Manual of Standards for Diagnostic Tests and Vaccines

Q fever is a zoonotic disease considered as emerging or re-emerging in many countries. It is caused by Coxiella burnetii, a bacterium developing spore-like forms that are highly resistant to the environment. The most common animal reservoirs are livestock and the main source of infection is by inhalation of contaminated aerosols. Although the culture process for Coxiella is laborious, advances on the knowledge of the life cycle of the bacterium have been made. New tools have been developed to (i) improve the diagnosis of Q fever in humans and animals, and especially animal shedders, (ii) perform epidemiological studies, and (iii) prevent the disease through the use of vaccines. This review summarizes the state of the knowledge on the bacteriology and clinical manifestations of Q fever as well as its diagnosis, epidemiology, treatment and prevention in order to understand what factors are responsible for its emergence or re-emergence.

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Is Q Fever an emerging or re-emerging zoonosis?

Q fever, a zoonotic disease caused by the bacterium Coxiella burnetii, can cause acute or chronic illness in humans. Transmission occurs primarily through inhalation of aerosols from contaminated soil or animal waste. No licensed vaccine is available in the United States. Because many human infections result in nonspecific or benign constitutional symptoms, establishing a diagnosis of Q fever often is challenging for clinicians. This report provides the first national recommendations issued by CDC for Q fever recognition, clinical and laboratory diagnosis, treatment, management, and reporting for health-care personnel and public health professionals. The guidelines address treatment of acute and chronic phases of Q fever illness in children, adults, and pregnant women, as well as management of occupational exposures. These recommendations will be reviewed approximately every 5 years and updated to include new published evidence.

Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group

Coxiella burnetii, the etiologic agent of Q fever, is a worldwide zoonotic pathogen. Although Q fever is present in the United States, little is known about its current incidence or geographic distribution in either humans or animals. Published reports of national disease surveillance, individual cases, outbreak investigations, and serologic surveys were reviewed to better characterize Q fever epidemiology in the United States. In national disease surveillance reports for 1948-1986, 1,396 human cases were reported from almost every state. Among published individual case reports and outbreak investigations, occupational exposures (research facilities, farm environments, slaughterhouses) were commonly reported, and sheep were most frequently implicated as a possible source of infection. In studies conducted on specific groups, livestock handlers had a significantly higher prevalence of antibodies to C. burnetii than did persons with no known risk. Animal studies showed wide variation in seroprevalence, with goats having a significantly higher average seroprevalence (41.6%) than sheep (16.5%) or cattle (3.4%). Evidence of antibody to C. burnetii was reported among various wild-animal species, including coyotes, foxes, rodents, skunks, raccoons, rabbits, deer, and birds. This literature review suggests that C. burnetii is enzootic among ruminants and wild animals throughout much of the United States and that there is widespread human exposure to this pathogen. Sheep and goats appear to be a more important risk for human infection in the United States than cattle or wild animals, and research studies examining the natural history and transmission risk of Q fever in sheep and goats in this country should be encouraged.

Q fever in humans and animals in the United States.

Q fever is an ubiquitous zoonosis caused by an resistant intracellular bacterium, Coxiella burnetii. In certain areas, Q fever can be a severe public health problem, and awareness of the disease must be promoted worldwide. Nevertheless, knowledge of Coxiella burnetii remains limited to this day. Its resistant (intracellular and environmental) and infectious properties have been poorly investigated. Further understanding of the interactions between the infected host and the bacteria is necessary. Domestic ruminants are considered as the main reservoir of bacteria. Infected animals shed highly infectious organisms in milk, feces, urine, vaginal mucus, and, very importantly, birth products. Inhalation is the main route of infection. Frequently asymptomatic in humans and animals, Q fever can cause acute or chronic infections. Financial consequences of infection can be dramatic at herd level. Vaccination with inactive whole-cell bacteria has been performed and proved effective in humans and animals. However, inactive whole-cell vaccines present several defects. Recombinant vaccines have been developed in experimental conditions and have great potential for the future. Q fever is a challenging disease for scientists as significant further investigations are necessary. Great research opportunities are available to reach a better understanding and thus a better prevention and control of the infection.

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Q Fever: Current State of Knowledge and Perspectives of Research of a Neglected Zoonosis

Adult ewes (17 months of age) were vaccinated against Coxiella burnetii, using a formalin-inactivated whole cell (WC) phase I Henzerling strain vaccine or a chloroform methanol residue (CMR) vaccine. Nineteen pregnant ewes were placed in 3 categories [(i) unvaccinated, (ii) WC vaccine, and (iii) CMR vaccine] and were challenge exposed at approximately the 100th day of gestation with 210,000 plaque-forming units of C burnetii inoculated subcutaneously. Shedding of rickettsiae was measurably reduced, but was not prevented in vaccinated groups, as shown by inoculating ewes' placental tissues, amniotic fluid, and colostrum into mice, as well as by histopathologic lesions of placental tissues. The rickettsiae were shed in the placenta, amniotic fluid, or colostrum in 6 nonvaccinated ewes. In comparison, rickettsiae were detected in placental inoculations from 2 of 6 ewes in the WC vaccine group and 1 of 6 in the CMR group. In contrast to those in the vaccinated ewes, placentitis, high concentrations of rickettsiae in microscopic preparations, and weak lambs were typical for the nonvaccinated ewes.

Q fever vaccination of sheep: challenge of immunity in ewes.

An enzyme-linked immunosorbent assay (ELISA) was developed to monitor antibodies against Coxiella burnetii among animal populations used in research and teaching facilities. Various antigenic components of C burnetii prepared from phase I and phase II whole cells and commercially available antigens were evaluated. A trichloroacetic acid extract was selected for routine use. There was a linear relationship between the transformed absorbance readings of the ELISA results and microagglutination (MA) titers. Comparison between positive or negative results of the MA test and ELISA gave 98.6% concordance. Using the MA test as the standard, ELISA results were 97.8% sensitive and 100% specific. The efficacy of ELISA was evaluated by testing ruminants with known histories of C burnetii infection. Antibody prevalence was 0 in 117 sheep with no history of C burnetii infection, 22% in 145 naturally infected sheep used for research, and 53% in 115 sheep used for vaccine field trials. Forty-eight percent of 120 dairy cows and 52% of 79 goats from endemically infected herds were seropositive. These results indicate that ELISA should be the test of choice for mass screening and surveillance of animals when Q fever is a suspected biohazard.

Enzyme immunoassay for surveillance of Q fever.

Two recent outbreaks of Q fever in research institutions prompted the authors to review extant data, in an effort to delineate hazards to humans from small ruminants used in research. Prevalence of Q fever antibodies was 24% among 2097 sheep and 57% among 1475 goats from various sources. In a facility using sheep for prenatal research, in which an epidemic of human Q fever later occurred, antibody prevalence among sheep was 77%, with larger than usual proportions of high (greater than or equal to 128) titers. Antibody prevalence was 5% in a sample from the general human population and 11% among 347 persons at three research institutions (17% among students, 8% among the research staff). Except for animal caretakers routinely exposed to sheep, antibody prevalence among research staff approximated prevalence in the general population. Suggestions are made for surveillance and vaccination of sheep and goats used in medical research institutions.

Brooks D

Papers

Q fever vaccination of sheep: challenge of immunity in ewes.

Enzyme immunoassay for surveillance of Q fever.

Q fever hazards from sheep and goats used in research.