L 76 Enteric Fever, The Plague

Question 1

Agent for Typhoid fever

Answer 1

Salmonella Typhi

Question 2

Hosts for Typhoid

Answer 2

Humans only host

Question 3

Common age for typhoid fever

Answer 3

School-aged kids and young adults

Question 4

How are most US cases of Typhoid fever contracted?

Answer 4

80% by people who have traveled to endemic areas

Question 5

How is typhoid transmitted

Answer 5

Fecal-Oral
Food or beverages
Sewage
Hand to mouth–using contaminated toilet, not washing hands

Question 6

Characteristics of Salmonella Typhi

Answer 6

Gram-negative, motile (peritrichous flagella), facultative anaerobe, growth on regular medium, non-lactose fermentation, produces H2S (black colonies on HE agar)

One of enterbacteriaciea: E.coli, klebsiella, shigella, all are g(-), oxidase neg and catalase pos and ferments glucose

Question 7

What is HE agar?

Answer 7

Hektoen Enteric Agar
Selects for Salmonella and Shigella and other enterics
Differentiates lactose and non-lactose fermenters

Question 8

What is MacConkey agar good for?

Answer 8

Differentiates lactose fermenters (purple colonies) from non-lactose fermenters (clear colonies)

Question 9

Virulence factors of Salmonella typhi

Answer 9

They are facultative intracellular parasites that like to live inside macrophages

Fimbriae allow attachment to M cells of Peyer’s patches

Structural antigens O and H are present

LPS (lipid A) can cause fever, shock, and DIC

Type 3 secretory system from two pathogenicity islands: SPI-1 & 2. Causes endocytosis and transport through mucosal cells of ileum

Vi antigen: capsule specific to S. typhi, provides extracellular protection, inhibits inflammatory response

Question 10

What is Type 3 Secretion System?

Answer 10

Assembly of proteins into a needle-like structure that is used by gram (-) bacteria to inject contents into eukaryotic cells in order to infect and spread.

Question 11

Pathogenesis of S. typhi (enteric fever)

Answer 11

(incubation can be 5-21 days)

1) Microbes gain entrance through food or drink (fecal-oral) and survive acid (sensitive to acid) and bile
2) Attach to CFTR on M cells in distal ileum with fimbriae
3) Induce endocytosis by T3SS activation from SPI-1 and travel through cells by SPI-2 direction to submucosa
4) Taken up by macrophages and begin replication
5) Travel to lymphatics to RES organs: bone, liver, spleen
6) Initiate apoptosis of macrophages and spread to blood stream causing fever
7) Repeat RES circuit or shed in stool or urine

Question 12

How is the gall bladder related to enteric fever?

Answer 12

Gall bladder is infected from the liver => cholecystitis
Infected bile => positive stool cultures
Gall stones predisposes to long term fecal carriage and induces polysaccharide formation of a biofilm for S. typhi
Infected bile re-seeds the intestines that get a second invasion of Peyer’s patches => hyperplasia and the intestines become necrotic and can perforate => secondary bacteremia

Question 13

Clinical manifestations of enteric fever in the first week after fever

Answer 13

Fever progresses in a stepwise fashion: rises day, drops by morning OR increases progressively to 39-40C
Bacteremia develops
Relative bradycardia or pulse-temp dissociation (one goes up and other goes down)

Question 14

Clinical manifestations of enteric fever in the second week after fever

Answer 14

Abdominal pain
Rose spots may appear (truncal maculopapules)
Constipation-diarrhea

Question 15

Clinical manifestations of enteric fever in the third week after fever

Answer 15

HSmegaly
Intestinal bleeding
Perforation => acute complications
Septic shock may occur or altered consciousness–LPS major player
Death possible

Question 16

Clinical manifestations of enteric fever in the fourth week after fever

Answer 16

In absence of acute complications: symptoms gradually decrease over weeks to months
Some become chronic carriers: more frequent in women, cholelithiasis, and in urine–urolithiasis, BPH

Question 17

How to diagnose enteric fever

Answer 17

Culture isolation is the best way (other tests like Widal test and Typhidot not as dependable)
Remember to do susceptibility tests looking for resistance to nalidixic acid (fluoroquinolones), and ESBL (extended spectrum beta-lactamases)
When looking for carriers, ELISA for Vi antigen is useful

Question 18

How to recover organisms for enteric fever diagnosis

Answer 18

In first week, check blood and stool (85-90%)

Bone marrow aspirate most sensitive (90%) even 5 days after antibiotics started

Question 19

Treatment of enteric fever

Answer 19

Difficult because of resistance
3rd generation cephalosporins, azithromycin, fluoroquinolones

In chronic carriers: prolonged course of ciprofloxacin or norfloxacin and consider cholecystectomy

Question 20

Enteric fever prevention

Answer 20

Two vaccines are available but neither one is completely effective and boosters are required

Oral: TY21A–live attenuated S. typhi
Injection: ViCPS–Vi capsular polysaccharide

Ensure clean food and WATER, dispose of sewage

Question 21

Causative agent for the plague

Answer 21

Yersinia pestis

Infective dose is 1-10 bacteria

Question 22

Physical characteristics of Yersinia pestis

Answer 22

Part of the family of Enterobacteriacea
Gram (-) coccobacillus
Safety Pin appearance with Wayson stain (and blue)
Non-motile
Wide range of temperature tolerance
Facultative intracellular pathogen

Question 23

Where does Yersinia pestis come from

Answer 23

It is a zoonotic infection that resides mostly in rodents, wild, and even domestic animals.
Transmitted by fleas
Humans are incidental hosts

Question 24

What are the bacteria in the family of enterobacteriacea?

Answer 24

Enterobacteriacea: (E PESSKY S) Enterobacter, Proteus, Escherichia, Shigella, Salmonella, Klebsiella, Yersinia, Serratia

Question 25

Virulence factors of Yersinia pestis

Answer 25

F1 protein: fimbrial capsule forming protein, prevents phagocytosis and aids transmission from flea to host

V and W antigens: reduce host inflammatory responses to prolong survival in host?

T3SS to inject LcrV ( may be the same as the V protein above)

Endotoxin LPS: hemorrhage, vascular collapse, DIC, focal necrosis

Question 26

Pathogenesis in relation to F1 capsule production

Answer 26

If the F1 capsule is produced early on, the bacteria is not phagocytosed => septicemia, dissemination and can => pneumonic plague

If F1 capsule is not produced early, it will be taken up by macrophages and transported to lymph nodes to cause bubonic plague

Question 27

Name the three forms of the plague

Answer 27

Remember acral ecchymosis (BLACK plague)

1) Bubonic plague: 80-95% of cases, sudden onset of fever, chills, headache, painful swollen nodes, incubation 2-6 days, when untreated can spread to lungs
2) Septicemic plague: 10-20%, no preceding bubo, febrile and extremely ill, GI symptoms can be seen N/V/D
3) Pneumonic plague: rarely primary infection, aerosolized droplets or respiratory secretions, short incubation of hours to days, sudden onset dyspnea, fever, cough, chest pain, rapidly fatal without immediate treatment

Question 28

How does one get the plague?

Answer 28

Flea bite, respiratory droplets, contacting sick animals, bites or scratches from infected cats

Question 29

Plague diagnosis

Answer 29

Aspirate fluid from nodes/sputum and culture
Stain with Wayson and look for safety pin
Stain with Lillie-Twort stain
Demonstrate 4x change in F1 titer
Chest radiograph

Question 30

Plague treatment

Answer 30

Streptomycin DOC
Otherwise IV/IM Gentamicin
Respiratory isolation

Question 31

Plague prophylaxis

Answer 31

Doxycycline or trimethoprim/sulfamethoxazole to those who may have been exposed