1. Live Attenuated Oral Vaccine

   • Strain: S. typhi Ty21a (Brand name: Vivotif)

   • Formulations: Enteric-coated capsules, liquid formulation

   • Revaccination interval: Every 5 years

   • Advantages: Convenient oral administration, suitable for adults and older children (>2 years)

2. Injectable Vi Capsular Polysaccharide Vaccine

   • Brand name: Typhium Vi

   • Revaccination interval: Every 2 years

   • Advantages: Broad use in eligible age groups, but not effective in children <2 years

2. Vaccine Effectiveness

• Overall protection: Around 70% (moderate efficacy)

• Limitations: Effectiveness may be lower in people frequently exposed to high doses of S. typhi

• Age restriction: Both current vaccines are not licensed for children younger than 2 years

3. New and Improved Vaccines

1. Vi-rEPA (Not yet widely licensed)

   • Composition: Vi polysaccharide conjugated to rEPA (a recombinant exoprotein A from Pseudomonas aeruginosa)

   • Advantages: Equally effective as current vaccines, with potential for longer-lasting immunity

2. Vi–Tetanus Toxoid Conjugate Vaccines

   • Licensed in India in 2013

   • Age eligibility: From 3 months and older

   • Significance: First typhoid vaccine suitable for infants, enabling earlier prevention and contributing to possible typhoid elimination

4. Explanation

• Why revaccination is needed:
  Polysaccharide vaccines (like Typhium Vi) produce limited immune memory, so periodic boosters are required. Live vaccines (Vivotif) stimulate both cellular and humoral immunity, but protection still wanes over time.

• Why children under 2 cannot receive current vaccines:
  Young children have weaker immune responses to pure polysaccharide antigens. Conjugate vaccines overcome this by inducing T cell–dependent immunity, which works well in infants.

• Importance of new generation vaccines:

  • Extend duration of immunity (fewer boosters)

  • Broaden age coverage (as early as 3 months old)

  • Crucial for future typhoid control and eradication programs

General Prevention Measures

• Food safety and hygiene

  • Cook meat, poultry, and eggs thoroughly (internal temperature ≥74 °C / 165 °F)

  • Avoid raw or undercooked eggs, poultry, meat, or unpasteurized milk/juice

  • Wash fruits and vegetables before eating

  • Keep raw and cooked foods separate to prevent cross-contamination

  • Maintain proper refrigeration (<4 °C) and avoid leaving food at room temperature for >2 hours

• Personal hygiene

  • Wash hands with soap and water before eating, after using the toilet, and after contact with animals (especially reptiles, amphibians, and birds)

  • Educate food handlers on proper hygiene and safe food preparation practices

• Animal contact precautions

  • Avoid direct contact with high-risk animals (turtles, lizards, baby chicks) for young children, elderly, and immunocompromised individuals

  • Practice strict handwashing after handling animals or cleaning cages

Some people with salmonella infection have no symptoms. Most people develop diarrhea, fever and stomach cramps within 8 to 72 hours after exposure. Most healthy people recover within a few days to a week without specific treatment.

Epidemiology of Salmonella

Transmission Sources

• Direct contact with infected animals.

• Indirect contact via contaminated environments.

• Common food sources: beef, poultry, eggs.

• Other contaminated foods: fruits, vegetables, dairy products, shellfish, peanut butter, powdered infant formula.

• Meat contamination

• Vegetable contamination: from animal fecal matter.

• Human-to-human and animal-to-human spread possible.

• High-risk animals: reptiles, amphibians, chicks, ducklings, kittens, hedgehogs, pet rodents

  
  

Notable Outbreaks

• Feb–May 2012:
  

  • 22 cases of S. infantis infection (20 in 13 US states, 2 in Canada).

  • 83% had dog contact; 8/11 recalled dog food from Diamond Pet Foods.

  
  

  2000:
  

  • S. enteritidis from eggshell fragments → ~182,060 US cases.

    
    

  Spring 2008:
  

  • 1,442 cases (S. enterica serotype Saintpaul) in 43 US states.

  • Linked to contaminated jalapeño & serrano peppers.

  
  

  2008 peanut butter outbreak:
  

  • 600 cases; peanut butter as source.

    
    

  Powdered infant formula:

  • Two large French outbreaks (S. enterica serotype Agona) among infants.

  
  

  Pet-related:

  • Reptile/amphibian exposure → ~74,000 US cases/year.

  • 2007: pet rodents identified as new infection source (S. Typhimurium).

  
  

  2007 US outbreaks:

  • Peanut butter (S. enterica Tennessee).

  • Frozen pot pies (S. enterica I 4,5,12:i:-).

  • Puffed vegetable snack (S. Wandsworth & S. Typhimurium).

  • Turtles (S. paratyphi B variant Java).

  
  

  2008–2009:
  

  • Nationwide S. Typhimurium from peanuts & frozen chicken.

  • Highlighted difficulty tracing multi-product contamination.

Frequency – United States

• Stable incidence since 2004; ~8% decrease from 1996–1998 levels.

  
  

  2007:

  • Reported annual incidence: 14.9 cases / 100,000 population.

  • True estimated burden: 520 cases / 100,000 (≈38.6× underreporting factor).

  • 5.4% of cases linked to outbreaks.

  
  

  High-risk groups:

  • Children.

  • Institutionalized populations (e.g., nursing homes).

    
    

  Typhoid & Paratyphoid fever:

  • 1 paratyphoid case for every 4 typhoid cases.

  • 72% of typhoid cases linked to travel to developing countries.

  • Common travel-related sources: India (30%), Pakistan (13%), Mexico (12%), Bangladesh (8%), Philippines (8%), Haiti (5%).

Frequency – International

• Many countries: incidence rising, but surveillance data limited.

• 2000: ~21.6 million typhoid fever cases; 216,500 deaths.

• 2010: ~26.9 million typhoid cases worldwide.

• Geographic incidence rates:
  

  • High (>100 cases/100,000/year): South-Central Asia, Southeast Asia, possibly Southern Africa.

  • Intermediate (10–100): rest of Asia, Africa, Latin America, Oceania (except Australia/NZ).

  • Low (<10): developed countries.

  
  

  Main drivers in low-/middle-income countries:

  • Poor sanitation.

  • Lack of clean water

• Usually self-limiting，treat with supportive care (fluid and electrolyte replacement if severe).

  • The main focus is to keep the patient hydrated and replace lost electrolytes (e.g., sodium, potassium) through oral rehydration solutions or IV fluids if needed.

  • Antibiotics not routinely used (may prolong carriage and do not shorten illness).（

    • doesn’t make symptoms go away faster, and in some cases, it can make the bacteria stay in the intestines longer (prolonged carrier state).

  • Antibiotics reserved for severe disease or high risk

    for invasive disease.

    
    

    2. Typhoid Fever (S. typhi / S. paratyphi)

    
    

    • Historical first-line: ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol (now limited by resistance).

    • Current preferred empiric therapy: quinolones, macrolides (e.g., azithromycin), or third-generation cephalosporins (e.g., ceftriaxone).

    • Resistance trends:
      

      • Declining quinolone sensitivity; nalidixic acid resistance predicts reduced fluoroquinolone effectiveness.

      • Growing resistance to nalidixic acid and ceftriaxone in nontyphoidal Salmonella.

        
        

    • Alternative agents: chloramphenicol reconsidered in some endemic areas due to lower resistance rates.

    
    

    
    

    3. Salmonella Bacteremia

    
    

    • Treat with single bactericidal drug for 10–14 days.

    • For life-threatening infections: third-generation cephalosporin + fluoroquinolone until sensitivities available.

    4. Complicated / Severe Infections

    
    

    • Endocarditis / Infectious arteritis: urgent surgical intervention + antimicrobial therapy (≥6 weeks after surgery).

    • If surgery not possible: long-term antibiotic therapy (months to years).

    • CNS involvement: high-dose ceftriaxone for optimal CNS penetration.

    5. Salmonella Infection in Pregnancy

    
    

    • Treat only invasive disease; use amoxicillin or cephalosporin.

    • Risk of fetal loss in disseminated infection.

      
      

    6. Surgical Care

    
    

    • Indicated for complications such as:
      

      • Intestinal perforation or hemorrhage

      • Cholecystitis (long-term carrier → cholecystectomy)

      • Endocarditis / arteritis

      • Osteomyelitis

      • Splenic abscess (splenectomy)

      • Soft-tissue abscess

        
        

    • Surgical intervention significantly improves survival in Salmonella endarteritis (especially abdominal aorta cases).

    
    

    
    

根据《沙门氏菌病》这份文件，以下是诊断沙门氏菌感染：

Laboratory Studies

实验室研究 (Laboratory Studies)

• Microbiology: Blood culture systems have an 80-100% accuracy in detecting bacteremia¹. However, as the disease progresses, the sensitivity of blood cultures decreases while the sensitivity of stool isolation increases². Freshly passed stool is the preferred sample for isolating nontyphoidal Salmonella species³. Bone marrow aspirate and culture is considered superior to blood culture because the bacterial concentration in bone marrow is ten times higher than in peripheral blood⁴. Even if blood cultures are negative, bone marrow aspirates may still be positive, especially in patients who have received antibiotics before hospitalization⁵. For typhoid fever,

  
  

  S typhi or S paratyphi can also be isolated from urine, rose spot biopsies, or gastric/intestinal secretions⁶.

  
  

• 微生物学: 现代血培养系统的细菌检测准确率达80-100%。然而，随着病程进展，血培养的敏感性会降低，而粪便分离培养的敏感性会增加。对于非伤寒沙门氏菌，最好使用新鲜排出的粪便样本进行分离。骨髓穿刺和培养被认为优于血培养，因为骨髓中的细菌浓度是外周血的十倍。即使血培养结果为阴性，骨髓穿刺物仍可能呈阳性，尤其是在住院前已接受抗生素治疗的患者。对于伤寒病，也可以从尿液、玫瑰疹活检或胃肠道分泌物中分离出伤寒沙门氏菌（S typhi）或副伤寒沙门氏菌（S paratyphi）。

  
  

• Rapid Identification: Polymerase chain reaction (PCR)-based multiplex GI pathogen identification panels are available for use with primary stool specimens⁷. These panels offer a faster turnaround time for diagnosis compared to culture-based methods⁸.

• 快速鉴定: 现已有基于聚合酶链式反应（PCR）的多重胃肠道病原体鉴定板，可用于初次粪便标本检测。与基于培养的方法相比，这些鉴定板的诊断周转时间更短。

• Serology: Serological tests, such as the Widal test, can be used to measure antibodies against S typhi O and H antigens⁹. Newer diagnostic tests like Typhidot and Tubex directly detect IgM antibodies against specific

  
  

  S typhi antigens¹⁰.

• 血清学: 血清学检测，如肥达氏反应（Widal test），可用于测量针对伤寒沙门氏菌O和H抗原的抗体。更新的诊断测试，如Typhidot和Tubex，可直接检测针对特定伤寒沙门氏菌抗原的IgM抗体。

  
  

Imaging Studies

影像学研究 (Imaging Studies)

Radiologic findings are often nonspecific¹¹.

放射学发现通常是非特异性的。

• CT Scans: A CT examination of patients with Salmonella infection has shown slight, symmetrical, and homogenous thickening of the terminal ileum wall, as well as circumferential thickening of the cecum and descending colon¹².

• CT扫描: 针对沙门氏菌感染患者的CT检查显示，末端回肠壁有轻微、对称、均匀的增厚，以及盲肠和降结肠的环状增厚。

  
  

• Ultrasonography: This may be helpful in distinguishing infectious ileocecitis from ileocecal Crohn disease and appendicitis¹³. Findings that suggest an infectious cause include prominent haustration of the cecum and right colon, and symmetrical mural thickening of the terminal ileum and cecum¹⁴.

• 超声检查: 这可能有助于区分感染性回盲肠炎（由沙门氏菌、耶尔森菌或弯曲杆菌引起）与回盲部克罗恩病和阑尾炎。提示感染的特异性发现包括盲肠和右结肠的结肠袋突出，以及末端回肠和盲肠的对称性壁增厚。

  
  

• Ruling out complications: Patients over 50 with nontyphoid Salmonella bacteremia may need CT or MRI scans to rule out concurrent vascular infections¹⁵.

  排除并发症: 建议50岁以上的非伤寒沙门氏菌菌血症患者进行CT或MRI检查，以排除并发的血管感染。

Other Tests

其他测试 (Other Tests)

• Nested PCR using H1-d primers has been used to amplify specific S typhi genes and may eventually replace blood culture as the gold standard for diagnosis¹⁶.

• 使用H1-d引物的巢式PCR（Nested PCR）已用于扩增伤寒沙门氏菌的特异性基因，具有高敏感性和特异性。这可能最终取代血培养，成为诊断的黄金标准。

  
  

Blood Culture

• Modern blood culture systems detect bacteremia with 80–100% accuracy.

• Sensitivity decreases as disease duration increases.

• Stool isolation sensitivity increases with longer disease duration.

  
  

Stool Specimens

• Freshly passed stool is best for isolating nontyphoidal Salmonella.

• S. typhi stool carriage can be prolonged → positive stool results should be interpreted with caution.

• Diagnosis of typhoid fever should be based on typical clinical findings in addition to positive cultures.

Bone Marrow Aspirate

• More sensitive than blood culture (10× higher bacterial concentration).

• Remains positive for Salmonella even after antibiotic therapy, when blood culture may be negative.

Other Specimens

• In typhoid fever, S. typhi or S. paratyphi can also be isolated from:

  • Urine

  • Rose spot biopsy

  • Gastric/intestinal secretions

  
  

Serologic Grouping

• Grouping performed using polyvalent antisera for O and Vi antigens.

  • S. typhimurium → Group B

  • S. enteritidis and S. typhi → Group D

PCR-based GI Pathogen Panels

• Detect Salmonella, Shigella, Yersinia directly from stool.

• Faster turnaround than culture.

• Culture still required for:

  • Taxonomic classification

  • Susceptibility testing

Public Health

• Salmonellosis is a reportable disease in the US.

General Features

• Family: Enterobacteriaceae

• Type: Gram-negative rods, catalase +ve, oxidase -ve, facultative anaerobes, fermentative.

• Other traits:

  • Generally motile (peritrichous flagella), non-lactose fermenters, citrate +ve, urease -ve, KCN-sensitive, acetyl methyl carbinol -ve.

  • Aerogenic (except S. Typhi, S. gallinarum).

• Habitat: Intestine of vertebrates, infect humans → enteric fever, gastroenteritis, septicemia, carrier state.

• Notable species: S. Typhi (typhoid fever).

• History: Discovered by Eberth (1880), isolated by Gaffky (1884), named by Salmon & Smith (1885).

• Survival: Weeks in water/soil, months in ice, killed at 55 °C (1 h) or 60 °C (15 min), destroyed by boiling, chlorination, pasteurization.

Classification (practical)

1. Enteric fever group – S. Typhi, S. Paratyphi A/B/C; human parasites.

2. Food poisoning group – Animal parasites but can infect humans (gastroenteritis, septicemia, local infections).

Morphology

• Size: 2–4 × 0.6 μm.

• Gram –ve, non-capsulated, non-sporing, non–acid fast.

• Most motile; exceptions: S. gallinarum, S. pullorum.

• Possess type I fimbriae.

Antigenic Structure

1. H antigen (flagellar) – Protein; heat & alcohol labile; formaldehyde preserves; 60 °C detaches flagella.

2. O antigen (somatic) – Part of LPS; heat & alcohol stable; identical with endotoxin (Boivin antigen); less immunogenic than H.

3. Vi antigen (capsular) – Acidic polysaccharide; virulence factor (anti-phagocytic, resists complement); heat labile; masks O antigen; lost on subculture.

Cultural Characteristics

• Growth: Aerobic/facultative anaerobes, pH 6–8, temp optimum 37 °C.

• On media:

  • Nutrient/Blood agar: Large, smooth, translucent grey-white colonies.

  • MacConkey: Pale colonies (non-lactose fermenters).

  • Brilliant green MacConkey: Pale green colonies; inhibits E. coli, Proteus.

  • DCA: Pale colonies, sometimes black center (H₂S).

  • BBBA: Especially for S. Typhi; black-centered colonies with metallic sheen.

  • XLD agar: Red colonies, often black center (H₂S).

Enrichment Media

• Selenite F broth (most used).

• Tetrathionate broth.

• Strontium chloride broth.

• Malachite green magnesium chloride broth.

Biochemical Reactions

• Fermentation: Glucose, mannitol, arabinose, maltose, dulcitol, sorbitol → acid/gas (except anaerogenic strains); no lactose, sucrose, salicin, adonitol. ONPG –ve.

• Decarboxylases: Lysine +, ornithine +, arginine + (exceptions: S. Typhi lacks ornithine; S. Paratyphi A lacks lysine).

• Other tests: Indole –ve, MR +, VP –ve, citrate + (except S. Typhi, S. Paratyphi A), urease –ve, H₂S + (except S. Paratyphi A), KCN –ve, gelatin not liquefied.

• 6 to 72 hours (depends on host and bacterial load)

Gastrointestinal Symptoms:

• Loose, non-bloody stools (most common)

• Occasionally large-volume, cholera-like diarrhea

• Tenesmus (rare)

• Diarrhea typically self-limiting (resolves in 3–7 days)

Systemic Symptoms:

• Fever (usually resolves in 48 hours)

• Abdominal cramping

• Chills

• Headache

• Myalgia

Physical Findings:

• Nonbloody, loose/watery stools

• No specific diagnostic physical signs

🔶 2. Nontyphoidal Focal Disease (Invasive NTS)

Due to: Bacteremia and hematogenous spread

Occurs in ~5% of NTS gastroenteritis cases; 40% of those develop extra-intestinal infections.

Sites Affected:

• Almost any organ

• Vulnerable: sites with preexisting structural abnormalities (e.g., brain tumors, post-operative sites)

• May lead to:

  • Brain abscess

  • Meningitis (especially post brain surgery)

  • Urinary tract infections (especially with urolithiasis or structural issues)

Risk Factors:

• Immunosuppression (e.g., corticosteroids, malignancy)

• Chronic Salmonella carriers

• Recent influenza infection

🔶 3. Typhoid Fever (Enteric Fever - Salmonella typhi)

Incubation Period:

• 10–14 days

Systemic Symptoms:

• Prolonged low-grade fever → becomes high-grade by end of 2nd week (can last up to 4 weeks if untreated)

• Dull frontal headache

• Malaise, myalgia

• Anorexia, nausea

• Dry cough

• Lethargy (can persist for months)

Gastrointestinal & Abdominal Symptoms:

• Constipation (more common in adults)

• Diarrhea (more common in children)

• Abdominal tenderness (≈ 50%)

• Hepatosplenomegaly (≈ 50%)

Characteristic Signs:

• Rose spots: pink, blanchable, slightly raised macules (chest, abdomen, back, limbs) – in ~25%

• Coated tongue

• Relative bradycardia (not specific)

Severe Features (10–15% of cases):

• Delirium, psychosis

• Focal neurological deficits (even without CNS infection)

• Myocarditis-like ECG changes (QT prolongation)

• Bowel perforation (sudden worsening of abdominal pain)

Atypical Presentations:

• Respiratory symptoms (especially in endemic regions)

• May mimic malaria or schistosomiasis