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Internal Medicine

Q fever

Febrile rickettsial zoonosis characterized by fever, malaise, muscle pain, and sometimes chronic endocarditis, caused by a bacterium (Coxiella burnetii) that infects many animal species.

Introduction

Febrile rickettsial zoonosis characterized by fever, malaise, muscle pain, and sometimes chronic endocarditis, caused by a bacterium (Coxiella burnetii) that infects many animal species.

History:

It was first described by Derrick in 1935 in Queensland, Australia, during an outbreak of a febrile illness among abattoir workers. Subsequently, Burnet and Freeman isolated a fastidious intracellular bacterium from guinea pigs that had been injected with blood or urine from Derrick’s patients and named it Rickettsia burnetii. This bacterium was morphologically and biochemically similar to other gram-negative bacteria. On the basis of cultural and biochemical characteristics, Philip classified R. burnetii in a new genus, Coxiella, named after Herald R. Cox, who first isolated this microorganism in the United States. This genus contained only one species, C. burnetii. Since then, it has been isolated from several mammals and from ticks, and it may persist in the environment.

Phylogenetic tree showing the relationships of C. burnetii to other species belonging to the Proteobacteria. The tree was constructed by the neighbor-joining method with 16S rRNA gene sequences. | Maurin, M., & Raoult, D. (1999). Q fever. Clinical microbiology reviews, 12(4), 518–553.

Microbiology

Coxiella burnetii:

Rckettsia-like Gram-negative intracellular pathogen commonly carried by livestock, including cattle, sheep and goats
C. burnetii. Transmission electron micrograph showing a gram-negative-like wall cell. Magnification, ×75,000. | Fournier, P. E., Marrie, T. J., & Raoult, D. (1998). Diagnosis of Q fever. Journal of clinical microbiology, 36(7), 1823–1834. https://doi.org/10.1128/JCM.36.7.1823-1834.1998

Risk factor:

Q fever is rimarily an occupational hazard in persons in contact with domestic animals such as cattle, sheep and, less frequently, goats.
  • Farmers, veterinarians, abattoir workers, those in contact with dairy products, and laboratory personnel performing Coxiella burnetii culture and more importantly working with C. burnetii-infected animals

Pathophysiology

Phase I infection:

Primary infection can symptomatic (acute Q fever) or not, depending on the strain involved and on the patient’s susceptibilities (due to age, sex, immunosuppression, or pregnancy).

Phase II infection:

If left untreated, diverse persistent focalized infections can develop, depending mainly on host susceptibilities.
Natural history of C. burnetii infection. | Eldin, C., Mélenotte, C., Mediannikov, O., Ghigo, E., Million, M., Edouard, S., Mege, J. L., Maurin, M., & Raoult, D. (2017). From Q Fever to Coxiella burnetii Infection: a Paradigm Change. Clinical microbiology reviews, 30(1), 115–190. https://doi.org/10.1128/CMR.00045-16

Clinical features

The clinical manifestations of acute Q fever range from asymptomatic infection to severe disease, and may be complicated by pneumonia, hepatitis and cardiac manifestations. The organism may also persistent to establish chronic, localized infection, such as endocarditis or osteomyelitis.

Acute Q Fever

Incubation period is approximately 20 days (14-39 days). There is no typical form of acute Q fever. The clinical signs vary greatly from patient to patient.
  • Self-limiting acute febrile illness lasting for 1-2 weeks (M/C presentation)
    • Severe headache, fatigue, chills, sweats, myalgia, pleuritic chest pain, nausea, vomiting, and diarrhea can all occur.
  • Atypical/rapidly progressive pneumonia (#2 M/C presentation)
  • Acute hepatitis (can complicate as cholestatic jaundice or acalculous cholecystitis)
  • Maculopapular/purpuric exanthema (10%)
  • Aseptic meningitis or encephalitis
  • Other neurological complications: Cerebellar dysfunction, cranial nerve palsies, extrapyramidal disease, and demyelinating polyradiculoneuritis
  • Hematological involvement: Hemolytic anemia and histiocytic hemophagocytosis
Persistence of symptoms following acute Q fever: The most frequent ongoing symptoms included a feeling of feverishness (but without documented fever), headache, joint pain, fatigue (waking up tired, weak muscles, heavy arms and legs, tired after rest), and psychological symptoms (frustrated, irritable, easily annoyed). | B. Hopper, B. Cameron, H. Li, S. Graves, J. Stenos, I. Hickie, D. Wakefield, U. Vollmer-Conna, A.R. Lloyd, The natural history of acute Q fever: a prospective Australian cohort, QJM: An International Journal of Medicine, Volume 109, Issue 10, October 2016, Pages 661–668, https://doi.org/10.1093/qjmed/hcw041

CNS manifestations:

  • Severe headache
  • Aseptic meningitis and/or encephalitis (0.2-1.3%), rarely accompanied by seizures and coma
  • Polyradiculoneuritis
  • Optic neuritis

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.
  • Pericarditis and/or myocarditis (frequently fatal)

Q fever during pregnancy:

  • Abortion
  • Premature birth
  • Low birthweight

Diagnosis

Serodiagnosis: Microimmunofluorescence

IgG and IgM antibodies directed against phase II organisms appear early in infection and are maintained for several months following acute Q fever. By contrast, IgA and IgG responses directed against phase I organisms are considered diagnostic of chronic Q fever, although some dispute this.
  • IgM and IgG anti-phase II antibodies (detected 2-3 weeks after infection)
  • IgG anti-phase I antibodies at titers of ≥1:800
Mean antibody titers in subjects with quickly resolving (n = 15) or prolonged (n = 6) symptoms following acute Q fever. Phase I specific antibody (left column) is consistently present at lower titres than phase II specific antibody (right column). IgM and IgG titres were determined by immunofluorescence assay (IFA), and total Ig was determined by complement fixation test (CFT). | B. Hopper, B. Cameron, H. Li, S. Graves, J. Stenos, I. Hickie, D. Wakefield, U. Vollmer-Conna, A.R. Lloyd, The natural history of acute Q fever: a prospective Australian cohort, QJM: An International Journal of Medicine, Volume 109, Issue 10, October 2016, Pages 661–668, https://doi.org/10.1093/qjmed/hcw041

Management

Antibiotic therapy:

Tetracyclines: Mainstay of antibiotic therapy of acute Q fever
  • Doxycycline 100 mg (twice daily for 14 days)
  • Alternative: Trimethoprim-sulfamethoxazole and moxifloxacin
  • Q fever endocarditis: Antibiotic combinations administered over prolonged periods (prevent relapses)
  • Pregnant: TMP-SMX (320mg to 1600mg) until the end of the 7 month
Management strategy for C. burnetii infection. | Eldin, C., Mélenotte, C., Mediannikov, O., Ghigo, E., Million, M., Edouard, S., Mege, J. L., Maurin, M., & Raoult, D. (2017). From Q Fever to Coxiella burnetii Infection: a Paradigm Change. Clinical microbiology reviews, 30(1), 115–190. https://doi.org/10.1128/CMR.00045-16

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