Salmonella typhi Infection

Organism:  Gram Negative, flagellated organism

Transmission:  faecal oral transmission

Epidemiology

• Natural Hosts: Ducks, birds
• Pets: Reptiles Birds
• Foodborne Illness Sources (95%)
  • Eggs
  • Cheese
  • Dry cereal
  • Unpasterurized milk or juice
  • Ice Cream
  • Poultry
  • Contaminated unpeeled fruit
  • Contaminated vegetables

Salmonella infection may manifest as

• Gastroenteritis
• Enteric fever
• Bacteremia

Gastroenteritis 

• Caused by Salmonella typhimurium (non-typhoid) and Salmonella enteritidis 
• usually starts 12 to 48 hours after ingestion of organisms, with nausea and cramping abdominal pain followed by diarrhea, fever, and sometimes vomiting. 
• Usually, the stool is watery but may be a pastelike semisolid. 
• Rarely, mucus or blood is present 
• The disease is usually mild, lasting 1 to 4 days
• Occasionally, a more severe, protracted illness occurs. 
• About 10 to 30% of adults develop reactive arthritis weeks to months after diarrhea stops. 
• This disorder causes pain and swelling, usually in the hips, knees, and Achilles tendon.

Enteric fever

• is a term often used interchangeably with typhoid fever
• organism:
  • S. enterica serotype Typhi (formerly S. typhi)
  • “Nontyphoidal” Salmonellae may also cause severe illness consistent with enteric fever
• characterized by
  • severe systemic illness with fever
  • abdominal pain
• most prevalent in impoverished areas that are overcrowded with poor access to sanitation. 

CLINICAL FEATURES

• incubation
  • first 5-21 days after ingestion depending on inoculum load
  • may be up to 60 days
  • Usually asymptomatic in Incubation Period
• Active infection
  • a febrile illness with onset of symptoms 5 to 21 days after ingestion of the causative microorganism in contaminated food or water.
• first week of illness
  • rising (“stepwise”) fever and bacteremia develop 
  • Intermittent Fever initially, then sustained Fever to high Temperatures later
• second week of illness
  •  abdominal pain develops
  • “rose spots” (faint salmon-colored macules on the trunk and abdomen)
• third week of illness
  • hepatosplenomegaly
  • intestinal bleeding

Complications (occurs in 10-15% of cases)

• Typhoid encephalopathy
• Bacteremia
• Peritonitis
• Septic Shock
• Peyer patch necrosis (sites of Salmonella infiltration at Small Intestine lymphoid Nodules)
• Gastrointestinal Bleeding (2-10% of cases)
• Bowel perforation
• Endocarditis/Mycotic aneurysm (10% of patients over age 50 years old)
• Septic Arthritis or Osteomyelitis
• Pneumonia

• Bacteremia is more likely to occur in immunologically compromised patients (eg, those with HIV/AIDS) and in patients with a hemolytic condition (eg, sickle cell anemia, malaria, Oroya fever)
• Recurrent or multiple episodes of Salmonella infection in a patient without other risk factors should prompt HIV testing.

Effect of antimicrobial therapy

• In the pre-antibiotic era, mortality rates were 15 percent or greater and survivors experienced a prolonged illness lasting weeks, with months of subsequent debilitation. 
• Approximately 10 percent of untreated patients relapsed, and up to 4 percent become chronic carriers of the organism.
• In the post-antibiotic era, the average mortality rate from typhoid fever is estimated to be less than 1%
• typhoid has become resistant to chloramphenicol,ampicillin, fluoroquinolones (Ciprofloxacin), and third generation cephalosporins. 
• Only azithromycin, members of the carbapenem class, and tigecycline remain effective

Oral Antibiotics (as per eTG)

• Azithromycin:
  • Adults: 1 g orally on the first day, then 500 mg daily for 4 days.
  • Children: 20 mg/kg (up to 1 g) on the first day, then 10 mg/kg (up to 500 mg) daily for 4 days.
• Ciprofloxacin:
  • Adults: 500 mg orally every 12 hours for 5 days.
  • Children: 12.5 mg/kg (up to 500 mg) orally every 12 hours for 5 days.
  • Note: Ciprofloxacin is not licensed for children due to potential cartilage development issues but can be used if it’s the drug of choice.
• Amoxicillin (if pathogen is susceptible):
  • Adults: 1 g orally every 8 hours for 5 days.
  • Children: 30 mg/kg (up to 1 g) orally every 8 hours for 5 days.

Intravenous Therapy

• When to Use:
• When oral therapy is not possible.
  • Children aged 1 to 3 months.
  • Patients with bacteremia, endovascular infection, or osteoarticular infection.
• Medications:
  • Ceftriaxone:
    • Adults: 2 g intravenously daily.
    • Children 1 month or older: 100 mg/kg (up to 2 g) intravenously daily.
    • For severe cases: 1 g (child 1 month or older: 50 mg/kg up to 1 g) intravenously every 12 hours.
  • Ciprofloxacin:
    • Adults: 400 mg intravenously every 12 hours.
    • Children: 10 mg/kg (up to 400 mg) intravenously every 12 hours.
• Duration of Therapy:
  • Depends on the infection site—seek expert advice.
  • For uncomplicated infection, switch to oral therapy when the patient becomes afebrile.
  • Intravenous therapy may be needed for the entire duration in patients with bacteremia, endovascular infection, osteoarticular infection, and in children younger than 3 months.

• Rates of chronic carriage after S. typhi infection range from 1 -6 %
• Represent an infectious risk to others, particularly in the setting of food preparation.
  • The story of “Typhoid Mary,” a cook in early 20th century New York who infected approximately 50 people (three fatally), highlights the role of asymptomatic carriers in maintaining the cycle of person-to-person spread
  • For this reason, eradication of carriage when identified should be attempted. 
• Excretion of the organism in stool or urine >12 months after acute infection. 
• Chronic carriage in the urine is almost always associated with a defect in the urinary tract (eg, urolithiasis, prostatic hyperplasia) or concurrent bladder infection with Schistosoma.
• as per eTG: Carrier State: Antibiotics are not indicated for asymptomatic short-term carriers of Salmonella. (🙄)
• Chronic Carriers:
  • defined as sn asymptomatic person who sheds S. Typhi for more than 12 months.
  • contact tracing is necessary
    • Those living in the same household, sharing a bathroom, or eating food prepared by the case while infectious.
    • Those who traveled with the case and were likely exposed to the same source of infection.
  • Investigation
    • Manage as with other positive cases (faecal clearance and exclusion).
    • Assess gall bladder function; consider cholecystectomy if gallstones are present.
    • Investigate urinary tract for possible urinary carriers
  • Treatment
    • Consult an infectious disease physician.
    • Recommended regimen: 750 mg ciprofloxacin or 400 mg norfloxacin twice daily for 28 days (80-90% success rate).
• High-Risk Cases:
  • Food handlers.
  • Carers of patients, children, and the elderly.
  • Those unable to maintain personal hygiene and their carers.
  • Excluded from high-risk duties until 2 consecutive stool specimens collected one week apart (and not sooner than 48 hours post cessation of antibiotics) are negative.
  • May return to work for non-high-risk duties after being symptom-free for 48 hours.
• Asymptomatic High-Risk Contacts:
  • Excluded from work, school, and childcare until 2 negative stool samples (at least 24 hours apart).
  • May undertake non-high-risk duties while awaiting results.
• Asymptomatic Non-High-Risk Household Contacts:
  • Provide 2 stool samples 24 hours apart.
  • No exclusion needed.
• Other Asymptomatic Non-High-Risk Contacts:
  • No stool samples or exclusion required.

Prevention

• Water Disinfection
• Steam or boil shellfish at least 10 minutes
• All milk and dairy products should be pasteurized
• Control fly populations

• Hand Hygiene:
  • Wash hands frequently and thoroughly with hot, soapy water.
  • Ensure hand washing before eating, preparing food, and after using the toilet.
  • Carry an alcohol-based hand sanitiser for use when water isn’t available.
• Water Safety:
  • Avoid drinking untreated water.
  • Drink only bottled water or canned/bottled carbonated beverages.
  • Avoid ice in drinks.
  • Brush teeth using bottled water.
• Food Safety:
  • Avoid raw vegetables or fruits that cannot be peeled.
  • Eat foods that have been thoroughly cooked and are still hot and steaming.
  • Avoid foods and drinks from street stalls.

Typhoid Vaccine

Vaccine Type	Vi Polysaccharide Vaccine (Typhim Vi)	Oral Typhoid Vaccine (Vivotif)
Administration	Injectable	Oral (live attenuated)
Dosing Schedule	Single dose	Four capsules taken on alternate days
Onset of Protection	Within 2 weeks after vaccination	1 week after the final dose
Duration of Protection	At least 2 years	At least 3 years
Booster Frequency	Every 2 to 3 years if at continued risk	Every 3 years if at continued risk
Efficacy	Approximately 50-80%	Approximately 50-80%
Suitable for	Individuals aged 2 years and older	Individuals aged 6 years and older
Special Considerations	Safe for immunocompromised individuals	Requires adherence to dosing schedule
Additional Notes	Non-live vaccine	Not suitable for immunocompromised individuals