eMedicine Specialties > Infectious Diseases > Bacterial Infections

Q Fever

Author: Alexandre Lacasse, MD, MSc, Fellow in Infectious Diseases, University of Tennessee at Memphis
Coauthor(s): Kerry O Cleveland, MD, Associate Professor of Medicine, University of Tennessee College of Medicine; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis; Hari Polenakovik, MD, Consultant Physician in Infectious Diseases and General Medicine, Department of Medicine, Western Health, Australia; Annie Ruest, MD, FRCPC, Consultant Physician in Infectious Diseases and Medical Microbiology, Departments of Medicine and Medical Biology, Laval University, Quebec City, Canada; Christian P Sinave, MD, Associate Professor, Department of Medical Microbiology and Infectious Diseases, University of Sherbrooke, Canada
Contributor Information and Disclosures

Updated: Nov 18, 2008

Introduction

Background

Q fever is a zoonosis caused by Coxiella burnetii, an obligate gram-negative intracellular bacterium. Most commonly reported in southern France and Australia, Q fever occurs worldwide (except in New Zealand). Edward Derrick first described the illness Q (for query) fever in 1937 during a cluster of acute febrile illness in abattoir workers in Queensland, Australia. The causative organism was later isolated from Derrick's patients by Burnet and Freeman. Simultaneously, Davis and Cox identified the same organism from ticks collected near Nine Mile Creek in Montana during an investigation of Rocky Mountain spotted fever. First named Rickettsia diaporica and Rickettsia burnetii, the current name of Coxiella burnetii was applied in 1948.

C burnetii infects various hosts, including humans, ruminants (cattle, sheep, goats), and pets. In rare cases, C burnetii infection in reptiles, birds, and ticks has been reported. C burnetii is excreted in urine, milk, feces, and birth products. These products, especially the latter, contain large numbers of bacteria that become aerosolized after drying. The bacterium is highly infectious, and only a few organisms can cause disease. Because of its sporelike life cycle, C burnetii can remain viable and virulent for months. Infection can be acquired via inhalation or skin contact, and direct exposure to a ruminant is not necessary for infection. Rare human-to-human transmissions involving exposure to the placenta of an infected woman and blood transfusions have been reported. Sexual transmission is also possible.

C burnetii infection in livestock often goes unnoticed. Acute C burnetii infection in humans is often asymptomatic or mistaken for an influenzalike illness or atypical pneumonia. In rare cases, C burnetii infection becomes chronic, with devastating results, especially in patients with pre-existing valvular heart disease. Because of its highly infectious nature, C burnetii is recognized as a potential agent of bioterrorism.

Pathophysiology

Initially classified as a species of the genus Rickettsia, C burnetii is now recognized as a bacterium within the gamma group of Proteobacteria. Genome and 16SrRNA sequencing have identified substantial homology with Legionella pneumophila, also a member of that taxonomic group. It is a pleomorphic gram-negative coccobacillus often acquired via inhalation of aerosols. Infection via ingestion of contaminated raw milk is possible but has not yet been confirmed.

C burnetii has two morphologic variants: the small-cell variant (SCV), which survives well in the environment because of its resistance to heat, pressure, and chemical agents; and the large-cell variant (LCV), which multiplies in the host monocyte and macrophage.¹ These variants are antigenically different.¹ The small-cell variant is a sporelike structure, enabling the organism to persist on fomites for more than a year. After passive entry into the host-cell phagosome, the organism delays the fusion of the phagosome with lysosomes, presumably using this delay to transform from the small-cell variant into the large-cell variant. Thereafter, the large-cell variant exploits and persists within the acidified phagolysosome of the monocytes and macrophages, using it as a nursery.² This process is thought to occur mainly in the lungs, the main port of entry of C burnetii.

Proliferation of organisms within the phagolysosome eventually ruptures the host cell. The infected pulmonary macrophages are also transported systemically, the reticuloendothelial system (liver, spleen, bone marrow) being the most heavily infected. Immune responses result in inflammation that manifests as formation of non-necrotizing granulomata, termed doughnut granulomata due to the characteristic appearance of a fibrin ring surrounding a fat vacuole. Although classically associated with acute Q fever, doughnut granulomata can develop in other conditions, such as visceral leishmaniasis, cytomegalovirus or Epstein-Barr infections, Hodgkin lymphoma, and allopurinol hypersensitivity reaction.

Like other gram-negative bacteria, C burnetii possesses a lipopolysaccharide as a virulence factor that is also responsible for an antigenic phase variation, an important property that was first utilized for serologic diagnosis by Bengtson in 1941.^1,2,3,4 Bacterial isolates from eukaryotic cell hosts are virulent and have a phase I (smooth) lipopolysaccharide that helps protect the microorganism from the host’s defense mechanisms. Isolates obtained after repeated passages through embryonated hens’ eggs are rendered avirulent by chromosomal deletions and have a phase II (rough) lipopolysaccharide. Antibodies against phase I and II antigens can be measured in sera of affected hosts. Phase II antibodies are positive in acute Q fever, whereas phase I antibodies remain elevated in chronic disease.

Frequency

United States

Q fever became a reportable disease in 1999. Prior to then, the annual incidence rate was 21 cases. From 2000 to 2004, the mean annual incidence of Q fever rose to 51 cases. The incidence was highest in the Midwest states, whereas the largest total number of cases was reported in California. Indeed, Q fever was reported to be endemic to California during the 1950s.⁵ More recently, Q fever has been reported in US military personnel deployed in Iraq and in Afghanistan, including some patients who were infected without known animal exposure.³

International

First described in Australia in 1937, multiple reports of Q fever clusters have been described over the years. In southern France and Spain, Q fever is highly prevalent, being the second most common cause of community-acquired pneumonia and causing 5-8% of endocarditis cases. More recently, a few clusters of Q fever were reported in the province of Nova Scotia, Canada, and were related to exposure to parturient cats.

Moreover, acute disease seems to have regional variations. An influenzalike illness is the most common presentation of Q fever in Australia. Hepatitis has been reported in France, southern Spain and Ontario, Canada. Pneumonia is more common in Crete; Switzerland; Nova Scotia, Canada; and the Basque region of Spain. The reason for these variations is unknown, but animal studies suggest important strain differences could be a factor.

Mortality/Morbidity

Acute Q fever is usually self-limited. Chronic Q fever, with its most common cause, endocarditis, carries mortality rates that can exceed 60%.

Race

Q fever has no reported racial predilection.

Sex

Symptomatic Q fever is more common in males.³ In Australia and France, males are 5-fold and 2.5-fold more likely than females to develop disease, respectively. Moreover, men accounted for 77% of Q fever cases reported in the United States. Occupational exposure could represent a selection bias. Infection during pregnancy can lead to premature birth, low birth weight, and spontaneous abortion. Chronic Q fever has also been associated with recurrent miscarriages.

Age

Where cattle are the reservoir, the disease is most prevalent in active men aged 25-40 years. Patients older than 15 years are more likely to present with clinical symptoms. Symptomatic Q fever is rare in children but, if present, manifests as in adults, whether acute or chronic.³

Clinical

History

• Acute Q fever
  • Sixty percent of patients with Q fever are asymptomatic. The incubation period varies from 2-6 weeks.
  • Acute Q fever has 3 main clinical presentations, as follows:^6,5,4
    • It may manifest as a self-limited influenzalike febrile illness of abrupt onset, which is often accompanied by headache, myalgia, and chills. The temperature returns to normal within 5-14 days.
    • Pneumonia, usually mild in nature or as an incidental radiographic finding, is rarely fulminant but occasionally progresses to acute respiratory distress syndrome.
    • Hepatitis, usually with mild elevation of transaminases (2-3 times the reference range), may be associated with antismooth muscle, antiphospholipid, or antinuclear antibodies. Jaundice and acute gastrointestinal symptoms are rare. Manifestations resolve within 2-3 weeks.
  • Cardiovascular and neurologic manifestations develop in approximately 1% of patients and include pericarditis, myocarditis, and meningoencephalitis.
  • Dermatologic manifestations in the form of erythema nodosum or other nonspecific exanthemas may also be associated with acute disease. Rash is not a typical feature of Q fever, but skin manifestations were reported in up to 20% of French patients.⁶
  • Obstetric manifestations include spontaneous abortion.
  • Other rare presentations have included thyroiditis, mediastinal lymphadenopathy, pancreatitis, mesenteric panniculitis, epididymitis, orchitis, priapism, inappropriate secretion of antidiuretic hormone, optic neuritis, Guillain-Barré syndrome, and extrapyramidal neurologic disease.
  • Most common symptoms include fever (88-100%), fatigue (97-100%), myalgia (47-69%), chills (68-88%), sweats (31-98%), headache (68-98%), dry cough (24-90%),
  • Less common symptoms include confusion, pleuritic chest pain, dyspnea, nausea, vomiting, and diarrhea.
• Chronic Q fever
  • Among patients with acute infection, 0.2%-1.4% may develop chronic infection, but few data are available regarding this. Chronic infection may not manifest until months or even years after acute infection.^6,5,4
  • Endocarditis is the main clinical presentation of chronic Q fever, usually occurring in patients with pre-existing cardiac disease including valve defects, rheumatic heart disease, and prosthetic valves. Patients in immunocompromised states (eg, due to AIDS, renal failure, hematologic cancer [including lymphoma], and long-term corticosteroid use) are also susceptible. Patients may present with heart failure or nonspecific symptoms, including low-grade fever, fatigue, chills, arthralgia, and night sweats.
  • Other systemic manifestations include the following:
    • Vascular (infections of aneurysms or grafts)
    • Osteoarticular (osteomyelitis, coxitis, spondylodiskitis, arthritis)
    • Obstetric (spontaneous abortion, premature labor [likely due to placentitis])
    • Hepatic (chronic hepatitis)
    • Pulmonary (interstitial fibrosis, pseudotumor)
    • Renal (glomerulonephritis)
  • Chronic fatigue syndrome has also been described in approximately 10% of patients, more than 6 months following acute Q fever.
  • Q fever could be added to the organisms involved in TORCH syndrome (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex).

Physical

• Acute Q fever⁴
  • Signs of pneumonia include high-grade fever and nonspecific crackles, rhonchi or wheezing; less frequently, patients present with signs of consolidation or pleural effusion.
  • Hepatitis manifests as hepatomegaly or, in rare cases, jaundice.
  • Meningeal signs, pericardial rub, and signs of heart failure may be present.
  • Up to 20% of patients with acute Q fever present with associated nonspecific exanthemas, most commonly a maculopapular rash on the trunk. Erythema nodosum has also been described.
• Chronic Q fever⁴
  • Endocarditis manifests as low-grade fever (or no fever), augmentation of a known heart murmur, signs of heart failure, hepatosplenomegaly, clubbing, arterial emboli, and purpuric rash.
  • Aortic and mitral valves are more often involved.

Causes

Q fever is most often related to animal exposure. However, because of the persistence of Coxiella organisms in nature as a sporelike structure, C burnetii can infect people with no known contact with animals. For example, an outbreak of Q fever was reported in people living along a road on which farm vehicles contaminated with straw and manure traveled.

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