Q fever pathophysiology

Q fever is a disease caused by C. burnetii, an intracellular, gram-negative proteobacterium. The disease can have a wide range of clinical presentations and affect many organ systems due to the unique virulence factors of the organism.

The organism is transmitted through:^[1]

• Aerosols: Inhalation of contaminated aerosols is the main mode of transmission
• Ingestion of raw dairy products
• Vertical (mother to fetus) transmission has been reported
• Parenteral
• Tick bites

The infection has two phases, which correlate to changes in the lipopolysaccharide of C. burnetii:^[2]

• Phase I: Characterized by a smooth lipopolysaccharide capsule. Despite being less efficient in the invasion of host cells, antibodies against phase I are always isolated from acute Q fever patients.
• Phase II: Characterized by a rough lipopolysaccharide capsule. Antibodies against phase II have been isolated from chronic Q fever patients.

C. burnetii can exist in two forms: the small cell form and the large cell form. The small and large cell forms are antigenically different, which plays a role in the virulence of the organism.

The small cell form is often described as the spore form of C. burnetii. It can resist external environmental factors such as heat, pressure, and disinfectants for long periods of time.

The large cell form is the active form of the organism. It persists in macrophages inside acidic vacuoles.

• The genome of C. burnetii was analyzed in 1995. Multiple genes encoding for Na+ ion proton exchange have been discovered, explaining the ability of the organism to survive in a low pH environment.

• There is a delay between the entry of the organism into the host cell and the fusion with lysosomes. This delay is thought to be due to the transformation from the small cell variant into the large cell variant.
• The acidic environment inside the lysosome has little effect on the large cell form of the organism.

• The lipopolysaccharide capsule is one of the most important virulence factors of the organism.

• The different phases of infection are associated with changes in the lipopolysaccharide capsule.

• Lipopolysaccharide phase I (smooth polysaccharide) is associated with protection against the host’s immune response.
• Lipopolysaccharide phase II (rough polysaccharide) is isolated from avirulent, non-infectious host cells and is not associated with protection of the virus from the host cell.

• Both humoral and cell mediated immunity are involved in the immune response against C. burnetii. However, cell mediated immunity is more important in defending against the organism and people with deficient cell mediated immunity are more susceptible to developing chronic infection.

• Because of its route of infection, C. burnetii can be used as a biological warfare agent.
• Q-fever is a category “B” agent. It is highly contagious and very stable in aerosols at a wide range of temperatures.
• Just 1-2 particles are enough to infect an individual.
• Q-fever microorganisms can survive on surfaces up to 60 days (like sporulating bacteria).
• According to WHO estimates, 50 kg of C. burnetii, if spread in an area of 2 square kilometers, is capable of:^[4]

• Infecting 500,000 humans
• Killing 150 individuals
• Causing acute illness in 125,000 individuals
• Causing chronic illness in 9,000 individuals

• C. burnetii is a gram negative, polymorphic, intracellular organism.^[5]
• It was previously classified as a Rickettsia, but now is considered a proteobacterium.