Version July 2025
INTRODUCTION —
Q fever is a zoonotic disease caused by the intracellular bacteria Coxiella burnetii. The most common mode of transmission to humans is inhalation of C. burnetii that has been excreted by animals, especially livestock. The organism grows in two forms: a phase I form and a phase II form. Antibodies against these phases are used to diagnose the infection.
The infection occurs throughout most of the world, although incidence is higher in the Middle East than in North America and Europe.
This topic discusses the epidemiology, microbiology, and diagnostic test characteristics of Q fever. Specific clinical, diagnostic, and treatment information are found in separate topics. (See "Acute Q fever in nonpregnant patients" and "Chronic Q fever, including endocarditis" and "Q fever in pregnancy".)
EPIDEMIOLOGY —
Seroprevalence studies demonstrate that many more people are infected with C. burnetii than the numbers of reported symptomatic Q fever cases suggest. Underreporting of Q fever cases probably results from a combination of subclinical infections and, in cases where infection does lead to disease, a failure to recognize it due to nonspecific clinical presentation.
Geography — Q fever likely occurs throughout most of the world, although the incidence and prevalence of infection are unknown in many countries due to lack of surveillance. Only New Zealand has been demonstrated to have no Q fever [1].
Incidence — Because of its nonspecific initial presentation, isolated cases of acute Q fever are often overlooked, and information about the rate of infection is unavailable in many parts of the world due to lack of surveillance. Diagnoses are commonly associated with outbreaks or with patients who have an epidemiologic link to other cases.
Rates of symptomatic Q fever in North America and Europe are relatively low:
●In the United States, the average annual incidence from 2008 to 2017 was 0.045 cases per 100,000 persons [2].
●In the European Union in 2019, the incidence was 0.2 cases per 100,000 persons; Spain had the highest incidence in the European Union with 0.7 cases per 100,000 persons [3].
Based on the available data, incidence is higher in the Middle East than in North America and Europe; in 2021, Israel reported 3.6 cases per 100,000 persons [4].
Outbreaks — Large outbreaks of Q fever have been reported, including in areas where the infection is uncommon. While animal contact is the most commonly reported exposure in sporadic cases, in outbreaks many affected individuals do not report animal contact but typically live near farms. Human infection in outbreaks is typically propagated by widespread environmental contamination (often due to abortion by infected animals), followed by wind dispersion of the organism [5,6].
From 2007 to 2010, the Netherlands experienced the largest outbreak that has been described; over 4000 infected individuals were identified [5]. Outbreaks have also been reported in Israel, Switzerland, Great Britain, Germany, southern France, and the United States [6-11].
Clusters of Q fever have been reported in armed forces personnel returning from Iraq [12,13].
Prevalence — Seroprevalence data suggest that Q fever is underreported.
After the aforementioned outbreak in the Netherlands, seroprevalence in the most impacted area was 11 percent (approximately 40,000 individuals), suggesting that actual infections during the outbreak were nearly 10 times the number of reported cases [14]. Prior to the outbreak, seroprevalence in the Netherlands was estimated at 2 percent.
In the United States, seroprevalence studies from 2003 to 2004 found 3 percent of the population was positive for immunoglobulin G (IgG) antibodies against C. burnetii [15].
In Iran, seroprevalence has been measured as high as 33 percent [16], and seroprevalence in Israel was reported as 14 percent in blood donor samples from 2021 [4].
In Australia, seroprevalence was 6 percent in samples from 2012 to 2013 [17].
Reservoirs
Animal reservoirs — The animals most often linked to human infections are cattle, sheep, and goats. (See 'Risk factors' below.)
In cattle, C. burnetii infection is usually asymptomatic, although mastitis is occasionally reported [18]. In sheep and goats, spontaneous abortion or stillbirth is the most common manifestation of infection; C. burnetii can replicate to high numbers in goat and sheep placenta [19]. Introduction of C. burnetii into naïve goat and sheep herds can lead to "abortion storms" [20] in which large numbers of pregnant animals experience abortions.
Besides livestock, C. burnetii is capable of infecting a large variety of other animal species, including birds, reptiles, fish, marine mammals, camels, dogs, cats, and the three-toed sloth.
Environmental reservoirs — C. burnetii organisms can contaminate the environment due to shedding of the organisms from infected animals. Viable organisms can be shed in birth products (eg, placenta), vaginal mucus, urine, feces, and milk from infected animals.
The organism is resistant to desiccation; after drying, it can remain viable in soil and standing water in a form that can be aerosolized. The organism has also been frequently detected in bulk milk tanks on cattle dairy farms [7,21,22].
Routes of transmission to humans — The most common mode of transmission appears to be inhalation of C. burnetii that has been excreted by animals. C. burnetii can travel long distances through the air, and inhalation up to 18 km from infected animals has been observed [6]. The infectious dose is suspected to be only 1 to 10 organisms [23]. (See 'Environmental reservoirs' above and 'Morphologic forms' below.)
Less common modes of transmission include ingestion of (raw) milk contaminated with C. burnetii and direct inoculation from a percutaneous injury [24].
Laboratory-acquired infections were quite common before the widespread use of biosafety cabinets; even with the implementation of strict laboratory safety measures, working with viable C. burnetii in the laboratory is still considered a risk for infection. Infections of health care workers have been rarely reported and are typically associated with procedures that produce aerosols, such as the use of bone saws or parturition [25,26]. Infection via blood transfusion is considered possible but is thought to be rare [27].
Human-to-human transmission is uncommon, although a few cases of possible sexual transmission have been reported [28,29]. Issues related to pregnancy and breastfeeding are discussed separately [25]. (See "Q fever in pregnancy".)
Although C. burnetii has been found in a variety of tick species, tick bites do not seem to be a common mode of transmission [25,30].
RISK FACTORS —
Risk factors include living or visiting an area where the disease is highly endemic or where an outbreak is occurring.
Additionally, occupations that involve livestock or direct laboratory exposure are known risk factors for the acquisition of Q fever (see 'Animal reservoirs' above):
●Veterinarians – Seroprevalence among veterinarians, especially those who work with livestock, can be high (22 percent in the United States, 18 percent in Italy, and 36 percent in Denmark) [31-33].
●Farmers – Livestock (goat, sheep, and cattle) farmers are especially at risk.
●Slaughterhouse workers – The first cases of Q fever identified in Australia were among slaughterhouse workers [34].
●Laboratory workers who work with C. burnetii.
Living downwind from livestock farms has been associated with several reported outbreaks, including the large outbreak in the Netherlands that occurred mainly among individuals who resided near an intensely farmed goat herd [35,36]. (See 'Routes of transmission to humans' above.)
Most cases are reported in adults, suggesting that children may be less likely to be infected; one study from the Netherlands found lower rates of infection in exposed children than exposed adults, suggesting that young age protected against acquiring the infection [37]. However, serosurveys from other countries reported similar rates of seroconversion in adults and children [38-41]. The true rate of Q fever in children is thought to be unknown due to underdiagnosis and underreporting [42].
MICROBIOLOGY —
C. burnetii is a gram-negative rod-shaped Gammaproteobacteria that grows in intracellular phagolysosomes inside of host cells. It has a circular genome of nearly two million base pairs, and many isolates also have a plasmid [43]. After entry into host cells by endocytosis, C. burnetii remains in the endosome through the endocytic pathway all the way through fusion with a lysosome and acidification of the C. burnetii-containing phagolysosome [44]. C. burnetii is exceptional in that it survives in the acidic compartment and even requires a low pH for growth. C. burnetii has a type 4 secretion system and uses it to secrete effector molecules into the host cell cytosol to modify cellular processes to create a favorable environment for its survival [45].
Morphologic forms — C. burnetii exists in two morphologic forms [46]:
●Small-cell variant – The "small-cell variant" is a dormant form that is very stable in the environment and resistant to desiccation and disinfectants. This form of the organism can survive for long periods of time outside of a host and is the form that is transmitted to animals via inhalation. (See 'Routes of transmission to humans' above.)
●Large-cell variant – Upon exposure to an animal host (eg, livestock, humans), C. burnetii transitions to the "large-cell variant." This form allows the organism to replicate inside of host cells.
Phase variation — Growth of C. burnetii in the laboratory results in phase variation [47]:
●"Phase I" form – The phase I form is the infectious form that is grown in initial cultures from infected animals, including humans. The phase I form is highly infectious, such that a single organism can lead to infection. This form is characterized by full-length lipopolysaccharide side chains, including a complex O-antigen.
●"Phase II" form – Once phase I organisms are grown in culture, subculturing results in an antigenic shift with loss of the majority of lipopolysaccharide side chains, including the O-antigen. This form is not virulent in animal infections [48].
Phase I and phase II isolates are essential for use as diagnostic antigens in Q fever serology tests. Acute infections are characterized by antibodies against phase II antigens, whereas chronic infections have high antibody titers to phase I antigens. (See 'Serology' below.)
DIAGNOSTIC TESTS
Serology — The indirect fluorescent antibody (IFA) test is the most common serologic (ie, antibody) test for human Q fever diagnosis.
IFA tests can quantify phase I and phase II antibodies, which is essential for differentiating past resolved infection from active infection, as well as acute from chronic infection. Phase II antibodies appear in the serum earlier than phase I antibodies.
Phase I antibodies — Antibodies against phase I antigen are often used for the diagnosis of chronic Q fever [25].
●Phase I IgG – A single phase I IgG antibody level that is very high (>512) is the most common result used to diagnose chronic Q fever. These antibodies appear at a median of 29 days after symptom onset [49]. (See "Chronic Q fever, including endocarditis", section on 'Serology'.)
Phase I IgG antibodies can also be detected in some patients with successfully treated or self-resolving acute Q fever. However, in these patients, phase I antibody levels are typically lower than phase II antibody levels. In contrast, 80 percent of patients with chronic Q fever have levels of phase I antibodies that are equal to or greater than phase II antibodies [50].
●Phase I IgM – Phase I immunoglobulin M (IgM) measurements have a limited role in the diagnosis of Q fever; IgG phase I antibodies have higher specificity for chronic infection than IgM. (See "Acute Q fever in nonpregnant patients", section on 'Serology' and "Chronic Q fever, including endocarditis", section on 'Serology'.)
Phase II antibodies — Phase II antibodies are used primarily for the diagnosis of acute infection. (See "Acute Q fever in nonpregnant patients", section on 'Serology'.)
The timing of phase II seroconversion from negative to positive varies by individual patient; IgG and IgM phase II antibodies frequently overlap, and IgG precedes IgM in some cases [49,51].
●Phase II IgG – Patients with acute Q fever develop positive IgG phase II serology results at a median of five days after symptom onset [49].
Acute and convalescent phase II IgG titers are the gold-standard tests for acute Q fever. Blood samples obtained in the first four days of illness are often negative, and a second serum sample taken 2 to 10 weeks after the first confirms the diagnosis by showing seroconversion from negative to positive or a fourfold increase in titer [25].
If serial blood samples are not possible, single samples with high phase II IgG titers in patients with at least one week of illness are suggestive of acute infection. However, phase II IgG antibodies can remain positive for years after initial infection, so low-level (1:16 to 1:128) phase II antibody levels may indicate past resolved infection as opposed to active acute infection [49].
●Phase II IgM – IgM antibodies against phase II antigen may become detectable at roughly the same time as IgG antibodies.
IgM positivity in the absence of IgG antibody detection should be interpreted with caution because false-positive IgM results are not uncommon and can persist for prolonged periods (beyond one year).
IFA tests rely on binding of a patient's serum antibodies to C. burnetii antigens bound to glass slides. Fluorescent secondary antibodies are added to bind to the patient's antibodies, and the fluorescence is visualized using a fluorescence microscope. Results are reported as reciprocal titers of the last dilution to produce specific fluorescence. Most Q fever IFA tests utilize whole cell antigens from Nine Mile phase I and Nine Mile phase II strains of the bacteria.
Instead of IFA serologic tests, enzyme-linked immunosorbent assay (ELISA) tests can be used to detect antibodies against C. burnetii. These are most useful as a screening test in areas with relatively high disease burden [52,53]; positive ELISA results can be followed with IFA to obtain confirmatory titers against phase I and phase II antigens.
Antibody cross-reactivity between C. burnetii and Legionella pneumophila has been reported and may confound diagnosis [54]. The ELISA may be less specific than IFA; ELISA cross-reactivity with Legionella, Chlamydophila, and Leptospira has been reported [55,56]. If testing is positive for C. burnetii and one of these organisms, additional diagnostic testing may be necessary to establish a specific diagnosis. (See 'Polymerase chain reaction' below.)
Polymerase chain reaction — Polymerase chain reaction (PCR) tests can be used to confirm the diagnosis of Q fever.
PCR is particularly useful for diagnosis of acute Q fever early in the illness, before serologic tests become positive [52,57]. Sensitivity of PCR is very high (100 percent on blood and serum) when used between days 3 and 7 of illness [58,59]. Sensitivity declines once IgG phase II antibodies become detectable (figure 1) [57,60].
For chronic Q fever, PCR testing of whole blood or serum has lower sensitivity (56 to 70 percent) than in patients with acute infection [58,59,61]. Higher sensitivity has been reported if the test is performed on explanted tissues (eg, heart valves) from patients with high phase I antibody titers [59].
PCR tests can target single-copy or multicopy genes. IS1111 insertion sequence is a common target as it is present in multiple copies in the organism's genome and therefore has a lower limit of detection [60].
Cell-free deoxyribonucleic acid (DNA) next-generation sequencing of blood is an emerging broad-spectrum diagnostic technique that has been reported to be useful in selected cases of Q fever [62]. The role of cell-free DNA testing in Q fever and other entities remains to be determined.
Culture — Common blood culture will not grow C. burnetii and is not an appropriate test to detect this organism. Culture of C. burnetii in host cells or axenic media is possible but is almost never used as a diagnostic technique [63].
Due to its transmission by inhalation and very low infectious dose, biosafety level 3 (BSL-3) facilities are required for C. burnetii culture, and strict security requirements are mandated in some countries.
Other tests — Immunohistochemistry can be used on tissues to detect C. burnetii. This is typically performed on explanted infected tissue from patients with chronic Q fever, such as heart valves and vascular tissue.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Q fever".)
SUMMARY AND RECOMMENDATIONS
●Epidemiology
•Geography – Q fever occurs throughout most of the world. Incidence is higher in the Middle East than in North America and Europe. Outbreaks have been reported in numerous countries; from 2007 to 2010, the Netherlands experienced the largest outbreak. (See 'Geography' above.)
•Animal reservoirs – Coxiella burnetii can infect a large variety of animals. The animals most often linked to human infections are cattle, sheep, and goats. (See 'Reservoirs' above.)
•Route of transmission to humans – The most common mode of transmission is inhalation of C. burnetii that has been excreted by animals. (See 'Routes of transmission to humans' above.)
●Risk factors – Risk factors include living or visiting an area where the disease is highly endemic or where an outbreak is occurring.
Additionally, occupations that involve livestock (eg, veterinarians, livestock farmers, slaughterhouse workers) or direct laboratory exposure are known risk factors for acquiring the infection. (See 'Risk factors' above.)
●Microbiology – C. burnetii is a gram-negative rod-shaped Gammaproteobacteria that grows inside of host cells.
Growth of C. burnetii in the laboratory results in phase variation:
•"Phase I" form – The phase I form is the infectious form that is grown in initial cultures from infected animals, including humans. The phase I form is highly infectious.
•"Phase II" form – Once phase I organisms are grown in culture, subculturing results in an antigenic shift. This form is not virulent in animals.
These phases can help to diagnose Q fever; acute infections are characterized by antibodies against phase II antigens, whereas chronic infections have high antibody titers to phase I antigens. (See 'Microbiology' above.)
●Diagnostic tests
•Serology – The indirect fluorescent antibody (IFA) test is the most common serologic (ie, antibody) test for human Q fever diagnosis. IgG antibodies are more specific for Q fever infection than IgM antibodies. (See 'Serology' above.)
-Phase I antibodies – These antibodies are used to diagnose chronic Q fever, although they can be detected in some patients with successfully treated or self-resolving acute Q fever. These antibodies appear at a median of 29 days after symptom onset. (See 'Phase I antibodies' above.)
-Phase II antibodies – These antibodies are used to diagnose acute Q fever, and they appear a median of five days after symptom onset. Acute and convalescent phase II IgG titers, obtained 2 to 10 weeks apart, are the gold-standard tests for acute Q fever. (See 'Phase II antibodies' above.)
•Polymerase chain reaction (PCR) – PCR is useful for diagnosis of acute Q fever early in the illness, before serologic tests become positive. Sensitivity of PCR is very high (100 percent on blood and serum) when used between days 3 and 7 of illness. (See 'Polymerase chain reaction' above.)
