Coxiella burnetii seroprevalence of shepherds and their flocks in the lower Saint-Lawrence River region of Quebec,Canada

OBJECTIVE:

To determine the seroprevalence of Coxiella burnetii among the shepherds and their sheep in the lower Saint-Lawrence River region (LSLRR) of Quebec, Canada.

DESIGN:

A prospective human-animal comparative study was conducted with 81 shepherds from 46 farms and a control group matched for sex and age. All participants answered a standardized questionnaire to evaluate their risk factors for Q fever, including a specific section on the work practices of the shepherds. All human subjects had a blood sample taken for serology to phase I and phase II antigens of C burnetii performed by indirect immunofluorescence assay. At each participating farm, seven to nine sheep had blood samples taken for C burnetii serology to be assessed by the complement fixation test.

RESULTS:

The seroprevalence to C burnetii was higher in the group of shepherds (28.4%) than the control group (1.2%) (P<0.005). Among the group of shepherds, spending more than 5 h/week in the sheep barn (P=0.06) and buying and/or trading sheep within the past six months (P=0.004) were associated with positive C burnetii serology. A total of 137 of 334 sheep (41%) were seropositive for C burnetii. These positive sheep were distributed in 41 of the 46 flocks (89%). No correlation could be demonstrated between a serology for C burnetii in the herds and the shepherds.

CONCLUSION:

Q fever is highly prevalent in the LSLRR of Quebec, affecting 89% of the flocks and 28% of the shepherds. Shepherds in this region are at increased risk for C burnetii infection in comparison to the general population.Key Words: Coxiella burnetii, Flock, Q fever, Quebec, Serology, Seroprevalence, Sheep, ShepherdQ fever is a worldwide zoonosis caused by an intracellular rickettsial agent, Coxiella burnetii. This bacteria shows a characteristic phase conversion: the virulent phase I is directly isolated from infected animals, and the avirulent phase II is obtained after successive passages on cellular cultures of embryonated eggs (1,2). Q fever is predominantly transmitted to humans by inhalation of contaminated aerosols from infected animal litters (3-5). The parturition products and the feces and urine of sheep, cats, goats and dogs are the more common sources of transmission of the bacteria (6-9). Although these animals rarely show any symptoms of the infection (10,11), abortions in sheep, goats and cattle can be seen in some cases (5,6,12-14).Human Q fever is often asymptomatic or manifests as a mild illness. Atypical pneumonia and hepatitis are the principal clinical manifestations of the acute symptomatic infection, while endocarditis is the most frequent presentation of chronic Q fever (1,3,15,16). Very few studies in North America have addressed the issues of prevention of Q fever. In Australia, a highly effective vaccine (Q-Vax, Commonwealth Serum Laboratories, USA) is available for workers with occupational exposition to C burnetii (17,18).Seroprevalence studies conducted in Canada have shown that 5% to 36% of blood donors (19,20), 20% of slaughterhouse workers of the Mauricie region of Quebec (12), 25% of personnel of the animal pathology laboratory in Rimouski in the lower Saint-Lawrence River region (LSLRR) (M Rochette, unpublished data) and 49% of veterinarians in Nova Scotia (21) were positive for C burnetii.Epizootiological studies have also been done on animal populations in Canada. A seroprevalence study in the Mauricie region of Quebec showed that C burnetii had infected 26.7% of the cats, 11.5% of the cattle and 7.7% of the sheep (22). Cats were reported as important vectors of transmission of C burnetii to humans in the Mauricie region of Quebec and in Nova Scotia (23,24). In Ontario, a seroprevalence study demonstrated that 21.3% of the sheep were positive for antibodies to C burnetii (25).Q fever is a notifiable disease in Quebec. From January 1990 to December 1998, 43 (36.1%) of 119 reported cases were from the LSLRR, which had the highest incidence rate of the province, although it represents only 5% of the population. A review of the cases of Q fever from the LSLRR between 1991 and 1999 showed that 67% of the Q fever cases were related to exposure to sheep (P Jutras, unpublished data). It is noteworthy that an important rise in the number of sheep was observed in LSLRR, with an increase from 11,000 animals distributed in 110 flocks in 1983, to more than 33,000 in 180 flocks in 1999 (Union des producteurs agricoles of Quebec, personal communication).To evaluate the association between Q fever and exposure to ovine in the LSLRR, a prospective human-animal seroprevalence study was undertaken to compare the seroprevalence of C burnetii between the shepherds, their flocks and the general population. The work practices of the shepherds were also evaluated.     

Seroprevalence to Coxiella burnetii among residents of the Hunter New England region of New South Wales, Australia

Exposure to Coxiella burnetii is a risk in the Hunter New England (HNE) region of New South Wales (NSW), Australia, based on yearly reported cases of Q fever. We assessed seroprevalence of phase II antibodies to C. burnetii by indirect immunofluorescence assay (IFA; screening at 1/50 dilution) of residents of 24 local government areas (LGA) of the HNE region of NSW. A total of 2,438 randomly selected sera sent to the Hunter Area Pathology Service for routine diagnostic purposes (not Q fever testing) during the period of 2006-2009 were tested. The overall seroprevalence in sample group was 7%. The proportion of males (59%) was higher than females (41%). In age distribution, the largest proportion (37%) of seropositives was in the > 60 years age group. Lower prevalence was observed in 0-9 years (1%) and 10-19 years (5%) age groups. The seroprevalence in different LGAs varied between 0.5% and 22%. It was highest in Guyra (22%), Gunnedah (21%), Tenterfield (18%), and Narrabri (16%), with Newcastle (0.5%), Port Stephens (2%), Lake Macquarie (3%), and Singleton (3%) being the lowest. In most of the LGAs, seroprevalence was between 6% and 12%. This report indicates a considerable exposure to C. burnetii of residents in rural areas of the HNE region and is consistent with the high notification rate for Q fever in this part of Australia.     

Q fever in humans and animals in the United States

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.     

Prevalence of Coxiella burnetii in Hungary: Screening of Dairy Cows, Sheep, Commercial Milk Samples, and Ticks

Abstract Q fever is an important zoonotic disease caused by Coxiella burnetii. There are few reliable data about C. burnetii infection available. The aim of this study was to assess the importance and potential infectious sources of Q fever in Hungary. A total of 215 milk samples (10 individual samples from each herd and 1 bulk tank milk sample from each cattle herd), and 400 serum samples (20 from each herd) were tested from 15 dairy cattle herds and 5 sheep flocks located in different parts of Hungary. The study found 19.3% (58/300) and 38.0% (57/150) seropositivity in cattle, and 0% (0/100) and 6.0% (3/50) seropositivity in sheep, by complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), respectively. C. burnetii DNA was detected by IS1111 element-based TaqMan real-time polymerase chain reaction (PCR) in 8.7% (13/150) of individual dairy cow milk samples, 4.0% (2/50) of individual sheep milk samples, and 66.7% (10/15) of dairy bulk tank milk samples. Samples taken from nine different commercially-available pasteurized cow milk products from different Hungarian producers were also tested for the presence of C. burnetii DNA, and eight of these samples were found to be positive (88.9%). The real-time PCR examination of 5402 ixodid ticks collected from different parts of the country yielded negative results. Knowledge of the true prevalence of Q fever is crucial for policymakers involved in evidence-based decision making.     

Epidemiology of Q fever in Sweden.

Q fever is known to be a worldwide disease, with Sweden supposed to be one of a few exceptions. The purpose of this pilot study was to elucidate whether or not a potential risk group for obtaining Q fever in Sweden was seropositive to the causative agent Coxiella burnetii. Blood samples were collected from sheep farmers on the island of Gotland, and from members of their families. Serum samples were examined by ELISA for the presence of antibodies against C. burnetii, phases I and II. Positive reactions were confirmed with Western blot analysis. It was found that 30% of the study group were seropositive to C. burnetii, thus indicating that Q fever is endemic in this area of Sweden.     

The serologic prevalence of Q fever (Coxiella burnetii) complement-fixing antibodies in the Peninsular bighorn sheep of Southern California

Q fever is a rare illness in the Southern California desert. During the past 34 years only 6 patients have been diagnosed with the disease at the Eisenhower Medical Center, a referral center for much of the desert and surrounding mountains. In all but 2 instances, Q fever was identified in patients who have been in contact with imported domestic sheep who are brought to the desert to graze and lamb in the fall and winter. The sheep are sent back to Idaho, Wyoming, and Montana in the spring. With frequent infection by Coxiella burnetii established in domestic sheep, we elected to study the prevalence of complement fixing antibodies to Coxiella burnetii in native bighorn sheep who reside in the lower levels of the mountains surrounding the desert. From 1992 to 1999, of 268 serum samples drawn from male and female lambs and adult sheep, 27 tested positive (10%), which is strikingly low when compared with Dall sheep in Alaska (12 of 15), kangaroos, wild rabbits, and brown rats. Because changes have been made in Peninsular bighorn sheep habitat since the animals were listed as endangered in 1998, further follow-up in Q fever serology testing will be of interest.     

Q fever prevention and vaccination

The simpliest way how to avoid the development and spreading of any infection, including Q fever in extenso, is prevention. The main principles of prevention are: educate the public on sources of infection, appropriately dispose of placenta, birth products, fetal membranes, and aborted fetuses at facilities housing sheep and goats, restrict access to barns and laboratories used in housing potentially infected animals, use only pasteurized milk and milk products, use appropriate procedures for bagging, autoclaving, and washing of laboratory clothing, quarantine imported animals, periodical monitoring of seroprevalence in cattle, sheeps and goats, vaccination of the risk groups etc. Four different basic types of Q fever vaccines have been developed: 1) live attenuated vaccines were derived from the Coxiella burnetii strain Grita in phase I of a highly reduced virulence but preserved immunogenicity, 2) highly purified corpuscular formalin-inactivated vaccine derived from the C. burnetii Henzerling strain in phase I, 3) a soluble vaccine prepared from the C. burnetii strain Nine Mile corpuscules in phase I by extraction with trichloracetic acid, and 4) in the USA, the use of a chloroform-methanol extraction residue subunit vaccine of C. burnetii strain Nine Mile in phase I of a low reactogenicity has been recommended.     

Effect of sex on Coxiella burnetii infection: protective role of 17beta-estradiol

Q fever is a zoonosis caused by Coxiella burnetii and recently has been recognized as a potential agent of bioterrorism. In Q fever, men are symptomatic more often than women, despite equal seroprevalence. We hypothesized that sex hormones play a role in the pathogenesis of C. burnetii infection. When C57/BL6 mice were injected with C. burnetii, bacteria load and granuloma numbers were lower in females than in males. Ovarectomized mice showed increased bacteria load in the spleen and the liver, similar to that found in males. The granuloma number was also increased in ovarectomized mice and reached the levels found in males. Tissue infection and granulomatous response are largely under the control of estrogens: treatment of ovarectomized mice with 17beta-estradiol reduced both bacteria loads and granuloma numbers. These results show that sex hormones control host response to C. burnetii infection and may account for host-dependent clinical presentation of Q fever.     

Epidemiologic features and clinical presentation of acute Q fever in hospitalized patients: 323 French cases.

PURPOSE: To contribute to the knowledge of epidemiologic and clinical features of patients hospitalized with Q fever in France. METHODS: We conducted a retrospective analysis of 22,496 sera submitted between 1982 and 1990 to the French National Reference Center for Rickettsial Diseases (NRC). The diagnosis of acute Q fever was based on an IgG titer greater than or equal to 1:200 and an IgM titer greater than or equal to 1:25 against phase II Coxiella burnetii antigen on an indirect immunofluorescence test (IFA). Fifteen cases prior to 1985 were diagnosed on the basis of a complement fixation titer greater than or equal to 1:8. A serosurvey of blood donors from Marseille was also conducted in 1988 on 924 sera, using IFA with a cutoff titer of 1:25. RESULTS: The serosurvey conducted in 1988 showed a seroprevalence of 4.03%, without age or sex prediction. The incidence rate of acute Q fever detection at the NRC was 0.58 per 100,000 inhabitants over the 9-year period. Three hundred twenty-three clinical cases were diagnosed, rising from 1 in 1982 to 107 in 1990. In patients hospitalized for acute Q fever, there was a significantly higher sex ratio of males to females (2.3), which, coupled with the age distribution, indicated that elder males, who are overrepresented due to our recruitment bias, are more susceptible to C. burnetii infections. The mean age of the patients was 45.5 years, while the risk was increased in the 30 to 39 age group as well as in the 60 to 69 age group. Usual epidemiologic risk factors were found in 20.1% of the cases. Hepatitis (61.9%) was a more common clinical presentation in our patients with Q fever than pneumonia (45.8%). This might reflect differences in strains of C. burnetii or the biology of the host. However, French farmers and stock breeders commonly drink unpasteurized raw milk from their cattle, which might indicate a relationship between hepatitis and infection via the digestive tract. CONCLUSION: Our results indicate that many cases of acute Q fever are undiagnosed. A greater awareness of the disease and more extensive serologic testing of patients with symptoms compatible with Q fever may improve the situation.     

Coxiella burnetii, the agent of Q fever, in domestic sheep flocks from Wyoming, United States

Coxiella burnetii, the agent of Q fever, is an intracellular bacterial pathogen. It has a nearly cosmopolitan distribution. We conducted a serological survey of domestic sheep herds for infections with C. burnetii in Wyoming following reports of abortion and open ewes. Based on the serologic evidence, there was no link between reproductive problems and exposure to C. burnetii. However, the overall prevalence of C. burnetii in WY sheep was 7%, which indicates that the agent is present in the environment and could pose a threat to public health.     

Q fever endocarditis in the United States.

A patient with Q fever endocarditis, which is almost unknown in the United States, was followed for a total of 32 months; the study was begun 3 1/2 months before aortic valve replacement. Diagnosis was confirmed by serology, visualization of Coxiella burnetii in excised aortic valve tissue by direct and immunofluorescence staining, and isolation of C. burnetii from aortic valve tissue. Serum antibodies against phase I and phase II antigens of C. burnetii were identified. Almost all phase I and phase II antibodies were IgG. These findings are compared with those in an uncomplicated case of acute Q fever. New findings on the immune response to chronic Q fever are presented.     

Short report: seroprevalence of human infection by Coxiella burnetii in Barcelona (northeast of Spain)

Coxiella burnetii is the causal agent of Q fever, a worldwide-distributed zoonosis, which is endemic in Spain. C. burnetii has an extensive reservoir, including farm animals and pets. The aim of this study was to determine the seroprevalence of C. burnetii in humans in Vallés Occidental (Barcelona, northeast of Spain) and its possible related risk factors. The prevalence of phase II antibodies from 216 subjects was determined by indirect immunofluorescence assay (IFA). Age, sex, living place, occupation, and contact with animals were surveyed. A 15.3% seroprevalence was found (> or = 1/40), and 8.8% of samples had titers > or = 1/80. Seropositive cases were significantly higher in patients > 44 years of age. No statistically significant correlation was found between seropositivity and the remaining variables studied. Therefore, infection by C. burnetii seems to be endemic in our region, with a prevalence ranging from 9% to 15%, depending on the titers that are to be considered significant.     

High seroprevalence of Coxiella burnetii antibodies in veterinarians associated with cattle obstetrics, Bavaria, 2009

Q fever is a zoonosis caused by Coxiella burnetii. Infection can result in severe disease. However, little is known about the risk of infection in veterinarians. In a cross-sectional study among German veterinarians, participants provided sera and completed an exposure questionnaire. We investigated predictors for seropositivity using multivariable logistic regression modelling. The 424 participants' median age was 40 (18-74) years, and 276 (65%) were female. Sera of 162 (38%) were positive for Coxiella burnetii phase II IgG antibodies (by ELISA and IFAT). Predictors for seropositivity were occupational exposure to cattle (aOR 2.83, 95% CI 1.64-4.87), occupational exposure to sheep (2.09, 1.22-3.58), male sex (1.9, 1.15-3.13), and increasing age (30-39 years: 4.91, 2.00-12.04; 40-49 years: 5.32, 2.12-13.33; >50 years: 6.70, 2.60-17.25; compared with <30 years). When investigating occupational exposure to cattle and sheep in detail in a separate model, the seroprevalence increased with increasing numbers of cattle obstetrics procedures performed per month, and with increasing numbers of individual cattle treated per week. The high antibody prevalence implies a high lifetime-risk of Q fever in veterinarians. Cattle veterinarians, especially those frequently performing obstetrics, should be counseled early in their career on the clinical picture of Q fever, and on specific risks.     

Q fever: current concepts

Persons with Q fever usually present with severe retrobulbar headache, a fever to 104 degrees F or higher with shaking chills, general malaise, myalgia, chest pain, and sometimes pneumonia and hepatitis. Cattle, sheep, goats, and ticks are the primary reservoirs of the etiologic agent, Coxiella burnetii. Humans are usually infected by inhaling infectious aerosols. Because C. burnetii can survive for long periods in the environment, it poses a continuing health hazard once it is disseminated. Q fever usually occurs sporadically, but large outbreaks are frequently observed throughout the world, particularly among abattoir workers and personnel working in research centers. Q fever endocarditis follows a chronic course and is frequently fatal. Tests for antibodies to C. burnetii are required for confirmation of the diagnosis. Tetracyclines remain the mainstay of treatment for acute Q fever, and tetracyclines in combination with other antibiotics have been advocated for patients with Q fever endocarditis. Vaccines for Q fever have been proven effective in clinical trials.     

Psoas abscess: An unusual manifestation of Q fever

Q fever may lead to serious complications in chronically infected patients. We report two cases of psoas abscess due to Coxiella burnetii associated with lumbar osteomyelitis secondary to an aortic aneurysmal infection. Diagnosis was based on serology, and PCR detected C. burnetii DNA in an abscess sample.     

Prevalence of Coxiella burnetii antibodies among febrile patients in Croatia, 2008-2010

Despite the widespread distribution of Q fever, the prevalence in humans is not accurately known, because many infected people seroconvert without symptoms or with a mild febrile disease. The aim of this study was to determine the seroprevalence of Q fever in different regions of Croatia. During a 2-year period (2008-2010), serum samples from 552 febrile patients with prolonged cough aged 1-88 were tested for the presence of Coxiella burnetii antibodies by using indirect immunofluorescent assay. Sera from 27.5% patients showed IgG antibodies. Serological evidence of C. burnetii infection was found in patients from all parts of Croatia. Seroprevalence rates significantly differed among regions from 21.5% to 41.2% (p=0.001). Men were more often seropositive (31.6%) than women (22.2%; p=0.016). According to age, a progressive increase in the IgG seropositivity rates was observed as ranging from 6.7% in children less than 10 years of age to 39.2% in patients aged 40-49 (p=0.001). Above the age of 50, the IgG seroprevalence remained stable. Patients from rural areas were more often seropositive than patients from urban areas (40.8% vs. 19%), p<0.001). Acute Q fever was confirmed in 5.8% of patients. Cases occurred throughout the year. A majority of cases were reported during summer months.     

42-jähriger Landwirt mit unklarer Leukozytose und erhöhten Transaminasen

We report about a 42-year-old farmer with leucocytosis, elevation of transaminases and liver cirrhosis as an underlying condition. The diagnosis of Q fever hepatitis was made through liver biopsy and serology. Under therapy with doxycycline, transaminases initially increased again; after switching to ciprofloxacin, the patient could be discharged 3 weeks after admission. Q fever is caused by Coxiella burnetii. The most frequent acute manifestation is a self-limiting flu-like illness. Chronic Q fever mostly presents as endocarditis. The diagnosis is made through histology ("doughnut" granulomas), PCR, serology (acute: anti-phase II antibodies, chronic: anti-phase I antibodies) and culture. Standard therapy is doxycycline.     

Q fever bioprosthetic aortic valve endocarditis (PVE) successfully treated with doxycycline monotherapy

Q fever is a zoonotic infection caused by Coxiella burnetii. The most common clinical manifestation of acute Q fever infection is as an atypical community-acquired pneumonia. The pulmonary findings are accompanied by extrapulmonary findings, most typically an increase in serum transaminases and splenomegaly. Because C. burnetii is difficult to culture, the diagnosis of Q fever is usually made serologically. The diagnosis of acute Q fever atypical community-acquired pneumonia is made by demonstrating a fourfold or greater increase in titer between acute and convalescent specimens or by demonstrating elevated immunoglobulin (IgM) (phase II) titers. Chronic Q fever is manifested as granulomatous hepatitis or more commonly as culture-negative endocarditis (CNE). Chronic Q fever (CNE) is a difficult diagnosis because of difficulty in culturing the organism from the blood and the vegetations with Q fever CNE are small or absent. The diagnosis of chronic Q fever CNE is based on serology. Such patients commonly have highly elevated IgM and IgG titers (phase I/II) titers. Chronic Q fever CNE may involve native or prosthetic heart valves. Q fever prosthetic valve endocarditis is rare compared with native valve Q fever endocarditis. Q fever prosthetic valve endocarditis usually requires valve replacement for cure. We present a case of chronic Q fever bioprosthetic aortic valve endocarditis that was successfully treated with doxycycline monotherapy that did not require aortic valve replacement.     

Outbreak of Q fever in Lohra-Rollshausen,Germany, spring 1996

Q fever is an acute (and sometimes chronic) febrile illness caused by the rickettsial organism Coxiella burnetii. The commonest animal reservoirs for C. burnetiiare cattle, sheep, and goats. Infected animals shed the organisms, which resist desiccation, i     

Pseudoepidemic of Q fever at an animal research facility

Serum samples from people exposed to sheep at a research facility were evaluated by a commercial laboratory and resulted in an overall Coxiella burnetii seroprevalence of 75%. We interviewed individuals to determine exposure history and compatible illness, and retested their sera. Analysis indicated that the commercial laboratory was misinterpreting its results; when corrected, the seroprevalence dropped to 27%. Test kits of the brand used by the commercial laboratory gave equivalent results to the in-house CDC assay when tested in parallel at CDC. Upon final analysis, only the attending veterinarian was confirmed as a Q fever case. This event resulted in increased risk reduction protocols at the research facility and improved public health communication among health authorities. This pseudoepidemic resulted from a lapse in laboratory quality control for testing. Similar errors can be avoided through standardization and improved review of laboratory procedures.