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Salmonellosis is a common bacterial disease that affects the intestinal tract. Salmonella bacteria typically live in animal and human intestines and are shed through stool . Humans become infected most frequently through contaminated water or food.

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.

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Incubation Period:

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

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1. General Management

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).

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Microbiology of Salmonella Detection

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.

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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

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The summary of the diagnostic methods for Salmonella infections:

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。

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1. Currently Available International Vaccines

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