Q fever

• Reporting criteria
• The disease and its epidemiology
• Case definition

• Laboratory testing
• Case investigation

• Disease control measures
• References

What and how to report to the Colorado Department of Public Health and Environment (CDPHE) or local public health agency

• Q fever cases must be reported within four days of diagnosis or health care provider suspicion, if an act of bioterrorism is not suspected. 
• Cases should be reported in EpiTrax. 

Purpose of surveillance and reporting

• To identify potential intentional release (bioterrorism event) of C. burnetii
• To prevent chronic infection when possible

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Etiologic agent

Q (query) fever disease is caused by an infection with C. burnetii, a Gram-negative bacterium in the Order Legionellales, Family Coxiellaceae. It is an intracellular pathogen that replicates in host monocytes and macrophages. It can infect a wide variety of animal species and is found in countries worldwide except for New Zealand.

This bacterium has two morphotypes. The small-cell variant (SCV) is a dormant, environmentally persistent form of the bacterium that survives outside of host cells. It is often referred to as a spore, though it is not. The SCV is also the bacterial form that infects susceptible host animals. The large-cell variant (LCV) is the bacterial form that replicates within phagolysosomes in host hells. The LCV expresses a different suite of genes than the SCV.

C. burnetii undergoes antigenic (also known as phase) variation during infection. Phase variation occurs when the bacterium modifies its lipopolysaccharides (LPS) during infection. When an animal or person is first infected, the bacteria is coated with Phase I LPS, or antigen. As the bacteria replicates in the body and the infection progresses, the bacteria express Phase II LPS. High levels of antibody to Phase II LPS are therefore associated with acute infection. A high or increasing antibody response to Phase I LPS is likewise associated with chronic (or persistent) Q fever infections.

Clinical description

Acute Q fever

Asymptomatic infections occur in ≥50% of people. The incubation period for the disease is normally 2-3 weeks following an exposure, but may be up to six weeks. Time to illness onset depends, at least in part, on the bacterial dose and route of transmission. 

Those with symptomatic infections may present with highly variable clinical pictures. Most cases report high fever and some combination of other symptoms such as chills, headache (sometimes severe), sore throat, malaise, fatigue, weight loss, and myalgia. Cases may develop atypical pneumonia with non-productive cough and pneumonitis on chest imaging. Hepatitis may appear as a granulomatous process or accompanied by hepatomegaly and, rarely, jaundice. Rash may also be present. 

Uncommon complications of acute infection have been reported involving the heart, nerves, gut, and bone marrow. Laboratory findings for acute infection include thrombocytopenia, and many cases will have moderately elevated serum transaminases. 

Over the last five years, Colorado has had an average of six acute Q fever cases reported annually.

Chronic Q fever

Chronic Q fever can develop months to years following acute symptomatic or asymptomatic infection. Patients with chronic Q fever will have persistently increased antibody (IgG) to Phase I LPS (antigen). Thrombocytopenia, anemia, and hematuria may be present. Immunosuppressed people or those with a pre-existing heart defect are most at risk of developing chronic Q fever.

At least 50% of Q fever infections are asymptomatic, and mild Q fever can resemble a simple flu-like illness, which is why infection can go unrecognized, leading to adverse outcomes. Risk of pregnancy complications exists for both acute and chronic Q fever. Cases of abortion and premature delivery have been associated with C. burnetii infection in pregnant women.

Endocarditis is the condition most commonly associated with chronic Q fever, though osteomyelitis, osteoarthritis, aortic aneurysms, hepatitis, and pulmonary or reproductive organ involvement are also reported. Healthcare providers should perform an echocardiogram on patients who present with chronic Q fever to assess for cardiac involvement. Patients with endocarditis will commonly have elevated sedimentation rates and C-reactive protein. 

Over the last five years, Colorado has had an average of one chronic Q fever case reported annually.

Pediatric Q fever

Reports of Q fever in children are uncommon. In general, children seem to demonstrate a milder course of illness than adults. Duration of fever tends to be shorter — only 7-10 days, as compared to 14 days in older people. Headaches are frequently reported. Gastrointestinal symptoms are reported in 50-80% of pediatric cases, whereas they are rarely reported in adults. Rash may be present in up to 50% of cases. Pneumonia, hepatitis, and cardiovascular and neurologic manifestations seem to occur less commonly than in adults. Cases of chronic Q fever in children are rare. Osteomyelitis and endocarditis are the chronic conditions that have been reported in children. 

Reservoirs

Mammals, birds, reptiles, and arthropods can carry  C. burnetii. Among domestic livestock, sheep, goats, and cattle are common reservoirs of C. burnetii. Infection in these animals can be asymptomatic, but abortion storms or stillbirths can occur in ruminants. Up to 50% of a sheep flock or goat herd may be infected. Bacteria can be shed or be present in parturition products, feces, milk, and urine. Parturition products in particular can contain very large numbers of bacteria. The bacteria are hardy and can persist in the environment for long periods. Winds can generate infectious bacteria-laden dust; massive outbreaks of Q fever have occurred in the Netherlands by this route of transmission. C. burnetii is found worldwide, except for New Zealand, and most cases are reported in residents of Africa and the Middle East.

Modes of transmission

Most people get Q fever by inhaling bacteria in dust generated from areas where infected animals such as sheep, goats, and cattle have given birth. Exposure to a single bacterium is sufficient to produce an infection, and inhalation and/or consumption of bacteria can produce an infection.

It should be noted that Q fever infections have also been acquired from animal species other than ruminants. Birds, reptiles, rodents, and other pet animals can also be infected and be a source of exposure to people. Infections acquired from contacts with parturient pet cats and dogs have been reported. Ticks can also transmit C. burnetii to people through a tick bite, though they are rarely identified as a source of infection. 

Incubation period

The incubation period for the disease is normally 2-3 weeks following an exposure, but may be up to six weeks. Time to illness onset depends, at least in part, on the bacterial dose and route of transmission. 

Infectious period

Person-to-person transmission of Q fever has not been documented in the United States. Soil and dust can contain bacteria. 

Epidemiology

Q fever has historically been seen as an occupational disease of slaughterhouse workers and people working with ruminants. But a number of outbreaks in recent decades have demonstrated that direct contact with these animals or materials derived from these animals is not necessary to acquire the infection.

In Colorado in 2005, a Q fever outbreak occurred at a horse boarding facility whose owners had purchased two goat herds. Persons who lived at or visited the ranch were infected through contact with the goats. An additional group of people living within one mile of the facility (n = 138) were also tested to determine their infection status. Eight of those who tested positive had had no direct contact with goats at the facility. Soil samples from the ranch revealed the presence of C. burnetii in the environment, and it was suspected that bacteria-laden dust had been dispersed by the wind into the surrounding community. Thus, people in the surrounding community were exposed to the bacterium without ever having direct contact with a goat. 

Similarly, a large-scale outbreak of Q fever occurred in the Netherlands between 2007 and 2010. Bacteria-laden dust from dairy goat and sheep farms in the country were dispersed across the landscape by winds, ultimately causing thousands of infections in susceptible people living in adjacent areas. 

Epidemiologically, a Q fever case patient may have never had direct contact with an infected animal. Still, direct contact, aerosol exposures to birthing fluids, or spending time in areas where ruminants are present remains a significant risk factor for Q fever. Ranching, farming, practicing veterinary medicine, and performing animal research, therefore, continue to be high risk occupations for the disease.

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Acute Q fever clinical description

Acute fever, usually accompanied by rigors, myalgia, malaise, and a severe retrobulbar headache. Fatigue, night-sweats, dyspnea, confusion, nausea, diarrhea, abdominal pain, vomiting, non-productive cough, and chest pain have also been reported. Severe disease can include acute hepatitis, atypical pneumonia with abnormal chest imaging, and meningoencephalitis.

Pregnant people are at risk for fetal death and spontaneous abortion. Serologic profiles of pregnant people infected with acute Q fever during gestation are more likely to rapidly progress to those characteristic of chronic infection.

Chronic Q fever clinical description

Infection that persists for more than six months. Endocarditis (infection of a heart valve) may develop months to years after acute infection. Persons with underlying cardiac valvular disease are at higher risk than those with normal native valves. Infections of pre-existing aneurysms and vascular prostheses have been reported. People with immunocompromising conditions are particularly susceptible to chronic infection. Rarely, chronic infection has presented as hepatitis without endocarditis, osteomyelitis, osteoarthritis, and pneumonitis. 

Acute Q fever case surveillance definitions

Clinical criteria

• Acute fever and one of the following:
• Rigors, severe retrobulbar headache, acute hepatitis, pneumonia OR elevated liver enzyme levels.

Laboratory criteria

Confirmed

• Serological evidence of a four-fold change in IgG-specific antibody titer to C. burnetii phase II antigen by indirect immunofluorescence assay (IFA) between paired serum samples (one sample collected in the first week of illness, the second 3-6 weeks later), or
• Detection of C. burnetii DNA in a clinical specimen via amplification of a specific target by PCR assay, or
• Demonstration of C. burnetii in a clinical specimen by immunohistochemical methods (IHC), or
• Isolation of C. burnetii from a clinical specimen by culture.

Supportive

• A single supportive IFA IgG titer of ≥1:128 to phase II antigen (phase I titers may also be elevated).
• Serologic evidence of elevated phase II IgG or IgM antibody reactive with C. burnetii antigen by enzyme-linked immunosorbent assay (ELISA), dot-ELISA, or latex agglutination.

Note: For acute testing, CDC uses in-house IFA IgG testing (cutoff of ≥1:128), preferring simultaneous testing of paired specimens, and does not use IgM results for routine diagnostic testing.

Acute Q fever case classification

Confirmed

• A laboratory confirmed case that either meets clinical case criteria or is epidemiologically linked to a lab confirmed case.

Probable

• A clinically compatible case of acute illness (meets clinical evidence criteria for acute Q fever illness) that has laboratory supportive results for past or present acute disease (antibody to Phase II antigen) but is not laboratory confirmed.

Chronic Q fever case surveillance definitions

Clinical criteria

• Newly recognized, culture-negative endocarditis, particularly in a patient with previous valvuloplasty or compromised immune system, suspected infection of a vascular aneurysm or vascular prosthesis, or chronic hepatitis, osteomyelitis, osteoarthritis, or pneumonitis in the absence of other known etiology. 

Laboratory criteria

Confirmed

• Serological evidence of IgG antibody to C. burnetii phase I antigen ≥1:800 by IFA (while phase II IgG titer will also be elevated, phase I titer is higher than phase II), or
• Detection of C. burnetii DNA in a clinical specimen via amplification of a specific target by PCR assay, or
• Demonstration of C. burnetii antigen in a clinical specimen by IHC, or
• Isolation of C. burnetii from a clinical specimen by culture.

Supportive

• Antibody titer to C. burnetii phase I IgG antigen ≥1:128 and <1:800 by IFA.

Chronic Q fever case classification

Confirmed

• A clinically compatible case of chronic illness (meets clinical evidence criteria for chronic Q fever) that is laboratory confirmed for chronic infection.

Probable

• A clinically compatible case of chronic illness (meets clinical evidence criteria for chronic Q fever) that has laboratory supportive results for past or present chronic infection (antibody to Phase I antigen).

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The State Public Health Laboratory does not offer Q fever testing. Commercial laboratories perform serologic testing. 

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Investigate all cases of Q fever:

• Review medical records to determine if they have a clinically compatible illness. Speak to the health care provider if you need additional medical information about the case to complete the CMR investigation form.
• If the patient will meet case definition based on the clinical presentation and laboratory tests, then interview the case patient.
  • Confirm illness onset date and symptoms. 
  • Identify possible exposures (particularly to pregnant animals, newborn livestock, and livestock abortion material).
  • Determine whether other people share any exposures and if they are ill.
• If you have concerns that there are multiple people ill or at risk from the same exposure, discuss with CDPHE staff. 
• Environmental investigations are not usually required.
• Once the investigation is complete, the CMR should be marked as “Approved by LPHA.” CDPHE staff will close the case and assign case status. 

Forms 

All data collected during the investigation should be recorded in the EpiTrax CMR in the “Investigation” or “Notes” tab.

Identify and evaluate contacts (if applicable, as not all pathogens are communicable)

No person-to-person transmission has been reported.

Reported incidence is higher than usual/outbreak suspected

If you suspect an outbreak (> two clustered cases), consult with CDPHE staff. CDPHE will assist you in evaluating the exposure scenario, in arranging and conducting an environmental health investigation, and can facilitate testing of suspect cases if it seems indicated.

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Treatment

The drug of choice for acute illness in adults is doxycycline. Doxycycline is also recommended for children who are severely ill with Q fever. Children with a mild infection and pregnant women who present with acute Q fever may be treated with co-trimoxazole. The duration of antibiotic treatment depends on the type of patient and severity of illness, but is generally 2–3 weeks. 

Chronic Q fever is commonly treated with a combination of doxycycline and hydroxychloroquine. The length of treatment depends on the patient’s response to therapy, but is generally at least 18 months. Cardiac valve replacement may be indicated if the patient has Q fever endocarditis. 

Treatment guidance can be found on CDC’s clinical guidance for Q fever webpage.

Prophylaxis

No prophylaxis is available for Q fever exposures. Primary prevention by minimizing exposures to infected livestock is recommended. 

Education

People living or working in areas near livestock facilities, especially areas where sheep, goats, and cattle are present, should be educated on the modes of transmission of the disease and methods to reduce exposures. 

Managing special situations

If an intentional release is suspected contact CDPHE staff immediately.

Environmental measures

C. burnetii is maintained in the soil for years after a zoonotic outbreak. Eliminating it from the environment is impossible.

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CDC's Q fever treatment webpage

Important telephone and fax numbers

CDPHE Communicable Disease Branch

• Phone: 303-692-2700 or 800-866-2759
• Fax: 303-782-0338
• After hours: 303-370-9395

CDPHE Microbiology Laboratory: 303-692-3480

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