Enteric Fever and Salmonella Characteristics

Enteric Fever (Typhoid Fever)

• Typhoid fever is a significant health problem in developing countries
• The World Health Organization (WHO) estimates over 21.7 million cases annually, with the majority in Asia, resulting in over 200,000 deaths
• Typhoid Mary Mallon, a food handler, was responsible for infecting at least 78 people, with 5 fatalities. She highlights the risk of infectious carriers to public health

Etiology

• Enteric fever is caused by Salmonella enterica serovar Typhi (S. Typhi), a gram-negative bacterium
• Similar, but often less severe, illnesses are caused by S. Paratyphi A, B, and C
• The ratio of illnesses caused by S. Typhi to S. Paratyphi is approximately 10:1

Salmonellae characteristics

• Salmonellae are motile, non-spore-forming, non-encapsulated, gram-negative rods that grow aerobically
• They are resistant to many physical agents, but susceptible to heating to 54.4°C for 1 hour or 60°C for 15 minutes
• The bacteria can survive for weeks in sewage, dried foods, and feces

Mode of Transmission

• Direct or indirect contact with an infected person (either sick or a carrier) is necessary for infection
• Ingestion of contaminated food or water (fecal-oral route) is the most common method of transmission
• Waterborne outbreaks, due to sanitation issues and poor personal hygiene, are common in developing nations
• Transplacental infection from an infected mother to her fetus is possible.

Who Can Be Infected?

• Anyone can be infected, but the elderly, infants, and immunocompromised individuals (e.g., those with AIDS or sickle cell anemia) are at higher risk

Clinical Features

• Incubation period typically ranges from 7-14 days, but can vary depending on the infecting dose (3-30 days)
• Clinical presentation can range from mild (low-grade fever, malaise, slight cough) to severe (abdominal discomfort, complications)
• Factors influencing the severity include the duration of illness before treatment, type of antimicrobial treatment, age, prior exposure/vaccination, virulence of the bacteria, quantity ingested, and other host factors..

Clinical Features in Children

• Onset is insidious (gradual)
• Initial symptoms (fever, malaise, anorexia, myalgia, headache and abdominal pain) can develop over 2-3 days
• Diarrhoea with subsequent constipation can be a prominent symptom
• Cough and epistaxis may occur
• Severe lethargy may develop in some children
• Temperature often reaches 40°C
• During the second week of illness, fever persists, fatigue, anorexia, cough, and abdominal symptoms worsen
• Patients can appear acutely ill, disoriented, and lethargic; delirium and stupor may be observed

Physical Findings

• Relative bradycardia, hepatomegaly, splenomegaly, and a distended abdomen with diffuse tenderness are common
• Macular- or maculopapular rash (rose spots) on the 7th-10th day in about 50% of patients; culture from the spots yields Salmonella in 60% of cases
• Auscultation may reveal rhonchi and scattered rales
• Nausea and vomiting during the 2nd or 3rd week may suggest complications
• Without complications, symptoms and findings resolve within 2-4 weeks

Infants and Young Children (<5 Years)

• Enteric fever is relatively rare in this age group
• Even though clinical sepsis may occur the presentation is typically mild, making diagnosis difficult
• Diarrhea is a more frequent symptom in this age group compared to adults, potentially misdiagnosed as a viral syndrome

Neonates

• Enteric fever during late pregnancy can be transmitted vertically (from the mother to the newborn)
• Neonatal disease usually begins within 3 days of delivery
• Symptoms may include vomiting, diarrhea, abdominal distention, fever (up to 40.5°C), seizures, hepatomegaly, jaundice, anorexia, and weight loss.

Common Clinical Features in Children

• High-grade fever, coated tongue, anorexia, vomiting, hepatomegaly, diarrhea, toxicity, abdominal pain, pallor, splenomegaly, constipation, headache, jaundice, obtundation, ileus, perforation

Complications

• Untreated enteric fever can lead to complications such as severe diarrhea, intestinal bleeding, perforation, persistent high fever, becoming a carrier, weight loss, delirium, hallucinations, meningitis, encephalopathy, hepatitis, cholecystitis, endocarditis, myocarditis, heart failure, shock, pneumonia, anemia, osteomyelitis, or septic arthritis

Diagnosis

• Mainstay is a positive culture from blood or other site
• Blood cultures positive 40-60% of the time, while stool and urine cultures become positive after 1 week
• Bone marrow cultures can confirm diagnosis (85-90% positive) but are invasive.
• Stool or urine cultures become positive after the first week

Widal Test

• Significant antibody titers can aid in diagnosis
• A rise in antibody levels in a paired sample (taken at different times) is more significant than a single sample. A four-fold increase in paired tests is the standard.
• Non-typhoid Salmonella infections can cause false positives
• Widal tests are not always standardized, hence can be unreliable

Direct Detection of Salmonella

• Detecting specific antigens in the urine (e.g., S. Typhi Vi antigen) can aid in diagnosis
• Polymerase Chain Reaction (PCR) amplifies specific genes in patient blood, enabling quick diagnosis (within hours)

Laboratory Investigations

• Normochromic, normocytic anemia often develops weeks after fever
• Leukocyte counts are often low (leukopenia) but can vary widely
• Thrombocytopenia may occur for a week or more
• Liver function tests are often disturbed.
• Proteinuria.
• Fecal leukocytes and fecal blood are common

Differential Diagnosis

• During the initial stage, enteric fever can be mistaken for gastroenteritis, viral syndromes, bronchitis, or bronchopneumonia.
• Other differential diagnoses in later stages include sepsis with other bacteria, intracellular infections (tuberculosis, brucellosis), and viral infections (infectious mononucleosis).

Treatment

• General principles: adequate rest, hydration, attention to fluid-electrolyte balance
• Antipyretic therapy (e.g., acetaminophen) as needed
• Soft, easily digestible diet, unless the patient exhibits abdominal distention or ileus
• Antibiotic therapy is crucial to reduce complications
• Examples of antibiotics that have been useful in many cases include ampicillin, amoxicillin, trimethoprim-sulfamethoxazole (TMP-SMZ), cefixime, ceftriaxone, and ofloxacin. Doses and duration are varied
• Short courses of antibiotics may be adequate in many cases

Treatment Duration

• Most children become afebrile within 7 days, but treatment of uncomplicated cases should continue for at least 14 days.
• Resistant strains are usually susceptible to third-generation cephalosporins.
• Other considerations for treatment of severe sepsis, shock, or coma (including dexamethasone) are indicated when appropriate

Eradication of Chronic Carriage

• A prolonged course (4-6 weeks) of high-dose ampicillin (or amoxicillin), possibly combined with probenecid or TMP-SMZ, can help eradicate the infection.
• Cholecystectomy might be an option alongside antibiotics, if gallstones exist
• Cholecystectomy would be considered if biliary tract problems are suspected

Prognosis

• Mortality rate is low (<1%) in developed countries, but higher (>10%) in developing countries, particular in children and young infants
• Patients with underlying conditions are at a higher risk
• Relapses after stopping antibiotics are possible, with symptoms similar to an initial infection
• Risk of prolonged shedding of pathogen (becoming a carrier) is lower in children but raises with age

Prevention

• Improved sanitation and clean water are crucial in preventing the disease.
• Good personal hygiene (handwashing) and food preparation practices are essential
• Preventing carriers from food- or water-handling jobs is worthwhile

Vaccine

• Two types exist: Oral (Ty21a; live-attenuated) and Intramuscular (Vi capsular)
• The oral vaccine is for people over 2 years old, and is given over time
• The IM vaccine is for individuals 2 years or older. One intramuscular injection, plus every 2 years for a booster is typical.