Infectious Disease · PANCE / PANRE

Q Fever (Coxiella burnetii)

Zoonotic obligate intracellular bacterium causing acute febrile pneumonia/hepatitis and chronic culture-negative endocarditis; classic exposure is parturient livestock.

Also known as: Coxiella burnetii, query fever, Q fever endocarditis, Q fever hepatitis

Overview

Infection with Coxiella burnetii, an obligate intracellular gram-negative coccobacillus that exists as a highly stable spore-like small-cell variant. Acute Q fever is a self-limited febrile illness; chronic Q fever causes culture-negative endocarditis and vascular infections months to years after exposure.

Epidemiology

Worldwide zoonosis with reservoirs in cattle, sheep, goats, and ticks. The US sees a few hundred reported cases annually, often in ranchers, veterinarians, abattoir workers, and military personnel returning from the Middle East. Highly infectious by aerosol — a CDC Tier 1 select agent.

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Risk factors

  • Exposure to parturient livestock, birth products, or contaminated dust
  • Occupational: farmers, veterinarians, slaughterhouse workers, laboratory workers
  • Unpasteurized dairy consumption
  • Pre-existing valvular heart disease, prosthetic valves, vascular grafts (predispose to chronic endocarditis)
  • Pregnancy (risk of placental infection and fetal loss)
  • Immunocompromise

Pathophysiology

Inhaled organisms infect alveolar macrophages, replicate within phagolysosomes, and disseminate to liver, spleen, and bone marrow. Granulomatous inflammation produces the characteristic 'doughnut' (fibrin-ring) granulomas on liver biopsy. Phase II antigen predominates in acute disease and Phase I antigen rises in chronic infection — the basis of serologic staging.

Clinical presentation

Symptoms

  • Acute: high fever, severe headache (often retro-orbital), myalgias, fatigue, dry cough
  • Granulomatous hepatitis: RUQ pain, anorexia
  • Atypical pneumonia: cough, dyspnea, fever
  • Chronic: prolonged low-grade fevers, weight loss, fatigue, dyspnea; often a new murmur

Signs / physical exam

  • Fever often very high; relative bradycardia
  • Hepatomegaly or splenomegaly
  • Pulmonary crackles in pneumonia presentation
  • Heart murmur and embolic findings in chronic endocarditis
  • Pregnant patients can be asymptomatic but with placental infection

Classic findings

Sheep farmer with fever, headache, transaminitis, and 'doughnut' granulomas on liver biopsy.

Differential diagnosis

  • Atypical pneumonia (Mycoplasma, Chlamydia, Legionella) — Similar dry cough and fever; livestock exposure favors Q fever
  • Viral hepatitis — Hepatocellular pattern with markedly elevated transaminases; serology distinguishes
  • Brucellosis — Same occupational and dairy exposure; serology and culture differentiate
  • Culture-negative endocarditis (Bartonella, HACEK) — Coxiella is one of the leading causes; pre-existing valve disease and rising Phase I IgG support
  • Tuberculosis — Granulomatous hepatitis and chronic illness; AFB stains, IGRA

Diagnostic workup

Diagnostic criteria

Acute: clinical syndrome plus Phase II IgG ≥1:128 (or fourfold rise). Chronic: persistent infection (≥3 months) plus Phase I IgG ≥1:1024.

Labs

  • Coxiella Phase I and Phase II IgG, IgM by IFA
  • Acute disease: rise in Phase II IgG (often ≥1:128)
  • Chronic disease: Phase I IgG ≥1:1024 or fourfold rise
  • PCR on serum or tissue useful early before serology positive
  • LFTs: transaminases 2-3x normal; alkaline phosphatase elevated
  • Blood cultures negative (intracellular pathogen)

Imaging

  • Chest x-ray: patchy infiltrates, often atypical
  • Liver biopsy (rarely needed): fibrin-ring 'doughnut' granulomas
  • Echocardiogram in chronic Q fever — vegetations or valvular damage
  • PET/CT may identify vascular graft and aortic infections in chronic disease

Treatment

First-line

  • Acute Q fever: doxycycline (cat scratch, Q fever, brucellosis, RMSF) 100 mg PO BID for 14 days
  • Children <8 and pregnancy: TMP-SMX (long course in pregnancy through delivery to reduce fetal loss)
  • Chronic Q fever / endocarditis: doxycycline 100 mg BID PLUS hydroxychloroquine 200 mg TID (alkalinizes phagolysosome) for ≥18 months for native valve, ≥24 months for prosthetic
  • Monitor Phase I IgG and IgG to track therapeutic response

Acute Q fever (uncomplicated)

  • Doxycycline 14 days
  • Avoid corticosteroids except in severe disease

Chronic Q fever / endocarditis

  • Doxycycline + hydroxychloroquine 18-24+ months
  • Valve replacement frequently required

Pregnancy

  • TMP-SMX through pregnancy
  • Post-delivery doxycycline + hydroxychloroquine if seroconverts to chronic disease

Second-line / adjunct

  • Public health reporting required
  • Risk-stratify patients with pre-existing valvulopathy after acute Q fever (serial Phase I IgG)

Complications

  • Chronic Q fever endocarditis and vascular infection
  • Granulomatous hepatitis
  • Atypical pneumonia
  • Spontaneous abortion, preterm delivery, low birth weight
  • Post-Q fever fatigue syndrome
  • Osteomyelitis

PANCE pearls

  • Phase II IgG dominates in acute disease; Phase I IgG dominates in chronic Q fever — opposite of intuition.
  • Chronic Q fever endocarditis is the prototype of culture-negative endocarditis; combine doxycycline and hydroxychloroquine.
  • Doxycycline is the workhorse: cat scratch, Q fever, brucellosis, RMSF, tularemia, ehrlichiosis, anaplasmosis.
  • Suspect Q fever in any febrile patient with livestock exposure and unexplained transaminitis.
  • Coxiella is highly stable in the environment and is a CDC Tier 1 select agent — laboratory exposures need post-exposure doxycycline.

References

  • CDC 2013 — CDC Diagnosis and Management of Q Fever — United States, 2013 (Anderson et al., MMWR Recomm Rep 2013;62(RR-03))
  • AHA 2015 — AHA Scientific Statement on Infective Endocarditis (Baddour et al., Circulation 2015)

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