Coxiella burnetii

See also: Q fever for a more detailed discussion of the disease it causes.

Coxiella burnetii, is a rickettsia that causes Q fever. It is endemic in animals worldwide. The disease was first described in Australia in 1935; its name derives from "Query", since it took so many questions to diagnose.

The organism has an exceptionally low infective dose, possibly a single organism. It was weaponized as a biological warfare agent, primarily casualty-producing, and is listed, as an overlap agent in the Select Agent Program and as a Category B organism in CDC Bioterrorism Agents-Disease list . In routine laboratory diagnosis, it should be handled at Biological Safety Level BSL-2, or BSL-3 if a large amount is to be cultured.

Taxonomy and genetics

Originally classified as a Rickettsiaceae because of its obligatory intracellular growth requirements, C burnetti has subsequently been reclassified. After DNA-DNA hybridization studies and genome sequencing identified that the organism more closely resembles the class Gamma Proteobacteria of the phylum Proteobacteria, C burnetti now sits as a monotypic species most closely related to the order Legionellales.

There may be immunologic cross-reactivity with Legionella pneumophilia, or concurrent infection with both agents.

Variants

The organism undergoes a virulent (Phase I) to avirulent (Phase II) transition upon serial laboratory passage in eggs or tissue culture.

Ecology

Q fever is present worldwide, except in New Zealand. The frequency ranges from 5% in urban areas to 30% in rural areas. The United Kingdom reports approximately 100 cases annually. Clinical presentations vary geographically as well, with pneumonia predominant in North America and hepatitis predominant in Europe. Q fever infection can frequently be asymptomatic or present as a flulike illness in its milder forms, resulting in an underrepresentation of the actual incidence. Epidemiological serological testing of specimens from blood donors has discovered a higher incidence throughout Africa, ranging from 18-37%, whereas "at-risk" farmers in the United Kingdom demonstrated 29% seropositivity.

C. burnetii is a bacterial obligate intracellular pathogen that undergoes its developmental cycle within an acidic vacuolar compartment exhibiting many characteristics of a phagolysosome. The developmental cycle consists of a large (approximately 1 μm in length) cell variant that is believed to be the more metabolically active, replicative cell type and a smaller, more structurally stable cell variant that is highly infectious and quite resistant to drying and environmental conditions.

Effects on host cells

The organism has multiple effects, the most basic of which is to enter cells, grow in the cytoplasmic vacuoles, and eventually rupture the host cell. The rupture of the vacuoles may release lysosomal enzymes that further damage the cell. In lung and liver manifestations, biopsies show vascular damage and hemorrhage. As opposed to the situation in most bacterial pneumonias, where the alveolar cells are polymorphonuclear leucocytes, C. burnetti seems to attract histiocytes. When there is lung or bone involvement, granulomas form.

In addition, in the chronic disease form when the organism causes endocarditis, vegetations form on the valves.

Reservoir

It is an animal pathogen, whose main reservoirs are sheep, cattle, and goats, although there may be opportunistic infection of domestic pets. In general, there seems little animal pathology, although there may be an increased incidence of abortion in goats and sheep. which transmits easily to humans in the laboratory or in animal handling. Cattle, sheep, and goats are the primary reservoirs of C. burnetii. Infection has been noted in a wide variety of other animals, including other species of livestock and in domesticated pets.

Organisms are excreted in milk, urine, and feces of infected animals. Most importantly, during birthing the organisms are shed in high numbers within the amniotic fluids and the placenta.

The organisms are resistant to heat, drying, and many common disinfectants. These features enable the bacteria to survive for long periods in the environment. Infection of humans usually occurs by inhalation of these organisms from air that contains airborne barnyard dust contaminated by dried placental material, birth fluids, and excreta of infected herd animals. Humans are often very susceptible to the disease, and very few organisms may be required to cause infection.

Control of the organism

In the United States, Q fever outbreaks have resulted mainly from occupational exposure involving veterinarians, meat processing plant workers, sheep and dairy workers, livestock farmers, and researchers at facilities housing sheep. Prevention and control efforts should be directed primarily toward these groups and environments.

Discussion of BSL and other precautions

Routine diagnostic work should be done at a minimum of Biosafety Level 2, although culture should be at BSL-3.

Immunization

A vaccine for Q fever has been developed and has successfully protected humans in occupational settings in Australia. However, this vaccine is not commercially available in the United States. A vaccine for use in animals has also been developed, but it is not available in the United States.

Chemoprophylaxis

Doxycycline is useful after exposure.

Laboratory aspects

Immunological methods form the core of diagnosis, although the organism can be visualized.

Morphology, staining, etc.

C. burnetii is acid-fast and can be visualized, in tissue samples with Stamp, modified Ziehl-Neelsen, Gimenez, Giemsa or modified Koster stains. Microscopic examination is more a veterinary than a human medical technique, used to determine if the organism is present in a herd.

Culture

It can be grown in conventional cell cultures or embryonated chicken yolk sacs or laboratory animals. Culture is not routinely done, but can be useful in isolating the organism from contaminated tissue samples, or to obtain phase I antigens. Inoculation of laboratory animals (guinea-pig, mouse, hamster) is helpful in cases requiring isolation from tissues contaminated with various microorganisms or in order to the [[#antigenic variation|phase I antigen.

Tests: immunologic, biochemical, etc.

Confirming a diagnosis of Q fever requires immunologic testing to detect the presence of antibodies to Coxiella burnetii antigens. Refinements of this testing can determine if a case is acute or chronic.

Immunologic methods

In most laboratories, the indirect immunofluorescence assay (IFA) is the most dependable and widely used method. PCR and ELISA also are used. PCR offers the advantage of being useful in herd screening, and also allowing heat inactivation of the organism to protect laboratory workers.

With IFA and immunoblotting, there may be cross-reaction between C. burnetii and Legionella pneumophilia.

Antigenic variation

Coxiella burnetii exists in two antigenic phases called phase I and phase II. This antigenic difference is important in diagnosis.

• Acute Q fever: Phase II antibodies are much greater than Phase I
• Chronic Q fever: Phase I antibodies predominate; it takes longer for them to appear.

The continued presence of Phase I suggests continuing exposure. Both types can persist for months or years. To confirm chronic disease, high Phase I levels are detectable along with general markers of an inflammatory process.