Salmonella

Question 1

What does the severity of salmonella infections in humans vary based on?

Answer 1

• serotype
• Health status of the human host (e.g immunosuppression)
• Children under 5 and elderly people

Question 2

Why are most strains of salmonella considered to be pathogenic?

Answer 2

They have the abilty to invade, replicated and survive in human host cells resulting in potentially fatal disease

Question 3

How does salmonella gain access to host cells?

Answer 3

It induces its own phagocytosis in order to gain access to the host cells

Question 4

What are salmonella pathogenicity islands (SPIs)?

Answer 4

Gene clusters located at the large chromosomal DNA region and endcoding for the structures involved in the invasion process.

1. SPIs encode for type III secretion systems, multichanel proteins that allow Salmonella to inject its effectors across the intestinal epithelial cell membrane into the cytoplasm
2. The bacterial effectors then activate the signal transduction pathway and trigger reconstruction of the actin cytoskeleton of the host cell, resulting in the outward extension or ruffle of the epithelial cell membrane to engulf the bacteria. The morphology of the membrane ruffle resembles the process of phagocytosis

Question 5

What makes some Salmonella strains non-virulent?

Answer 5

Their lack of to ability persist in the host cell

Question 6

What happens following following the engulfment of Salmonella into the host cell?

Answer 6

1. The bacterium is encased in a membrane compartment called a vacuole, which is composed of the host cell membrane.
2. Under normal circumstances, the presence of the bacterial foreign body would activate the host cell immune response, resulting in the fusion of the lysosomes and the secretion of digesting enzymes to degrade the intracellular bacteria.
3. However, Salmonella uses the type III secretion system to inject other effector proteins into the vacuole, causing the alteration of the compartment structure.
4. The remodelled vacuole blocks the fusion of the lysosomes and this permits the intracellular survival and replication of the bacteria within the host cells.

Question 7

What does the capability of the bacteria to survive within macrophages allow for?

Answer 7

It allows them to be carried in the reticuloendothelial system (RES)

Question 8

How are salmonella strains commonly grouped?

Answer 8

Typhoid Salmonella and non-typhoid Salmonella (NTS)

Question 9

In human infections, what are the four different clinical manifestations?

Answer 9

1. Enteric fever
2. gastroenteritis
3. bacteraemia
4. other extraintestinal complications, and chronic carrier state

Question 10

Clinical manifestations of Salmonella: Enteric fever

Answer 10

Salmonella Typhi is the aetiological agent of typhoid fever, while paratyphoid fever is caused by S. ParatyphiA, B and C. Since the clinical symptoms of paratyphoid fever are indistinguishable from typhoid fever, the term ‘enteric fever’ is used collectively for both fevers, and both S. Typhi and S. Paratyphi are referred as typhoid Salmonella

Question 11

TRUE or FALSE: Humans are the sole reservoir for the two strains of typhoid Salmonella

Answer 11

TRUE

Question 12

How are the two strains of typhoid Salmonella transmitted?

Answer 12

Via the ingestion of food or water contaminated with the waste of infected individuals

Question 13

Enteric fever is characterized by an incubation period of

Answer 13

One week or more, with prodomal symptoms such as headache, abdominal pain and diarrhoea (or constipation), followed by the onset of fever

Diarrhoea is more commonly observed in children, whereas patients with immunosuppression are more likely to develop constipation

Question 14

During the illness, enteric fever displays a specific fever pattern.

Describe this pattern

Answer 14

An initial low-grade fever (> 37.5°C to 38.2°C) which slowly develops to high-grade fever (> 38.2°C to 41.5°C) in the second week.

If the patient is left untreated, fever can persist for a month or more

Question 15

What may infected patients develop besides fever?

Answer 15

Myalgia, bradycardia, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), and rose spots on their chest and abdomen

Question 16

15% of the infected patients develop gastrointestinal complications which include

Answer 16

pancreatitis, hepatitis and cholecystitis

Question 17

What is one of the most severe gastrointestinal complications?

Answer 17

Haemorrhage is one of the most severe gastrointestinal complications that occur as a result of perforation of Peyer’s patches, lymphatic nodules located at the terminal ileum, resulting in bloody diarrhoea

Question 18

The ability of typhoid Salmonella to survive and persist in the RES results in relapse in what percentage of patients?

Answer 18

10%

Question 19

Gastroenteritis Salmonella strains other than S. Typhi and S. Paratyphi are referred to as NTS. Where are they predominantly found?

Answer 19

in animal reservoirs

Question 20

Clinical manifestations: NTS infections are characterized by gastroenteritis or ‘stomach flu

Answer 20

An inflammatory condition of the gastrointestinal tract which is accompanied by symptoms such as non-bloody diarrhoea, vomiting, nausea, headache, abdominal cramps and myalgias. Symptoms such as hepatomegaly and splenomegaly are less commonly observed in patients infected with NTS

Question 21

TRUE or FALSE: Compared to typhoid infections, NTS infections have a Longer incubation period

Answer 21

Compared to typhoid infections, NTS infections have a shorter incubation period (6–12 h) and the symptoms are usually self-limiting and last only for 10 days or less

Question 22

What do Gastrointestinal complications of NTS infections include?

Answer 22

Cholecystitis, pancreatitis and appendicitis, while the perforation of the terminal ileum has no association with NTS infections

Question 23

Who are highly susceptible to NTS infections?

Answer 23

Infants, young children, elderly people and immunocompromised patients are highly susceptible to NTS infections and develop more severe symptoms than normal individuals

Question 24

Clinical manifestations: Salmonella bacteraemia

Answer 24

A condition whereby the bacteria enter the bloodstream after invading the intestinal barrier.

Almost all the serotypes of Salmonella can cause bacteraemia, while S. Dublin and S. Cholearaesuis are two invasive strains that are highly associated with the manifestations of bacteraemia

Question 25

What are the symptoms of bacteriaemia?

Answer 25

• Similar to enteric fever, high fever is the characteristic symptom of bacteraemia, but without the formation of rose spots as observed in patients with enteric fever.
• In severe conditions, the immune response triggered by bacteraemia can lead to septic shock, with a high mortality rate.

Question 26

TRUE or FALSE: The clinical manifestation of bacteraemia is more commonly seen in NTS infections than in typhoid Salmonella infections

Answer 26

TRUE

The difference in the clinical manifestation is believed to be associated with the presence of the spv (Salmonella plasmid virulence) gene in NTS which causes non-typhoidal bacteraemia, based on genetic analysis

Question 27

Describe the mechanism of the e spv (Salmonella plasmid virulence) gene

Answer 27

Expression of the gene is required to prolong apoptotic cell death and this may allow the bacteria to persist in the host cells for a longer period

Question 28

Approximately what percentage of patients infected with NTS develop bacteraemia?

Answer 28

Approximately 5% of patients infected with NTS develop bacteraemia and, in some cases, extraintestinal complications occur, with the lung being the most commonly compromised organ

Question 29

Name some other extraintestinal complications

Answer 29

Cellulitis, urinary tract infections, pneumonia, endocarditis and meningitis

Question 30

The status of chronic carrier is defined as

Answer 30

The shedding of bacteria in stools for more than a year after the acute stage of Salmonella infection

• Since humans are the only reservoir of typhoid Salmonella, carriers of S. Typhi and S. Paratyphi are responsible for the spreading of enteric fever in endemic regions, as the common transmission route is the ingestion of water or food contaminated with the faeces of chronic carrier

Question 31

What are chronic carriers?

Answer 31

Chronic carriers are those who continue to harbor a pathogen e.g. Salmonella Typhi, the causative agent of typhoid fever, for months or even years after their initial infection

Question 32

What percentage of patients become chronic carriers?

Answer 32

About 4% of patients with enteric fever, predominantly infants, elderly people and women, may become chronic carriers

Question 33

TRUE or FALSE: the carrier state of NTS is less frequent

Answer 33

TRUE

with an occurrence rate of 0.1% in patients with non-typhoidal salmonellosis. This is because the primary reservoir of NTS is animals, instead of humans

Question 34

When was the first incidence of Salmonella resistance reported?

Answer 34

In the early 1960s, the first incidence of Salmonella resistance to a single antibiotic, namely chloramphenicol, was reported

Question 35

What are the traditional first line treatments for Salmonella?

Answer 35

Antimicrobial agents such as ampicillin, chloramphenicol and trimethoprim– sulfamethoxazole are used as the traditional first line treatments for Salmonella infections. Salmonella spp. resistant towards these agents are referred to as multi-drug resistant (MDR).

Question 36

Describe MDR of Salmonella

Answer 36

• For many years, the phenotypic trait of MDR was widely distributed among S. Typhi and, at a lower rate, among S. Paratyphi
• Africa and Asia are two continents with a high isolation frequency of S. Typhi displaying MDR phenotype

Question 37

What has the the emergence of resistance towards traditional antibiotics prompted?

Answer 37

Fluoroquinolones and extended-spectrum cephalosporins have been introduced as the antimicrobial agents of choice in treating MDR S. Typhi

Question 38

Describe the MDR phentotype for NTS

Answer 38

• As for NTS, the number of strains developing MDR phenotype has increased in many countries since the first emergence of MDR S. Typhimurium DT104 strains in 1990
• Based on data from 2005 to 2006 presented by the National Antimicrobial Resistance Monitoring System (NARMS), 84% of clinical isolates of NTS displayed MDR phenotype and 4.1% of the isolates had reduced susceptibility to cephalosporins in the USA.

Question 39

What is the emergence of Salmonella with antimicrobial resistance is mainly promoted by?

Answer 39

• The use of antibiotics in animal feed to promote the growth of food animals and in veterinary medicine to treat bacterial infections in those animals
• This poses a high risk of zoonotic disease with the transmission of MDR Salmonella strains from animals to humans via the ingestion of food or water contaminated with the animals’ faeces, direct contact or the consumption of infected food animals

Question 40

TRUE or FALSE: MDR Salmonella strains were found in some exotic pet animals such as tortoises and turtles

Answer 40

TRUE

Question 41

Describe Salmonella’s mechanisms of resitance

Answer 41

• Studies show that the serotypes of Salmonella displaying MDR phenotype have the ability to generate various types of hybrid plasmids. The majority of the gene cassettes located within these plasmids consist of resistance genes that confer the antimicrobial resistance property of the serotypes against traditional antibiotics such as chloramphenicol, tetracycline, ampicillin and streptomycin
• The emergence of Salmonella serotypes with reduced ciprofloxacin susceptibility is a result of chromosomal mutation at the quinolone resistance-determining regions of the gyrA gene
• Some serotypes of Salmonella have begun to develop resistance towards broad-spectrum cephalosporins as a result of mutated genes that encode for extended-spectrum βlactamases, hydrolysing antibiotics with β-lactam rings such as cephalosporin and cephamycins