AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

First described in 1935 by Derrick, Q fever is an acute infectious disease. Derrick investigated a cluster of febrile illnesses of unknown etiology in Australian abattoir workers and subsequently named the malady Q (for query) fever. Most commonly spread by means of inhalation or ingestion, Q fever can also be tick-borne. Q fever usually presents as an undifferentiated febrile illness with predominant respiratory or hepatic manifestations.

Pathophysiology

The causative organism is Coxiella burnetii. Classically grouped with the rickettsial organisms, C burnetii differs from the other organisms in that group; in fact, its genetic makeup is more closely related to Legionella species than to the other Rickettsia species.

C burnetii is a small gram-negative organism that lives inside acidic lysosomes, a point that has therapeutic implications. The organism exists in 2 forms, phase I and phase II, which are analogous to the lipopolysaccharide rough and smooth phase of Enterobacteriaceae organisms. The phase I form is isolated from animals and is the infectious form. The organism is remarkably resistant to environmental extremes. A spore form also exists.

The reservoir in nature includes mammals, birds, and ticks; the last is an important vector in infecting mammals. A strong association between the disease and exposure to farm animals exists. Furthermore, because the organism is reactivated in pregnant animals, a strong association between the disease and contact with parturient animals (especially cows, sheep, goats, dogs, cats, rabbits) also exists. Aerosol from newborn animals and their placentas can spread Q fever. Other modes of transmission include aerosol from contaminated wool, hides, and dust; ingestion of raw milk or goat cheese; blood transfusions; and tick bites.

Even wind patterns may make a difference by spreading aerosolized organisms downwind. Outbreaks of Q fever have occurred in an industrial setting from straw board that had been drilled open during part of the construction process.

Recent studies in patients with chronic Q fever in which polymerase chain reaction (PCR) was used to detect C burnetii DNA revealed evidence that the organism persists in human liver, blood monocytes, and most commonly, bone marrow.

Frequency

United States

Q fever is present throughout the United States. The precise incidence is unknown. Although the actual frequency is likely low, the Centers for Disease Control and Prevention still regularly report cases that occur in the United States.

International

Q fever exists worldwide. A seroprevalence study of blood donors in Marseille, France, showed that 4% of donors had antibodies to C burnetii. Similar studies in other European countries have shown figures of 5-30%, with lower figures seen in urban areas and higher figures in rural zones.

Mortality/Morbidity

• Acute Q fever generally is self-limited. In fact, about one half of the cases in one study had asymptomatic seroconversion. Of symptomatic patients, only 4% required hospitalization.
• Chronic Q fever, which often presents as culture-negative endocarditis, is difficult to treat and can be fatal.
• Mortality is uncommon, even in hospitalized patients, and tends to occur in older patients.

Age

Patients of all ages can contract Q fever. The incidence, as determined by the age at which seroconversion of blood donors occurs, can be deceptive because children, elderly persons, and sick persons do not donate blood.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Q fever can manifest various signs; no one classic presentation exists. The major clue is the epidemiologic circumstance, exposure to parturient mammals or their newborn, and tick bites. The most common presentation of Q fever may vary with geography. For example, in the Basque region of northern Spain, pneumonia is a common finding, whereas in southern Spain, hepatitis predominates.

Finding with acute and chronic Q fever may include the following:

• Acute Q fever
• • Fever and systemic symptoms: Abrupt onset of high fever with or without a flulike illness is common. The incubation period ranges from 14-39 days but averages 20 days. Arthralgias can occur.
  • Respiratory symptoms: While some patients with respiratory involvement have a cough, shortness of breath, and chest pain, others with pneumonia have no respiratory symptoms. Respiratory involvement is discovered only when a chest radiograph is obtained during the evaluation of fever.
  • Skin symptoms: Q fever often is assumed not to be associated with a rash. However, one French study of acute Q fever revealed that roughly 20% of patients have a nonspecific exanthem, most commonly a maculopapular rash on the trunk.
  • Cardiovascular symptoms: Some patients with acute Q fever pericarditis report chest pain. Patients with myocarditis also may experience palpitations, chest pain, or dyspnea. Q fever myocarditis can be fatal.
  • GI symptoms: Hepatitis is a common manifestation and usually is associated with elevated hepatic transaminase levels, since Q fever rarely causes jaundice or acute GI symptoms.
  • Neurologic symptoms: Some patients have headache, confusion, and neck stiffness. The 3 major neurologic syndromes of Q fever are meningoencephalitis or encephalitis, meningitis, and myelitis and peripheral neuropathy.
• Chronic Q fever: Endocarditis with negative culture findings is, by far, the most common manifestation of chronic Q fever. It can occur months to years after the acute infection. Symptoms include fever, fatigue, dyspnea, and rash from septic thromboembolism.

Physical

Physical findings vary with the presenting clinical syndrome. No pathognomonic findings exist.

• During the acute phase, fever can be high or low grade.
• Tachypnea, rales, rhonchi, and wheezing can be present in patients with pneumonia.
• A pericardial rub can be observed in pericarditis. Patients with myocarditis can have tachycardia, an irregular pulse, and a gallop rhythm.
• Jaundice rarely is observed in patients with hepatitis.
• In endocarditis with chronic Q fever, cardiac murmurs, purpuric rash, and hepatomegaly can be present.

Causes

The cause of Q fever is infection with the bacteria C burnetii.

In this age of concern for terrorism with biological agents, Q fever is on the list of possible agents. It is highly infectious and spread by aerosol. Although the mortality rate is low, it could provoke considerable disability and disorganization. Initial diagnosis might be delayed by the fact that it is so uncommon in most locations.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Atypical pneumonia caused by viruses, Chlamydia species, or Mycoplasma should be considered in the differential diagnosis.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Findings of standard laboratory tests are not diagnostic.
• The WBC count usually is normal.
• The platelet count can be low initially, with a reactive thrombocytosis reported during convalescence.
• An elevated hepatic transaminase level is a common finding and is present in nearly 70% patients who require hospitalization.
• The organism is very infectious, and isolation ought to be done in Biosafety Level 3 laboratories. If a clinician thinks Q fever is a likely diagnosis, the laboratory should be notified so that they can take appropriate precautions.

Imaging Studies

• A chest radiograph is the only imaging study that is likely to be useful. An atypical pneumonia pattern may be observed, similar to the pattern seen with pneumonia caused by viruses and Mycoplasma, Chlamydia, and Legionella species.
• In the rare patient with prominent neurologic symptoms, CT scanning of the brain may be indicated.
• In cases of Q fever endocarditis, the cardiac echocardiogram demonstrates vegetations in only 12% of cases.
• Pericardial effusion may also be seen in Q fever.

Other Tests

• The diagnosis is based on a high index of suspicion suggested by the epidemiologic features and is proven by serologic testing.
• • Determination of antibodies to C burnetii can be achieved by means of complement fixation, indirect immunofluorescent antibody testing, and enzyme-linked immunosorbent assay. These tests are performed in reference laboratories, and indirect immunofluorescent antibody testing is the reference method of choice.
  • Culturing this organism can be accomplished, but this is dangerous because laboratory-transmitted cases are reported.
  • Polymerase chain reaction (PCR) can be used with tissue specimens, but these are not generally available commercially.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Emergency Department Care

As with any patient with a febrile illness, the physician must exclude other potentially life-threatening diseases, which, in the case of tick-borne disease, involves presumptive antibiotic therapy.

• While specific antimicrobial therapy is indicated, most patients improve spontaneously. However, when Q fever is diagnosed, the administration of antibiotics is appropriate to prevent progression to chronic disease, which is far more resistant to treatment.
• Supportive care with fluids and antipyretics may improve patient comfort.

Consultations

In select cases, the emergency physician may consult an infectious disease specialist.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Despite the fact that most untreated patients improve, specific antibiotic therapy is indicated to help the patient improve faster and to reduce the likelihood of progression to chronic disease. Patients with Q fever who are misdiagnosed with legionellosis have responded well to intravenous erythromycin, which probably is effective for pregnant patients, although no controlled trials have been performed. Some investigators use lysosomal alkalinizing agents (eg, hydroxychloroquine) for patients with chronic Q fever to increase the effectiveness of antibiotics. Treatment of chronic Q fever is beyond the scope of emergency medicine practice.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive, covering all likely pathogens in context of the clinical setting. Doxycycline is the drug of choice.

In one series of pregnant patients with Q fever, trimethoprim-sulfamethoxazole was used with some success.

In the chronic setting, the addition of chloroquine to doxycycline may improve outcomes, although data are sparse.

Drug Name	Tetracycline (Sumycin)
Description	Treats susceptible bacterial infections of both gram-positive and gram-negative organisms, as well as infections caused by Mycoplasma, Chlamydia, and Rickettsia organisms. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult Dose	250-500 mg PO q6h Mild-to-moderate infections: 500 mg PO bid or 250 mg PO qid for 7-14 d Severe infections: 500 mg PO qid for 7-14 d
Pediatric Dose	<8 years: Not recommended >8 years: 10-20 mg/lb/d (25-50 mg/kg) PO divided qid
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity (with prolonged exposure to sunlight or tanning equipment); reduce dose in renal impairment; consider determining drug serum levels in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can permanently discolor teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Chloramphenicol (Chloromycetin)
Description	Used in patients who do not tolerate tetracycline.
Adult Dose	50-100 mg/kg/d PO/IV divided q6h for 10 d; not to exceed 4 g/d
Pediatric Dose	50-75 mg/kg/d PO/IV divided q6h
Contraindications	Documented hypersensitivity
Interactions	Concurrently with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum levels, presumably because of hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; levels may be increased or decreased
Pregnancy	D - Unsafe in pregnancy
Precautions	Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; perform baseline and periodic blood studies approximately every 2 d during therapy; discontinue with reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)

Drug Name	Sulfamethoxazole and trimethoprim (Bactrim, Bactrim DS, Septra, Septra DS)
Description	Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. This would be a drug to use in pregnant women after consultation with the patient's obstetrician and an infectious disease specialist.
Adult Dose	320 mg TMP/1600 mg SMZ PO q12h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Interactions	May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Do not use during last trimester of pregnancy because of potential toxicity to newborn (eg, jaundice, hemolytic anemia, kernicterus) Dosage adjustments (adult adjustments) CrCl (mL/min) 80-50: Recommended IV dose q18h CrCl 50-10: Recommended IV dose q24h CrCl <10: Not recommended HD: 4-5 mg/kg after HD During peritoneal dialysis: 0.16-0.8 g q48h Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholics, elderly persons, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in G-6-PD deficient individuals; AIDS patients may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Drug Category: Antipyretics

Treatment of Q fever is symptomatic and supportive. Bed rest and mild analgesic-antipyretic therapy often are helpful in relieving the lethargy, malaise, and fever associated with the disease.

Drug Name	Ibuprofen (Motrin, Nuprin, Advil, Ibuprin)
Description	One of the few NSAIDs indicated for reduction of fever.
Adult Dose	200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d
Pediatric Dose	<6 months: Not established 6 months to 12 years: 30-70 mg/kg/d PO divided tid/qid; start with lower dose and titrate to maximum of 2.4 g/d >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
Interactions	Coadministration with aspirin increases risk of serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy

Drug Name	Acetaminophen (Aspirin Free Anacin, Tylenol, Feverall)
Description	DOC for treatment of pain in patients with documented hypersensitivity to aspirin, NSAIDs, or upper GI disease and in those taking oral anticoagulants. Inhibits action of endogenous pyrogens on heat-regulating centers.
Adult Dose	325-650 mg PO q4-6h or 1000 mg PO tid/qid; not to exceed 4 g/d Alternative: 1000 mg PO tid/qid; not to exceed 4 g/d
Pediatric Dose	<12 years: 10-15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d >12 years: 325-650 mg PO q4h; not to exceed 5 doses in 24 h
Contraindications	Documented hypersensitivity; known G-6-P deficiency
Interactions	Rifampin can reduce analgesic effects; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Hepatotoxicity possible in chronic alcoholism with various doses; severe or recurrent pain or high or continued fever may indicate serious illness; may contain acetaminophen, and combined use may cause cumulative acetaminophen doses to exceed recommended maximum doses

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Follow-up is important to ensure complete recovery.
• If the patient's epidemiologic risk factor suggests that other people may share that risk factor (eg, an abattoir worker's coworkers and family members in a case contracted from a pregnant pet), the physician should notify the appropriate public health authorities.

Deterrence/Prevention

• Avoid consuming unpasteurized milk and goat cheese.
• Take proper precautions while working on a farm, and avoid exposure to parturient mammals.
• See Tick-borne Diseases, Introduction for suggestions regarding the prevention of tick bites.

Complications

• Acute respiratory distress syndrome
• Thrombocytopenia
• Endocarditis caused by chronic infection

Prognosis

• The prognosis with acute Q fever is excellent, with a low mortality rate (about 1%) in hospitalized patients. Children usually are more mildly affected than adults.
• Chronic Q fever has a mortality rate of about 25%.

Patient Education

• Educate patients to avoid consumption of unpasteurized dairy products and exposure to parturient animals.
• For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Ticks.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Q fever is difficult to diagnose, primarily because physicians tend not to think of it in the differential. Consider the possibility of tick-borne illnesses in all patients with febrile illnesses. Also, exposures to animals, animal by-products, and parturient animals are risk factors.
• In patients with a presentation consistent with hepatitis or pneumonia, Q fever must be included in the differential diagnosis. A cluster of either of these presentations should suggest Q fever.
• The most important pitfall is failure to consider (or make) the diagnosis because the disease is so uncommon.
• In patients with culture-negative endocarditis, consider infection with C burnetii.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Bernit E, Pouget J, Janbon F, et al. Neurological involvement in acute Q fever: a report of 29 cases and review of the literature. Arch Intern Med. Mar 25 2002;162(6):693-700. [Medline].
• Brouqui P, Dupont HT, Drancourt M, et al. Chronic Q fever. Ninety-two cases from France, including 27 cases without endocarditis. Arch Intern Med. Mar 8 1993;153(5):642-8. [Medline].
• CDC. Q fever--California, Georgia, Pennsylvania, and Tennessee, 2000-2001. MMWR Morb Mortal Wkly Rep. Oct 18 2002;51(41):924-7. [Medline].
• Domingo P, Munoz C, Franquet T, et al. Acute Q fever in adult patients: report on 63 sporadic cases in an urban area. Clin Infect Dis. Oct 1999;29(4):874-9. [Medline].
• Harris RJ, Storm PA, Lloyd A, et al. Long-term persistence of Coxiella burnetii in the host after primary Q fever. Epidemiol Infect. Jun 2000;124(3):543-9. [Medline].
• Madariaga MG, Rezai K, Trenholme GM, Weinstein RA. Q fever: a biological weapon in your backyard. Lancet Infect Dis. Nov 2003;3(11):709-21. [Medline].
• Maltezou HC, Raoult D. Q fever in children. Lancet Infect Dis. Nov 2002;2(11):686-91. [Medline].
• McQuiston JH, Holman RC, McCall CL, et al. National surveillance and the epidemiology of human Q fever in the United States, 1978-2004. Am J Trop Med Hyg. Jul 2006;75(1):36-40. [Medline].
• Parker NR, Barralet JH, Bell AM. Q fever. Lancet. Feb 25 2006;367(9511):679-88.
• Raoult D, Marrie T. Q fever. Clin Infect Dis. Mar 1995;20(3):489-95. [Medline].
• Raoult D, Fenollar F, Stein A. Q fever during pregnancy: diagnosis, treatment, and follow-up. Arch Intern Med. Mar 25 2002;162(6):701-4. [Medline].
• Raoult D, Marrie T, Mege J. Natural history and pathophysiology of Q fever. Lancet Infect Dis. Apr 2005;5(4):219-26. [Medline].
• Scola BL. Current laboratory diagnosis of Q fever. Semin Pediatr Infect Dis. Oct 2002;13(4):257-62. [Medline].
• Tissot Dupont H, Raoult D, Brouqui P, et al. Epidemiologic features and clinical presentation of acute Q fever in hospitalized patients: 323 French cases. Am J Med. Oct 1992;93(4):427-34. [Medline].

Article Last Updated: Oct 16, 2006