May 19, 2022
Years published: 1989, 1991, 1998, 2005, 2009, 2012, 2022
NORD gratefully acknowledges Emilia Wang and Rioke Diejomaoh, NORD Editorial Interns from the University of Notre Dame, Joseph Farris, PhD, Professor of Biology, Saginaw Valley State University, and Kerry O. Cleveland, MD, Professor of Medicine, Department of Medicine, Division of Infectious Diseases, University of Tennessee Health Science Center, for assistance in the preparation of this report.
Q fever is an infectious disease that is spread by the inhalation or ingestion of a bacterium known as Coxiella burnetii, which belongs to the order of Legionellales. Animals such as cattle, sheep and goats are common bacterial hosts for this bacterium. C. burnetii is spread mainly by breathing contaminated air or eating or drinking contaminated food. Farm workers, especially those who work with animals, people who work in slaughterhouses and veterinarians are especially vulnerable to this disease. Other forms of transmission are rare but include tick bites and human to human transmission. Q fever causes highly variable symptoms ranging from acute (often self-limited) infection to fatal chronic infection. Progression of Q fever from acute infection to chronic fever occurs in less than 5% of patients. Infections that do not cause outward symptoms (subclinical) or no symptoms (asymptomatic) are also common. Acute Q fever is treated with antibiotics. Treatment for chronic Q fever is more complex and depends on an individual’s presenting symptoms. People of all ages are susceptible to Q fever.
Since infection can occur because of airborne transmission and the bacterium is very resistant to environmental conditions such heat and pressure, C. burnetti was included on the list of possible bacteriological weapons.
The symptoms of Q fever can vary dramatically from one person to another. Infection can result in no apparent symptoms (asymptomatic); an acute form of disease characterized by a flu-like illness that either goes away on its own (self-limited) or causes more serious symptoms; or a chronic form that can be associated with serious complications. Researchers believe that a variety of factors may influence the severity of Q fever including age, gender and a person’s general health, including pre-existing medical conditions (e.g., heart disease).
Acute Q Fever
The acute form of Q fever starts approximately two to three weeks after exposure to the bacterium. Acute Q fever is characterized by flu-like symptoms such as high fevers, chills, muscle pain (myalgia), muscle weakness, fatigue and headaches. In some patients, fevers do not occur. Additional nonspecific symptoms can potentially occur including cough, chest pain, sore throat, skin rash or gastrointestinal symptoms. Many people also suffer from small areas of inflammation (granuloma).
Pneumonia and inflammation of the liver (hepatitis) are commonly associated with acute Q fever. Pneumonia is often mild but can potentially progress to cause acute respiratory distress syndrome (ARDS). Hepatitis may cause abnormal enlargement of the liver (hepatomegaly). More rarely, it can cause yellowing of the skin and the whites of the eyes (jaundice). Other symptoms can occur in some affected individuals including inflammation of the muscular wall of the heart (myocarditis), inflammation of the sac-like membrane that surrounds the heart (pericarditis) and the development of a purple skin rash caused by bleeding (hemorrhaging) from tiny blood vessels just below the surface of the skin.
Acute Q fever may present as a neurological disease caused by inflammation of the thin membrane covering the brain and spinal cord or the brain (meningoencephalitis). In some individuals, acute Q fever can affect the kidneys, thyroids or genitals.
Chronic Q Fever
Chronic Q fever may occur months to years after acute disease or may occur without a previous history of symptomatic acute Q fever. Most cases of chronic Q fever occur in individuals with predisposing conditions such as existing heart valve or blood vessel (vascular) abnormalities or a compromised immune system.
The most common manifestation of chronic Q fever is inflammation of the thin membrane lining the inside of the heart and heart valves (infective endocarditis), potentially damaging the heart valves or heart tissue. Inflammation of heart muscle (myocarditis) is rarely seen but also possible. Other symptoms include inflammation of blood vessels (vasculitis), low red blood cell count (hemoglobin), low platelet count (thrombocytopenia), anticardiolipin IgG antibody positivity, antimitochondrial antibody positivity and blood in urine (hematuria). Affected individuals can develop congestive heart failure, a serious complication in which a limited ability to circulate blood to the lungs and the rest of the body results in fluid buildup in the heart, lungs and various body tissues. In addition, Q fever can cause liver inflammation (hepatitis), enlarged liver (hepatomegaly), enlarged liver and spleen (hepatosplenomegaly), fluid around lungs (pleural effusions) and respiratory distress.
Less commonly, chronic Q fever can present as an infection of the bones and joints (osteoarticular infection) such as osteomyelitis or osteoarthritis, which can cause bone and joint pain. Vascular infections, chronic hepatitis and chronic pulmonary disease are also seen in some patients. Chronic hepatitis can cause enlargement of the liver or jaundice. Chronic pulmonary disease can cause difficulty breathing (dyspnea) and other respiratory abnormalities. Other less common symptoms include abnormal heart valve morphology, immunodeficiency, increased circulating antibody level, flat and raised skin lesions (maculopapular exanthema), pneumonia, red or purple spots on the skin (purpura) and rheumatoid factor positivity.
Individuals with chronic Q fever may also experience a variety of symptoms similar to those experienced by acute Q Fever patients, including prolonged fevers (although fevers are often absent), joint pain (arthralgia), muscle pain (myalgia), night sweats, chills, fatigue and unintended weight loss.
Some individuals with Q fever develop long-term complications such as chronic, persistent fatigue. Some researchers believe that infection with Q fever increases an individual’s risk of developing cardiovascular disease later in life.
The rarest symptoms (approximately 1%- 4% of individuals) include abnormal function of the left ventricle, abnormal amyloid build-up (amyloidosis), inflammation of the gallbladder (cholecystitis), inflammation of the brain (encephalitis), lupus anticoagulant, swollen lymph nodes (lymphadenopathy) or inflammation of fluid and membrane around the brain and spinal cord (meningitis).
Q fever is caused by inhalation or ingestion of the bacterium Coxiella burnetii. People are most often exposed to the bacterium from the milk, urine and feces of infected animals (for example, by inhaling contaminated air in a barnyard). When these waste substances dry in the air, the bacteria are able to mix with the barnyard dust that floats around. Consequently, this infection is primarily transferred to humans through their lungs when they breathe the contaminated dust. Also, when an infected animal gives birth, the bacteria may be present in high numbers in the amniotic fluid and placenta. Q fever bacterium primarily infects farm animals such as cattle sheep and goats. However, it has been reported in a wide variety of animals including domesticated animals such as dogs, cats and rabbits. The C. burnetii bacterium is highly infectious. The bacterium can survive in the environment for lengthy periods of time because it is resistant to environmental conditions such heat and pressure. It is also resistant to many common disinfectants.
Less common modes of transmission to humans include working in a slaughterhouse, drinking unpasteurized milk and hunting, slaughtering or dressing infected animals. According to the medical literature, in extremely rare cases, human-to-human transmission has been reported.
The mode of transmission in wild and domestic animals is different from the mode of transmission in humans. Animals become infected with C. burnetii from infected ticks. Originally, Q fever was classified as a rickettsial disease, a group of infectious diseases most often spread to humans from ticks. However, based on DNA-DNA hybridization studies and genome sequencing, C. burnetii was placed to the order of Legionellales, which also contains Legionella pneumophila, the bacterium that causes Legionnaires disease.
People with pre-existing conditions are at higher risk of developing chronic Q fever. These conditions include heart valve disease, blood vessel abnormalities, weakened immune system or an impaired kidney function.
Q fever occurs worldwide and can affect individuals of every racial and ethnic background. The incidence of Q fever is unknown because in many countries it is not a reportable disease. Researchers believe that the infection is underreported. From 2000-2012, the incidence rate for this disease in the United States was 0.38 cases per million people per year. There have been higher incidence rates in certain countries such as the Netherlands, where there were reports of thousands of human cases.
Q fever has occurred more often in men than women, however, this trend is attributed to the fact that more men work in occupations where exposure to C. burnetii bacterium is likely to occur. Q fever can affect individuals of any age, but affected children are rarely reported. Some researchers have speculated that children develop symptoms that are milder and occur less often compared to adults.
The signs and symptoms of Q fever are nonspecific and can be associated with a wide variety of diseases. A diagnosis of Q fever usually requires serological examination, which measures and characterizes antibodies. Q fever has two antibody-producing (antigenic) phases called phase I and phase II. These phases can help confirm a diagnosis and can help distinguish acute Q fever infection from chronic Q fever infection. Infected individuals develop specific antibodies against Q fever including immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM). Measuring the levels of these classes of antibodies can help confirm a diagnosis of Q fever. During the acute phase of Q fever, IgG and IgM antibodies may be detected. In chronic Q fever, IgG or IgA levels may be detected.
In acute Q fever, the levels of antibodies to phase II antigen of C. burnetii are higher than those to the phase I antigen. Phase II antigens of C. burnetii are normally detected during the second week of the illness. In chronic Q fever, a high level of phase I antibodies with a constant or falling level of phase II antibodies are common along with other elevated inflammatory markers.
The three most common serological tests for Q fever are indirect immunofluorescence, complement fixation and enzyme-linked immunosorbent assay (ELISA). Indirect immunofluorescence is a test that can detect the presence of specific antibodies in the blood or other fluids. The antibodies are tagged with a substance that causes them to glow when exposed to ultraviolet light. Complement fixation and ELISA tests can also detect the presence of specific antibodies or antigens. Isolation of the infectious agent in cell cultures, embryonated hen’s eggs and laboratory animals is also possible, but requires a special laboratory with biosafety level three (BSL3).
A common test that has been used to aid in the diagnosis of Q fever in some cases is a polymerase chain reaction (PCR) test. A PCR test is a highly sensitive test that amplifies a specific segment or sample of DNA, creating billions of copies of that segment There are three key steps to create the multitude of copies of a segment. First, the DNA strands are heated so they separate. Next, the reaction is cooled so the primer can bind to the DNA. A primer is a short sequence of nucleotides used to provide a starting point for the DNA synthesis reaction. Finally, the temperature of the reaction is raised again to extend the primers and synthesize new DNA strands. This amplified segment can then be studied to detect the presence of C. burnetii infection. It has been employed successfully to detect C. burnetii DNA in cell cultures and biological samples. Although a PCR test is highly sensitive, a negative result does not necessarily rule out a Q fever infection. Reasons for a negative result include inhibition of the PCR or low levels of C. burnetti that are not detectable by the polymerase chain reaction.
Clinical Testing and Work-Up
A physician may order some imaging tests to check the health of the internal organs. A chest X-ray may be used to evaluate for pneumonia, which affects some individuals with Q fever. Additionally, an echocardiography is used if chronic Q fever is suspected. This test can reveal any issues with heart valves.
Antibiotic therapy is used to treat individuals with Q fever. Some mild cases of Q fever may improve without treatment, although antibiotic therapy can usually help reduce the duration of the infection. Physicians recommend that all individuals in whom Q fever is detected receive antibiotic therapy, even those with no recognizable symptoms.
Doxycycline is currently the most used antibiotic therapy for the treatment of individuals with Q fever and is most effective when started within three days of infection. Anti-inflammatory drugs may be used if individuals do not respond to antibiotics. Hydroxychloroquine, which is often used to treat malaria, has also been used to treat Q fever. Hydroxychloroquine can help raise the pH of lysosomal compartments, allowing more effective antibiotic activity toward the bacteria.
Chronic Q fever is more difficult to treat. Endocarditis may require prolonged antibiotic treatment which usually involves treatment with multiple drugs. One such combination is the use of doxycycline and hydroxychloroquine. For patients allergic to doxycycline, trimethoprim-sulfamethoxazole may be used instead. The optimal duration of therapy is unknown and varies from person to person. In individuals with damage to the heart valves or a history of heart failure, surgery may be necessary.
There is currently no vaccine approved by the U.S. Food and Drug Administration (FDA) for Q fever.
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