INTRODUCTION	Section 2 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Background: Q fever is a zoonosis caused by a strictly intracellular pathogen, Coxiella burnetii. It occurs worldwide, with the exception of New Zealand. The suspicion of a new disease was first made by Derrick in 1935 during a cluster of acute febrile illness in abattoir workers of Queensland, Australia, hence the name of Q fever (for query). The causative organism was later isolated from Derrick's patients by Burnet and Freeman. In the meantime, Davis and Cox isolated a similar organism from ticks. In 1938, these organisms were recognized as the same and named Coxiella burnetii.

The reservoir of the disease primarily is farm animals (eg, cattle, goats, sheep), but domestic animals also are implicated. C burnetii is excreted in urine, milk, and feces and attains high concentration in birth products. It is extremely resistant because of its sporelike life cycle. Rare human-to-human transmission has been described from exposure to the placenta of an infected woman and from blood transfusions. The possibility of sexual transmission also exists.

Pathophysiology: First thought to be a Rickettsia, C burnetii is now classified within the gamma group of proteobacteria. It is a gram-negative bacterium that is acquired most often via inhalation of aerosols. The possibility of becoming infected by ingesting contaminated raw milk exists but has not yet been confirmed. In the lungs, it proliferates in macrophages (in the acidic phagolysosome vacuole) and then gains access to the blood, producing a transient bacteremia. Thereafter, it can invade many organs but most frequently invades the lungs and liver. Immune responses result in inflammation manifested by granulomas in the liver, spleen, and bone marrow, and are the classic doughnut granulomas. They disappear with convalescence.

C burnetii undergoes phase variation. Phase I antigens occur in animals and in nature and are highly infectious. Phase II antigens are those obtained after subculture and are not infectious. In the acute form of the disease, antiphase II antibodies are elevated. The chronic form is characterized by an augmentation of both antiphase I and antiphase II antibodies. Immunity is due to cellular immune response. Accordingly, a patient with defects in cellular immunity is more prone to develop the chronic form of the disease.

Frequency:

• In the US: Prevalence of Q fever is extremely difficult to assess because it usually is not a reportable disease and because of surveillance bias. The disease was reported to be endemic to California during the 1950s.

• Internationally: In certain regions of France and Spain, the organism is highly prevalent, being the second most common etiology of community-acquired pneumonia and causing 5-8% of endocarditis cases. Multiple reports of clusters have been described for many years. A few clusters were reported in the province of Nova Scotia, Canada and were related to exposure through parturient cats.

Mortality/Morbidity: Acute Q fever most often is self-limited illness, but the chronic form, with its most common cause, endocarditis, carries mortality rates that can exceed 60%.

Sex: No particular susceptibility to Q fever has been related to sex. However, a predominance of male infections has been reported in regions where a cattle-type reservoir is present, mainly due to occupational trends. Pregnant women seem to be predisposed to the chronic form of the disease and to reactivation during subsequent pregnancies.

Age: Where cattle are the reservoir, a predominance in active men aged 25-40 years has been noted.

	CLINICAL	Section 3 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

History:

• Acute Q fever: Sixty percent of affected patients will have an asymptomatic infection. The incubation period varies from 2-6 weeks. Three main clinical presentations are described for acute Q fever, as follows:

• The first is a self-limited febrile illness, which often is accompanied by headache, myalgia, and chills, with an abrupt onset.

• The second, pneumonia, most frequently is atypical, rarely fulminant, and progresses to acute respiratory distress syndrome. It also can be found incidentally upon chest x-ray examination.

• The third, hepatitis, often is associated with smooth-muscle and antiphospholipid or antinuclear antibodies. Patients rarely have gastrointestinal symptoms. Pericarditis, myocarditis, meningoencephalitis, abortion, and dermatologic manifestations are less commonly associated. Thyroiditis, mediastinal lymphadenopathy, pancreatitis, mesenteric panniculitis, epididymitis, orchitis, priapism, inappropriate secretion of antidiuretic hormone, optic neuritis, Guillain-Barré syndrome, and extrapyramidal neurological disease are rare. Symptoms include fever (88-100%), fatigue (97-100%), myalgia (47-69%), chills (68-88%), sweats (31-98%), headache (68-98%), dry cough (24-90%), confusion, pleuritic chest pain, dyspnea, nausea, vomiting, and diarrhea.

• Chronic Q fever: Several manifestations of chronic Q fever are described, as follows:

• Endocarditis is the main clinical presentation, usually occurring in patients with cardiac valve defects. Immunocompromised patients (AIDS, renal failure, hematologic cancer) also are susceptible. Patients present with heart failure or with nonspecific symptoms, including low-grade fever, fatigue, chills, arthralgia, and night sweats.

• Other manifestations include vascular (infections of aneurysms or grafts), osteoarticular (osteomyelitis, coxitis, spondylodiscitis, arthritis), obstetric (spontaneous abortion, premature labor, due to placentitis), hepatic (chronic hepatitis), pulmonary (interstitial fibrosis, pseudotumor), and renal (glomerulonephritis) complications. Q fever could be added to the organisms of the TORCH syndrome (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex), and chronic fatigue syndrome also has been described following acute Q fever.

Physical:

• Acute Q fever

• Pneumonia signs include high-grade fever and inspiratory crackles; less frequently, patients present with signs of consolidation or pleural effusion.

• Hepatitis presents with hepatomegaly and jaundice (rarely).

• Meningeal signs, pericardial rub, and maculopapular or petechial rash also may appear.

• Chronic Q fever: Endocarditis manifests with low-grade fever (or no fever), augmentation of a known heart murmur, signs of heart failure, hepatosplenomegaly, clubbing, and signs of embolic complications.

Causes:

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