by Chantal Coutu and Jason Niness
Coxiella burnetii (figure 1), a gram negative intracellular pathogen, is known for causing Q Fever. This zoonotic pathogen was first studied in the late 1930’s after an outbreak of Q Fever affected slaughterhouse workers in Brisbane, Australia; while almost simultaneously being studied in Nine Mile, Montana as an infectious agent in ticks. Typically this pathogen produces symptoms that resemble those of the flu, however an infection by C. burnetii may also lead to pneumonia or hepatitis.
Figure 1: Coxiella burnetii. Source: National Institutes of Health, United States Department of Health and Human Services.
C. burnetii is spread via the urine, feces, birth products (placenta and amniotic fluid) and the milk of infected animals. It can be transmitted to humans if they come into contact with or inhale contaminated dust from infected animals, such as goats, sheep and cattle. It can also be transmitted from a tick bite or by ingesting unpasteurized milk and dairy products (Figure 2). An infection from C. burnetii can be acute or chronic with symptoms similar to those of the flu; for example fever, chills, fatigue, stomach pain and muscle pain. However, about half of the people that are exposed to the bacteria do not get sick. Those that develop a severe case typically get inflammation in their lungs (pneumonia) or their liver (hepatitis). C. burnetii may also cause complications during pregnancy such as miscarriage, stillbirth, pre-term delivery or low infant birth weight. Chronic Q Fever, a more serious infection, can be fatal if not treated with antibiotics. This usually develops in people with pre-existing conditions, such as heart valve disease, blood vessel abnormalities like aneurysms (which are blood filled bulges in the wall of a blood vessel), or if they are immunocompromised. Chronic Q fever has also been linked to endocarditis, an infection in one or more heart valves, which can be fatal if not diagnosed early.
Figure 2: Possible transmission paths and potential hosts of C. burnetii. Source: Chantal Coutu.
C. burnetii has shown itself to be more common than previously thought due to its interactions with both domesticated animals and humans. In recent studies, from the United States, C. burnetii was found in 28% of samples taken from various locations including farms and grocery stores. Also, the seroprevalency of Q Fever was found to be 3.1% in U.S. adults, meaning that antibodies against the bacteria were found in their bodies. These two studies indicate that C. burnetii is affecting a larger population of humans than has been reported.
The ability of C. burnetii to infect the host in the form of an aerosol is likely the reason it is so infectious. When it is in the form of a spore, used for survival outside of the host, it is easily picked up by dust particles and carried into the throat and lungs of the host. This mode of infection was recently documented as the likely cause of a 2005 outbreak at an Israeli school, implicating the air conditioning system as the mechanism of transmission. Once within the host, C. burnetii changes to its active form and can invade the host’s tissues.
Infection by inhalation of C. burnetii targets the alveolar macrophages in the lungs. Infection via the bloodstream or the digestive tract targets the Kupffer cells of the liver. C burnetii enters the cells of the host using a specific receptor called an integrin; either LRI (leukocyte response integrin avβ3) or IAP (integrin-associated protein). After the bacteria has entered the host, a macrophage engulfs the bacteria by a process called phagocytosis. This process forms a sack-like structure around the bacteria called a phagosome. The phagosomes proceed to fuse with lysosomes, organelles that have a variety of enzymes to help breakdown and digest bacterial invaders, to form phagolysosomes (Figure 3).
Figure 3: C. burnetii infection into a host cell and release out of a cell. Source: Chantal Coutu
Usually, the phagolysosome creates harsh conditions that prevent bacteria from growing and leads to the bacteria’s death. However, C. burnetii is an acidophilic bacterium, meaning its growth is enhanced in acidic conditions. This characteristic is what allows it to overcome the acidic conditions created by the phagolysosome and persist in the host.
Furthermore, the bacteria can create spores which are highly resistant dormant forms of the bacteria to preserve itself and its DNA under extreme conditions or when there is a lack of nutrients. These spores can be released by the host either by cell lysis, the breakdown of the cell, or exocytosis, the release of internal contents enclosed in a cell membrane (Figure 3). These spores can survive in the environment until conditions are adequate to allow for growth again and can be carried by the wind to spread the infection over long distances.
Different antibiotics are prescribed depending on the severity of the infection. Patients with acute Q fever can recover without treatment or with an antibiotic such as doxycycline. Patients with chronic Q fever typically require several months of treatment with a combination of antibiotics like doxycycline and hydroxychloroquine or chloroquine or amantadine. Doxycycline and hydroxychloroquine are especially effective as the hydroxychloroquine causes alkalization of the phagolysosome, allowing doxycycline a greater advantage to destroy the bacteria. For patients with medicinal allergies or pregnant women, alternative antibiotics such as moxifloxacin or rifampin may be prescribed. These antibiotics are effective against C. burnetii since, when combined, they reduce the amount of infected cells in the body by sterilizing the bacteria, preventing it from multiplying, and thereby destroying the bacterial cells.
Also, a Q Fever vaccine known as Q-Vax is available in Australia. However, there is limited availability and it causes adverse reactions in those previously infected with C. burnetii. A skin test is required prior to vaccination to test if the patient should receive it or not.
Centers for Disease Control and Prevention. (2016). Q Fever. Atlanta, Georgia. https://www.cdc.gov/qfever/index.html
Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Lysosomes. https://www.ncbi.nlm.nih.gov/books/NBK9953/
Maurin, M. and Raoult, D. “Q Fever.” Clinical Microbiology Reviews 12.4 (1999).. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88923/
“NIAID BSL-3 Priority Pathogens.” Tufts New England Regional Biosafety Laboratory, vetsites.tufts.edu/ne-rbl/resources/niaid-bsl-3-priority-pathogens/.
Tjelle, T. E., Løvdal, T. and Berg, T. (2000), Phagosome dynamics and function. Bioessays, 22: 255–263. doi:10.1002/(SICI)1521-1878(200003)22:3<255::AID-BIES7>3.0.CO;2-R
Toman, Rudolf. Coxiella Burnetii: Recent Advances and New Perspectives in Research of the Q Fever Bacterium. Dordrecht: Springer, 2012. Internet resource.