eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Q Fever

Author: Alexandre F Migala, DO, Staff Physician, Department of Emergency Medicine, Denton Regional Medical Center
Coauthor(s): Leah Neumann, LP, Licensed Paramedic, Williamson County Emergency Serves, Georgetown, Texas
Contributor Information and Disclosures

Updated: Oct 16, 2007

Introduction

Background

In 1937, Derrick first described Q fever after investigating a 1935 outbreak of a febrile illness among abattoir workers in Brisbane, Australia. The illness was named Q (for query) fever because the etiology of the new malady was so elusive. Burnet and Freeman isolated the organism from blood samples and identified it as a Rickettsia species in 1937. Although primarily disseminated as an aerosol via inhalation or ingestion, Cox and Davis identified vector transmission when the organism was isolated from ticks at Nine Mile Creek in Montana in 1938. As a result of this discovery, the causative organism subsequently became known as Coxiella burnetii.

Pathophysiology

Q fever is a ubiquitous zoonotic disease caused by C burnetii, with protean clinical manifestations not yet fully understood. C burnetii has a worldwide distribution from its reservoirs, which include mammals, birds, and ticks. The development of Q fever is strongly related to exposure to farm animals (primarily cattle, sheep, and goats) and particularly parturient animals (including cats and rabbits). In one reported case, an obstetrician developed symptoms of Q fever one week after delivering a child to a woman who had Q fever. A characteristic of infection with C burnetii is that only humans regularly express the disease.

C burnetii is a strict, intracellular, pleomorphic, gram-negative organism with an incubation period of 9-40 days; the average incubation period is 20 days. Q fever is primarily transmitted by (1) aerosolization from newborn animals, their placentas, and contaminated hides and fur; (2) ingestion of raw milk and goat cheese; (3) transfusions of blood products; (4) mother to offspring (ie, vertical) transmission; and (5) tick bites. A characteristic of infection with C burnetii is that only humans regularly express the disease.

Originally classified as a Rickettsiaceae because of its obligatory intracellular growth requirements, C burnetti has subsequently been reclassified. After DNA-DNA hybridization studies and genome sequencing identified that the organism more closely resembles the class Gamma Proteobacteria of the phylum Proteobacteria, C burnetti now sits as a monotypic species most closely related to the order Legionellales.

C burnetii possess a sporelike form that resists heat and dessiccation, permitting its persistence for months or years in harsh environments. Because of the characteristics of this small (0.2 x 0.7 microns) sporelike form, in addition to its high infectivity, as few as 1-10 organisms can cause infection. This feature promoted its development as an agent for biologic warfare. C burnetii has been mass produced and weaponized. It is classified as a category B agent because it lacks the capacity to cause mass fatalities while causing notable debilitation. The potential effect of an intentional release of 50 kg of C burnetii along a 2-km line upwind of a population of 500,000 is an estimated 150 deaths, 125,000 cases of acute illness, and 9000 cases of chronic illness.

Marrie explains that C burnetii can exist in different morphological forms.¹ The small cell variant (SCV), which is similar to a sporelike structure, provides the ability to endure extreme environmental conditions, to persist on fomites for over a year, and to withstand disinfectants and extremes of temperature. The large cell variant (LCV) is able to persist within the acidified phagolysosomes of monocytes and macrophages. Marrie postulates that these create an impairment in the bacterial responses within the host, enabling the persistence of the illness in chronic cases.²

C burnetii exists in 2 phases. The phase 1 form is virulent and has been isolated from naturally infected and laboratory-infected animals and humans. The phase 1 form is responsible for acute Q fever infections. The phase 2 form has been identified during transmission of C burnetii in immunoincompetent hosts, such as embryonated hen eggs or cell-culture systems.³ (Raoult, 2000). Variations between phase 1 and phase 2 appear to be correlated with changes in smooth or rough lipopolysaccharides.

During acute Q fever, immunoglobulin M (IgM) antibodies develop against phase 1 and phase 2 forms, whereas immunoglobulin G (IgG) antibodies develop only against the phase 2 form. In chronic Q fever, both IgG and immunoglobulin A (IgA) antibodies are formed against both phase 1 and phase 2 forms. The selective development of the antibodies against each of the 2 forms of C burnetii has become the basis for serologic testing for acute versus chronic Q fever.

C burnetii attaches to host macrophages by means of spectrin-binding proteins called ankyrin and is internalized into the cell, where it fuses with lysosomes to form phagolysosomes. The acidic environment of the phagolysosomes has little effect in defending the host against the invading organism, which multiplies and disseminates itself from this environment.

The immune response against C burnetii is both cell mediated and humeral, with cell-mediated immunity (CMI) appearing to be most important in fending off this organism. Individuals with certain conditions (eg, pregnancy, immunosuppression, heart-valve lesions, and vascular abnormalities) and impaired CMI are at increased risk for chronic Q fever.

Frequency

United States

Although C burnetii is present in the United States, the true incidence of Q fever is difficult to ascertain because it is not a reportable condition and because most American physicians either do not suspect the disease or lack serologic testing capabilities to make the diagnosis.

International

Q fever is present worldwide, except in New Zealand. The frequency ranges from 5% in urban areas to 30% in rural areas. The United Kingdom reports approximately 100 cases annually. Clinical presentations vary geographically as well, with pneumonia predominant in North America and hepatitis predominant in Europe. Q fever infection can frequently be asymptomatic or present as a flulike illness in its milder forms, resulting in an underrepresentation of the actual incidence.  Epidemiological serological testing of specimens from blood donors has discovered a higher incidence throughout Africa, ranging from 18-37%, whereas "at-risk" farmers in the United Kingdom demonstrated 29% seropositivity.

Mortality/Morbidity

• Acute Q fever is generally a self-limited disease (in 38% of cases); more than one half of patients are asymptomatic, and only 2-4% require hospitalization. The mortality rate for symptomatic patients is less than 1%.
• Chronic Q fever, which is practically synonymous with Q fever endocarditis, is more difficult to treat than acute Q fever. Mortality is almost universal if untreated, but the mortality rate is less than 10% with appropriate treatment.

Sex

Male individuals are affected more frequently than female individuals (ratio of 1.5-3.5:1). This difference is possibly attributable to increased occupational and recreational exposure (eg, on farms, in industry [abattoirs], in work as veterinarians, while hunting).

Age

Adults are affected more often than children; the average age of infected individuals is approximately 45-50 years. This age distribution may be because of increased exposure in industrial and farming activities.

• During the largest outbreak in Switzerland, symptomatic Q fever was 5 times more likely to occur in those aged 15 years or older than those younger than 15 years, whereas a study in Greece indicated that the prevalence of clinical cases in children increased with age.⁴
• Data from one study suggested an increasing incidence of hepatitis with young age and an increasing incidence of pneumonia with aging.

Clinical

History

Q fever is a protean disease that lacks a distinct clinical presentation. Almost one half of patients are asymptomatic. Common presentations vary geographically. The primary factor leading to the identification of Q fever is a history of exposure, particularly occupational exposure, exposure to parturient animals, or tick bites.

• Acute Q fever
  • General or systemic symptoms - Flulike syndrome, fever (abrupt onset, temperature up to 40°C), chills, headache (typically retrobulbar), and myalgias
  • Respiratory symptoms - Dry nonproductive cough, pleuritic chest pain, dyspnea, pneumonia (predominant in North America) (Crackles can be auscultated in 50% of cases.)
  • Cardiovascular symptoms - Dissociation between heart rate and temperature in one third of cases, potentially fatal myocarditis, pericarditis
  • GI symptoms - Nausea and vomiting, diarrhea (rare), hepatitis (predominant in Europe), abdominal pain (right upper quadrant)
  • Musculoskeletal symptoms - Myalgia (common), arthralgia (uncommon), osteomyelitis
  • Dermatologic symptoms - Maculopapular rash, diffuse punctiform pruritic rash, and rarely erythema nodosum
  • Neurologic symptoms - Headache (severe retrobulbar), meningismus (meningitis), encephalitis
• Chronic Q fever
  • Chronic illness is defined as infection lasting longer than 6 months. Chronic Q fever occurs in approximately 1% of patients and classically manifests as endocarditis in patients with abnormal or prosthetic valves.
  • Endocarditis may cause fever, fatigue, rash, and/or dyspnea. Laboratory studies most commonly results in negative culture findings and seropositivity; culture positivity and seropositivity or culture negativity and seronegativity are relatively uncommon.
  • Vascular infections are chronic infections associated with a vascular aneurysm or prosthesis.
  • Osteoarticular infection may be characterized by septic arthritis, osteomyelitis, no associated host factors in children, and either immunocompromise or prosthetic joints in adults.
  • Chronic hepatitis is usually associated with endocarditis.

Physical

Specific physical findings may be absent in acute Q fever. When present, physical findings vary with the clinical presentation.

• Acute Q fever
  • Hepatitis - Fever, malaise, abdominal pain (right upper quadrant), hepatomegaly, jaundice
  • Pneumonia - Fever, dry cough, pleuritic chest pain, dyspnea
  • Isolated fever (may be low grade but usually as high as 40°C)
  • Meningitis or encephalitis (rare, approximately 1%) - Severe headache, stiff neck, fever
• Chronic Q fever - Endocarditis (vegetations, clubbing, embolization, rash, hepatosplenomegaly)

Causes

The causative organism for Q fever is C burnetii, a strict, intracellular, pleomorphic, gram-negative coccobacillus classified as a Legionellales species. The primary means of infection in Q fever are inhalation of aerosolized organisms during occupational exposure, exposure to parturient animals, and from tick bites. Current understanding of chronic Q fever indicates activation of a previously asymptomatic infection.

• Highly infectious and extremely virulent organism, requiring a single organism to cause infection (phase 1 form)
• Spore-forming organism, therefore highly resistant to inactivation
• Primarily spread by aerosol, usually during parturient period when concentration of organism rises, but cases also identified in laboratory technicians
• Spread by tick bites, usually to domesticated household and farm animals

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