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PubMed2003

SCID mouse model for lethal Q fever.

Q fever, a worldwide zoonosis caused by Coxiella burnetii, has many manifestations in humans. Endocarditis is the most serious complication of Q fever. Animal models are limited to acute pulmonary or hepatic disease and reproductive disorders. An appropriate experimental animal model for Q fever endocarditis does not yet exist. In this study, severe combined immunodeficient (SCID) mice infected with C. burnetii showed persistent clinical symptoms and died, whereas immunocompetent mice similarly infected became asymptomatic and survived. The SCID mice examined in this study had severe chronic lesions in their primary organs: the heart, lung, spleen, liver, and kidney. The heart lesions of the SCID mice were similar to those in humans with chronic Q fever endocarditis: they had focal calcification and expanded macrophages containing C. burnetii. The 50% lethal dose of C. burnetii in SCID mice was at least 10(8) times less than that in immunocompetent mice. The SCID mouse is highly susceptible to C. burnetii, and the immunodeficiency of the host enhances the severity of Q fever. This animal model could provide a new tool for the study of chronic Q fever and Q fever in immunodeficient hosts.

Animals↗

PubMed2005

Oligo-chip based detection of tick-borne bacteria.

We have developed an oligonucleotide-chip based assay for detection of 16S ribosomal PCR products from tick-borne bacteria. This chip contains 14 specific probes, which target variable regions of 16S rDNA of tick-borne bacteria including Borrellia spp., Rickettsia spp., Anaplasma spp., Coxiella burnetii and Francisella tularensis. The specificity of these probes was tested by hybridization of the chip with fluorescently labeled PCR products amplified from the genomic DNA of selected tick-borne bacteria. The assay was also tested for detection of tick-borne bacteria in single ticks.

Anaplasma↗

PubMed2004

Q fever (coxiellosis): epidemiology and pathogenesis.

Q fever is a widespread zoonosis caused by the Gram-negative bacterium Coxiella burnetii. Aborting domestic ruminants are the main sources of human infection but the reservoir of infection is extremely wide. In humans, Q fever may occur as acute pneumonia, hepatitis or flu-like illness or may take a severe chronic form, characterized by endocarditis, chronic hepatitis and chronic fatigue syndrome. In animals, the main clinical manifestation is late abortion. Infection with C. burnetii can be diagnosed using cultural, serological and genetic methods but because the organism is potentially dangerous and requires specialized skills only specialist laboratories are capable of undertaking diagnostic tests. This paper provides a brief overview of the epidemiology and pathogenesis of Q fever (coxiellosis).

Abortion, Induced↗

PubMed2005

Natural history and pathophysiology of Q fever.

Q fever is a zoonosis caused by Coxiella burnetii. Infection with C burnetii can be acute or chronic, and exhibits a wide spectrum of clinical manifestations. The extreme infectivity of the bacterium results in large outbreaks and makes it a potential bioweapon. In the past decade, the complete genome sequencing of C burnetii, the exploration of bacterial interactions with the host, and the description of the natural history of the disease in human beings and in experimental models have all added to our knowledge about this fascinating disease. Advances in understanding the pathophysiology and natural history of Q fever are reviewed.

Coxiella burnetii↗

PubMed2005

Bacterial zoonoses and infective endocarditis, Algeria.

Blood culture-negative endocarditis is common in Algeria. We describe the etiology of infective endocarditis in this country. Samples from 110 cases in 108 patients were collected in Algiers. Blood cultures were performed in Algeria. Serologic and molecular analysis of valves was performed in France. Infective endocarditis was classified as definite in 77 cases and possible in 33. Causative agents were detected by blood cultures in 48 cases. All 62 blood culture-negative endocarditis cases were tested by serologic or molecular methods or both. Of these, 34 tested negative and 28 had an etiologic agent identified. A total of 18 infective endocarditis cases were caused by zoonotic and arthropodborne bacteria, including Bartonella quintana (14 cases), Brucella melitensis (2 cases), and Coxiella burnetii (2 cases). Our data underline the high prevalence of infective endocarditis caused by Bartonella quintana in northern Africa and the role of serologic and molecular tools for the diagnosis of blood culture-negative endocarditis.

Adolescent↗

PubMed1994

Prevalence, significance, and specificity of antibodies to phospholipids in Q fever.

A cross-sectional study of the prevalence, significance, and specificity of antibodies to phospholipids (aPL) in patients with Q fever was undertaken in a university-based tertiary care medical center. The results of the lupus anticoagulant (LA) test, VDRL test, fluorescent treponemal antibody absorption test, and ELISA with different phospholipid antigens were determined for 26 patients with Q fever diagnosed by clinical and serological criteria. Plasma from four patients with Q fever and antibodies to cardiolipin (aCL) was purified by affinity chromatography in a cardiolipin column and tested against all phospholipids. For 17 patients with high levels of aCL, a modified ELISA without fetal calf serum was performed to determine if the serum cofactor was needed for a CL activity. Fisher's exact test was used for the statistical analysis. From the results of our study we conclude the following: patients with Q fever have a high incidence of aPL, with techniques with aCL or LA being the most sensitive to determine aPL (these antibodies can help diagnose Q fever presenting only as a fever); antibodies (phase II) to Coxiella burnetii and aCL are different antibodies; and the aCL activity in patients with Q fever is cofactor-independent.

Adolescent↗

PubMed1993

Q fever and HIV infection.

OBJECTIVE: To study the frequency of Q fever in HIV-infected individuals. DESIGN: A seroprevalence study. SETTING: French National Reference Centre for Rickettsial Agents, Marseille, France. PATIENTS AND METHODS: Five out of the 68 hospitalized cases of Q fever diagnosed in 1987-1989 were also HIV-infected and are described here. Sera from a blood-donor bank (n = 925) and from HIV-positive individuals selected at random, irrespective of clinical or immunological status (n = 500) were tested for Q fever. RESULTS: Comparisons of the two groups showed a statistically significant difference (2.4 versus 0.8%; Fisher's exact test) at the diagnostic dilution 1:200 and at the dilution considered positive for seroprevalence study (1:1000). CONCLUSIONS: Using the estimated incidence of HIV infection in Marseille, the number of Q fever cases in 1987-1989 was 13 times higher and the clinical expression more frequently symptomatic in the HIV-positive population than in the general one. The prevalence:seroprevalence ratio for Q fever was 1.37% in the HIV-positive group and 0.36% in the blood-donor group. Sera positive for Q fever were confirmed by Western blot analysis in order to minimize cross-reaction. Transmission of Q fever appears to be more frequent in HIV-positive individuals than in the general population; this is not surprising, since Coxiella burnetii lives in the phagolysosome, like other micro-organisms described in immunocompromised hosts. Q fever should be added to the spectrum of diseases that occur more frequently during HIV infection.

AIDS-Related Opportunistic Infections↗

PubMed1993

Q fever mimicking herpetic encephalitis.

We describe a patient with temporal lobe encephalitis associated with primary Coxiella burnetii infection who presented with CT and MRI findings suggestive of herpes simplex encephalitis and an initial improvement during treatment with acyclovir. Q fever should be considered in the differential diagnosis of patients whose manifestations suggest herpes encephalitis.

Coxiella burnetii↗

PubMed1993

Coxiella (Q fever)-associated myelopathy.

We describe six men with a slowly progressive myelopathy characterized by asymmetric, incomplete spinal cord syndrome manifested with a thoracic sensory level, mild spastic paraparesis, and urinary incontinence. The spinal cord lesions were evident by MRI in four of them. Coxiella burnetii infection was confirmed in the blood of all patients by immunofluorescence microscopic assay (IFA) and transmission electron microscopy (TEM). In two patients, we detected C burnetii by TEM and IFA using CSF from the patients inoculated onto fresh peripheral blood lymphocyte. Four patients, treated with appropriate antibiotics, responded either with partial resolution of symptoms or arrest of further neurologic progression. In three, the MRI lesions decreased in size.

Adult↗

PubMed2006

Clinical and epidemiological features of hospitalized acute Q fever cases from Split-Dalmatia County (Croatia), 1985-2002.

BACKGROUND: Q fever shows a wide diversity of clinical manifestation. Q fever is endemic in northern Croatia, but the epidemiological and clinical characteristics of this disease in various ecological areas of southern Croatia are unclear. MATERIAL/METHODS: From January 1985 to December 2002, acute Q fever cases hospitalized at Split University Hospital were analyzed. Acute Q fever was defined as fever (>38 degrees C) with clinical findings in lung and/or liver verified by serologic testing with Coxiella burnetii phase II antigen. RESULTS: During the period of observation, 155 acute Q fever cases were hospitalized. The mean incidence of acute Q fever in the study region was 0.20/100,000/year (95%CI:0-0.78) in the coastal area and 4.64/100,000/year (95%CI:0.44-8.85) in the non-coastal areas, with a male predominance (chi2=60.0; p=0.0000) and a mean male to female ratio of 4.2:1. People of essentially all ages (4-76 years) were affected, the highest rate of infection being recorded in 20- to 49-year-old age groups. In contrast to adults, girls were more frequently affected than boys (2:1). No case of acute Q fever was recorded on any of the nearby islands. Clinically, acute Q fever most commonly presented with both pneumonia and hepatitis (60.0%), followed by pneumonia (25.8%), hepatitis (9.0%), and nonspecific febrile illnesses (5.2%). CONCLUSIONS: C. burnetii is endemic in rural, coastal, and non-coastal areas of southern Croatia and is associated with stock breeding. In these areas, Q fever occurs sporadically and epidemically. Males 20-49 years of age were the prevalent cases.

Acute Disease↗

PubMed1994

A refined guinea pig model for evaluating delayed-type hypersensitivity reactions caused by Q fever vaccines.

The previously established model for determining dermal granulomatous reactivity of Q fever vaccines uses footpad injections to sensitize Hartley guinea pigs. We describe a substantial refinement to that model by substituting an alternate injection route and replacing the model with the hairless Hartley guinea pig. The experimental design incorporates a matrix of various antigen and adjuvant combinations administered by subcutaneous (SC) and intradermal routes of administration. The two Coxiella burnetii antigens evaluated were phase-I whole-cell vaccine (WCV) and phase-I chloroform-methanol residue vaccine. The adjuvants used were complete Freund's (CFA), incomplete Freund's, and RIBI's De-Tox. Phase-I C. burnetii WCV in CFA administered SC provided the most efficacious regimen evaluated for sensitizing hairless guinea pigs. The establishment of this animal model allows evaluation of candidate Q fever vaccines in a more humane model than that previously available.

Adjuvants, Immunologic↗

PubMed2000

The 75-kD tumour necrosis factor (TNF) receptor is specifically up-regulated in monocytes during Q fever endocarditis.

Q fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular microorganism that inhabits monocytes/macrophages. The dysregulated production of TNF-alpha in Q fever endocarditis has been associated with defective killing of C. burnetii by patient monocytes. As soluble receptors for TNF-alpha (TNF-R55 and TNF-R75) regulate TNF-alpha activity, we investigated their release by monocytes in Q fever. Spontaneous and C. burnetii-stimulated release of TNF-R75, but not of TNF-R55, was up-regulated in patients with ongoing endocarditis compared with controls. The increase in TNF-R75 release was related to the activity of Q fever endocarditis, since TNF-R75 release was similar in patients with cured endocarditis and controls. While spontaneous release of TNF-R75 by monocytes from patients with ongoing Q fever endocarditis occurred without changes in its membrane expression, C. burnetii increased the surface expression of TNF-R75. In addition, TNF-R75 transcripts were increased in resting and C. burnetii-stimulated monocytes from patients with ongoing endocarditis. On the other hand, TNF-R75 release was not related to TNF-alpha secretion. These results indicate that the modulation of TNF-R75 is a critical feature of the pathophysiology of Q fever endocarditis.

Adult↗

PubMed1995

Cross-species complementation of the indispensable Escherichia coli era gene highlights amino acid regions essential for activity.

Era is an essential GTP binding protein in Escherichia coli. Two homologs of this protein, Sgp from Streptococcus mutans and Era from Coxiella burnetii, can substitute for the essential function of Era in E. coli. Site-specific and randomly generated Era mutants which may indicate regions of the protein that are of functional importance are described.

Amino Acid Sequence↗

PubMed2001

Sexually transmitted Q fever.

We report the sexual transmission of Coxiella burnetii from a man with occupationally acquired Q fever to his wife. Fifteen days after coitus, his wife also developed serologically proven acute Q fever. C. burnetii DNA sequences were detected by polymerase chain reaction (PCR) performed on semen samples obtained from the husband at 4 and 15 months after the onset of acute Q fever, but PCR results were variable at 23 months, indicating the presence of few organisms.

Antibodies, Bacterial↗

PubMed2006

Veterinary and medical aspects of abortion in Danish sheep.

The Danish sheep population totals around 144,000 animals, but little is known of the causes and prevalance of diseases. This study focuses on the causes of abortion in Danish sheep. During one breeding season, aborted foetuses and stillbirths with signs of intrauterine death or malformation were submitted for laboratory examination from a population of 3,758 breeding ewes. Samples from 24 incidents of abortion and 21 ewes delivering malformed lambs or lambs with ante partum decomposition were submitted. A specific aetiology was established in 66.7% and 14.3% of the cases, respectively. Bacterial pathogens were the most prevalent cause of abortion. Several of the abortifacients were zoonotic microorganisms, for example Listeria monocytogenes, Campylobacter fetus subsp. fetus, Yersinia pseudotuberculosis and Toxoplasma gondii. The identified microorganisms probably represent the most common causes of abortion in Danish sheep but occurrence in Denmark of other pathogens such as Coxiella burnetii and Chlamydophila abortus cannot be excluded. Due to the high prevalence of zoonotic microorganisms, precautions must be taken in handling abortions or assisting lambing, especially for pregnant women.

Aborted Fetus↗

PubMed2003

Q Fever in human and livestock populations in Oman.

In 2000, Q fever was documented for the first time in the Sultanate of Oman in two patients, one with chronic pericarditis and the other with acute pneumonia. In 2001, a study of a randomly selected group of 102 adult patients from different provinces in northern Oman, presenting to the University Hospital in Muscat with unrelated conditions (e.g., diabetes mellitus, ischemic heart disease), revealed that 10 (9.8%) were seropositive for previous Coxiella burnetii infection. Examination of sera from a randomly selected group of 54 healthy goats from eight different herds from three different provinces of Oman, obtained by the Veterinary Research Center in Muscat, revealed that 28 (52%) had been infected, and 5 sheep, each from one of four herds, were seropositive for C. burnetii. We suspect that Q fever is widely prevalent in human populations in Oman, and that infection is widespread in goat, and probably sheep and other livestock populations, throughout the country.

Adult↗

PubMed2002

[Acute myocardial failure in a young man: Q-fever myocarditis].

Coxiella burnetii myocarditis is a rare but severe clinical form of acute Q fever. We report the case of a 40-year-old man hospitalized for acute febrile syndrome. Forty-eight hours later, he presented dyspnea, orthopnea, and paroxysmal nocturnal dyspnea; cardiac auscultation revealed a third sound and echocardiography showed a diffusely hypokinetic and dilated left ventricle (30% ejection fraction). Serological studies showed antibodies against phase-II C. burnetii antigens (IgG titer 1:320 and IgM 1:50). The patient was treated with losartan, furosemide, and clarithromycin, resulting in rapid improvement. Six months after admission, the echocardiographic changes had completely disappeared.

Acute Disease↗

PubMed2006

Q fever endocarditis: a case report and review of the literature.

The case of a 31-year-old man from Alberta diagnosed with Q fever endocarditis is presented. To the authors' knowledge, this is the first case of Q fever endocarditis diagnosed in the province of Alberta. The patient had undergone open valvulotomy for congenital aortic stenosis as an infant. He presented with congestive heart failure secondary to severe aortic regurgitation and underwent mechanical aortic valve replacement. Early failure of the mechanical prosthesis and numerous laboratory abnormalities prompted an investigation for endocarditis, which was initially negative. Markedly positive serology eventually established the diagnosis of chronic Q fever. The patient subsequently underwent a second aortic valve replacement following initiation of appropriate antimicrobials directed against Coxiella burnetii. The present report reviews the clinical presentation and diagnosis of Q fever endocarditis. It highlights the insidious and nonspecific nature of the presenting symptoms, and emphasizes the use of serology for diagnosis. Increased awareness and earlier diagnosis can significantly decrease the morbidity and mortality associated with this disease.

Adult↗