Q fever: Understanding a little-known bacterial disease

Q fever, a bacterial disease caused by Coxiella burnetii, is often overlooked despite its potential seriousness. This bacterium infects a variety of animals, including sheep, goats, cattle and wildlife, making it an important zoonosis. Transmission to humans is mainly by inhalation of contaminated airborne particles. These may come from the excrement, urine or abortion products of infected animals. Other modes of transmission are also possible. Q fever presents a range of symptoms, from acute flu-like forms to more severe chronic forms. Potentially fatal complications can occur, such as heart or liver infections. Although relatively rare, proper vigilance is essential to diagnose and treat this disease quickly in order to avoid serious complications.

What bacteria cause Q fever?

Q fever, also known as coxiellosis, is a disease caused by the Coxiella burnetii bacterium. This bacterium is widespread throughout the world, with numerous reservoirs in wild and domestic mammals such as cattle, sheep and goats, as well as cats and dogs. C. burnetii can be detected in a variety of environments, with the notable exceptions of Antarctica and New Zealand.

The bacterium enters cells, particularly monocytes and macrophages, passively by phagocytosis. Once inside, it proliferates in the acidic environment of the phagosome using a variety of mechanisms, including production of high isoelectric point enzymes, inhibition of free radical production and secretion of superoxide dismutase.

Q fever is remarkably infectious, with a single bacterium being sufficient to cause infection. It also has the ability to modulateapoptosis, contributing to its virulence. The survival and multiplication of C. burnetii in the acid vacuole protect it from antibiotics . This makes it a unique bacterial species.

The vacuole containing the bacterium, initially considered to be a “large phagolysome“, is now recognised as a specialised compartment. This is known as the ” parasitophorous vacuole”(PV), actively modified by C. burnetii. This vacuole is distinct from other cellular compartments.

C. burnetii has a development cycle comprising an intracellular form and an extracellular form, produced by pseudosporulation. These pseudospores, which are metabolically inactive, are extremely resistant in the external environment. This contributes to the bacterium’s persistence in the environment.

T lymphocytes provide immune control of C. burnetii. However, the infection can develop into a chronic form, characterised by prolonged bacteremia despite the presence of antibodies. Various factors, such as immunosuppression and female hormones, can favour this chronicity.

How does the disease manifest itself in animals?

In France, Q fever is a disease that is particularly widespread in regions with high small ruminant production. Most animal species, especially domestic ruminants such as sheep, goats and cattle, contract the infection. Calving products, faeces and urine from infected animals are the main vectors for transmission of the disease. They carry the bacteria by inhaling contaminated particles.

The clinical signs of Q fever are generally mild. In small ruminants, abortions, premature births and births of sickly animals may be observed. In cattle, signs include abortions, limp or sickly calves, premature calving, fertility problems and endometritis. Infected animals, even without symptoms, can excrete the bacteria in the products of calving, vaginal secretions, faeces, urine and milk. Dogs and cats can also be infected with Q fever. This makes them a source of infection for both animals and humans.

In small ruminants, late abortions are the most frequent clinical signs, occurring in isolated or massive cases in up to 90% of pregnant animals. Pneumonia, keratoconjunctivitis and stillborn or weak young have also been reported. In cattle, it is not mainly abortion that is observed, but disorders such as infertility, metritis, retained placenta and the birth of weak calves. Infection with C. burnetii has also been detected in many other animal species, with clinical manifestations varying from species to species.

How is it transmitted?

The bacterium survives in the environment in a resistant form. It can be carried over long distances, especially in dry weather and in areas exposed to the wind. Contamination occurs mainly by the respiratory route, through inhalation of particles contaminated by the farrowing products, faeces and urine of infected animals. People exposed to high-risk professional activities, such as working in the presence of infected animals or their contaminated environment, are particularly vulnerable. This includes breeders, vets, zoo keepers and slaughterhouse workers.

Sheep and goats are the main carriers of the bacteria responsible for Q fever. Cattle can also transmit the infection, although less frequently.

Q fever can be transmitted by direct contact with infected animals or their products, as well as by inhalation of airborne or wind-borne bacteria and dust. Other modes of contamination, such as consumption of raw milk from infected animals or transmission by ticks, are considered to be less effective.

Infected animals, even without apparent symptoms, can excrete bacteria in vaginal secretions, placenta, milk and faeces. The main route of infection for humans is respiratory. Bacteria can be inhaled once they have become airborne.

The distinctive feature of Coxiella burnetii is its ability to develop forms of resistance that enable it to survive in the environment for several weeks or months. These resistant forms, similar to spores, can be dispersed by various factors that encourage their airborne spread. The risk of infection following ingestion of contaminated food is still under discussion. However, current knowledge indicates that it can lead to an immune response without any clinical manifestation.

What are the symptoms of Q fever in humans?

Q fever generally presents a flu-like clinical picture, with a sudden onset characterised by fever, malaise, intense headache, myalgia (muscle pain), loss of appetite, dry cough, chest pain, chills, confusion and gastrointestinal symptoms such as nausea, vomiting and diarrhoea. Fever generally persists for 7 to 14 days. The disease may progress to atypical pneumonia. This is life-threatening due to acute respiratory distress syndrome (ARDS), usually within the first 4-5 days.

More rarely, it can cause granulomatous hepatitis, characterised by fever, hepatomegaly, abdominal pain and possibly jaundice. The chronic form can lead to infective endocarditis in people with pre-existing heart valve disease. The risk of mortality is estimated at 10% without appropriate treatment.

Acute Q fever

Theincubation period for Q fever lasts an average of 18 to 21 days (but can vary from 9 to 28 days), and often precedes an acute phase marked by a variety of symptoms. Some patients may be asymptomatic, while others present with a sudden onset of flu-like symptoms. This phase is characterised by a high fever of up to 40°C, sweating, intense headaches, chills, profound malaise, muscle pain and loss of appetite. Respiratory symptoms, such as dry cough and chest pain, generally appear 4 to 5 days after the onset of the disease. They can be severe in frail or elderly individuals. Sometimes, acute Q fever can be complicated by encephalitis or meningoencephalitis.

Acute liver damage, similar to viral hepatitis, manifests itself in some patients as fever associated with general malaise, hepatomegaly, pain in the right hypochondrium and, possibly, jaundice. Post-Q fever fatigue syndrome, observed in up to 20% of patients, is characterised by severe fatigue, muscle pain, headaches, photophobia and sleep disturbances. It generally occurs 9 to 28 days after exposure to the pathogen.

In children, Q fever is often characterised by a shorter duration of fever (7 to 10 days), a higher prevalence of digestive symptoms (up to 80%), the presence of a rash in half the cases, and less pronounced respiratory symptoms than in adults. These varied manifestations underline the complexity of the clinical spectrum of Q fever. This is why it requires special attention to ensure appropriate identification and management of the disease.

Chronic Q fever

Chronic Q fever is a serious complication that occurs in approximately 1-5% of individuals who have had acute Q fever. It can occur several years after the initial infection. It is mainly characterised by endocarditis, affecting the heart valves. This form of the disease leads to significant mortality if diagnosed late. Symptoms of the chronic form may include intermittent fever, persistent fatigue and shortness of breath. Any unexplained case of endocarditis should raise the suspicion of chronic Q fever. It requires immediate therapeutic intervention to avoid serious complications. People with a history of heart valve disease, arterial aneurysms or vascular transplants are particularly at risk of developing a chronic form of the disease. Pregnancy and immunosuppression are also risk factors.

Endocarditis associated with Q fever generally manifests itself as subacute, culture-negative bacterial endocarditis. It mainly affects the aortic valve but can also affect other heart valves. Symptoms may include digital hippocratic features, arterial emboli, hepatomegaly, splenomegaly and purpuric exanthema. Only 20-40% of patients show symptoms of acute infection when this complication develops.

The mortality rate of untreated acute Q fever is low, at around 1%. In contrast, chronic endocarditis associated with Q fever is often fatal if left untreated. However, appropriate antibiotic management can reduce mortality to less than 5%. Some people with neurological damage may suffer sequelae after treatment. Chronic Q fever therefore remains a serious condition requiring close monitoring and appropriate treatment to avoid serious complications.

How is this disease diagnosed?

The diagnosis of Q fever is based on a series of specific clinical, biological, radiological and histological signs. Clinically, the disease generally manifests itself as an infectious syndrome. This is characterised by high fever, myalgias, asthenia and respiratory signs such as a dry cough and chest pain. Changes in general condition and liver damage may also be observed.

Biologically, patients often present with a marked inflammatory syndrome and hepatic cytolysis . This is reflected in elevated ALAT and ASAT transaminases. However, to diagnose Q feverhepatitis with certainty, a liver biopsy is required. Serology, based on the detection of antibodies to Coxiella burnetii, is a commonly used diagnostic method for identifyinginfection . In particular, it is used to differentiate between acute and chronic infections.

Radiological signs often include atypical pneumonitis.Echocardiography can reveal endocarditis in patients with heart valve disease. Liver biopsies often reveal granulomas characteristic of Q fever.

Although blood cultures and sputum cultures are often negative, PCR can be used to identifybacterial DNA in biopsy and blood samples. However, a negative PCR result does not rule out the diagnosis. Chest X-rays may reveal abnormalities such as atelectasis, pleural opacities and pleural effusions, which are often seen in Q fever-associated pneumonitis.

What treatment should be given?

The mainstay of treatment for Q fever isantibiotic therapy, adapted according to the clinical form of the disease and any risk factors for complications. The HCSP guidelines provide recommendations for the management of complex cases. During the acute phase, an infectious diseases specialist should supervise the essential administration of antibiotics. Cyclines, notably doxycycline and tetracycline, are generally used, along with other antibiotics such as chloramphenicol, ciprofloxacin and ofloxacin in combination with hydroxychloroquine.

Treatment of the chronic form may be more complex and require a prolonged course of up to four years, with doxycycline combined with quinolones or hydroxychloroquine. However, during pregnancy, the use of doxycycline and ciprofloxacin is contraindicated. In this case, cotrimoxazole is recommended for five weeks.

Treatment of acute Q fever generally involves the administration of doxycycline until the patient shows significant clinical improvement, has been apyretic for approximately five days and has received treatment for at least 14 days. A longer duration may be necessary in cases of severe disease.

Treatment of Q feverendocarditis requires a prolonged course, typically at least 18 months, with a combination of doxycycline and hydroxychloroquine. The adverse cardiac effects of hydroxychloroquine require regular monitoring of theQTc interval by repeated ECGs. The medical profession bases its decision to discontinue treatment on the assessment of clinical signs, blood test results and antibody titres.

In the case ofchronic granulomatous hepatitis, the optimal treatment protocol remains undetermined. Prolonged administration of doxycycline is generally recommended for up to two to three weeks after fever subsides.

Finally, although antibiotic treatment may be partially effective, surgery is often required to replace the affected heart valves, particularly in cases of Q feverendocarditis.

How can contamination be prevented?

Vaccines have proved effective, particularly in Australia where a Q fever vaccine is commercially available. Vaccination is recommended for individuals exposed to occupational risks. These include slaughterhouse workers, dairy industry workers, farmers, livestock breeders and wool handlers. Before administering the vaccine, skin and blood tests are carried out to detect pre-existing immunity. Vaccinating individuals who are already immune can lead to serious local reactions.

Preventive measures against Q fever mainly include proper sanitary practices and testing for the bacterium in establishments where sheep, cattle and goats are kept. Exclusive consumption of pasteurised milk and milk products is also recommended to reduce the risk of infection.

Action with regard to animals

Actions at reservoir level aim to control the spread of Q fever in livestock and reduce the risk of transmission to humans. This includes regular monitoring of herd health, with systematic reporting and diagnostic investigation of abortions. Vaccination of the herd is recommended to limit the risks of abortion, environmental contamination and transmission between animals and humans.

Actions on transmission include measures such as :

• isolating animals during calving,
• limiting access to essential professionals,
• and banning public visits during calving periods
• or the isolation of females giving birth in specific areas.

Farmers must treat farrowing waste carefully while awaiting veterinary intervention. They must manage livestock effluents correctly to prevent the spread of the bacteria. Regular cleaning and disinfection of contaminated facilities and equipment is alsorecommended.

Non-medical prevention of Q fever includes measures such as the isolation of aborted animals, the collection and destruction of farrowing products, and the reduction of aerosol formation when handling livestock effluents.

The experts also recommend the rational use of antibiotics. However, their effectiveness in preventing and treating Q fever remains open to debate. On some farms, tetracyclines are often used at specific times. However, their ability to completely eliminate C. burnetii or prevent clinical signs over the long term remains contested.

Finally, the authorities have authorised a phase 1 vaccine based on C. burnetii on the European market. This offers another preventive measure against Q fever. This vaccine, similar to that used in human medicine, is recommended for all animals over three months of age on farms, with the exception of pregnant animals.

Individual prevention

Personal protective equipment is essential to reduce the risk of transmission of Q fever when handling animal tissues. This includes:

• wearing protective clothing
• boots
• disposable gloves and sleeves, especially when handling abortion products.

Where there is a suspected risk, a well-fitting FFP2 respirator is recommended, especially for aerosol-generating activities.

Hygiene instructions are also crucial in preventing the spread of the disease. It is important not to drink, eat or smoke in the workplace, or eat with work clothes. Hands must be washed with soap and drinking water after any contact with animals, waste or faeces, before meals, during breaks and at the end of the working day, as well as after removing gloves. Training and informing workers about the risks and prevention of Q fever is essential.

Intradermal vaccination with a vaccine composed of killed Coxiella burnetii organisms is an effective means of preventing Q fever. Before vaccination, a skin test and blood analysis should be carried out to check for any pre-existing immunity. Vaccinating immunised subjects can cause severe local reactions.

Under the Animal Health Act, Q fever is categorised as Class E, which makes it subject to compulsory surveillance and reporting. It is not notifiable for human health. Q fever is also recognised as a compensable occupational disease. It is covered by Table 53 of the general scheme and Table 49 of the agricultural scheme. The Coxiella burnetii pathogen is classified in group 3 under the Labour Code.

Some epidemiological data…