Coxiella burnetii (Q fever): Interest in human, animal and environmental contamination: IgM, IgA, IgG and total antibodies (ELISA); Phases I and II antibodies (Immunofluorescence); Molecular diagnosis (PCR)


Information 25-03-2018.


Q fever is a zoonosis of worldwide distribution, caused by the bacterium Coxiella burnetii, which affects various animal species and accidentally affects humans. The term fever Q was coined to refer to a febrile illness originally observed in workers of slaughterhouses in Queensland (Australia), and that has adapted to the veterinary medicine, in spite of presenting another clinical picture in animals, where the correct term would be coxielosis. Among the animals, it especially affects parturient ruminants, although C. burnetii also infects domestic animals such as cats and a wide variety of wild animals. In humans, Q fever is more frequent in people who have working contact with species at risk. It is a very contagious disease, usually humans acquire Q fever by inhaling contaminated aerosols or dust, and inhaling a single organism can cause infection. With a very varied clinical presentation, Q fever is a systemic disease that ranges from asymptomatic infection or mild influenza, to pneumonia, hepatitis and endocarditis.

The bacterium Coxiella burnetii which is a gram-negative bacillus of small size (0.3-1.0 μm) that multiplies exclusively inside eukaryotic cells. It survives long-term inside acidic vacuoles (pH 4.8) of macrophages and monocytes, inhibiting the phagolysosomal activity and mechanisms of cellular apoptosis. Outside the cells, it forms metabolically inactive pseudospores, responsible for its extreme resistance to environmental variations and physico-chemical conditions. In addition, C. burnetii presents two highly useful antigenic forms in the diagnosis of Q fever. Its lipopolysaccharide (LPS) undergoes changes that give rise to phase variations in the antigen and are used to serologically distinguish the acute and chronic stages of the disease by detection of antibodies against phase I or phase II. The phase I antigen corresponds to virulent microorganisms with smooth LPS and that of phase II to avirulent microorganisms with rough LPS.

C. burnetii has a universal distribution, with the exception of New Zealand, and the range of hosts includes various wild and domestic mammals, arthropod transmitters, fish and birds. The epidemiology of C. burnetii is complex and there are two main transmission patterns: in one of them, the organism circulates among wild animals and their ectoparasites, especially ticks, and in the other, it is transmitted between ruminants and domestic animals, regardless of the cycle of wild animals. Infection in nature is maintained and transmitted by ticks (Ixodids and Argasids), which act as the main vector and reservoir due to transovarial transmission to its descencedens. In the domestic cycle, cattle, sheep and goats are the most frequent animal reservoirs and the most important source of human infections, considering the enzootic disease in most areas where there are livestock. Other domestic or peridomestic animals may be infected by C. burnetii, including horses, pigs, camels, rabbits, dogs and cats. The latter can explain the appearance of urban epidemics.

Infection in animals is usually subclinical, but can cause anorexia, late abortion and other reproductive problems. Experimental infection in cats causes transient fever, apathy and anorexia of several days. In ruminants, C. burnetii has been implicated as a cause of infertility and sporadic abortion due to necrotizing placentitis. In these animals, macroscopic lesions are nonspecific, and the differential diagnosis must include infectious and noninfectious agents that cause abortion. It is considered that during the pregnancy the infection is activated, which can cause abortions, especially in goats and sheep, and infertility, metritis and mastitis in cattle. The percentage of abortions is much higher in goats, where animals can also suffer abortions in the next gestation. Infected mammals eliminate the microorganism resistant to desiccation in urine, feces, milk and, especially, through the products related to childbirth. C. burnetii is located mainly in the uterus and in the mammary glands of the females of the animals, the infection is activated during gestation, so that in the placenta are high concentrations of the microorganism (> 109 bacteria/g of tissue). Because of this, the greatest risk of transmission occurs during delivery by inhalation, ingestion or direct contact with the fluids of delivery or the placenta. During delivery the germ is dispersed in the form of an aerosol and is deposited in the soil. As it can persist viable in the soil, from it and for several weeks can be generated new contagious aerosols. Ticks can also act as a vector of disease among domestic animals.

Human beings acquire Q fever mainly by inhaling aerosols or dust contaminated with C. burnetii pseudospores from the waste products of infected animals. The disease occurs mainly in people who have contact with cows, goats, sheep, or parturient cats, mainly in areas with animal activity such as dairy farms, ranches, livestock farms and slaughterhouses, as well as veterinary medical centers. As a result of the inhalation of pseudospores, alveolar cell involvement and blood dissemination occur. Also, other routes of contagion are admitted, such as the ingestion of contaminated raw dairy products, professional exposure and handling of contaminated animals and, sporadically, interhuman transmission has been documented through transfusion of infected blood or congenital infection by transplacental route. Also, it is believed that C. burnetii can be transmitted sexually and through the skin, and some cases of Q fever have been described after tick bites.

The diagnosis of fever Q in humans should be considered in cases of fever of unknown origin, especially if the subject has been in contact with probably contaminated mammals. The clinical presentation is very varied and includes severe forms with a poor prognosis. Certain host factors, such as the presence of an underlying disease and cell-mediated immunity, play a decisive role in the clinical expression of the disease. C. burnetii infection in humans is often asymptomatic, but it can also manifest as an acute illness (usually a self-limited illness similar to influenza, pneumonia or hepatitis) or as a chronic form (mainly endocarditis, but also hepatitis and chronic fatigue). In addition, C. burnetii infection in pregnant women can cause abortions, premature births and intrauterine fetal death.

The best methods of microbiological diagnosis are those that allow direct detection of bacteria, cell culture and polymerase chain reaction (PCR). For indirect diagnosis, the reference method is indirect immunofluorescence (IIF), because it is very sensitive and speci fic. In cases of acute Q fever, the diagnosis must be confirmed by antibody titres (IgG and/or IgM), obtained by immunofluorescence, above the cut-off point calculated for each geographical area, or by seroconversion. Serology continues to be the most used diagnostic procedure. Of the different existing modalities, the most recommendable one is based on indirect immunofluorescence, to establish the diagnosis of acute disease it is necessary to demonstrate an increase of four or more times in the antibody titer between the acute and convalescent phases. To establish the diagnosis of chronic disease, with a compatible clinical picture, it is usually sufficient to detect an antibody titer against phase I antigens of IgG type equal to or greater than 1:800. It is also characteristic of chronic disease that the IgG antibody titre against phase I antigens is much higher than that of these antibodies against phase II antigens, just the opposite of what happens in acute disease (greater titre of antibodies against phase II antigen, compared to phase I).

Tests offered by IVAMI:

  • Molecular detection (PCR) in human, animal and environmental samples.
  • Detection of total, IgG, IgM, and IgA antibodies in humans.
  • Detection of phase I and II antibodies by indirect immunofluorescence.

Recommended sample:

  • For molecular detection (PCR) in animals and in humans, samples of whole blood extracted with EDTA (2 to 5 mL) are recommended. Also, other animal secretions such as urine, feces, milk, and material related to childbirth are accepted.
  • Samples for the analysis of C. burnetii in the environment, may include bulk sampling (25 g of soil material), filters of aerosol samples taken indoors near solid surfaces with particles, or sampling of surfaces with swabs. In IVAMI, samples will be processed for DNA extraction and analysis of the presence of Coxiella burnetti DNA by PCR.
  • For the detection of antibodies in humans, samples of serum or plasma (2 mL), or whole blood extracted with EDTA (2 to 5 mL) are accepted for the subsequent extraction of the serum in our laboratory.

Conservation and shipment of the sample:

  • Refrigerated (preferred) for less than 2 days.
  • Frozen for more than 2 days.

Delivery of results:

  • Molecular detection (PCR): 24 to 48 hours.
  • Detection of total, IgG, IgM, and IgA antibodies in humans: 48 hours.
  • Detection of antibodies by immunofluorescence: 48 hours.

Cost of the test:

  • Detection of total antibodies, IgG, IgM, and IgA in humans: Consult