PATHOPHYSIOLOGY OF TYPHOID FEVER

Aka enteric fever

Caused by Salmonella enterica serovar Typhi (gram negative bacilli)
Serovar- aka serotype, distinct variation within a species of bacteria or
viruses or among immune cells of different individuals; based on cell Ag.
MOT: ingestion of organism by ingesting food or contaminated water with
feces of a carrier
Carrier: 1) chronic carrier recovered from typhoid fever but harbour the
organism asymptomatically in gallbladder
2) silent carrier asymptomatic carriers without even suffering
the disease
Includes street foods and contamination of water reservoir
Sources of fecal contamination includes street foods and contamination of
water source
Incubation period: 4-14 days, depending on the inoculating dose of viable
bacteria
Mean Infective dose: 105-108 organisms

1) Attachment of S. enterica serovar Typhi to epithelial cells of the ileum

Assemble type III secretion system (TTSS or T3SS)
Encoded in SPI-1 gene (Salmonella pathogenicity Island-1)
Also called as injectiosome or injectosome
Protein appendage
Needle-like structure
Used as sensory probe to detect the presence of eukaryotic cells
Secretes protein (effector protein)
2) TTSS translocate effectors in the cytoplasm
Activates host Rho guanosine triphosphatases
Leads to:
Rearrangement of the actin cytoskeleton into membrane ruffles
bacterial uptake
Induction of mitogen-activated protein kinase pathways activates
the transcription factors activator protein-1 and nuclear factor kB
production of IL-8 (aka neutrophil chemotactic factor)
Destabilization of tight junction allows the transmission of PMN from
the basolateral surface to the apical surface, paracellular fluid leakage
and access of bacteria to basolateral surface
Tight junction aka occluding junction r zonulae occludentes
- Closely associated areas of two cells whose membranes join
together forming a virtually impermeable barrier to fluid

3) Bacterial uptake (macropinocytosis)

4) Salmonella are enclosed in spacious phagosome that is formed by membrane
ruffles
5) phagosome + lysosome = Vacuole (phagolysosome)
6) Produces toxin induces cell cycle arrest
7) Enter the mesenteric lymphoid system

1
 Lies between the layers of mesentery
Mesentery fold of membranous tissue that arises from the posterior wall
of the peritoneal cavity and attaches to intestinal tract
8) Enter blood via lymphatics primary bacteraemia (asymptomatic and blood
culture negative)
9) Colonize the Reticuloendothelial system (RES), replicate within macrophages
RES class of cells that occurs in widely distributed parts of the human
body and that have in common the property of phagocytosis
- Aka mononuclear phagocytic system, part of immune system that
consists of phagocytic cells located in reticular connective tissue
reticular connective tissue found around the liver, kidney, spleen and
lymph nodes and bone marrow
10) After replication, S. enterica serovar Typhi are shed back into the blood
leads to secondary bacteraemia
coincide with onset of clinical symptoms
end of incubation period

Virulence
avoiding triggering early inflammatory response in gut
colonize deeper tissue and organ system
ulcer, perforation
TTSS
Vi polysaccharide capsular Ag interfere with phagocytosis by preventing
binding of C3 to the surface of bacterium
Ability of organism to survive and replicate within macrophages
Encoded in PhoP regulon
Toxin diarrhea
Illicit proinflammatory cytokines (IL-6, IL-, TNF-) fever