Overview -
Salmonella infections (salmonellosis) are caused by bacteria of the genus Salmonella. These Gram-negative, rod-shaped enterobacteria commonly colonize the intestines of humans and animals. While there are many different serotypes, Salmonella enterica subspecies enterica serovars Typhimurium and Enteritidis are among the most frequent causes of human disease worldwide. Infection can range from a self-limited, gastrointestinal illness to a severe, invasive systemic disease depending on host factors, serotype, and bacterial load.
1. Epidemiology
• Global burden: Salmonellosis is one of the leading causes of foodborne illness worldwide. Roughly 93.8 million cases of gastroenteritis and 155,000 deaths occur annually in humans (predominantly in low- and middle-income countries).
• Common reservoirs: Poultry (especially eggs and poultry meat), reptiles, and contaminated produce or water. Animals such as cattle, pigs, and rodents can also harbor various Salmonella serotypes and shed bacteria without showing symptoms.
• Age groups: Infants, young children, the elderly, and immunocompromised individuals (e.g., HIV/AIDS, diabetics, cancer patients) are at higher risk for severe disease.
• Seasonality: In many regions, incidence peaks during warmer months when bacterial replication in food and water is more rapid and food-handling practices may be less stringent.
2. Transmission
1. Fecal-oral route: Ingestion of food or water contaminated with feces from infected humans or animals.
2. Foodborne outbreaks:
o Undercooked poultry, eggs, and meat
o Raw fruits and vegetables irrigated or washed with contaminated water
o Unpasteurized milk or dairy products
3. Direct contact: Handling infected pets (especially reptiles like turtles, snakes, iguanas) or contact with carriers (e.g., farmworkers in close contact with livestock).
4. Cross-contamination: Using the same cutting boards or utensils for raw meat and ready-to-eat foods without proper cleaning.
3. Pathogenesis
1. Acid resistance: Salmonella can survive gastric acidity (pH ~2), particularly when ingested in large numbers or with buffering food.
2. Invasion of intestinal epithelium: Bacteria use a Type III secretion system (T3SS) to inject effector proteins into enterocytes (M cells over Peyer’s patches), prompting uptake.
3. Intracellular survival: Once inside macrophages, Salmonella manipulates host vacuoles to avoid lysosomal fusion, replicating within a “Salmonella-containing vacuole.”
4. Inflammation and diarrhea: The release of cytokines (IL-8, TNF-α) and other effectors causes neutrophil recruitment, leading to fluid secretion (secretory diarrhea).
5. Systemic spread: In invasive serotypes (e.g., S. Typhi or S. Paratyphi), bacteria traverse the lamina propria, enter the bloodstream (bacteremia), and localize in organs like the liver, spleen, and bone marrow.
4. Clinical Manifestations
4.1 Non-Typhoidal Salmonellosis (NTS)
• Incubation period: Typically 6–72 hours after ingestion.
• Symptoms (last ~4–7 days):
o Abrupt-onset fever (often low-grade)
o Abdominal cramps (periumbilical, possibly diffuse)
o Diarrhea (mucoid and sometimes bloody)
o Nausea and vomiting (in ~50% of cases)
o Headache, myalgias, malaise
• Complications (rare in healthy hosts):
o Dehydration (especially in young children or elderly)
o Reactive arthritis (enthesitis, asymmetric oligoarthritis) developing 1–3 weeks post-infection (occurs in ~2–5% of infected adults)
o Bacteremia (more common in neonates, elderly, immunocompromised), possibly leading to focal infections (e.g., osteomyelitis, endocarditis, septic arthritis)
4.2 Typhoidal Salmonellosis (Salmonella enterica serovar Typhi and Paratyphi)
• Incubation period: 7–14 days (can range from 3 days to 60 days).
• Symptoms (Typhoid fever):
1. Week 1: Gradually rising fever (stepwise), malaise, anorexia, headache, constipation or diarrhea, relative bradycardia (“Faget sign”).
2. Week 2: High sustained fever (39–40 °C), abdominal distension, “rose spots” (faint salmon-colored maculopapular rash on trunk), hepatosplenomegaly.
3. Week 3: Potential for intestinal hemorrhage or perforation (especially ileal perforation), encephalopathy (“typhoid state”: delirium, obtundation).
4. Week 4+: Convalescence—gradual resolution, though chronic carrier state can develop (especially in gallbladder).
• Complications:
o Intestinal perforation (1–3 weeks after onset) leading to peritonitis (mortality high if untreated)
o Neuropsychiatric manifestations (delirium, psychosis)
o Myocarditis, hepatitis, cholecystitis
o Chronic carrier state (≈2–5% remain carriers, shedding in stool for >1 year)
5. Diagnosis
1. Stool culture (non-typhoidal)
o Obtain stool sample during acute diarrhea.
o Selective media: XLD agar, SS agar, Hektoen enteric agar.
o Colonies are typically lactose-nonfermenting, H₂S-producing (black center on XLD).
o Serotyping based on O (somatic) and H (flagellar) antigens.
2. Blood culture (typhoidal & invasive NTS)
o Best yield during first week of fever for typhoid; sensitivity ~40–80%.
o Use tryptic soy broth or BACTEC systems.
3. Bone marrow culture (typhoid)
o Highest sensitivity (≥80%) even after antibiotics started.
o Considered if blood cultures negative but high clinical suspicion.
4. Widal test (serology)
o Detects agglutinating antibodies to O and H antigens of S. Typhi.
o Limited value in endemic areas (cross-reactivity, false positives).
o A fourfold rise in titer over 7–10 days suggests acute infection; single high titer may be misleading.
5. PCR and rapid tests
o PCR-based assays on stool or blood: higher sensitivity but limited availability.
o Rapid immunochromatographic tests for O antigen (variable accuracy).
6. Additional investigations
o Complete blood count: leukopenia in typhoid; mild leukocytosis in NTS.
o Liver function tests: mild transaminase elevation in typhoid.
o C-reactive protein (CRP) and procalcitonin may be elevated but nonspecific.
6. Treatment
6.1 Non-Typhoidal Salmonellosis
• Supportive care (mainstay):
o Fluid and electrolyte replacement: oral rehydration solution (ORS) for mild/moderate dehydration; IV fluids if severe.
o Antipyretics and analgesics for fever and cramps.
• Antibiotic therapy (selective):
o Indicated for:
Infants <3 months, elderly (>65 years), immunocompromised (HIV, on chemotherapy, etc.)
Signs of bacteremia (sepsis, high fever persists >48 hours)
Focal infections (e.g., osteomyelitis, meningitis)
o Common choices (guided by local resistance patterns):
Fluoroquinolones (e.g., ciprofloxacin 500 mg twice daily for 5–7 days), though rising resistance in many regions
Third-generation cephalosporins (e.g., ceftriaxone 1–2 g IV/IM once daily for 5–7 days)
Azithromycin (10 mg/kg once daily for 3–5 days in children; 500 mg daily in adults)
o Duration: Typically 5–7 days, but extend to 10–14 days if severe or slow to respond.
6.2 Typhoidal Salmonellosis
• Antibiotic therapy (first-line):
o Ceftriaxone (preferred in areas with fluoroquinolone resistance): 2 g IV/IM once daily for at least 7 days.
o Azithromycin: 1 g orally on day 1, then 500 mg once daily for 4 more days.
o Fluoroquinolones (e.g., ciprofloxacin 750 mg twice daily for 7 days) only if local susceptibility confirmed (high-level resistance now common in South Asia).
• Supportive care:
o Manage dehydration, monitor for intestinal perforation (observe for sudden worsening abdominal pain, shock).
o Nutritional support—small frequent feedings as tolerated.
Note on antibiotic resistance: Multi-drug resistant (MDR) strains (resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) remain prevalent in many regions. Extensively drug-resistant (XDR) S. Typhi strains (resistant to first-line agents, fluoroquinolones, and third-generation cephalosporins) have emerged (e.g., in parts of Pakistan). Always check current local antibiogram before selecting empiric therapy.
7. Prevention and Control
1. Food safety
o Cook poultry, eggs, and meat thoroughly (internal temperature ≥74 °C).
o Avoid raw or undercooked eggs in sauces, dressings, or desserts.
o Wash fruits and vegetables under safe, clean water.
o Prevent cross-contamination: use separate cutting boards for raw meat and produce; wash utensils, hands, and surfaces with soap and hot water.
o Refrigerate perishable foods at ≤4 °C; discard leftovers after 2 days.
2. Personal hygiene
o Frequent handwashing with soap, especially after using the toilet, changing diapers, and before handling or eating food.
o Use alcohol-based hand sanitizers only if soap and water are unavailable.
o Educate food handlers (in homes, restaurants, street stalls) about proper hygiene and safe food-handling practices.
3. Water safety
o Drink boiled or properly treated water in areas with unsafe municipal supply.
o Avoid ice from uncertain sources.
o Use point-of-use filters or chlorine tablets where needed.
4. Animal handling
o Avoid direct contact with reptiles, amphibians, or pet rodents if high-risk individuals are present at home.
o Wash hands thoroughly after handling pets or their environments; supervise children.
o Ensure poultry and livestock are raised in sanitary conditions; limit human exposure to animal feces.
5. Vaccination (typhoid)
o Oral live attenuated vaccine (Ty21a): 4 capsules on alternating days (days 1, 3, 5, 7); booster every 5 years.
o Injectable Vi polysaccharide vaccine: Single 0.5 mL dose for adults and children ≥2 years; booster every 2 years.
o Conjugate Vi vaccines (e.g., Typbar-TCV®): Single dose in children ≥6 months; booster recommendations vary (some guidelines suggest every 3–5 years).
o Vaccination recommended for:
People traveling to endemic regions (e.g., South Asia, sub-Saharan Africa)
Household contacts of chronic carriers
Laboratory workers handling Salmonella
o Note: Neither vaccine confers 100% protection; safe food and water practices remain essential.
6. Public health measures
o Prompt identification and isolation of carriers (especially food handlers); stool cultures to confirm clearance after treatment.
o Rigorous outbreak investigation: tracing source (food, water, animal), testing environmental samples, enforcing recalls of contaminated products.
o Education campaigns to increase awareness of risk factors, signs/symptoms, and when to seek medical care.
o Surveillance systems to monitor trends in antimicrobial resistance and emerging serotypes.
8. Special Populations
• Infants and Young Children
o Higher risk of dehydration from diarrhea; monitor fluid intake/output carefully.
o Tend to have more prolonged shedding even after symptoms resolve—emphasize strict hygiene to caregivers.
o Breastfeeding offers some protection (maternal antibodies).
• Elderly
o May present atypically (e.g., confusion without prominent diarrhea).
o Higher likelihood of bacteremia or focal complications (e.g., endocarditis).
o Adjust antibiotic dosages for renal function; monitor for drug interactions.
• Pregnant Women
o Increased risk of bacteremia; potential for vertical transmission or preterm labor.
o Use antibiotics safe in pregnancy (e.g., third-generation cephalosporins, azithromycin).
• Immunocompromised Individuals
o HIV/AIDS patients: risk of chronic carriage and recurrent invasive disease; consider prophylactic antibiotics if CD4 count is very low (<200 cells/µL).
o Organ transplant recipients and cancer chemotherapy patients: higher risk for bacteremia; treat promptly with broad-spectrum agents until sensitivities are known.
9. Complications
1. Dehydration and Electrolyte Imbalance
o Severe diarrhea leads to hypovolemia, electrolyte abnormalities (hyponatremia, hypokalemia).
o Monitor vital signs, electrolytes; replace losses promptly.
2. Metastatic Infections
o Bacteremia can seed distant sites:
Osteomyelitis (particularly in children with sickle cell disease)
Septic arthritis (older adults, joint prostheses)
Endocarditis (patients with preexisting valvular disease or prosthetic valves)
Meningitis (neonates, very young children)
3. Intestinal Perforation and Hemorrhage (typhoid)
o Occurs in weeks 2–3 of untreated or inadequately treated cases.
o Presents with sudden severe abdominal pain, rigidity, shock.
o Requires emergency surgery (ileal resection or primary repair) and broad-spectrum antibiotics (covering gut flora and Salmonella).
4. Reactive Arthritis (Reiter’s Syndrome)
o Onset 1–3 weeks after acute infection; triad of arthritis, conjunctivitis, urethritis.
o More common in HLA-B27 positive individuals.
o Supportive care: NSAIDs, sometimes short course of antibiotics if stool cultures remain positive.
5. Chronic Carrier State
o Defined as shedding for >1 year after acute illness (common in S. Typhi infections).
o Gallbladder often serves as reservoir (bile, gallstones harbor bacteria).
o Chronic carriers can contaminate food or water, perpetuating outbreaks.
o Management: prolonged antibiotic courses (e.g., amoxicillin 4 g/day + probenecid for 4 weeks) or cholecystectomy if medical therapy fails (especially in the presence of gallstones).
10. Prognosis
• Non-typhoidal Salmonellosis
o Most healthy adults recover fully within 4–7 days with supportive care alone.
o Mortality is <1% in uncomplicated cases; rises if bacteremia or invasive disease occurs.
• Typhoid Fever
o With appropriate antibiotic therapy, mortality is <1–2%.
o If untreated, mortality can approach 10–20%, primarily due to intestinal perforation or hemorrhage.
o Chronic carrier state persists in 2–5% of treated patients, necessitating follow-up.
11. Key Takeaways
• Maintain strict food and water hygiene to prevent Salmonella transmission: thoroughly cook poultry/eggs, wash produce, avoid cross-contamination, and practice good hand hygiene.
• Recognize the clinical spectrum: self-limited gastroenteritis in most, but watch for signs of dehydration, bacteremia, or shock.
• Use culture-based methods (stool, blood) for definitive diagnosis; serology (Widal) has limited reliability in endemic areas.
• Initiate supportive therapy primarily; reserve antibiotics for high-risk patients or invasive disease. Be mindful of local resistance patterns, especially for fluoroquinolones and third-generation cephalosporins.
• Vaccinate travelers and at-risk populations against typhoid fever, but remember that no vaccine guarantees complete protection—safe food/water practices remain essential.
• Monitor for and manage complications such as reactive arthritis, metastatic infections, intestinal perforation, and chronic carriage.
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