A. Cause

1. Coxiella burneti
2. Obligate intracellular coccobacillus (Rickettsia-like organism)
3. Gram negative cell wall
4. Antigenic variants exist, called phase I and II
   1. Phase I variants isolated from patients or animals
   2. Phase II less virulent; distinct surface lipopolysaccharide, obtained after hen's egg passage
   3. Chromsomal deletions lead to Phase I to II switch
5. Passive entry into host cell phagosome, delays fusion of phagosome with lysosome
6. Lives in host phagosome

B. Epidemiology

1. Reservoirs are sheep, goats, cattle and ticks
2. May be isolated from various other animals, fish, arthropods
3. Highly contagious, with inhalation of aerosol particles (incubation ~20 days)

C. Clinical Presentation

1. Presents as acute or chronic disease, or with long-term sequallae
2. Acute Illness
   1. Abrupt onset in most cases, but can be insidious
   2. Rigors with fevers to 104°F
   3. Systemic symptoms common (malaise, anorexia, myalgia)
   4. Severe headache
3. Primarily a Respiratory Pathogen
   1. Usually asymptomatic infiltrate in febrile patient
   2. Cough, often productive
   3. Pleuritic chest pain
   4. Pneumonia usually mild, but respiratory distress can require mechanical ventilation
4. Severe Headache ~75% of patients [3]
   1. Frank cerebritis (meningitis / meningoencephalomyelitis) can occur
   2. Cerebrospinal fluid abnormalities may occur
   3. Most cases of meningoencephalitis occur in absence of pneumonia
   4. Actual neurological symptoms may occur in 25% of persons
5. Liver Involvement [2]
   1. Hepatomegaly with hepatitis may occur
   2. Jaundice is rare
   3. Granulomatous hepatitis may be found
   4. Hyperbilirubinemia, hypoalbuminemia, coagulopathy can occur
6. Hemolytic anemia may occur
7. Chronic llness
   1. Chronic disease can occur 1 month or years after acute illness, or without acute phase
   2. Endocarditis responsible for ~65% of chronic Q fever [4]
   3. Infected joints or osteomyelitis can occur
   4. Vascular infections (nincluding grafts)
   5. Granulomatous or chronic hepatitis
   6. Chronic pulmonary infections
   7. Q fever may relapse during pregnancy
8. Endocarditis [4]
   1. Can be life threatening
   2. Usually develops in patients with abnormal heart valves or blood vessels
   3. Often culture negative endocarditis
   4. Relapses are frequent
   5. Treatment with valve resection and long-term antibiotics
   6. Doxycycline or minocycline + (hydroxy)chloroquine for 18-36 months
   7. Moxifloxacin + chloroquine second line
9. Long Term Sequelae
   1. Post-Q fever fatigue syndrome
   2. Cardiovascular Disease
   3. Abortion and prematurity
10. Asymptomatic seroconversion in up to 50% of exposed persons

D. Diagnosis

1. Clinical Suspicion
   1. Exposure to animal carriers or patient with Q fever
   2. Fever, rales, and pleural effusion are most common physical findings
   3. Leukocytosis, progressive liver dysfunction, in severe disease
2. Isolation difficult and hazardous
3. Serologic titer increased 4-fold
   1. Indirect Immunofluorescence IgM versus IgG; IgA also elevated
   2. Can be used for diagnosis and to follow treatment
4. Complement fixation and Indirect immunofluorescence are used
5. Pathology
   1. Disseminated disease not infrequent
   2. Granulomatous reaction
   3. Granulomas may show fibrous ring surrounding central lipid vacuole
   4. Q fever is most common cause of these vacuolated granulomas
   5. Also found with Typhoid fever, lymphoma, vasculitis, cytomegalovirus, Epstein-Barr virus
6. Negative Weil-Felix Reaction

E. Treatment

1. Acute Disease
   1. Doxycycline 100-200mg po (or IV) bid x 2 weeks
   2. Better response to azithromycin than erythromycin
   3. Trimethoprim/sulfamethoxazole (Bactrim®, Septra®) in children
   4. Newer fluoroquinolones appear effective as well
   5. Penicillins do not have activity
2. Chronic Disease
   1. Lifelong antibiotics have been advocated for chronic disease
   2. However, addition of hydroxychloroquine 200mg tid raises pH of phagolysosome
   3. This inhibits the replication of Coxiella
   4. Generally, 12-18 months of doxycycline 100mg bid + hydroxychloroquine advocated
3. Endocarditis requires prolonged course of therapy [5]
   1. Standard therapy is doxycycline + quinolone (ofloxacin) for 3 years
   2. Doxycycline + hydroxychloroquine for 18-30 months is as effective as standard
   3. As little as 12 months with hydroxychloroquine + doxycycline ± fluoroquinolone may be effective [1]

References

1. Parker NR, Barralet JH, Bell AM. 2006. Lancet. 367(9511):679
2. Bonilla MF, Kaul DR, Saint S, et al. 2006. NEJM. 354(18):1937 (Case Discussion)
3. Ropper AH and Caliendo AM. 1996. NEJM. 335(24):1829
4. Raoult D, Abbara S, Jassal DS, Kradin RL. 2007. NEJM. 356(7):715 (Case Record)
5. Raoult D, Houpikian P, Tissot-Dupont H, et al. 1999. Arch Intern Med. 159(2):167