L 76 Enteric Fever, The Plague Flashcards
Agent for Typhoid fever
Salmonella Typhi
Hosts for Typhoid
Humans only host
Common age for typhoid fever
School-aged kids and young adults
How are most US cases of Typhoid fever contracted?
80% by people who have traveled to endemic areas
How is typhoid transmitted
Fecal-Oral
Food or beverages
Sewage
Hand to mouth–using contaminated toilet, not washing hands
Characteristics of Salmonella Typhi
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
What is HE agar?
Hektoen Enteric Agar
Selects for Salmonella and Shigella and other enterics
Differentiates lactose and non-lactose fermenters
What is MacConkey agar good for?
Differentiates lactose fermenters (purple colonies) from non-lactose fermenters (clear colonies)
Virulence factors of Salmonella typhi
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
What is Type 3 Secretion System?
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.
Pathogenesis of S. typhi (enteric fever)
(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
How is the gall bladder related to enteric fever?
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
Clinical manifestations of enteric fever in the first week after fever
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)
Clinical manifestations of enteric fever in the second week after fever
Abdominal pain
Rose spots may appear (truncal maculopapules)
Constipation-diarrhea
Clinical manifestations of enteric fever in the third week after fever
HSmegaly Intestinal bleeding Perforation => acute complications Septic shock may occur or altered consciousness–LPS major player Death possible
Clinical manifestations of enteric fever in the fourth week after fever
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
How to diagnose enteric fever
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
How to recover organisms for enteric fever diagnosis
In first week, check blood and stool (85-90%)
Bone marrow aspirate most sensitive (90%) even 5 days after antibiotics started
Treatment of enteric fever
Difficult because of resistance
3rd generation cephalosporins, azithromycin, fluoroquinolones
In chronic carriers: prolonged course of ciprofloxacin or norfloxacin and consider cholecystectomy
Enteric fever prevention
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
Causative agent for the plague
Yersinia pestis
Infective dose is 1-10 bacteria
Physical characteristics of Yersinia pestis
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
Where does Yersinia pestis come from
It is a zoonotic infection that resides mostly in rodents, wild, and even domestic animals.
Transmitted by fleas
Humans are incidental hosts
What are the bacteria in the family of enterobacteriacea?
Enterobacteriacea: (E PESSKY S) Enterobacter, Proteus, Escherichia, Shigella, Salmonella, Klebsiella, Yersinia, Serratia
Virulence factors of Yersinia pestis
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
Pathogenesis in relation to F1 capsule production
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
Name the three forms of the plague
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
How does one get the plague?
Flea bite, respiratory droplets, contacting sick animals, bites or scratches from infected cats
Plague diagnosis
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
Plague treatment
Streptomycin DOC
Otherwise IV/IM Gentamicin
Respiratory isolation
Plague prophylaxis
Doxycycline or trimethoprim/sulfamethoxazole to those who may have been exposed
