Salmonella typhi

Question 1

S. typhi epi and clinical pres.

Answer 1

Epi:
22 million cases a year and more than 200,000 deaths, rare in N. America, Europe and Australia, common in developing world

Clinical Pres:
disease referred to as typhoid fever
incubation period: 7-14 days (early GI phase may be subclinical with + stool culture)
Episodic fever, bradycardia, skin rash (Rose spot), leukopenia (low WBC count), enlarged liver and spleen (bacteremic phase)
Intestinal hemorrhage or perforation during late stages (late GI phase)

Question 2

S. typhi pathogenesis

Answer 2

only infects humans (contaminated water or food)
somewhat resistant to killing by stomach acid
has adhesins promote attachment to intestinal epithelium
induce bacterially-mediated endocytosis after adherence to apical membrane of epithelial cells
macrophages take up extracellular bacterial cells
survival inside phagocytic vacuoles of macrophages (possibly due to Vi antigen–polysaccharide capsule)
survives acidic environment of lysosome in macrophages
kills macrophage and disseminates via thoracic duct to blood, liver, spleen, and gall bladder
bacterial factors in blood cause fever and shock
reinvasion of GI tract from gall bladder
GI bleed and sometimes diarrhea

Question 3

S. typhi virulence determinants

Answer 3

Invasion and intracellular survival are aided by T3SS(type 3 secretion system) found on pathogenicity islands (are acquired through horizontal gene transfer)

Gram-negative LPS in outer membrane contains endotoxin, and endotoxin causes fever and shock

Question 4

SPI-1

Answer 4

Salmonella pathogenicity island 1

-encodes genes for invasion

Question 5

SPI-2

Answer 5

encodes genes for intracellular survival

Question 6

T3SS

Answer 6

Type 3 Secretion System
Specialized form of secretion where a protein moves across the bacterial cytoplasmic and outer membrane AND across the host cell membrane through an injection needle

Types of pathogens
Effector proteins- virulence factors delivered to host cell via secretion apparatus

In S., T3SS delivers toxins that induce membrane ruffling by stimulating actin polymerization, and endocytosis

Question 7

S. typhi diagnosis

Answer 7

isolation of organism during typhoid fever varies depending on the stage of the disease
1st week- subclinical pt may have + stool culture
Blood cultures are + btw 2nd and 3rd week and pts are symptomatic
Stool culture + again after 3rd week when the gall bladder is colonized during bacteremia

Question 8

S. typhi treatment

Answer 8

S. typhi lives inside macrophages–consider tissue penetrations of antibiotics
-Fluoroquinolones (ciprofloxacin) or 3rd generation cephalosporin (ceftriaxone)
Chronic carrier states, 1) ampicillin or cipro, 2) cholecystectomy
-Relapse can occur in 10% of pts in endemic areas

Question 9

S. typhi prevention

Answer 9

Control of water supplies and sewage disposal
food safety
pasteurization of milk and screening for carriers among food handlers

Two vaccines

• oral attenuated vaccine (Ty21a)
• Vi capsular polysaccharide vaccine (ViCPS)

Question 10

Salmonella basic features

Answer 10

member of the Enterobacteriaciae (along with shigella and E. coli)
gram negative rod

3 clinically distinguishable syndromes related to salmonellosis

1. typhoid or enteric fever caused by S. Typhi
2. Septicemias caused by S. cholerasuis
3. Acute gastroenteritis caused by S. enteriditis or S. typhimurium