Coxiella burnetii (Q Fever)

The Pathogen

Q fever (or “query” fever) is caused by the intracellular bacterium Coxiella burnetii, which belongs to the order Legionellales, family Coxiellaceae. C. burnetii primarily is a zoonotic pathogen. The organism can be present in high concentrations in the placenta and amniotic fluid of parturient animals and can be transmitted to humans through inhalation or direct contact. ^, C. burnetii is highly infectious to humans, with infection possible by inhalation of <10 organisms. ^, The organism survives and replicates in eukaryotic cells but also is remarkably long-lived in the environment, where it is resistant to environmental extremes and desiccation. ^, The organism is classified as a Select Agent by the US Department of Health and Human Services. Human Q fever was made a nationally notifiable disease in the US in 1999.

Variation in the outer lipopolysaccharide of C. burnetii causes two antigenic phases: phase I is the pathogenic phase, and phase II is derived after laboratory passage and has low virulence. Persons with acute infection show primarily antibodies directed against phase II antigen, whereas people with chronic Q fever infections predominantly have a phase I antibody response.

Epidemiology

Q fever is enzootic in domestic ruminants throughout the world, and human cases have a similar worldwide distribution. Large outbreaks of Q fever have been reported from numerous geographic locations, including the US, Australia, and various European countries. A large series of outbreaks occurred in the Netherlands from 2007–2010, with >4000 Q fever cases documented. Classically, outbreaks are linked to occupational exposure (farm or slaughterhouse workers) or research institutions that use pregnant livestock in research. Several outbreaks of Q fever have been documented among persons living downwind from infected livestock, strongly implicating windborne transmission. ^, Although sheep, cattle, and goats are most commonly implicated in the transmission of Q fever to humans, outbreaks also have been associated with other parturient animal species, including dogs and cats. ^, Ticks are known to harbor C. burnetii and can transmit infection in rare circumstances. ^, Consumption of unpasteurized dairy products also has been suggested as a possible means of transmission.

In the US, Q fever is widespread in cattle, sheep, and goats, with seroprevalence rates of antibodies to C. burnetii of 3%, 16%, and 42% in these animals, respectively. In disease-endemic areas, contact with infected animals can result in sporadic cases or localized outbreaks of Q fever in humans. From 2013–2018, the average US annual reported incidence rate was 0.55 cases per million persons per year. Because of difficulties in recognizing infection and establishing a diagnosis, the true incidence of infection likely is much higher. A nationally representative seroprevalence survey suggested that 3% of the general US population have antibodies to C. burnetii. Seroprevalence is likely to be higher among persons with livestock contact; a survey of US veterinarians found a seroprevalence of 22%.

Q fever is considered a disease primarily of middle-aged adults rather than children, probably because of its strong occupational associations. In 2018 only 3 (1.4%) of 215 reported cases occurred in children aged <15 years. The reported annual incidence of Q fever in children in the US is less than 0.02 cases per million persons ( Fig. 169.1 ). Studies examining age distribution in large outbreaks have shown that children less frequently develop symptomatic illness, even when exposures and seroconversion rates are similar to those observed in adults. However, pediatric Q fever cases are recognized, especially in countries where Q fever is reported frequently. ^, A report of Q fever infections among children in Greece suggests that specific pediatric age groups (11−14 years of age) and risk factors (livestock contact, consumption of unpasteurized dairy products) may be associated with infection.

Clinical Manifestations

Outbreak investigations have suggested that >50% of adults and >80% of children exposed to C. burnetii have asymptomatic infection. ^, Apparent infections can result in signs and symptoms ranging from mild to severe. Although acute infection may be self-limited, all recognized cases should be treated. Chronic forms of infection are more severe, can be life-threatening, and require long-term treatment. ^, Classic symptoms of acute respiratory Q fever include sudden onset with fever, headache (often frontal), chills, general malaise, cough, anorexia, and myalgia. These symptoms should prompt the inclusion of Q fever in the differential diagnosis, particularly in patients with a history of exposure to ruminants. However, the lack of direct animal contact should not preclude a clinical suspicion because of airborne transmission of C. burnetii .

Acute Q fever manifests 1–3 weeks after exposure, and symptoms in children usually are similar to those recognized in adults. Acute infection typically is a self-limited febrile illness or pneumonia. ^{, ,} In children, Q fever pneumonia may be characterized by a cough (≤90% of cases) and radiographic changes that include bilateral infiltrates, atelectasis, and pleural effusion. Respiratory failure and death are uncommon but can occur in patients with underlying conditions. A review of 18 cases of Q fever in infancy listed fever of unknown origin as the most frequent clinical manifestation; pneumonia, convulsions, and malaise also were reported. Common clinical signs among infants in the series included anorexia, cough, and diarrhea. In a review of hospitalized children with Q fever in Spain, common symptoms included fever (92%), gastrointestinal tract symptoms (83%), hepatomegaly (67%), fatigue (50%), cough (50%), headache (42%), splenomegaly (25%), arthralgia (17%), and nuchal rigidity (8%). ^, In a review of pediatric Q fever cases in Australia, most experienced a clinical illness similar to illness observed in adults, and 14% reportedly experienced protracted symptoms of fatigue > 3 months after acute infection. More severe manifestations of acute disease include severe atypical pneumonia, hepatitis, myocarditis, pericarditis, rhabdomyolysis, or meningoencephalitis. ^{, , , ,} A case of hemolytic uremic syndrome has been reported.

Chronic Q fever occurs months or years after the initial acute infection and can be difficult to diagnose because of its lack of a temporal association with specific exposures. Chronic infection is most often characterized by development of osteomyelitis, infective endocarditis, or vascular infection. ^{, , , , ,} Children with Q fever osteomyelitis may not show systemic illness but often experience recurrent episodes at multiple sites, which are poorly responsive to traditional treatment. Children with a history of underlying heart valve disease or immunocompromising conditions may be at increased risk for developing chronic Q fever endocarditis, which manifests as culture-negative endocarditis. Chronic Q fever endocarditis can be fatal, especially if it is not recognized and treated.