 

Prevention of enteric fever focuses on interrupting fecal–oral transmission, improving sanitation, vaccination, and early treatment of cases.

A. Personal Preventive Measures

  • Drink safe and treated water (boiled, filtered, chlorinated).

  • Avoid consumption of:

    • Uncovered street food

    • Raw vegetables washed with unsafe water

  • Practice proper hand hygiene:

    • Before eating

    • After using toilet

  • Maintain proper food hygiene:

    • Thorough cooking

    • Safe storage

  • Avoid close contact with infected individuals during acute illness.

B. Community-Level Control Measures

  • Provision of safe drinking water supply.

  • Proper sewage disposal systems.

  • Improvement of sanitation facilities.

  • Health education regarding hygiene practices.

  • Regular inspection of food establishments.

  • Surveillance during outbreaks.

C. Identification and Management of Carriers

  • Chronic carriers may harbor organisms in the gallbladder.

  • Regular stool examination in food handlers.

  • Appropriate antibiotic therapy for carriers.

  • In some cases, cholecystectomy may be required.

D. Vaccination

Vaccination plays a key role in prevention, especially in endemic areas.

Available Vaccines:

  1. Vi Polysaccharide Vaccine

    • Injectable

    • Given after 2 years of age

    • Booster every 3 years

  2. Ty21a Vaccine

    • Live attenuated oral vaccine

    • Given in capsule form

  3. Typhoid Conjugate Vaccine (TCV)

    • Can be given from 6 months of age

    • Provides longer immunity

    • Recommended in national immunization programs of endemic countries

E. Public Health Strategies

  • Early diagnosis and prompt treatment.

  • Antibiotic sensitivity testing to monitor MDR strains.

  • Reporting and surveillance of cases.

  • Mass vaccination campaigns in high-risk areas.

 

MCQs

  1. Enteric fever is caused by:
    A. E. coli
    B. Vibrio cholerae
    C. Salmonella Typhi
    D. Shigella
    Answer: C

  2. Typhoid fever is caused by:
    A. Salmonella Typhi
    B. Salmonella Paratyphi
    C. Shigella
    D. Campylobacter
    Answer: A

  3. Salmonella Typhi is:
    A. Gram-positive cocci
    B. Gram-negative bacilli
    C. Acid-fast bacilli
    D. Spirochete
    Answer: B

  4. The Vi antigen is a:
    A. Flagellar antigen
    B. Capsular antigen
    C. Nuclear antigen
    D. Ribosomal antigen
    Answer: B

  5. Salmonella belongs to which family?
    A. Vibrionaceae
    B. Enterobacteriaceae
    C. Neisseriaceae
    D. Bacillaceae
    Answer: B

  6. Main mode of transmission is:
    A. Airborne
    B. Fecal–oral
    C. Vector-borne
    D. Blood-borne
    Answer: B

  7. A common source of infection is:
    A. Mosquito bite
    B. Contaminated water
    C. Animal bite
    D. Soil contact
    Answer: B

  8. Chronic carriers usually harbor organisms in the:
    A. Kidney
    B. Gallbladder
    C. Lung
    D. Heart
    Answer: B

  9. Enteric fever is common in areas with:
    A. Good sanitation
    B. Poor sanitation
    C. Cold climate
    D. High altitude
    Answer: B

  10. Mechanical vector in transmission is:
    A. Mosquito
    B. Housefly
    C. Tick
    D. Louse
    Answer: B

  11. Salmonella invades which intestinal structure?
    A. Brunner’s glands
    B. Peyer’s patches
    C. Villi tips
    D. Gastric glands
    Answer: B

  12. Primary bacteremia occurs in the:
    A. Early stage
    B. Late stage
    C. Recovery phase
    D. Carrier stage
    Answer: A

  13. Salmonella multiplies mainly inside:
    A. RBCs
    B. Macrophages
    C. Platelets
    D. Neurons
    Answer: B

  14. Incubation period of enteric fever is:
    A. 1–2 days
    B. 3–5 days
    C. 7–14 days
    D. 30 days
    Answer: C

  15. Classical fever pattern is:
    A. Intermittent
    B. Remittent
    C. Step-ladder
    D. Biphasic
    Answer: C

  16. Rose spots appear during the:
    A. 1st week
    B. 2nd week
    C. 3rd week
    D. 4th week
    Answer: B

  17. Relative bradycardia is called:
    A. Murphy sign
    B. Faget sign
    C. Kernig sign
    D. Romberg sign
    Answer: B

  18. Most common symptom is:
    A. Rash
    B. Fever
    C. Paralysis
    D. Jaundice
    Answer: B

  19. Intestinal perforation usually occurs in the:
    A. 1st week
    B. 2nd week
    C. 3rd week
    D. Recovery stage
    Answer: C

  20. Most serious complication is:
    A. Pneumonia
    B. Intestinal perforation
    C. Arthritis
    D. Otitis
    Answer: B

  21. Gold standard test in 1st week is:
    A. Widal test
    B. Stool culture
    C. Blood culture
    D. Urine test
    Answer: C

  22. Most sensitive diagnostic method is:
    A. Blood culture
    B. Widal test
    C. Bone marrow culture
    D. ELISA
    Answer: C

  23. Widal test detects antibodies against:
    A. Capsule only
    B. O and H antigens
    C. Toxin
    D. DNA
    Answer: B

  24. Widal test becomes positive after:
    A. 2 days
    B. 4 days
    C. 7–10 days
    D. 1 month
    Answer: C

  25. Stool culture is useful in:
    A. 1st week
    B. 2nd–3rd week
    C. Before symptoms
    D. Never
    Answer: B

  26. Salmonella on MacConkey agar is:
    A. Lactose fermenter
    B. Non-lactose fermenter
    C. Hemolytic
    D. Swarming
    Answer: B

  27. TSI reaction shows:
    A. A/A
    B. K/K
    C. K/A with H2S
    D. No reaction
    Answer: C

  28. Leukocyte count is usually:
    A. Increased
    B. Decreased
    C. Very high
    D. Extremely high
    Answer: B

  29. Drug commonly used is:
    A. Penicillin
    B. Ceftriaxone
    C. Metronidazole
    D. Acyclovir
    Answer: B

  30. MDR typhoid means resistance to:
    A. One drug
    B. Two drugs
    C. First-line drugs
    D. All antibiotics
    Answer: C

  31. Supportive therapy includes:
    A. ORS
    B. Insulin
    C. Steroids in all cases
    D. Antifungals
    Answer: A

  32. Main preventive measure is:
    A. Isolation only
    B. Sanitation
    C. Bed rest
    D. Vitamins
    Answer: B

  33. Vi polysaccharide vaccine is given after:
    A. Birth
    B. 6 months
    C. 2 years
    D. 10 years
    Answer: C

  34. Oral live typhoid vaccine is:
    A. BCG
    B. Ty21a
    C. OPV
    D. MMR
    Answer: B

  35. Typhoid conjugate vaccine can be given from:
    A. Birth
    B. 6 months
    C. 5 years
    D. 12 years
    Answer: B

  36. Most common organ enlargement is:
    A. Kidney
    B. Spleen
    C. Pancreas
    D. Brain
    Answer: B

  37. Chronic carrier detection is done by:
    A. Blood test
    B. Stool culture
    C. Urine dipstick
    D. X-ray
    Answer: B

  38. Endotoxin of Salmonella is:
    A. Protein toxin
    B. Lipopolysaccharide
    C. Enzyme
    D. Capsule
    Answer: B

  39. Paratyphoid fever is usually:
    A. More severe
    B. Milder
    C. Always fatal
    D. Chronic
    Answer: B

  40. Rose spots are seen on:
    A. Face
    B. Trunk
    C. Hands
    D. Feet
    Answer: B

  41. Major risk factor is:
    A. Cold weather
    B. Poor hygiene
    C. Exercise
    D. Sunlight
    Answer: B

  42. Intestinal hemorrhage is due to:
    A. Liver damage
    B. Peyer’s patch ulceration
    C. Kidney failure
    D. Platelet excess
    Answer: B

  43. Bone marrow culture remains positive even after:
    A. Vaccination
    B. Antibiotic therapy
    C. Recovery
    D. Carrier state ends
    Answer: B

  44. Enteric fever primarily affects:
    A. Respiratory system
    B. Gastrointestinal system
    C. Nervous system
    D. Skin only
    Answer: B

  45. Early constipation later changes to:
    A. Vomiting
    B. Diarrhea
    C. Paralysis
    D. Jaundice
    Answer: B

  46. Step-ladder fever means:
    A. Sudden rise and fall
    B. Gradual daily rise
    C. Biphasic fever
    D. Intermittent fever
    Answer: B

  47. Antibiotic sensitivity testing is done by:
    A. Widal test
    B. Culture
    C. ELISA
    D. PCR
    Answer: B

  48. Gallbladder involvement is important in:
    A. Acute phase
    B. Carrier state
    C. Recovery
    D. Vaccination
    Answer: B

  49. Most effective long-term prevention is:
    A. Antibiotics alone
    B. Vaccination only
    C. Improved sanitation
    D. Bed rest
    Answer: C

  50. Enteric fever is also known as:
    A. Cholera
    B. Dysentery
    C. Typhoid fever
    D. Malaria
    Answer: C