Salmonella Typhi: Comprehensive Insights into Pathogenesis, Symptoms, and Global Antibiotic Resistance

Table of Contents

• Introduction to Salmonella Typhi
• Taxonomy and Classification of Salmonella Typhi
• Morphology and Microscopy of Salmonella Typhi
• Cultural and Growth Characteristics of Salmonella Typhi
• Biochemical and Identification Tests of Salmonella Typhi
• Pathogenesis of Salmonella Typhi
• Virulence Factors of Salmonella Typhi
• Genotype of Salmonella Typhi 
• Epidemiology of Salmonella Typhi
• Transmission of Salmonella Typhi
• Clinical Manifestations of Salmonella Typhi
• Laboratory Diagnosis of Salmonella Typhi
• Treatments of Salmonella Typhi Infections
• Prevention and Control of Salmonella Typhi Infections
• Antibiotic Resistance of Salmonella Typhi
• Conclusion
• References

Introduction to Salmonella Typhi

• Salmonella Typhi is a serovar of Salmonella enterica and belongs to a group of pathogenic bacteria that are widely distributed in nature and capable of infecting living hosts.
• These bacteria are commonly acquired through the consumption of food or water contaminated with fecal material, which serves as the primary route of transmission.
• After ingestion, the bacteria enter and infect the intestinal tract, where they begin colonization and invasion.
• Following intestinal infection, the bacteria spread into the bloodstream, allowing systemic dissemination throughout the body.
• The infection caused by these bacteria results in a disease known as Typhoid fever, which is also referred to as Enteric fever.

Taxonomy and Classification of Salmonella Typhi

• Classification of Salmonella is complex and involves multiple taxonomic levels and serological distinctions.
• The genus mainly consists of two species: Salmonella enterica and Salmonella bongori.
• Salmonella enterica is further divided into several subspecies based on genomic relatedness and biochemical characteristics.
• These subspecies are designated using Roman numerals, including:
• S. enterica subspecies enterica (I)
• S. enterica subspecies salamae (II)
• S. enterica subspecies arizonae (III)
• S. enterica subspecies diarizonae (IIIa)
• S. enterica subspecies houtenae (IV)
• S. enterica subspecies indica (V)
• Among these, Salmonella enterica subsp. enterica (subspecies I) is the most common subspecies and is responsible for approximately 99% of infections in humans and warm-blooded animals.
• The remaining subspecies of S. enterica and Salmonella bongori mainly infect cold-blooded animals, and infections in humans are rarely reported.
• Within subspecies I, several important serotypes exist, including:
• Salmonella Typhi
• Salmonella Typhimurium
• Salmonella Enteritidis
• Salmonella Choleraesuis
• These serotypes are generally named according to the geographic location where the strain was first isolated.
• The taxonomic classification of Salmonella Typhi is as follows:
• Domain: Bacteria
• Kingdom: Pseudomonadati
• Phylum: Pseudomonadota
• Class: Gammaproteobacteria
• Order: Enterobacterales
• Family: Enterobacteriaceae
• Genus: Salmonella
• Species: Salmonella enterica
• Serotype: Typhi

Morphology and Microscopy of Salmonella Typhi

• Salmonella Typhi is a Gram-negative bacterium that appears as rod-shaped (bacilli) cells.
• The bacterial cells typically measure approximately 0.7–1.5 µm in width and 2–5 µm in length.
• It is catalase-positive and oxidase-negative, which are important biochemical characteristics used in laboratory identification.
• The organism is non-spore forming (non-sporing) and does not produce resistant endospores.
• The bacterium is motile due to the presence of peritrichous flagella, meaning flagella are distributed around the entire surface of the cell.
• It can grow in the presence of oxygen as well as in its absence, therefore it is classified as aerobic or facultatively anaerobic.
• When observed under a microscope after Gram staining, the cells appear as pink-colored rod-shaped structures, which is characteristic of Gram-negative bacteria.

Cultural and Growth Characteristics of Salmonella Typhi

• Salmonella Typhi grows best at an optimum temperature of approximately 37 °C, which corresponds to the normal human body temperature.
• The bacterium shows optimal growth within a pH range of 6–8, allowing it to survive and multiply effectively in physiological conditions.
• It is aerobic or facultatively anaerobic, meaning it can grow in the presence of oxygen as well as in its absence.
• When cultured on solid media, the colonies are typically round, large, about 2–3 mm in diameter, smooth, convex, and translucent in appearance.
• On Nutrient Agar, colonies of the bacterium are usually 2–3 mm in size, moist, off-white in color, smooth, convex, and possess complete (entire) margins.
• On Blood Agar, the colonies are generally 2–3 mm in diameter, off-white in color, convex, moist, and exhibit complete (entire) margins.

Biochemical and Identification Tests of Salmonella Typhi

The identification of Salmonella Typhi in microbiology laboratories relies on a series of biochemical, fermentation, and enzymatic tests that help differentiate it from other members of the family Enterobacteriaceae.

Basic Biochemical Tests

Test	Result
Gram Staining	Negative
Catalase	Positive
Oxidase	Negative
Indole	Negative
MR (Methyl Red)	Positive
VP (Voges–Proskauer)	Negative
Citrate	Negative
H₂S Production	Positive
Motility	Motile
Gas Production	Negative
Gelatin Hydrolysis	Negative
Urease	Negative
Triple Sugar Iron Agar (TSIA)	Alkali/Acid (K/A)
Nitrate Reduction	Positive

Carbohydrate Fermentation Tests

Carbohydrate	Result
Glucose	Positive
Maltose	Positive
Glycerol	Negative
Lactose	Negative
Mannitol	Positive
Arabinose	Negative
Cellobiose	Negative
Sucrose	Negative

Additional Enzymatic and Identification Tests

Test	Result
DNase	Negative
Arginine Dehydrolase	Negative
Acetate Utilization	Negative
Tyrosine Hydrolysis	Negative
Lipase	Negative
Lysine Decarboxylase	Positive
Ornithine Decarboxylase	Negative
ONPG (β-galactosidase)	Negative

Pathogenesis of Salmonella Typhi

• Infection by Salmonella Typhi primarily occurs through the ingestion of contaminated food or water containing the bacteria.
• After entering the host, the bacteria adhere to the surface of intestinal epithelial cells, followed by internalization into host cells.
• Internalization can occur either through phagocytosis by immune cells or through active bacterial invasion of host cells.
• Phagocytosis involves complex mechanisms that depend on the engagement of various host receptors, particularly Pattern Recognition Receptors (PRRs).
• PRRs include cytosolic nucleotide-binding receptors and Toll-like receptors (TLRs), which detect pathogen-associated molecular patterns (PAMPs) such as flagellin and lipopolysaccharides (LPS) present on the bacterial surface or inside phagosomes.
• Recognition of these microbial components influences phagosome maturation, activates signaling pathways, and regulates host gene expression involved in immune responses.
• Several studies indicate that interaction between TLRs and lipopolysaccharides (LPS) plays a critical role in the development of septic shock.
• However, typhoidal serovars such as Salmonella Typhi can evade recognition by TLR4, allowing them to escape immune detection.
• This immune evasion prevents the recruitment of neutrophils and reduces the production of pro-inflammatory cytokines, including TNF-α and interleukin-1β, thereby suppressing the typical antimicrobial response of host cells.
• The cytokine production pattern in human infections resembles that observed with non-typhoidal Salmonella, but immune evasion allows systemic spread.
• This stage represents a critical step in the invasion process, as the bacteria infiltrate both phagocytic and non-phagocytic cells.
• The invasion and survival of Salmonella Typhi within host cells depend on several specialized virulence factors that support colonization, immune evasion, and systemic infection.

Virulence Factors of Salmonella Typhi

1. Capsular Antigen (Vi Antigen)

• The Vi antigen capsule is a linear homopolymer of α-1,4-linked galactosaminuronic acid that is acetylated at the C3 position.
• This capsule inhibits activation of complement component C3 and reduces phagocytosis, enabling the bacteria to evade host immune defenses.

2. Virulence Plasmid

• Virulence plasmids are large genetic elements present in low copy numbers, which reduces metabolic stress on the bacterial cell and ensures stability during cell division.
• These plasmids carry genes responsible for antimicrobial resistance and virulence factors.
• Important genes include:
• spcC, which inhibits pyroptosis and inflammation.
• spvB, which encodes an ADP-ribosylating toxin.

3. Flagella (H Antigen)

• Flagella contribute to bacterial motility and host interaction.
• They assist in adhesion, invasion of host cells, protein export, and biofilm formation.

4. Toxins

• Salmonella Typhi produces toxins that contribute to the development of Typhoid fever.
• These toxins belong to the AB toxin group, consisting of:
• A subunit: enzymatic component
• B subunit: receptor-binding component
• Salmonella-containing vacuoles release toxins from infected cells, allowing them to affect surrounding target cells.

5. Somatic O Antigen (LPS)

• The O antigen is part of the lipopolysaccharide (LPS) located in the bacterial cell wall.
• LPS contains outer membrane proteins (OMPs) that are antigenic in nature.
• These proteins include:
• Porins, which form channels that facilitate the uptake of solutes.
• Non-porin proteins, which function mainly as structural components.
• O antigens are highly immunogenic and stimulate strong antibody responses in patients with typhoid fever.

6. Superoxide Dismutase

• Superoxide dismutase is an enzyme that protects the bacteria from oxidative stress.
• It converts superoxide radicals into molecular oxygen and hydrogen peroxide, helping the bacterium survive inside immune cells.

7. Biofilm Formation

• Biofilm formation is an adaptive survival strategy that alters bacterial gene expression to enhance resistance to antibiotics and environmental stress.
• Biofilms are formed through the secretion of a polymeric extracellular matrix containing factors such as curli fimbriae and cellulose.
• Biofilm production is regulated by csgD, a curli subunit regulatory gene belonging to the LuxR family.

8. Type I and Type III Secretion Systems

• Type I secretion systems transport various molecules including surface proteins, toxins, lipases, and adenylate cyclase into the extracellular environment.
• These systems also facilitate bacterial adhesion, invasion of host immune cells, and biofilm formation.
• Two important surface-associated proteins secreted via this system include:
• SiiE, which assists in initial attachment to host cells followed by invasion.
• BapA, which is involved in host cell adherence and biofilm formation.
• The Type III secretion system functions as a molecular syringe, allowing bacteria to inject effector proteins directly from the prokaryotic cytoplasm into the cytosol of eukaryotic host cells, thereby manipulating host cellular processes.

Genotype of Salmonella Typhi 

• Salmonella Typhi is a genetically monomorphic pathogen with limited DNA sequence variation, which makes genotyping challenging but extremely important for epidemiological studies and surveillance of typhoid fever.
• The global population structure of S. Typhi is highly organized and consists of numerous subclades that often show strong geographical restriction and regional dominance.
• The GenoTyphi genotyping framework, first introduced in 2016 and later updated in 2021, uses 68 marker single nucleotide polymorphisms (SNPs) to classify S. Typhi into 4 primary clades, 16 clades, and more than 49 subclades arranged in a hierarchical nomenclature system.
• The H58 haplotype, also known as genotype 4.3.1, is the most globally disseminated genotype of S. Typhi and is strongly associated with multidrug resistance (MDR) and extensively drug-resistant (XDR) phenotypes.
• The H58 lineage has two major sublineages: Lineage I (4.3.1.1) and Lineage II (4.3.1.2), both of which are widely distributed across Asia and Africa.
• Historical genomic analysis indicates that the H58 lineage originated in India in the late 1980s as a multidrug-resistant clone and rapidly spread across South Asia, Africa, and other regions of the world.
• Extensively drug-resistant S. Typhi strains that show resistance to first-line antibiotics, fluoroquinolones, and third-generation cephalosporins have emerged within the H58 lineage, particularly in Pakistan.
• In South Asia, including India, Pakistan, and Bangladesh, the H58 genotype is the dominant circulating lineage, although other genotypes such as 3.3, 2.5, and several country-specific subclades are also present.
• In Africa, genotype 3.1.1 is commonly reported in West Africa, while East Africa contains a mixture of locally evolved lineages and imported H58 clones.
• Certain geographically isolated regions have their own endemic genotypes; for example, Papua New Guinea predominantly harbors genotype 2.1.7, while Samoa has genotype 2.5.4.
• These localized genotypes generally remain susceptible to most antibiotics but remain vulnerable to the introduction and spread of resistant clones such as H58.
• Multidrug-resistant and extensively drug-resistant phenotypes are closely associated with specific genotypes, especially the H58 genotype 4.3.1.
• Resistance in H58 strains is frequently linked to chromosomal integration or plasmid-mediated acquisition of resistance genes, particularly plasmids belonging to the IncHI1 and IncY incompatibility groups.
• Non-H58 genotypes are also capable of acquiring antimicrobial resistance through local evolutionary processes or horizontal gene transfer mechanisms.
• Key antimicrobial resistance determinants include mutations in the gyrA and parC genes that confer resistance to fluoroquinolones.
• Resistance to third-generation cephalosporins is often associated with the blaCTX-M-15 gene.
• Resistance to traditional first-line antibiotics such as chloramphenicol, trimethoprim-sulfamethoxazole, and ampicillin is commonly mediated by genes including catA1, dfrA7, sul1, and sul2.
• Whole-genome sequencing (WGS) has become an essential tool for studying the genomic diversity of S. Typhi, enabling high-resolution tracking of transmission pathways, outbreak investigation, and monitoring of antimicrobial resistance patterns.
• Genomic surveillance using travel-associated cases has also been shown to provide valuable information about genotype distribution in regions where local sequencing infrastructure is limited.
• Continuous genomic monitoring is critical for detecting newly emerging resistant clones, guiding vaccine strategies, supporting public health interventions, and informing empirical treatment guidelines for typhoid fever.

Epidemiology of Salmonella Typhi

• Infections caused by Salmonella Typhi, commonly known as Typhoid fever, represent a major public health concern, particularly in low- and middle-income countries.
• The disease is highly prevalent in regions such as Sub-Saharan Africa and South and Southeast Asia, where sanitation and safe water access may be limited.
• Unlike many other bacterial pathogens, Salmonella Typhi does not have a significant animal reservoir, therefore transmission mainly occurs from human to human.
• Outbreaks have been associated with consumption of shellfish contaminated with raw sewage and improperly processed canned meat products.
• According to the World Health Organization, Salmonella is considered one of the four major global causes of diarrheal diseases.
• Data from the Centers for Disease Control and Prevention indicate that approximately 1.35 million people are infected with Salmonella annually, with around 420 deaths reported each year.
• Globally, between 200 million and 1 billion Salmonella infections are estimated to occur annually, and about 85% of these infections are linked to the consumption of contaminated food.
• Although there has been a decline in global cases since 2000, the disease remains endemic in many developing countries.
• Transmission primarily occurs through the fecal–oral route, and its spread is strongly associated with socioeconomic conditions, population density, and poor hygiene practices.
• In 2004, it was estimated that approximately 21.6 million cases occurred in Asia and Africa.
• In the United Kingdom, about 500 cases were reported between 2006 and 2010.
• In Sri Lanka, higher incidence of enteric fever has been reported in regions such as Vavuniya, Jaffna, Nuwara Eliya, Colombo, and Kegalle, largely linked to consumption of food or water contaminated with fecal matter.
• Poor sanitation systems and unsafe dietary practices contribute significantly to outbreaks in such regions.
• According to the 2019 report from the World Health Organization, approximately 9 million cases and about 110,000 deaths occur annually due to typhoid fever.
• Children aged 5–9 years and elderly individuals, particularly those living in low-income communities, are considered high-risk groups for infection.

Transmission of Salmonella Typhi

Typhoid fever is primarily transmitted through the fecal–oral route, where bacteria from infected individuals contaminate food or water that is later consumed by others.

Major Factors Responsible for Transmission

• Contaminated Water: Drinking water contaminated with fecal material containing Salmonella Typhi can lead to infection.
• Poor Sanitation: Living in unsanitary environments with inadequate sewage disposal systems increases the risk of disease transmission.
• Food Handling: Consuming food prepared under unhygienic conditions or handled by infected individuals can facilitate the spread of the bacteria.

Clinical Manifestations of Salmonella Typhi

• Infection caused by Salmonella Typhi leads to Typhoid fever, a systemic illness affecting multiple organs.
• The incubation period is typically 1–3 weeks, after which symptoms begin to appear.
• The severity of symptoms may range from mild to severe, depending on the patient’s immune status and stage of infection.

Common Symptoms

• Persistent and severe headache.
• Chills accompanied by general malaise.
• Loss of appetite, which may eventually lead to weight loss.
• Abdominal discomfort and pain.
• Appearance of flat, red-colored spots called rose spots, usually visible on the chest and abdomen.
• Cough and mild respiratory discomfort.
• Muscle pain and generalized weakness.
• Nausea and vomiting.
• High fever that may reach up to 104°F (40°C).
• Constipation or diarrhea, which may vary among patients.

Complications of Untreated Typhoid Fever

If typhoid fever remains untreated, several serious complications may develop, including:

• Intestinal perforation, which can lead to life-threatening infection of the abdominal cavity.
• Internal bleeding, particularly from the intestinal tract.
• Neurological complications such as confusion, delirium, and seizures.
• Swelling or rupture of the gallbladder.
• Meningitis, an inflammation of the protective membranes surrounding the brain and spinal cord.
• Osteomyelitis, an infection of the bones.
• Inflammation of the heart, which may involve cardiac tissues.
• Kidney failure, resulting from severe systemic infection.
• Respiratory complications, including Bronchitis and Pneumonia.
• Miscarriage, which may occur in pregnant women infected with the pathogen.

Laboratory Diagnosis of Salmonella Typhi

Laboratory diagnosis of Salmonella Typhi, the causative agent of Typhoid fever, involves appropriate sample collection, microscopic examination, culture techniques, biochemical identification, and serological tests.

Sample Collection

The type of clinical sample collected depends on the stage and duration of infection.

Time of Infection	Sample Collected
First Week	Blood
Second Week	Serum
Third Week	Stool
Fourth Week	Urine

Gram Staining

On Gram staining, the organism appears as pink-colored short rod-shaped cocco-bacilli, which is characteristic of Gram-negative bacteria.

Blood Culture

• Blood culture is one of the most important diagnostic methods during the early stage of infection.
• The blood sample is inoculated into bile broth in a ratio of 1:10 to dilute bactericidal substances present in blood.
• The inoculated broth is incubated under appropriate conditions.
• Blood culture bottles are monitored for turbidity for up to 7 days, which indicates bacterial growth.
• Bottles showing growth are sub-cultured onto solid culture media for further identification.

Colony Characteristics on Different Culture Media

Culture Medium	Colony Characteristics
Blood Agar	2–3 mm diameter, smooth white colonies, non-hemolytic
MacConkey Agar	Colorless colonies
Xylose Lysine Deoxycholate Agar (XLD Agar)	Smooth red colonies with black centers
Salmonella-Shigella Agar (SS Agar)	Smooth colorless colonies with black spots

Biochemical Tests

• Colonies obtained from cultured plates are subjected to biochemical tests for confirmation.
• The results of these tests help differentiate Salmonella Typhi from other members of the family Enterobacteriaceae.

Slide Agglutination Test

• A milky suspension of bacterial culture is prepared using normal saline.
• A drop of the suspension is placed on reaction circles labeled O, H, AH, and BH.
• The mixture is observed for agglutination, which indicates the presence of specific Salmonella antigens and confirms identification of the organism.

Treatments of Salmonella Typhi Infections

• The treatment of infections caused by Salmonella Typhi, which leads to Typhoid fever, primarily involves the use of appropriate antibiotic therapy.
• Selection of antibiotics depends on disease severity, antibiotic resistance patterns, and patient condition.

Commonly Prescribed Antibiotics

Antibiotic Class	Examples	Use
Fluoroquinolones	Ciprofloxacin, Levofloxacin, Ofloxacin	Often used as first-line treatment for Salmonella infections in susceptible cases
Macrolides	Azithromycin	Used when fluoroquinolone resistance is present
Cephalosporins	Ceftriaxone, Cefotaxime, Cefixime	Prescribed for resistant or severe infections
Carbapenems	Meropenem, Imipenem	Used in serious or complicated typhoid fever cases

Additional Supportive Therapy

• Dexamethasone, a corticosteroid, may be administered in severe cases of typhoid fever to reduce inflammation and complications.
• Supportive care such as adequate hydration, electrolyte balance, and nutritional support is also important during treatment.

Prevention and Control of Salmonella Typhi Infections

Preventing infection caused by Salmonella Typhi, the causative agent of Typhoid fever, mainly involves improving sanitation, maintaining hygiene, ensuring safe food and water consumption, and vaccination in high-risk areas.

Proper Sanitation

• Proper waste disposal systems help prevent contamination of water and food sources.
• Regular hand washing with soap and clean water significantly reduces the risk of bacterial transmission.
• Public education about sanitation and hygiene practices plays a major role in controlling the spread of typhoid fever.

Practicing Food Safety

• Consuming thoroughly cooked food helps eliminate harmful microorganisms.
• Avoiding raw or contaminated food items reduces the risk of infection.
• Safe food handling and preparation practices are essential to prevent bacterial contamination.

Personal Hygiene

• Avoid sharing utensils such as cups, plates, and food items with infected individuals.
• Maintaining clean and hygienic bathrooms and living environments helps prevent disease transmission.

Safe Drinking Water

• Consumption of clean, safe, and contamination-free drinking water is crucial in preventing typhoid infection.

Vaccination

• Typhoid vaccination is recommended for individuals living in or traveling to high-risk regions where the disease is endemic.

Antibiotic Resistance of Salmonella Typhi

• Antibiotic resistance in Salmonella Typhi, the causative agent of typhoid fever, is a major global health concern, particularly in low- and middle-income countries across Asia and Africa.
• The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has significantly limited effective treatment options, increasing morbidity, mortality, and healthcare costs.
• MDR strains are typically resistant to first-line antibiotics such as chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole, while XDR strains additionally resist fluoroquinolones and third-generation cephalosporins.
• Resistance rates for key antibiotics in endemic regions often exceed 60%, with children disproportionately affected.
• Molecular studies show resistance arises via both chromosomal mutations, notably in genes such as gyrA and parC, and through plasmid acquisition carrying multiple resistance genes.
• Sporadic reports of azithromycin resistance, the last widely effective oral antibiotic, have raised concerns about future treatment failures.
• MDR S. Typhi has been reported across Asia and Africa since the late 20th century, and XDR strains have become dominant in Pakistan (~70% prevalence by 2020) and are spreading regionally.
• Resistance rates documented for specific antibiotics include: ampicillin up to 91%, ciprofloxacin >60%, chloramphenicol >60%, ceftriaxone >50%, and azithromycin rising but still below 10%.
• While MDR rates are declining in some regions due to improved antibiotic stewardship and vaccination campaigns, XDR strains continue to expand rapidly, particularly in South Asia.
• Resistance mechanisms include chromosomal mutations (gyrA S83F/Y/L, parC S80I, parE mutations) conferring fluoroquinolone resistance, and plasmid-mediated genes encoding extended-spectrum β-lactamases (ESBLs), PMQR genes (qnrS), and catA1/dfrA7/sul1/sul2 for first-line drugs.
• The H58 haplotype lineage is strongly associated with MDR and XDR phenotypes globally.
• Carbapenems remain effective for most XDR isolates, while azithromycin is threatened by emerging mutations such as acrB R717L/Q, which reduce drug efficacy.
• South Asia is the epicenter for MDR and XDR S. Typhi; Pakistan reports the highest XDR burden, while India shows high fluoroquinolone/cephalosporin resistance but lower XDR rates.
• Africa shows rising MDR prevalence but comparatively lower XDR rates.
• Children under 15 years of age are disproportionately affected by resistant infections.
• Due to XDR emergence, empirical treatment options are increasingly limited. Carbapenems are effective but costly and injectable, whereas azithromycin is the last widely available oral option.
• Combination therapies with β-lactam/β-lactamase inhibitors show promise against some XDR strains, but clinical data remain limited.
• Surveillance data demonstrate that MDR/XDR prevalence remains high (>30%) in South Asia, supported by multiple large-scale studies.
• Genomic studies consistently identify the H58 lineage as the dominant driver of global MDR/XDR spread.
• Chromosomal and plasmid mechanisms underlie most resistance, confirmed via whole genome sequencing and molecular studies.
• Emerging azithromycin resistance is currently at low prevalence but poses a major concern for future oral treatment options.
• Carbapenems retain efficacy against most XDR strains, but their cost and intravenous administration limit accessibility.
• Declining MDR rates in some regions are linked to stewardship efforts, vaccination campaigns, and changes in first-line drug usage.
• Research gaps include the need for real-time genomic surveillance, monitoring vaccine impact on AMR patterns, clinical trials of novel combination therapies or non-antibiotic interventions, and understanding the drivers of azithromycin resistance emergence and spread.
• Pediatric populations remain a critical focus due to higher vulnerability to resistant infections.
• Coordinated efforts in surveillance, antibiotic stewardship, vaccination, and alternative therapy research are urgently required to contain MDR/XDR S. Typhi and preserve effective treatment options.

Conclusion

• Salmonella is a leading bacterium responsible for food poisoning in humans.
• It is the primary cause of typhoid fever, a potentially life-threatening illness.
• Typhoid fever represents a significant global public health issue, particularly in regions with poor sanitation.
• The bacterium is commonly found in raw or undercooked meat products, as well as in fruits and vegetables contaminated with human feces.
• Symptoms of infection can range from mild—such as headache, nausea, and vomiting—to severe complications, including meningitis, osteomyelitis, and kidney failure.

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