Pathology of Typhoid Fever

Question 1

What is typhoid?

Answer 1

Typhoid fever is an acute systemic illness caused by motile, gram-negative bacilli of the genus Salmonella (enterobacteriaceae)

Salmonella typhi ( Salmonella enterica Serovar Typhi )

Salmonella paratyphi

Question 2

Bacterial morphology

Answer 2

Rod shaped, flagellated, aerobic, Gram negative bacterium

Enterobacteriaceae

Fimbriae, adhesins, biofilm

Secreted proteins involved in host cell invasion and intracellular proliferation

Question 3

Epidemiology

Answer 3

Spread: Oral-fecal route, oral-anal sexual contact

More common in children and young adults

Developing countries and overcrowded areas with poor sanitation

High incidence (more than 100 cases per 100,000 person years) in South central Asia, Southeast Asia, southern Africa

Developed countries: Travelers

Question 4

Pathogenesis of typhoid

Answer 4

1. S.typhi is swallowed, causing contamination to it’s human host
2. Gets to terminal ileum
3. Invades through M cells (specialized epithelial cells) and peyers patches in the terminal ileum and gets to macrophages beaneath which ingest bacteria
4. It then enters into the lymphatics and into blood
5. It proliferates in blood and moves to various organs (brain, lungs, spleen, liver etc)
6. When it gets to the liver, some will be released into bile which will enter the gallbladder.
7. From the gallbladder it will enter back into the ileum of the intestine
8. More macrophages will attempt to destroy it and in the process will cause destruction of some M cells causing lower GI bleeding and ulceration

Question 5

GIT Pathology and stages

Answer 5

Lymphoid tissue of small and large bowels

Peyer’s patches at terminal ileum most affected

Jejunum, ascending colon

Stages:
Hyperemia (an excess of blood in the vessels supplying an organ or other part of the body)
Necrosis
Ulceration
Healing (if treated or perforation of abdomen if untreated)

Question 6

Discuss hyperemia

Answer 6

Hyperemia is an
active process in which arteriolar dilation (e.g., at sites of
inflammation or in skeletal muscle during exercise) leads to increased blood flow. Affected tissues turn red (erythema) because of increased delivery of oxygenated blood.
Occurs due to release of inflammatory cytokines

Hyperemia:
Congested lymphoid tissue (projects from surface)

Infiltration by monocytes (macrophages): eccentric nuclei with pale eosinophilic cytoplasm (Typhoid cells). May contain RBC, bacilli

Lymphocytes and plasma cells also present; polymorphs are rare

Question 7

Discuss Necrosis

Answer 7

Necrosis

Results from toxins released by dead bacilli

Involves mucosa and submucosa

Also caused by thrombosis and blockage of small vessels

Question 8

Discuss Ulceration and difference between tb ulcers

Answer 8

Ulceration

1. Occurs by 3rd week
2. Usually 3-4cm
3. Ulcers are oval, long axis, anti-mesenteric border
4. Edges are soft, raised, floor may contain greenish-black slough
5. May become confluent
6. Cellular exudate: typhoid cells, lymphocytes, plasma cells

Normal ulcers
- oriented along longitudinal axis
- heal without fibrosis

Tb ulcers
- oriented along transverse axis of small intestine
- heal fibrosis
- Can cause interstitial obstruction because fibrosis can cause narrowing

Question 9

Discuss Healing

Answer 9

Healing (4th week)
Fibrosis and scarring are minimal

Strictures hardly occur

Question 10

Discuss liver pathology

Answer 10

Liver
Typhoid nodules present in parenchyma

Macrophages and lymphocytes with or without central necrosis

Bacilli may be present

Ballooning of hepatocytes and small at droplets

Abscess formation

Question 11

Discuss Gall bladder pathology
What is the seat of infection in carriers?

Answer 11

Gall bladder

Usual seat of infection in carriers

Acute cholecystitis rare

Chronic cholecystitis- carrier state (not common either)

Gallstones a common secondary complication in Europe, rare in tropical Africa

Question 12

Discuss RES (Spleen)

Answer 12

Spleen

Enlarged, hyperaemic, cherry red or grayish red

Proliferating histiocytes in sinuse and pulp; they predominate in germinal centres

Typhoid nodules may be present

Question 13

Discuss Mesenteric Lymph nodes

Answer 13

Mesenteric Lymph nodes
Enlarged and hyperemic; may be hemorrhagic

Sinusoids packed with histiocytes

Rarely purulent

Question 14

Discuss bone marrow pathology

Answer 14

Bone Marrow
Typhoid nodules may be seen
Myeloid hypoplasia

Question 15

Discuss GUS pathology

Answer 15

Typhoid nodules in the kidney

Acute tubular necrosis may result from massive hemolysis

Perinephric abscesses

Orchitis is rare (typhoid nodules in the interstitium of the testes)

Question 16

Discuss CVS Pathology

Answer 16

Fatty degeneration of myofibrils
Pericarditis is rare
Sudden death from heart failure (anesthesia may be dangerous in these patients)

Venous thrombosis and subsequent embolism not uncommon in tropical areas

Question 17

Discuss CNS Pathology

Answer 17

Meningism (CSF findings may be normal)
Pyogenic Meningitis
Peripheral neuritis

May be associated with Guillaine-Barre syndrome

Question 18

Discuss skeletal

Answer 18

Osteomyelitis may occur years after infection.
Seen in long bones
Typhoid spine
Common with blood dyscrasias

Question 19

Other pathologies

Answer 19

Rose-spots
Otitis media
Parotitis
Zenckers degeneration
Typhoid arthritis

Question 20

Diagnostic tests

Answer 20

Urine diazo test (5 days of clinical illness)
Blood culture (bile-salt broth): 2 weeks
Stool culture

Question 21

What enables the Pathogenesis of salmonella typhi

Answer 21

Low inoculum required

Favored by low gastric acid concentration

Transfer of bacterial proteins to enterocytes

Bacterial endocytosis and bacterial growth in endosomes

Flagellin activates inflammatory response

LPS activates TLR4

Epithelial cells release hepaoxilin A3 drawing neutrophils into the lumen and causing mucosal damage

TH1 and TH17 limit infection

Disseminated salmonellosis