Q Fever (Coxiella burnetii)

Etiology

Although previously classified within the order Rickettsiales, Coxiella burnetii (the causative agent of Q fever) is genetically distinct from the genera Rickettsia, Orientia , Ehrlichia, and Anaplasma. Hence, based on small genome analysis, it best aligns within the order Legionellales, family Coxiellaceae. C. burnetii is highly infectious for both humans and animals; even a single organism can cause infection. The agent has been nationally notifiable since 1999 and is listed as a Category B agent of bioterrorism by the Centers for Disease Control and Prevention (CDC). Unlike Rickettsia, the organism can enter a sporogenic differentiation cycle, which renders it highly resistant to chemical and physical treatments.

C. burnetii resides intracellularly within macrophages. In vitro, the organism undergoes a lipopolysaccharide phase variation similar to that described for smooth and rough strains of Enterobacteriaceae. Unlike Ehrlichia, Anaplasma, and Chlamydia, C. burnetii survives and proliferates within acidified phagosomes to form aggregates of >100 bacteria.

Epidemiology

The disease is reported worldwide, except in New Zealand. Although seroepidemiologic studies suggest that infection occurs just as often in children as in adults, children less often present with clinical disease than adults. During the large outbreak of Q fever in the Netherlands in 2007–2009, only 3.5% of those diagnosed with Q fever were age 19 yr or younger. Although infections are recognized more often in men than in women, reported cases in boys and girls are equal. Approximately 60% of infections are asymptomatic, and only 5% of symptomatic patients require hospitalization. Seroprevalence surveys show that 6–70% of children in endemic European and African communities have evidence of past infection. In France, the overall incidence of Q fever is estimated to be 50 cases per 100,000 persons. A similar estimate is not available for Africa, where cases are likely misdiagnosed as malaria. The seroprevalence of Q fever in the United States is estimated to be 3.1%. Reported cases of Q fever in the United States have been received from every state, but 35% are reported from 4 states (California, Texas, Colorado, and Illinois). In the United States, reported Q fever cases increased by greater than 9-fold from 17 cases in 2000 to 167 cases in 2008, reflecting an increase in incidence, increased reporting after September 11, 2001, improved diagnostic tools, or a combination of factors. Cases decreased significantly in 2008–2013 relative to 2007 but returned to previous high levels in 2014 (173 cases, including 147 acute and 39 chronic). Beginning in 2008, reported cases in the United States have been classified as acute or chronic. Between 2002 and 2014, more than 50% of recognized cases in the United States required hospitalization. Reported cases in Asia and Australia have also increased. Most infections in children are identified during the lamb birthing season in Europe (January through June), following farm visits, or after exposure to placentas of dogs, cats, and rabbits. The largest (~4,000 human cases) community outbreak ever described occurred in the Netherlands in 2007–2012 and was associated with intensive farming of dairy goats and dairy sheep. In 2011, the 1st multistate outbreak of Q fever in humans was linked to interstate sale of infected goats; an outbreak of unknown source was also reported. From 2000 to 2010, 60% of cases reported to CDC occurred in individuals without reported exposure to livestock. More than 20% of cases of clinically recognized acute or chronic Q fever occur in immunosuppressed hosts or in persons with prosthetic valves or damaged native valves or vessels. These findings highlight the need for considering Q fever in those with clinically compatible illness, especially but not exclusively in those with likely exposures and in vulnerable hosts. Epidemiologic investigations and control efforts require a One Health approach, with consideration of the interactions between humans, animals, environment, and public health.

Transmission

In contrast to other rickettsial infections, humans usually acquire C. burnetii by inhaling infectious aerosols (e.g., contaminated barnyard dust) or ingesting (and likely aspirating) contaminated foods. Ticks are rarely implicated. Cattle, sheep, and goats are the primary reservoirs, but infection in other livestock and domestic pets is also described. Organisms are excreted in milk, urine, and feces of infected animals, but especially in amniotic fluids and the placenta. An increase in incidence is associated with the seasonal mistral winds in France that coincide with lamb birthing season and with consumption of cheese among children in Greece. In Nova Scotia and Maine, exposure to newborn animals, especially kittens, has been associated with small outbreaks of Q fever in families. Exposure to domestic ruminants is the major risk in Europe and Australia, although many urban dwellers in France also acquire Q fever without such an exposure. Person-to-person transmission is possible but rare. Clinical Q fever during pregnancy can result from primary infection or reactivation of latent infection and is associated with miscarriage, intrauterine growth retardation, and premature births. Obstetricians and other related healthcare workers are at risk for acquiring infection because of the quantity of C. burnetii sequestered in the placenta. Sexual transmission and cases attributable to blood transfusion or bone marrow transplantation are also reported. Transmission following live cell therapy (injected live animal cells) has also been reported.