Coxiella burnetii - Q fever
Q fever is a disease caused by bacteria. It is a zoonosis. This means that infection in humans usually occurs by the passage of the bacteria from animals to humans. The transmission is done by inhalation of dust or droplets, by ingestion of soiled food or more rarely by tick bite. Symptoms of the acute phase are usually prolonged fever and signs of hepatitis. Some people may develop chronic disease. Endocarditis is one of the most common forms of chronic Q fever. The infection can be treated with antibiotics. Treatment is very long, several months, for the chronic form.
Q fever is a disease caused by an intracellular bacterium called Coxiella burnetii. The natural reservoir of this bacterium is domestic animals, pets, some wild animals, and more rarely ticks. It should be noted that the main ticks associated with the transmission of Coxiella appear to be Rhipicephalus evertsi and Amblyomma variegatum.
In Switzerland, Q fever has been notifiable only since November 2012, following an epidemic in the Lavaux region linked to the presence of infected sheep flocks that resulted in about 10 human cases. The introduction of this mandatory notification was made despite the small epidemic in humans because the epidemic potential of C. burnetti is high, as demonstrated by the epidemics in Bagnes in 1982 and the Netherlands in 2009, where more than 1000 human cases were documented. Today in Switzerland, between 40 and 60 cases are reported each year. In addition to sporadic cases, epidemics also occur occasionally, but they are usually limited by active prevention measures.
Acute phase or phase II
Les symptômes de la phase aiguë sont généralement:
- une fièvre prolongée (> 10 jours) avec un nombre normal de globules blancs
- une thrombocytopénie
- des enzymes hépatiques élevées.
Les sujets présentant des facteurs prédisposants, comme une valvulopathie, peuvent développer une maladie chronique.
Chronic phase or phase I
The most common forms of chronic Q fever are
- infections of aneurysms or vascular prostheses
and are usually fatal if left untreated.
Underdiagnosis can occur in individuals with initially pauci-symptomatic endocarditis that may later become superinfected with S. aureus or other Gram-positive cocci. In this case Coxiella should be systematically sought. Chronic Coxiella hepatitis is also common.
While Q fever is rarely reported in children, the chronic picture is very different from that in adults, with osteomyelitis being the most common.
Acute Q fever is usually treated with 2 weeks of doxycycline while chronic Q fever requires a prolonged treatment of at least 1 year with a dual therapy combining for example doxycycline and hydroxychloroquine. Note that in this duo, only doxycycline has a real antibacterial effect, hydroxychloroquine being added only to increase the pH of the vacuole containing Coxiella (a phagolysosome). This increases the efficacy of doxycyline which is not very active at acidic pH. These drugs must be dosed regularly to ensure that therapeutic doses are below the toxicity threshold; the indication for this prolonged treatment should be the subject of a specialized consultation with an infectious disease specialist.
Diagnosis is based on PCR or serology.
PCR can be performed on whole blood or serum in the acute phase, and allows the diagnosis of acute Q fever within the first 2 weeks of infection. PCR can also be performed on infected tissues (heart valve samples, liver biopsies, bone biopsies, …).
Serology can be performed using a highly sensitive screening test followed by an immunofluorescence test for confirmation which also allows serum titration.
A fourfold increase in phase II IgG antibody titer by immunofluorescence between paired acute and convalescent specimens is the gold standard for confirming the diagnosis of acute Q fever. However, negative serology in the acute phase does not exclude Q fever. Indeed, immunofluorescence is negative during the early stages of acute disease, while PCR is usually still positive. Most patients seroconvert before the third week of illness. A single high “convalescent” serum collected after the acute phase of the disease is sufficient for diagnosis (positive if >1/256); however, a quadruplicate between acute and convalescent specimens has much higher sensitivity (can be considered positive with titers >1/64) and specificity than a single high convalescent titer.
Diagnosis of chronic Q fever requires demonstration of a high phase I IgG antibody titer (≥ 1:800) greater than the phase II IgG titer and an identifiable focal infection (e.g., endocarditis, hepatitis, or spondylodiskitis).
PCR, immunohistochemistry, or culture of affected tissue can provide definitive confirmation of C. burnetii infection. However, these approaches have low sensitivity and are somewhat difficult to implement because specimens are not routinely available. Thus, the diagnosis of Q fever relies heavily on serologic monitoring of the patient. It should be noted that immunofluorescence requires considerable expertise. Specific and relatively sensitive PCR is also a challenge and few laboratories offer it.
All the methods mentioned for detection by molecular biology and serology are available at the CNRT.
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