The clinical presentation varies based on age, underlying immune status, and geography. Acute Q fever is more common and is a systemic illness, whereas chronic Q fever is seen in less than 5% as a persistent, localized infection of a specific organ system.

Acute Q Fever

The most common presentation is that of a self-limiting acute febrile illness lasting for 1 to 2 weeks. Atypical or rapidly progressive pneumonia is the next common clinical presentation, especially in older adults. Severe headache, fatigue, chills, sweats, myalgia, pleuritic chest pain, nausea, vomiting, and diarrhea can all occur. A rash is commonly seen in children. Acute hepatitis is also a common presentation in younger adults and can complicate as cholestatic jaundice or acalculous cholecystitis. Aseptic meningitis or encephalitis have also been reported along with neurological complications such as cerebellar dysfunction, cranial nerve palsies, extrapyramidal disease, and demyelinating polyradiculoneuritis. Hematological involvement results in hemolytic anemia and histiocytic hemophagocytosis. Infection during the first trimester of pregnancy carries a high risk of abortion. QFFS is seen in 20%, characterized by arthralgia, myalgia, fatigue, headaches, blurry vision, intermittent diaphoresis, muscle fasciculation, and tender lymphadenopathy

Chronic Q Fever

Infective endocarditis is the most common manifestation, followed by infection of the vascular prosthesis and existing aneurysms, pseudotumor of the lung, granulomatous hepatitis, and rarely osteomyelitis and interstitial pulmonary fibrosis. Preexisting abnormalities in native valves and prosthetic valves predispose to infection. It is typically culture-negative endocarditis and is included as one of the typical organisms in the modified Duke criteria. It is also associated with an increased risk for lymphoma. Residual neurological impairment includes weakness, recurrent meningismus, blurry vision, sensory loss, and paraesthesias.[6][16][17][18]

In acute Q fever, white cell count can be normal or elevated; the platelet count can be elevated or decreased. A frequent finding is elevation in liver enzymes, while serum bilirubin can be normal. CSF reveals mononuclear pleocytosis with elevated protein levels. Chest x-ray reveals opacities that are multiple, rounded, segmental, or nonsegmental or pleural based along with hilar adenopathy. An echocardiogram may reveal vegetations, but often in only half of the cases of chronic Q fever. Diagnosis is confirmed by serology or PCR. Tissue samples obtained from Q fever patients should be handled under biosafety level 3 for culture as they are highly infectious. The serological test of choice to diagnose both acute and chronic Q fever is an indirect immunofluorescent test. In this test, two different IgG antibodies are detected: Anti phase I IgG antibody and anti-phase II IgG antibody. Seroconversion typically occurs in the second week. In acute Q fever, anti-phase II IgG antibody is higher (typically >1:128) than anti-phase I IgG antibody and a fourfold rise in anti-phase II titers between acute and convalescent samples is diagnostic of acute Q fever. A positive blood culture, PCR, and or anti-phase I IgG antibody titer ≥ 1:800 (>1:1024 in the U.S.) is diagnostic of chronic Q fever (endocarditis).[19][20][21][22]

The best treatment for acute Q fever is doxycycline 100 mg orally twice a day for 14 days. In cases of resistance or intolerance to doxycycline, trimethoprim-sulfamethoxazole and moxifloxacin are valid options. Defervescence is quicker with doxycycline, and both doxycycline and moxifloxacin reduce both the severity and duration of illness. In pregnancy, acute non-life threatening Q fever should be treated with trimethoprim-sulfamethoxazole 160 mg - 800 mg twice daily from diagnosis till 32 weeks of pregnancy (high risk of hyperbilirubinemia in the last eight weeks), despite being a pregnancy category C drug because the risk of untreated Q fever (stillbirth or miscarriage) is higher for the fetus than the adverse effects of trimethoprim-sulfamethoxazole (intra-uterine growth retardation and premature delivery). Informed decision making should guide therapy, and for life-threatening infection or reaction to trimethoprim-sulfamethoxazole, doxycycline should be used. Serologic follow up is essential at 3, 6, 12, 18, and 24 months post-delivery. Future pregnancies will require resumption of serological monitoring, and treatment with trimethoprim-sulfamethoxazole is necessary with a four-fold rise in titers. Chronic Q fever that occurs during pregnancy is treated with doxycycline 100 mg twice daily and hydroxychloroquine 200 mg three times daily for a year post-delivery. For Q fever endocarditis, the therapeutic regimen includes doxycycline and hydroxychloroquine, given for 18 months in native valve endocarditis and 24 months for prosthetic valve endocarditis. A fourfold decrease in IgG antibody levels implies treatment completion. Hydroxychloroquine enhances the antibacterial action of doxycycline as it increases the pH of the phagolysosome. Ciprofloxacin or rifampin can substitute hydroxychloroquine in cases of intolerance or contraindication. Valve surgery is a must in prosthetic valve involvement. Antibiotic treatment is not effective for QFFS.[23][24][25][26]

Acute viral infections such as Epstein Barr virus, cytomegalovirus, influenza, hepatitis A, B, or C virus present with similar complaints such as febrile illness, hepatitis, and myalgia. Serological tests and PCR assays used to identify these infections. Atypical pneumonia caused by Legionella and Mycoplasma needs to be considered. They can be ruled out by the detection of urine antigen or serum antibody titers. Tick-borne illnesses such as Lyme disease, relapsing fever, and Rocky Mountain spotted fever manifest with fever headache with or without a rash. Anaplasmosis and ehrlichiosis present with fever, headache, and hepatitis with a lesser incidence of rash. Tick-borne diseases are detected via PCR and/or serology. Zoonotic diseases such as brucellosis and leptospirosis can manifest as an acute flu-like illness with a history of exposure to animals or animal products.

Acute Q fever, has an excellent prognosis when promptly diagnosed and treated. Patients with known valvular heart disease and pregnant females with acute Q fever are at risk of developing endocarditis. Monitoring serology at frequent intervals and an echocardiogram for elevated serologic titers is recommended. Q fever treatment in pregnancy often results in better outcomes. For endocarditis, treatment outcomes are better with dual therapy than monotherapy.

Acute Q fever can result in fatal interstitial pneumonia, myopericarditis, aseptic meningitis, encephalitis, and cholecystitis. Immunocompromised patients are at higher risk of developing complications. Chronic Q fever can result in infection of the vascular prosthesis and prosthetic valve infections. Endocarditis, if not treated, can result in serious cardiac complications. Chronic persistence can result in Q fever fatigue syndrome, hemolytic anemia, and bone marrow necrosis. Pregnant females with Q fever when not treated have poor fetal outcomes, including abortion.

Consumption of pasteurized milk and its byproducts must be encouraged. The public should be advised on the appropriate removal and dispensation of infected animal products. Education resources on sources of infection and how to prevent it should be provided to livestock and farm workers handling ungulates and their byproducts. 

Q fever is infrequently fatal, and no precise data exist whether to screen pregnant women for infection during an outbreak. The mortality rate is 2.4%. Some authors strongly advocate serology monitoring after an episode of acute Q fever for two years for earlier detection of chronic Q fever or endocarditis. The reason for this is an increased risk (39%) of endocarditis in patients with valvular lesions. In such a population, a transthoracic screening echocardiogram can be done to detect endocarditis. If the echocardiogram is negative and the serological titers rise, additional tests such as PCR of blood and positron emission tomography to look for a focus of persistent infection may help. Serological and drug level monitoring is recommended during the treatment of endocarditis. If hydroxychloroquine replaced by ciprofloxacin or rifampin, then the patient will need long-term serological follow-up. Biannual eye evaluation is a must when a patient is on hydroxychloroquine to monitor for visual deficits. Aneurysmal and vascular prosthetic device infections are associated with higher mortality. Patients with Q fever and persistent lymphadenopathy may need to undergo evaluation for lymphoma.[2][27][28][29]

Vaccination of individuals employed in high-risk occupations is an efficient approach in halting the disease. The formalin-killed, whole-cell vaccine Q-VAX is 92% to 98% effective at clinical disease prevention. Vaccination recommended after skin testing as priorly exposed individuals are more likely to have untoward reactions. Coxevac is an inactivated vaccine used in veterinary animals. Isolation in a hospital recommended if an infected patient undergoes a procedure that can result in aerosolization of contaminated tissue (autopsies, obstetrical/gynecological procedures). Avoiding raw milk, ectoparasite containment, promoting safe veterinary practices, and disinfection of infected tissue, are strategies to decrease exposure. For decontamination, commercial disinfectants containing benzalkonium chloride or 5% hydrogen peroxide are successful.[30]