Laboratory Diagnosis, Treatment and Prevention of Coxiella burnetii

Coxiella burnetii is a bacterium that causes Q fever, a zoonotic disease that can affect humans and animals. Q fever can manifest as a mild or severe flu-like illness, pneumonia, hepatitis, or chronic infections such as endocarditis and osteomyelitis.

C. burnetii is an obligate intracellular pathogen, meaning that it can only survive and multiply within host cells. It has a unique biphasic developmental cycle that involves two forms: a small cell variant (SCV) and a large cell variant (LCV). The SCV is the infectious form that is resistant to environmental stresses and can persist in soil, dust, water, and animal products for long periods. The LCV is the replicative form that grows within a specialized vacuole inside the host cell.

C. burnetii is also characterized by phase variation, which is a change in the expression of surface antigens. There are two phases: phase I and phase II. Phase I bacteria have a full set of antigens and are highly virulent. Phase II bacteria have lost some antigens and are less virulent. Phase variation occurs when bacteria are exposed to host immune responses or subcultured in vitro.

C. burnetii can infect a wide range of animals, such as cattle, sheep, goats, dogs, cats, rodents, birds, and ticks. The main reservoirs of infection are domestic ruminants, which can shed large amounts of bacteria in their milk, urine, feces, and placenta during parturition.

Humans can acquire Q fever by inhaling aerosols or dust contaminated with animal secretions or tissues, by consuming raw or unpasteurized dairy products, by direct contact with infected animals or their products, or by tick bites. The incubation period ranges from 2 to 40 days, depending on the dose and route of exposure.

Q fever is a global public health problem that affects both rural and urban areas. It is endemic in many countries and regions, such as Australia, Europe, Africa, Asia, and North America. It can cause outbreaks in occupational settings (e.g., farms, slaughterhouses, veterinary clinics) or in communities (e.g., due to windborne dispersion of contaminated dust). It can also pose a bioterrorism threat due to its high infectivity and stability in the environment.

The diagnosis of Q fever, the disease caused by Coxiella burnetii, can be challenging because the symptoms are often nonspecific and vary from person to person. Moreover, the organism is highly infectious and requires biosafety level 3 facilities for culture and handling. Therefore, laboratory diagnosis relies mainly on serological and molecular methods .

Specimen

The choice of specimen depends on the stage and type of infection. For acute Q fever, serum samples are usually collected for serology and PCR. For chronic Q fever, especially endocarditis, serum samples are also used for serology, but tissue samples (e.g., cardiac valve) or blood cultures are preferred for PCR and culture . Other specimens, such as sputum, urine, cerebrospinal fluid, or placenta, may also be tested depending on the clinical presentation.

Culture

Culture is rarely performed for the diagnosis of Q fever because it is technically demanding, time-consuming, and hazardous. C. burnetii is an obligate intracellular bacterium that can be grown in cell cultures (e.g., human embryonic lung fibroblast cell lines) or in a cell-free medium . However, culture is only available in specialized research laboratories that are licensed to work with these highly contagious organisms .

Serology

Serology is the most commonly used diagnostic test for Q fever. It measures the antibody response of the host to the antigens of C. burnetii. The organism has two antigenic phases: phase I and phase II. Phase I antigens are expressed by virulent strains that cause chronic infection, while phase II antigens are expressed by avirulent strains that cause acute infection .

A variety of methods are used to measure antibody production, such as microagglutination tests, indirect immunofluorescence antibody (IFA) tests, enzyme-linked immunosorbent assays (ELISA), and complement fixation tests . IFA is the test of choice, although ELISA is used in many laboratories and appears to be as sensitive .

In acute Q fever, immunoglobulins IgM and IgG antibodies are developed primarily against phase II antigens. A fourfold increase in phase II IgG concentration between acute and convalescent sera is considered diagnostic for acute Q fever . In chronic Q fever, antibodies against both phase I and II antigens are detected, with the titers to phase I antigen typically higher. A phase I IgG titer of ≥1:800 is suggestive of chronic Q fever .

Molecular Methods

Molecular methods, such as polymerase chain reaction (PCR), have been used to detect C. burnetii DNA in clinical samples from acute and chronic Q fever patients. PCR is more sensitive and specific than culture and can provide rapid results . PCR can also be used to differentiate strains of C. burnetii based on their plasmid types. QpH1 plasmids are found in acute Q fever isolates, whereas QpRS plasmids are found in strains isolated from endocarditis patients. PCR can also be combined with sequencing or hybridization techniques to identify genotypes or variants of C. burnetii.

Most infections caused by Coxiella burnetii resolve without antibiotic treatment, but administration of antibiotics can reduce the duration of fever and other symptoms in acute cases, and prevent complications and relapse in chronic cases . The choice and duration of antibiotic therapy depend on the clinical presentation, the stage of infection, and the patient`s characteristics.

The main antibiotic used for treating Coxiella burnetii infection is doxycycline, which can be given orally or intravenously. Doxycycline is effective against both phases of the bacterium and can penetrate intracellularly where the bacterium resides. For acute Q fever, doxycycline is usually given for 14 to 21 days, starting within 3 days of symptom onset . For chronic Q fever, doxycycline is usually given for at least 18 months, often in combination with another antibiotic .

The most common antibiotic used in combination with doxycycline for chronic Q fever is hydroxychloroquine, which has antimalarial and immunomodulatory properties. Hydroxychloroquine can increase the intracellular pH and impair the survival of Coxiella burnetii. Hydroxychloroquine also enhances the activity of doxycycline and reduces the risk of resistance. Hydroxychloroquine is usually given for 18 to 36 months, with regular monitoring of blood levels and ocular toxicity .

Other antibiotics that have been used as alternatives or adjuncts to doxycycline and hydroxychloroquine for Coxiella burnetii infection include fluoroquinolones (e.g., ciprofloxacin, ofloxacin, pefloxacin), macrolides (e.g., azithromycin, clarithromycin), rifampin, and trimethoprim-sulfamethoxazole. These antibiotics may have different advantages and disadvantages depending on the patient`s age, pregnancy status, comorbidities, drug interactions, and side effects .

In some cases of chronic Q fever, especially those involving endocarditis or vascular infection, antibiotic therapy alone may not be sufficient to eradicate the infection. In these cases, surgical intervention may be required to remove or replace the infected tissue or prosthetic material. Surgery should be performed in conjunction with antibiotic therapy and under the guidance of a multidisciplinary team .

In addition to antibiotic therapy and surgery, supportive care and symptomatic relief may be needed for patients with Coxiella burnetii infection. This may include antipyretics, analgesics, anti-inflammatory drugs, oxygen therapy, fluid replacement, and nutritional support .

Coxiella burnetii is a bacterium that causes Q fever, a zoonotic disease that can affect humans and animals. The infection can be acute or chronic, and can involve various organs and systems. Laboratory diagnosis of Q fever relies mainly on serology, but culture and molecular methods can also be used in some cases. Treatment of Q fever depends on the severity and duration of the infection, and usually involves antibiotics such as doxycycline, ciprofloxacin, or rifampicin. Chronic Q fever may require long-term combination therapy and sometimes cardiac surgery.

Prevention of Q fever is challenging, as the bacterium is highly resistant and can survive in the environment for long periods. There is no vaccine available for Q fever in the US, although one exists in Australia. The best way to prevent Q fever is to avoid contact with animals that may be infected, especially during their birthing process. This is particularly important for people who work in occupations that expose them to livestock, such as farmers, veterinarians, or meat processors. Other preventive measures include using only pasteurized milk and dairy products, disposing of animal waste properly, quarantining imported animals, and monitoring the seroprevalence of C. burnetii in cattle. People who have been diagnosed with Q fever should also consult their healthcare provider about their risk of developing chronic Q fever, especially if they have a history of heart valve disease, blood vessel abnormalities, a weakened immune system, or are pregnant.

Q fever is a serious and potentially life-threatening disease that requires prompt diagnosis and treatment. By following the recommendations for prevention and control of C. burnetii infection, we can reduce the risk of transmission and complications of Q fever in humans and animals.

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