Yersinioses. Plague and Tularemia.

Question 1

what are the CHARACTERISTICS OF YERSINIA ?

Answer 1

enterobacteriae
gram negative and rod shaped
motile except Y pests
aerobic

Question 2

what are the different subtypes of yersinoses?

Answer 2

Y pestis
Y pseudotuberculosis
Y enterocolitica

Question 3

what is the epidemiology of yersinosis?

Answer 3

there is a worldwide distribution of yersinosis

the reservoir - wild and domestic animals - ESP pigs

3rd commonest zoonosis in europe

Question 4

what is the transmission of yersina ?

Answer 4

consumption of raw meat , unpasteurized milk products

contaminated water

direct / indirect contact with infected animal

Question 5

what is the etiology of yersinosis

Answer 5

yersinia enterocolitica

yersina pseudotuberculosis

Question 6

what is the incubation period for yesrinosis ?

Answer 6

4-6 days

Question 7

what is the pathogenesis of yersinosis ?

Answer 7

oral route of infection

initial replication in the small intestine - invasion into the Peters patch of the distal ileum via the M cells

spread to the mesenteric lymph nodes

involvement of the liver and spleen is common

attachment to the hosts cells surface by targeting immune effector cells - alteration of host innate immunity

toxins are injected into the macrophages , neutrophils and dendritic cells - reduction of phagocytosis and inhibiting production of ROS and triggering apoptosis of macrophages

Question 8

what are the clinical features of yersinosis ?

Answer 8

lasts 1-46 days

Y enterocolitica

inflammatory diarrhea - may be bloody in severe cases
low grade fever
vomiting
pseudo appendicitis - mesenteric lymphadenitis , particularly in the ileum with typical signs of appendicitis

children < 4y = self limiting diarrhea
- sometimes bloody

> 4yr - abdominal pain in the right iliac fossa (mimicking appendicitis)
mesenteric adeninitis and terminal ileitis

========
Y pseudotuberculosis

mostly associated with mesenteric adeninitis

present with fever and abdominal pain in all age groups

=======

both subtypes can present septicaemia - fever

Question 9

what is the complication of yersinosis ?

Answer 9

post infectious

in patients with HLA-B27
reactive arthritis - 2-4wks

erythema nodosum

granulomatosis appendicitis

mycotic aneurysms

focal abscesses

Question 10

how do you diagnose yersinosis ?

Answer 10

blood / csf / stool sample cultures

direct pathogen detection in culture

agglutinating or ELISA to specific o antigens

Question 11

what is the treatment to yersinosis ?

Answer 11

spontaneous resolution
sever cases - fluoroquinilones for 2 weeks

or 3rd gen cephalosporins

Question 12

what is the EPIDEMIOLOGY OF YERSINIA PESTIS / BUBONIC PLAGUE

Answer 12

systemic zoonosis - affecting small rodents

its in western US

reservoir - prairie dogs , squirrels , rodents

Question 13

what’s the vector yersinia pestis?

Answer 13

vector - fleas

Question 14

what’s the route of transmission of the black plague?

Answer 14

flea bites

Question 15

what is the pathogenesis of yersinia pestis?

Answer 15

3 virulent plasmids are necessary :

1) classical plasmid - genres form yersinia outer protein - yops - manipulate host cell
2) larger plasmid - coding for capsule protein - counteracts phagocytosis

3) smaller plasmid - coding for
pesticin & coagulase

===

multiplication within flea & transmission to humans depend on coagulase =
temperature- dependent enzyme:

<30°C: coagulation promoting

>30°C: fibrinolysis promoting

-

flea: environmental temperature
 blood coagulation within the stomach
 coagulation mixture extends into oesophagus
 blockage of the oesophagus
 flea cannot take up any more blood
 stimulation of hunger
 next blood meal
 mixing of fresh blood with old coagulated blood
blood mixture triggers gag reflex
 injection of bacteria into new host

-
host: body temperature of 37°C causes fibrinolysis
 improves systemic dissemination
of agent

Question 16

what is the incubation period for bubonic plague ?

Answer 16

2-6 days

Question 17

what are the clinical manifestation of bubonic plague

Answer 17

sudden onset of fever, malaise, myalgia, dizziness & increasing pain due to progressive lymphadenitis

lymphadenitis affects LN (buboes) near the fleabite-
tense, tender swelling
 mostly affecting the
inguinal , crural, axillary, cervical & submaxillary LN

 abdominal pain from mesenteric LN involvement

===========

without treatment dissemination occurs causing severe illness
 pneumonia
(secondary pneumonic plague) & meningitis

============
primary septicemic plague
: septicaemia without preceding lymphadenopathy
 increased risk for persons
older than 40y & persons with chronic conditions

=========

primary pneumonic plague
: caused by inhalation of infectious bacteria of droplets
from other persons/animals

with secondary/primary pneumonic plague

 incubation: 2 -3d

 sudden onset of fever, headache, myalgia
, weakness, vomiting,

respiratory symptoms arising after 24h: cough, dyspnea, chest pain, sputum
with haemoptysis

initially segmental pneumonitis
lobar pneumonia
bilateral lung
involvement

==========

plague pharyngitis
: consumption of contaminated meat or contact with an infected
person with pneumonic plague

 resembles tonsillitis with peritonsillar abscess & cervical lymphadenopath

Question 18

what is the prognosis of bubonic plague ////

Answer 18

with appropriate treatment before dissemination of the plague : fever resolution within 2 -5d,

buboes remain enlarged for >1w

Question 19

what are the COMPLICATION OF PRIMARY BUBONIC PLAGUE ?

Answer 19

secondary pneumonic plague
\: consequence of
bacteraemia in 10-
15% of patients with
bubonic plague

=======

• meningeal plague
  : >1w after onset of bubonic/septicemic plague due to suboptimal antimicrobial therapy
   fever & headache

Question 20

what is diagnosis of bubonic plague ?

Answer 20

bacterial culture from buboes aspirate, blood or sputum

=====

Microscopy with Wayson stain taken from buboes, blood, or sputum show bipolar staining of bacteria (appearance of “closed safety pin”

=========

PCR
anti- F1 antibody

Question 21

what is the treatment of bubonic plague

Answer 21

Do not delay treatment for diagnosis

First-line: IV gentamicin OR fluoroquinolones for 10–14 days

Second-line: doxycycline OR tetracycline

Question 22

what is the prevention of yersina pestis ?

Answer 22

post - exposure

antimicrobial prophylaxis : 7d with Levofloxacin & Ciprofloxaci

Question 23

what is the etiology of tularemia?

Answer 23

zoonosis Francisella tularensis

Question 24

what is the reservoir of tularemia ?

Answer 24

rabbits, hares, and rodents (e.g., voles, muskrats)

Question 25

what is the vector of tularemia ?

Answer 25

intermediate vector Ticks (Amblyomma americanum, Dermacentor spp.) Deer flies (Chrysops species) Transmission without a vector is also possible via: Inhalation of contaminated dust or aerosols (may result in pulmonary disease) Ingestion of contaminated food or water

Question 26

epidemiology of Francisella tularensis ?

Answer 26

The bacterium is extremely infectious, even very small amounts can initiate disease!

Question 27

what is the transmission of Francisella tularensis ?

Answer 27

usually occurs with direct contact with infected rodents - voles, muskrats) ``` through intermediate vector bites Ticks (Amblyomma americanum, Dermacentor spp.) Deer flies (Chrysops species) ``` Person-to-person transmission does NOT occur!

Question 28

what is the incubation period of tularemia ?

Answer 28

typically 3–5 days (range 1–21 days

Question 29

turalemia is also called ?

Answer 29

rabbit fever

Question 30

characteristics of turalemia ?

Answer 30

mall, aerobic, nonmotile, non-spore-forming, gram- negative coccobacilli can enter through skin, mucous membranes, or respiratory tract - 2 subspecies of F. tularensis, subsp. tularensis and subsp. holarctica cause human tularemia

Question 31

epidemiology of F. Tularensis

Answer 31

widely distributed but is primarily a disease of the Northern Hemisphere -> Arkansas, Kansas, Missouri, and Oklahoma - also present in Europe, has been reported in Bulgaria - peaks in late spring and summer in US can cause illness in domestic animals (cats and dogs)

Question 32

what are the risk groups in tularemia ?

Answer 32

hunters, wildlife specialists, hikers, campers, veterinarians more common in males than females, and higher incidence in children < 10 years of age

Question 33

what is the pathogenesis of tularemia ?

Answer 33

obligate intracellular pathogen that enters and replicates within the cytoplasm of various host cells (macrophages, dendritic cells, and polymorphonuclear neutrophils) - within the host -> replicates locally -> then spreading to local lymphnodes - -> systemic spread to the liver, spleen, and lungs - uncontrolled replication -> cell death, substantial tissue damage,and impairment of vital organs - no toxin production, but it causes the failing to stimulate the host’s innate immunity!! - When there is no innate immunity, bacteria can easily grow and replicate -> triggers a systemic inflammatory reaction that overwhelms the host defense system -> followed by cell death - => extensive tissue injury - Histologic hallmark: Inflammatory cell infiltration and necrosis within lymph nodes

Question 34

clinical manifestation of tularemia ?

Answer 34

Flu-like symptoms High fever Tender regional lymphadenopathy ====== Localized signs depending on manifestation: ``` usually tick bite Ulceroglandular tularemia (45–85%): first a small papule appears at the site of organism entry -> then onset of fever papule undergoes necrosis, leaving a tender ulcer with a raised border at the entry site of F. tularensis ``` painful regional lymphadenopathy - in one or more adjacent lymph nodes In children more commonly affected are cervical and occipital; and inguinal adenopathy in adults ========== ``` Glandular tularemia (10–25%): tender regional lymphadenopathy with no skin ulcer more common in children ``` ============ Oculoglandular tularemia (<5%): entry of organism into the eye fever unilateral conjunctivitis with mucopurulent discharge photophobia, eyelid swelling, and ulcers or pustules on the palpebral conjunctivae tender preauricular and/or cervical lymphadenopathy ========== Oropharyngeal tularemia (<5%): fever sore throat, mouth ulcers, tonsillitis, tender cervical lymphadenopathy ======== ``` Pneumonic tularemia (< 5%): MOST severe form nonproductive paroxysmal cough, pleuritic/ retrosternal pain, dyspnea lobar and multilobar infiltrates, lung abscesses, and hilar adenopathy ``` exudative Pleural effusions may occur ============ Typhoidal tularemia (< 5%): hepatosplenomegaly

Question 35

what is the diagnosis of turalemia ?

Answer 35

specific hints in the anamnesis: hunters or persons in contact with rabbits/bunnies are especially at risk!  Serology: IFA test: four-fold increase in F. tularensis-specific antibody titers between acute and convalescent serum samples  Microbiological culture - on charcoal yeast extract agar - from infected ulcer-scrapings, pharyngeal swab, sputum specimen - Risky procedure since organism is very infectious! E.g. can also infect via inhalation!  PCR

Question 36

what is the treatmnet of turalemia ?

Answer 36

10-14 days with Streptomycin or Gentamicin  Alternatives: Doxycycline, Fluorochinoloes or Macrolide

Question 37

what are the complication of turalemia ?

Answer 37

``` Usually from delay of treatment - Most common: suppuration of infected lymph nodes requiring surgical drainage(s) - hepatic abscesses, hepatitis - renal failure ```

Question 38

prevention of tularaemia ?

Answer 38

insect repellents and wearing of long pants, long sleeves, and long socks can reduce the risk of tick and deerfly bites - If tick bites are found -> must be removed by tweezers