Q Fever

Q fever has no distinct clinical features and nearly 50% of patients have no symptoms. At presentation, the most common feature is a low grade fever.

Q fever may have an acute or chronic presentation. The acute form of the infection can present with a limited febrile illness, flu like symptoms, pneumonia, hepatitis, pericarditis or meningoencephalitis. Other features of the illness include a headache, muscle and joint pain. These symptoms may last 5-14 days. Pneumonia is a common feature with dry cough, vague chest discomfort and shortness of breath. In rare cases, it may become fulminant with progression to ARDs.

Hepatitis is a common presentation in Europeans who acquire Q fever; these patients may have mild elevations of liver enzymes. Other associated symptoms may include nausea, vomiting, diarrhea and right upper quadrant pain.

Cardiac presentation may include myocarditis or pericarditis. These patients may experience chest pain, palpitations and dyspnea.

Rash is not a common feature of Q fever but may present as erythema nodosum or maculopapular rash.

Other rare presentations include mediastinal adenopathy, thyroiditis, pancreatitis, orchitis, optic neuritis, Guillain Barre Syndrome and SIADH.

About 1-2 percent of patients with acute Q fever will develop chronic disease. This infection may not manifest for months or years after the initial acute infection. The chronic form of Q fever is a serious illness and usually involves the heart valves. In some cases, the infection may result in aneurysms. Patients may present with heart failure, arrhythmias, dyspnea, night sweats, fevers and chills. The same organ systems involved in acute Q fever can be affected in chronic disease.

Q fever during pregnancy can result in chronic uterine infection with relapse during subsequent pregnancies.

The symptoms and signs of Q fever are not specific and hence some type of laboratory test is needed to confirm the diagnosis. The majority of labs do not have the capability to isolate C. burnetii. Hence serological tests are the most common means to diagnose the organism. Other tests used to detect C burnetii include indirect fluorescent antibody test and complement fixation. PCR is now also available to detect C. burnetii [6].

Other tests

• ECG may show evidence of pericarditis or myocarditis [7].
• CBC may show hemolytic anemia
• WBC
• Liver function may show mild elevation of transaminase
• ESR may be elevated
• Blood cultures are usually negative
• Lumbar puncture to sample CSF if patient has meningoencephalitis

Imaging

Depends on which organ system is involved:

• CXR may show opacification, pleural effusions or interstitial fibrosis if the lung is involved.
• CT brain is needed if patient has neurological symptoms
• Ultrasound to assess the liver
• Echo to look for function of heart valves, presence of vegetations and pericardial effusions

Many patients with acute Q fever have a self-limited disease which can spontaneously resolve. Thus, the decision to start antibiotics requires clinical judgment and experience. In patients who have chronic Q fever, it is important to consult with an infectious disease expert. All patients who have endocarditis need evaluation by a cardiologist and a cardiac surgeon. Pregnant women need to be seen by an obstetrician.

However, because these is a remote chance that acute Q fever may become chronic, most healthcare providers do start a course of antibiotics.

Other supportive treatments include the following:

• Antitussives
• NSAIDs for fever
• Oral hydration
• Antiemetics

Management of acute Q fever

Nearly 2/3rd of patients with acute Q fever have no symptoms. Since the disease is self-limiting and resolves spontaneously in 7-14 days, the decision to treat remains questionable. Even if antibiotics are used, the disease period is only shortened by a few days if started at the onset of the infection.

• The drug of choice for Q fever pneumonia is doxycycline. The second line drug of choice is ciprofloxacin. The third line drugs of choice are the macrolides. All these agents have been well studied in prospective randomized trials and shown to be effective against Q fever. The chief reason why macrolides are drugs of 3rd choice is because of the gastrointestinal adverse effects. Both erythromycin and azithromycin have been proven to be effective against Q fever pneumonia. Patients who have respiratory distress need to be admitted to an ICU and be treated with a fluoroquinolone in such a setting.
• The optional duration of treatment is 14-21 days in an outpatient setting.
• In children the drugs of choice is macrolides or trimethoprim sulfamethoxazole.
• If the patient has hepatitis, adjuvant corticosteroid treatment may be of benefit.

Management of chronic Q fever

• Chronic Q fever is not easy to treat because of the multiple organ system involvement. In most cases admission to the hospital is required and a prolonged course of antibiotics needed. In most cases, combination antibiotic therapy is used because of high rates of relapse.
• The duration of therapy is not known but experts suggest at least 12 months. The treatment response can be followed by measuring antibody titers.
• If endocarditis is diagnosed, combination of doxycycline and hydroxychloroquinine/fluoroquinolone for at least 18 months is recommended to eradicate any remaining C burnetii and prevent relapses [8].
• Other organ system involvement may also require combination therapy for prolonged periods.

Follow up

All patients with a diagnosis of Q fever need follow up with a healthcare provider because the condition can become chronic. Serology is needed on a regular basis to ensure that the infection does not reoccur.

If the patient has endocarditis a follow up with a cardiologist and a surgeon is necessary because there is a possibility of valve replacement. If surgery is not undertaken serial echo is required to monitor heart and valve function. Echo and ultrasound may also be required to ensure that the patient is not developing thoracic or aortic aneurysms.

Patients who are receiving hydroxychloroquine also need a follow up with an ophthalmologist to assess the eye for retinal toxicity.

Q fever in pregnancy

Only a few reports exist on Q fever in pregnancy. If infection occurs, then therapy may be undertaken with doxycycline or rifampin. In addition the treatment must eb continued after pregnancy, while the infant must be clinically monitored with serology for signs of Q fever. The decision to treat the infant must be individualized.

Therapy with biological modifying agents

There are some patients who fail to respond to the conventional drugs and in such cases use of biological agents may help [9] [10]. Isolated reports indicate that use of interferon gamma can help kill C. burnetii in monocytes through an apoptotic mechanism that is mediated by tumor necrosis factor [8]. Patients who develop granulomatous hepatitis due to Q fever and have a prolonged illness often fail to respond to antibiotics. These individuals may benefit from prednisone.

There are no commercial vaccines to prevent Q fever. An experimental vaccine is only available from the U.S. Army Medical Research Institute for Infectious Diseases in Fort Detrick, Maryland.

Acute Q fever is a self-limited disease and the outcome is excellent in patients who are promptly diagnosed and treated. At least 50% of patients are asymptomatic and less than 2% of patients need admission. The mortality for acute Q fever is very low.

Chronic Q fever is a serious illness and most patients require admission and long term follow up. This infection is associated with frequent relapses and has a high mortality rate. The most common feature of chronic Q fever is the development of endocarditis, which can be fatal if left untreated. Even with treatment, the mortality rate approaches 10-20 %.

Other complications of chronic Q fever include the following

• Abortions
• Acute respiratory distress syndrome
• Chronic fatigue syndrome
• Congestive heart failure
• Meningoencephalitis
• Premature labor
• Reactivation of infection during pregnancy
• Spontaneous abortion
• Thrombocytopenia
• Vascular aneurysms

Several studies from England and Australia have shown at least 10% of patients with acute Q fever go on to develop fatigue that may last 6 months.

Q fever is acquired by inhalation of aerosolized particles containing the bacteria. The organism is often found in animal waste like urine, feces and placenta. When these products dry out, the bacteria enter a spore stage and dries up, making it easily prone to inhalation.

Sometimes it can be acquired by direct contact with parturient animals or the placenta. C. burnetii can sometimes be found in dust, soil or other contaminated environmental waste that are carried for long distances by wind. Once inhaled the microorganism starts to proliferate in the lungs and then invades the blood, especially in patients who are immunocompromised. Once in the blood stream, C burnetii can infect bone, heart valves or liver resulting in chronic Q fever.

Other means of acquiring C.Burnetii include tick bites and sexual transmission, which is rare. C.Burnetii is known to localize to animal reproductive organs and is readily excreted. The infection can also be acquired in people who have no known exposure to animals. This may occur in scenarios when farm vehicles carrying contaminated hay, animal feeds or manure come into contact with humans. Human to human transmission is very rare and only one documented case has been reported.

Q fever is a very common zoonotic infection. The animal reservoir depends on the country. By far the most common animal reservoirs include sheep, cattle and goats. Cats are the primary reservoirs for Q fever in Nova Scotia, Canada. In rare cases, dogs have also been identified as reservoirs. Except for Antarctica and New Zealand, Q fever has been reported in most parts of the globe. The precise numbers of people infected remains unknown because the symptoms are nonspecific, diagnostic tests are not always performed and reporting of the infection is not mandatory. With recognition of the disease, more cases have been reported in the USA in the past decade than previous ones. Q fever cases have also been reported in US military personnel deployed in the Netherlands and Middle East. Clusters of outbreak have been reported in Australia, Spain, UK, France and parts of Africa [3][4]. Q fever is endemic in the Middle East; the reason for this is the hot dry environment and livestock farming practices which make it easy for the organism to spread and thrive.

Q fever can occur at any age and is slightly more common in men compared to women, primary because the former are more likely to work outdoors. When Q fever occurs at a young age there is an increased risk of developing hepatitis and pneumonia. If the infection is acquired during pregnancy, there is a risk of low birth weight, spontaneous abortions or premature birth.

The causative agent of Q fever is C. burnetii. This small gram negative organism usually multiplies fast in acidic environments and can form spores, which explains its ability to survive for prolonged periods in hostile environments and the ability to develop resistance to a variety of chemical agents. C. Burnetii has two antigenic phases: phase I and phase ll. In animals it exists in phase 1 and is very infectious. Phase II is less infectious.

C. burnetii is known to infect many animal species. Once the bacterium is excreted from feces, milk, urine or placenta, the bacteria survives in the soil as a spore. C. burnetii is extremely infectious and only requires a few microorganisms to produce disease. Because of the ability to form spores, C. burnetii remains viable for prolonged periods. Once the spores are inhaled by the human, the organism thrives in the lung and may escapes into the systemic circulation and infects the bone, heart or liver.

The organism is known to proliferate in lysozymes and then transported to other organs. Because of its high infectivity, C. burnetii is classified as potential agent for bioterrorism [5].

To avoid Q fever, the following recommendations are made:

• Avoiding consumption of unpasteurized milk and other dairy products- especially cheese from goat;
• Avoiding contact with pregnant farm animals and their birth products;
• Avoiding contact with urine, feces and other fluids from farm animals;
• Encourage birthing of animals inside;
• Safely disposing birthing tissues like the placenta and aborted fetuses;
• Minimize exposure to farm animals, especially in dry arid areas. Wear proper garments when outdoors to avoid tick bites. Use tick repellants and other chemicals if needed;
• When animals are sick, get them seen by a veterinarian on time;
• Wear mask and gloves when handling sick farm animals.

To prevent Q fever it is essential to eradicate the reservoir. One approach is to use seronegative sheep in research facilities and minimize contamination of livestock. Isolation of patients who are infected with Q fever is not necessary since person to person transmission does not occur.

Q fever is a common zoonosis caused by the gram negative organism Coxiella burnetii. The primary reservoirs for this organism are sheep, cattle and goats but many other animal species may also be infected. Human transmission is primarily via inhalation of aerosolized particles from contaminated soil, dirt or animal water. In rare cases, the organism may be acquired following a tick bite and ingestion of unpasteurized milk. Human to human transmission has been reported but is extremely rare. Q fever occurs as an acute or chronic illness. The acute illness has nonspecific symptoms and spontaneously resolves in many cases. The chronic phase is a serious infection that primarily causes endocarditis. C.Burnetii is susceptible to several antibiotics including doxycycline, fluoroquinolones and macrolides [1][2].

Q fever is an infectious disorder acquired following an infection from the organism, C. burnetii. The organism is often found in sheep, cattle and goats and acquired in humans after inhalation of dried spores. Once in the lungs, the bacteria can spread to other parts of the body. In most cases the acute phase of the illness lasts 5-12 days and presents with non-specific symptoms. In about 1% of cases, the organism will persist and result in a chronic infection. This is a serious illness which primarily affects the heart valves. Q fever does respond to antibiotics, but close follow up with a healthcare provider is recommended to ensure that recovery is taking place.

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