Coxiella burnetii

Coxiella burnetii is an intra-cellular bacteria that causes Q fever

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Coxiella burnetii

• Cattle, sheep, and goats are the primary reservoirs, although a variety of species may be infected.

• Organisms are excreted in milk, urine, and feces of infected animals with the highest numbers shed during birthing in the amniotic fluids and the placenta.

• The organism is extremely hardy and resistant to heat, drying, and many common disinfectants, which enable the bacteria to survive for long periods in the environment.

• Exposure usually occurs by inhalation of these organisms from air that is contaminated by excreta of infected animals.

• Other modes of transmission, including tick bites, ingestion of unpasteurized milk or dairy products, and person-to-person transmission, are rare.

• People are very susceptible to the disease, and very few organisms may be required to cause infection.

Epidemiology

A dry fracture of a Vero cell showing Coxiella burnetii

• Q fever was first recognized as a human disease in Australia in 1935 and in the United States in the early 1940s.

• The “Q” stands for “query” and was applied at a time when the cause was unknown.

• Q fever is caused by infection with the bacteria Coxiella burnetii.

• Cattle, sheep, and goats are commonly infected and people often become exposed by breathing in dust contaminated with infected animal body fluids.

• People in direct contact with animals during birthing, such as veterinarians and farmers, may be at higher risk for infection.

• C.burnetii can survive for long periods of time in the environment and may be carried long distances by wind.

Q Fever in the United States

• Q fever was made a nationally notifiable disease in the United States in 1999.

• CDC compiles the number of cases reported by state and local health departments and reports national trends.

• The number of Q fever cases reported to CDC increased, from 19 cases reported in 2000, to 173 cases reported in 2007.

• In 2008, the Q fever case definition was changed to allow for the reporting of chronic and acute Q fever separately.

• During 2008–2013 the number of reported cases decreased slightly, relative to 2007, returning to high levels in 2014.

• In 2017, 153 acute Q fever cases were reported, as well as 40 chronic Q fever cases.

Transmission

Immunohistochemical detection of Coxiella burnetii

• People get infected by breathing in dust that has been contaminated by infected animal feces, urine, milk, and birth products that contain Coxiella burnetii.

• Direct contact (e.g.

• touching, being licked) with an animal is not required to become sick with Q fever.

• People may also get sick with Q fever by eating contaminated, unpasteurized dairy products.

• Rarely, Q fever has been spread through blood transfusion, from a pregnant woman to her fetus, or through sex.

Risk factors

• Certain professions are at increased risk for exposure to C.

• burnetii, including veterinarians, meat processing plant workers, dairy workers, livestock farmers, and researchers at facilities housing sheep and goats.

• People working in these areas may need to take extra precautions

Signs and symptoms

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Freeze-Fractured Specimens

• Q fever can cause acute or chronic illness, and people are commonly exposed from contact with infected animals or exposure to contaminated environments.

• The acute symptoms usually develop within 2-3 weeks of exposure, although as many as half of infected people are asymptomatic.

• The following is a list of symptoms commonly seen with acute Q fever.

• However, it is important to note that the combination of signs and symptoms vary greatly from person to person.

• High fever (up to 105°F)

• Fatigue

• Severe headache

• General malaise

• Myalgia

• Chills or sweats

• Non-productive cough

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Chest pain

• Most people with acute Q fever infection recover completely; however, some may experience serious illness with pneumonia, granulomatous hepatitis, myocarditis, or central nervous system complications.

• Pregnant women who are infected (even without clinical illness) may be at risk for miscarriage, stillbirth, pre-term delivery, or low infant birth weight.

Clinical course

• Treatment with doxycycline will shorten the course of illness for acute Q fever.

• Although the majority of people with acute Q fever recover completely, a post-Q fever fatigue syndrome has been reported to occur in up to 20% of patients with acute Q fever.

• This syndrome is characterized by constant or recurring fatigue, night sweats, severe headaches, photophobia, pain in muscles and joints, mood changes, and difficulty sleeping.

• No consensus has been reached in the medical community on the pathogenesis or treatment of post Q fever fatigue syndrome.

• Chronic Q fever occurs in <5% of acutely infected patients.

• It may present within weeks after an acute infection or may manifest many years later.

• Anyone who was infected with C. burnetii may be at risk for developing chronic Q fever, however, people with a history of valvular defects, arterial aneurisms, or vascular grafts are at increased risk.

• Women infected by C. burnetii during pregnancy and those with immunosuppression have also been linked to the development of chronic Q fever.

• Endocarditis is the most commonly identified manifestation of chronic Q fever and is fatal if untreated.

• Patients with endocarditis require early diagnosis and long-term antibiotic treatment (at least 18 months) for a successful outcome.

• Other forms of chronic Q fever include infections of vascular aneurysms, bone, liver, or reproductive organs.

Diagnosis

• Several aspects of Q fever make it challenging for healthcare providers to diagnose and treat.

• The symptoms vary from patient to patient and can be difficult to distinguish from other diseases.

• Diagnostic tests based on the detection of antibodies will frequently appear negative in the first 7-15 days of illness.

• For this reason, healthcare providers must treat patients based on clinical suspicion alone and not wait for the return of confirmatory tests.

• Detection of burnetii DNA by polymerase chain reaction (PCR) can rapidly confirm an acute Q fever infection.

• Samples are ideally taken during the first 2 weeks of illness and before or shortly following doxycycline administration.

• For definitive diagnosis in the early stages of illness it is recommended to use serologic tests in combination with PCR of whole blood or serum.

• Treatment should be initiated as soon as Q fever is suspected and should never be withheld pending the receipt of diagnostic test results.

Patient history

• Information such as recent travel to rural or agricultural communities where infected livestock may be present, or employment in high-risk occupations, such as veterinarians or farmers, can be helpful in making the diagnosis.

• Chronic Q fever is a risk for anyone with a history of acute Q fever, but are more frequent in persons with valvular disease, blood vessel abnormalities, immunosuppressed persons, and women who were pregnant when they became infected.

• Persons with these risk factors should be routinely monitored using serologic methods for the 2 years following diagnosis of acute Q fever to ensure rapid diagnosis and treatment of chronic Q fever.

Other clinical evidence

• Healthcare providers should also look at routine blood tests, such as a complete blood cell count or a chemistry panel.

• Clues such as a prolonged fever with low platelet count, normal leukocyte count, and elevated liver enzymes are suggestive of acute Q fever infection, but may not be present in all patients.

• After a suspect diagnosis is made based on clinical suspicion and treatment has begun, specialized laboratory testing should be used to confirm the diagnosis of Q fever.

Laboratory Confirmation

• The reference standard test for the serologic diagnosis of acute Q fever is the indirect immunofluorescence antibody (IFA) using C. burnetii antigen, performed on paired serum samples to demonstrate a significant (fourfold or more) rise in antibody titers.

• The first sample should be taken as early in the disease as possible, preferably in the first week of symptoms, and the second sample should be taken 3 to 6 weeks later.

• In most cases of Q fever, the first IgG IFA titer is typically low, or “negative,” and the second typically shows a fourfold or greater increase in IgG antibody levels.

• A negative test during the first week of illness does not rule out Q fever as a cause of illness.

• There are two distinct antigenic phases (phase I and phase II) to which humans develop antibody responses.

• In acute infection, an antibody response to C. burnetii phase II antigen is predominant and is higher than antibody levels to phase I antigen; the reverse is true in chronic infection which is associated with a rising phase I IgG titer that may be higher than phase II IgG.

• IgM antibodies usually rise at the same time as IgG, near the end of the first week of illness, and remain elevated for months or longer and therefore provide limited diagnostic value on their own.

• Furthermore, IgM antibodies are less specific than IgG antibodies and more likely to result in a false positive.

• For these reasons, physicians requesting IgM serologic titers should also request concurrent IgG titers.

Persistent antibodies

• Antibodies to C. burnetii may remain elevated for months or longer after the disease has resolved.

• Approximately 3% of healthy people in the U.S.

• adult population and up to 20% of people in high-risk professions (e.g., veterinarians, ranchers, etc.) have elevated antibody titers from past infection with C. burnetii.

• Therefore, if only one sample is tested it can be difficult to interpret the findings.

• Paired samples taken 3 to 6 weeks apart demonstrating fourfold or greater rise in antibody titer provides the best evidence for a correct diagnosis of acute Q fever.

PCR

• During the acute phase of illness, a sample of whole blood (or serum at some laboratories) can be tested by polymerase chain reaction (PCR) assay to determine if a patient has Q fever.

• This method is most sensitive in the first week of illness (before the appearance of C. burnetii-specific antibodies), and rapidly decreases in sensitivity following the administration of doxycycline.

• Although a positive PCR result is helpful, a negative result does not rule out the diagnosis, and treatment should not be withheld due to a negative result.

Culture

• Culture isolation of C. burnetii is not recommended for routine diagnosis because it is difficult, time consuming and is only available at specialized laboratories; routine hospital blood cultures cannot detect the organism.

Diagnosis of chronic Q fever

• Chronic Q fever is confirmed by elevated phase I IgG antibody ≥1:1024 (and is typically higher than phase II IgG) and an identifiable persistent focus of infection (e.g., endocarditis).

• Whole blood, serum or tissue biopsies may be tested by PCR for C. burnetii.

• PCR of whole blood has low sensitivity in patients with chronic Q fever endocarditis, so serum antibody titers should also be tested.

• PCR or immunohistochemistry of biopsy specimens from the site of active infection has also been used to diagnose chronic Q fever.

• These tests may be appropriate for endocarditis patients undergoing valve replacement surgery or patients with hepatitis.

• For more in-depth information about the diagnosis of Q fever, please see the diagnostic section in the MMWR Diagnosis and Management of Q fever—United States, 2013.

• For information on submitting a sample to CDC for testing, please see Information for Public Health Officials.

Treatment

• Doxycycline is the recommended first-line treatment for non-pregnant adults with Q fever and is most effective at preventing severe complications if it is started within the first 3 days of symptoms.

• Treatment must be based on clinical suspicion and should always begin before laboratory results return.

• If the patient is treated within the first 3 days of the disease, fever generally subsides within 72 hours.

• Severely ill patients may require longer periods before their fever resolves.

• Treatment is generally not recommended for patients who are asymptomatic or who have already recovered from their illness, but might be considered for those at high risk of developing chronic Q fever.

• There is no role for prophylactic antimicrobial agents in preventing Q fever after a known, naturally occurring exposure and prior to symptom onset; attempts at prophylaxis will likely extend the incubation period by several days but will not prevent infection from occurring.

Recommended Treatment and Dosage for Acute Q Fever

• Adults: Doxycycline, 100 mg every 12 hours for 14 days

• Pregnant women: trimethoprim/sulfamethoxazole, 160 mg/800 mg given twice a day throughout pregnancy, but not beyond 32 weeks gestation

• Children 8 years or older: doxycycline, 2.2 mg/kg body weight (up to 100mg) given twice a day for 14 days

• Children under 8 years with high risk criteria (i.e., those that are hospitalized, have severe illness, preexisting heart valvulopathy, immunocompromised, or delayed treatment for Q fever > 2 weeks): doxycycline, 2.2 mg/kg body weight (up to 100 mg) given twice a day for 14 days

• Children under 8 years with mild or uncomplicated illness: doxycycline, 2.2 mg/kg body weight (up to 100 mg) given twice a day for 5 days.

• If patient remains febrile past 5 days of treatment, treat with trimethoprim/sulfamethoxazole 4-20 mg/kg/24 hours (dose based on trimethoprim component) in equally divided doses every 12 hours (maximum: 320 mg trimethoprim per 24 hours).

Recommended Treatment and Dosage for Chronic Q Fever

• Duration of treatment for chronic Q fever is based on serologic response and evidence of clinical improvement.

• Serologic monitoring of a patient with chronic Q fever should be done in consultation with an infectious disease specialist.

• Adults with endocarditis or vascular infection: doxycycline, 100 mg every 12 hours and hydroxychloroquine, 200 mg every 8 hours, for at least 18 months.

• Adults with non-cardiac organ disease: doxycycline, 100 mg every 12 hours and hydroxychloroquine, 200 mg every 8 hours.

• Postpartum women with titers elevated >12 months after delivery: doxycycline, 100 mg every 12 hours and hydroxychloroquine, 200 mg every 8 hours for 12 months.

Pregnant women

No current recommendations but consultation with an infectious disease and obstetric specialist is encouraged.

Children

No current recommendations but consultation with a pediatric infectious disease specialist is encouraged.

Doxycycline and Children

• Short course therapy (e.g., <5 days) with doxycycline does not cause staining of permanent teeth, and most experts consider the benefit of doxycycline in treating Q fever greater than the potential risk of dental staining.

• Children with mild illness who are less than 8 years of age may be treated with a shorter dose (5 days) of doxycycline to minimize their exposure to the medication.

• Children with preexisting cardiac valve disease, or who are immunocompromised, or have delayed Q fever diagnosis and have experienced illness for 2 weeks without resolution of symptoms are considered to be at high risk for developing severe disease and should be treated with doxycycline for 2 weeks.

Other Treatments

• People with life-threatening allergies to doxycycline may need to consider alternate antibiotics such as moxifloxacin, clarithromycin, trimethoprim/sulfamethoxazole and rifampin.

Prevention

• Q fever vaccines are not available in the United States.

• Reduce your risk of getting Q fever by avoiding contact with animals, especially while animals are giving birth.

• Animals can be infected with Coxiella burnetii and appear healthy.

• Do not consume raw milk or raw milk products.

• If you have been diagnosed with Q fever and have a history of heart valve disease, blood vessel abnormalities, a weakened immune system, or are pregnant, talk to your healthcare provider about your risk for developing chronic Q fever.