Coxiella burnetii Flashcards
- Coxiella is also known as ?
- (Q fever)
- The “Q” in Q fever stands for ______ fever or _______ fever because its cause was ______ until 1937.
- It is an _______ ______ disease = Vets, farmers, slaughterhouse workers, and laboratory workers.
- It is categorized as a _______ agent by CDC
- Query, Queensland, unknown
- occupational, zoonotic
- bioterrorism
Coxiella burnetii is recorded as a bioterrorism agent. Why?
Coxiella is registered a category __ bioterrorism agent by CDC due to the following reasons:
1. causes _______, ____ outbreak, & epidemics of ________ in ruminants
2. ______ transmission up to ___ km away (i.e. the ____ route for its dissemination)
3. _____ infectious with a ___ infective dose = __-__ cells
4. viable in the environmental for ____ using a ______-_____-like life form = small cell variant
B
1. disability, fever, abortion
2. airborne, 20, major
3. highly, low, 1-10, years, pseudo, spore
Characteristics of Coxiella burnetii
* A typical Gram ______ bacteria because it has:
1. outer membrane composed of ________ and _____ proteins
2. _________
3. but staining by _____ stain is not suitable.
4. Stain by _____ method
- Unlike Chlamydia, Anaplasma, Ehrlichia and Rickettisia, Coxiella is not ____ parasite on the host cell, thus:
1. Its cell ______ does not transport ____ across its membranes from host cell
2. Synthesize its own ____
negative
1. lipopolysaccharide, surface
2. peptidoglycan
3. Gram
4. Gimenez
ATP, envelop, ATP, ATP
Reasons for being an obligate intracellular pathogen:
- Can not synthesize some amino acids such as cysteine, arginine, …. hence, has to steal from host cytoplasm
The life cycle of the two
Coxiella morphotypes: SCV vs. LCV
The life cycle of the two
Coxiella morphotypes: SCV vs. LCV
- What is the host range of Coxiella?
- What are the primary reservoirs for C. burnetti?
- all vertebrates and ticks
- Cattle, sheep, and goats are the primary reservoirs for C. burnetii
C. burnetti infects which species?
- wildlife,
- marine mammals,
- domestic mammals,
- birds, and
- reptiles
C. burnetii has been isolated from approximately ___ species of ____. It is a ______ (humans) disease
40, ticks, zoonotic
What are the routes of transmission of C. burnetti?
What are the Host ranges of C. burnetti?
Coxiella is transmitted by _______ in ______ animals as well as via ________ and infected _______. Exposure to animal ______, _____, ______ and ______ are other forms of transmission.
ticks, wild, aerosols, milk, skin, dust, placenta, excreta
Ticks may transmit Coxiella _______________ and/or ______________ between which species?
Transstadially, transovarian
Between wildlife, wildlife and domestic animals, wildlife and humans, reservoir for maintenance in sylvatic environment.
People are infected with Coxiella by:
1. ___________/__________
2. Direct/indirect contact with infected animals in the process during ________ or __________ products in the environment.
3. Ingestion of _________ milk (_____ level transmission)
- inhalation/airborne
- Direct/indirect contact with infected animals in the process during parturition or parturition products in the environment.
- Ingestion of infected milk (low level transmission)
______, _____, and ______ are the most common reservoirs of the organism for human infection, but infected ____ and less commonly _____ can also transmit infection to humans.
Sheep, cattle, goats, cats, dogs
Dogs, cats, and humans can be infected when they _____, or ____, _____ species.
contact, ingest, wildlife
______ harbor coxiella and are thought to maintain transmission to _____ species, especially _____ (such as small ____) and ________, but also _____.
Ticks, wildlife, rodents, mice, rabbits, birds
How is C. burnetii able to live
inside bactericidal host cells?
List the virulence factors of Coxiella
- LPS
- Pilus = Type IV Secretion System for Adhesion and Invasion
- Ability to form Vacuole acidifcation by colliding with cell lysozyme (pH decline from 5.4 to 4.5)
- Ability to form different cell variants and obligate intracellular life.
LPS protects Coxiella for its optimal growth in ______, ____-______ cells, and in ____-___ culture media.
phagocytes, non-phagocytic, cell-free
The type IV secretion system is used for:
1. _________ as well as to inject ______ proteins into host cells.
2. ____ different proteins are injected into host cell cytoplasm
3. Promote Coxiella ________ ______ and ________.
attachment, effector, 13, intracellular, survival, replication
Coxiella’s ability to form vacuole acidification by colliding with cell lysozymes allows the organism to:
1. _______ and _____ inside the vacuole.
2. protect it from damage by the ________ of the host cell.
Does this by using _______ and ______
develop, replicate, phagolysosomes, EEA1, Rab5
SCV = ?
Dormant extracellular life form
LCV = ?
Replicative intracellular life form
In Coxiella LCV Virulent Phase 1, the LPS has ?
An intact O-antigen (smooth surface)
In Coxiella LCV Avirulent Phase 2 (attenuated), the LPS has ?
Lost its O-antigen (rough surface)
Its preference/ tropism in the host cells
Coxiella is an obligate
intracellular bacteria because
Coxiella does not produce
some amino acids; hence,
obtain from host cells
- What cells does C. burnetti target?
- What happens once C. burnetti enters the body?
- What cell type does C. burnetti target in birds, mammals, and humans? What organs do they localize in? .
- What parts of the body does C. burnetti target in ticks?
- Monocytes and macrophages of birds, mammals, humans
- Both blood cells disseminate it to the blood vessels endothelial cells
- Endothelial cells of vital body of birds, mammals, humans; Coxiella can localize in:
lung
placenta & reproductive tract
liver
mammary gland
Lymph nodes
heart
Joints and bones
Brain - The midgut & salivary gland of ticks
What are the clinical signs in the acute form of C. burnetti infection? What happens in the organs listed below?
- Phagocytes
- Lung
- Placenta
- Liver
- Mammary
- Lymph nodes
- endothelium
- Acute form = fever + pneumonia are common
Phagocytes (fever) = Q fever
Lung (pneumonia)
Placenta (abortion & still birth)
Liver (jaundice, granulomatous hepatitis)
Mammary (mastitis)
Lymph nodes (lymphadenitis, linked with B
lymphocyte cancer called lymphoma?)
endothelium (vasculitis, rash/hemorrhage)
What are the clinical signs in the chronic form of C. burnetti infection? What happens in the organs listed below?
1. Heart valves
2. bones and joints
3. Brain
- Chronic form = endocarditis/heart failure
Heart valves (endocarditis)
bones and joints (Osteoarthritis)
Brain (neurological signs)
Majority (60%) of infected animals and
humans are ___________ ___________
asyptomatic/subclinical
Apply your ice-berg concept
What samples would you collect from an animal you suspect has C. burnetii?
- Vaginal discharge
- Abortion cases
- Milk
- Nasal discharge
- Blood (septicemia)
- Serum
What SEROLOGY test is the gold standard of testing for C. burnetii? What does this test allow you to test for? What parameters are you looking at and what is considered to be significant?
Indirect Immunofluorescence assay (IFA). Allows you to check for Antibody titers of Phase 2.
- IgG of > 200 and/or
- IgM > 50
are considered significant for the diagnosis of primary Q fever infection.
What serology tests can be performed to diagnose C. burnetii?
IFA, ELISA
What other diagnostics can be run?
- PCR or sequencing
- Culturing on cell lines to isolate in a BL3 containment lab
- Broth or agar media
Culturing on cell lines –> ?
- For attachment as well as to inject effector proteins into host cells
- Cell lines of chick fibroblast
Recently a breakthrough was made in the propagation of Coxiella in a cell-free growth media using ?
Acidified citrate cysteine medium.
As of today,
C. burnetii stands as the sole example of an _______ _______ bacterial pathogen for which a specific _____ culture medium has been developed.
obligate intracellular, axenic
Breakthrough in ___ or ___ media for propagation of Coxiella and laboratory
diagnosis –>
agar, broth
- How do you treat Coxiella?
- What is the most effective drug used to treat Coxiella? How long do you typically prescribe it for?
- What drug is typically prescribed to pregnant animals in their last trimester?
- Antibiotics (various)
- Doxycycline 200 mg daily for 14 days – the most effective drug for acute Q fever
- Oxytetracycline (20 mg per kg body weight) in the last trimester pregnant animals
- Combination of doxycycline & hydroxychlroquine
- Other antimicrobials
- Trimethoprim-sulfamethoxazole – the safest
- chloramphenicol
- erythromycin
- fluoroquinolones
How do you Control and prevention Coxiella outbreaks?
- a whole-cell killed vaccine licensed in Australia and Europe
used in cattle to lower the risk of spreading
Coxiella burnetii infection
used in goats to reduce abortions as well as reduce spreading the infection - Tick control
- Protect yourself
Work a biosafety level 3 by wearing appropriate personal protective equipment (PPE) during
isolation and manipulations of
Coxiella
Wear an N95 respiratory protection mask during performing Q fever positive/suspected autopsies
and/or assisting parturition - Clean the environment with quaternary ammonium-detergent compound or
household bleach to decontaminate surfaces from spore-like form of
C. burnetii
Summary
* An obligate intracellular pathogens of monocytes, macrophages, and endothelial cells of reptiles, birds,
mammals, and humans
* Transmissible by air, contact, ingestion, and tick bite between different host ranges
* Majority of its infection is silent (subclinical)
* The two clinical signs are acute (phagocytes, placenta, lung, liver, udder, and lymphnode) forms and chronic
(heart, bones, and brain) forms
* Diagnosis is done by testing samples using serology, PCR, cell line culture, and amino-acid enriched agar/broth
culture media
* Treatment using tetracycline and oxycycline
* Control by vaccine, tick control, and disinfection/decontamination of the infected environment