Coxiella burnetii pneumonia.

This report reviews the pulmonary and extrapulmonary manifestation of infections due to Coxiella burnetii. Q fever, a zoonosis, is due to infection with C. burnetii. This spore-forming microorganism is a small gram-negative coccobacillus that is an obligate intracellular parasite. The most common animal reservoirs are goats, cattle, sheep, cats, and occasionally dogs. The organism reaches high concentrations in the placenta of infected animals. Aerosolisation occurs at the time of parturition and infection follows inhalation of this aerosol. There are three distinct clinical syndromes of the acute form of the illness: nonspecific febrile illness, pneumonia, and hepatitis. The chronic form of Q fever is almost always endocarditis, but occasionally it is manifest as hepatitis, osteomyelitis or endovascular infection. The pneumonic form of the illness can range from very mild-to-severe pneumonia requiring assisted ventilation. Multiple round opacities are a common finding on chest radiography. Treatment with doxycycline or a fluoroquinolone is preferred. Susceptibility to macrolides is variable. In conclusion, Coxiella burnetii pneumonia should be considered when there is a suitable exposure history and when outbreaks of a pneumonic illness are being investigated.     

Q fever in children

Q fever is a zoonosis caused by Coxiella burnetii. Farm animals and pets are the main reservoirs of infection, and transmission to human beings is mainly accomplished through inhalation of contaminated aerosols. This illness is associated with a wide clinical spectrum, from asymptomatic or mildly symptomatic seroconversion to fatal disease. Q fever in children has been rarely reported. We reviewed published work on this topic. Seroepidemiological studies show that children are frequently exposed to C burnetii. However, children are less frequently symptomatic than adults following infection, and may have milder diseases. Using the standard diagnostic criteria, we identified 46 published paediatric cases only. Self-limited febrile illness and pneumonia were the most common manifestations of acute Q fever. Chronic disease manifested as endocarditis and osteomyelitis. A history of exposure to possible sources of infection with C burnetii in a child with a compatible infectious syndrome should prompt testing for Q fever. Studies are required to determine the spectrum of morbidity associated with Q fever during childhood.     

Cellular immunity in Q fever: specific lymphocyte unresponsiveness in Q fever endocarditis

Human infection with the rickettsia Coxiella burnetii presents as acute influenza-like primary Q fever, subacute granulomatous hepatitis, or chronic endocarditis with hepatitis. To investigate whether persistent infection is associated with a possible immunologic defect, we tested lymphocyte proliferation specific for Coxiella in vitro in peripheral blood mononuclear cells from patients and controls. All four patients with endocarditis had profound lymphocyte unresponsiveness to Coxiella antigens with normal proliferation to control antigens. Hepatitis and primary Q fever were associated with vigorous responses in vitro to Coxiella antigens. Suppression of lymphocyte unresponsiveness was in part mediated by an antigen-nonspecific, glass-adherent cell. We hypothesize that specific T cell unresponsiveness is an important factor in persistent infection with C. burnetii and offer in vitro lymphocyte stimulation as a more specific diagnostic test to distinguish cases of endocarditis among those with chronic hepatitis due to Q fever.     

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.     

Link between impaired maturation of phagosomes and defective Coxiella burnetii killing in patients with chronic Q fever

Q fever is caused by Coxiella burnetii, a bacterium that survives in monocytes/macrophages by resisting their natural microbicidal activity. Because the link between bacterial killing and phagosome maturation has yet to be demonstrated, we evaluated responses in monocytes from both immunologically naive control subjects and patients with various manifestations of Q fever. Monocytes from patients with chronic Q fever in evolution, who do not control the infection, exhibited defective phagosome maturation and impaired C. burnetii killing. Both responses were stimulated in patients recovering from Q fever. Phagosome maturation and C. burnetii killing were significantly correlated. Defective phagosome maturation and impaired C. burnetii killing were induced by adding interleukin (IL)-10 to monocytes from convalescent patients and were restored by IL-10 neutralization in chronic Q fever in evolution. We show that phagosome maturation and microbial killing are linked in Q fever and that IL-10 regulates both features of microbicidal activity.     

Coxiella burnetii and acute exacerbations/infections in patients with chronic lung disease

The aim of the present study was to determine the incidence of Q fever in patients with an acute exacerbation of a chronic lower respiratory tract infection. Eighty patients treated for acute exacerbation of chronic lower respiratory tract infections during a 30-month period were studied. Q fever was diagnosed by ELISA. Two elderly woman with pre-existing bronchiectasis (2.5%) were diagnosed as having an acute infection by Coxiella burnetii. The acute illness was considered to be a result of mixed infection with Pseudomonas aeruginosa and Haemophilus influenzae with C. burnetii. Co-infection with C. burnetii can occur during a bacterial exacerbation of a chronic lower respiratory tract infection.     

Seroepidemiology of Coxiella burnetii infection and its frequency as a cause of community-acquired pneumonia in Canada

The present study tested acute and convalescent serum samples from 788 patients hospitalized for community-acquired pneumonia in seven Canadian provinces for antibodies to Coxiella burnetii. One hundred nine patients (13.8%) had antibodies to this microorganism, and seven patients had acute Q fever. Serological evidence of infection with C burnetii was present in patients from all seven provinces. Three of the seven cases of acute Q fever were from Manitoba, suggesting that there may be unrecognized cases of Q fever in this province. In addition, a case of acute Q fever in Newfoundland, where there had previously been no reported cases, was noted, although subsequently, an outbreak of Q fever on goat farms has been reported.     

Q fever pneumonia

Pneumonia is one of several clinical syndromes that results from inhalation of Coxiella burnetii. This microorganism, the etiologic agent of "Q" (query) fever, infects a wide range of animals and insects. Cattle, sheep, goats, and cats are the reservoirs whereby this agent is spread to humans. High concentrations of C burnetii are present in the placenta and at parturition, the organism is shed into the environment to be inhaled by humans. Following an incubation period that ranges from four to 30 days (mean 14 days), fever, headache, malaise, and cough ensue. The clinical presentation of pneumonia may range from a mild to a severe illness--the latter with the clinical picture of rapidly progressive pneumonia. There are no characteristic features of Q fever pneumonia but the severe headache and the epidemiological history should serve as clues. Treatment with tetracycline or rifampin for two weeks usually results in cure. Many cases of Q fever pneumonia remit without antibiotic therapy. The diagnosis is usually confirmed serologically using a complement fixation or microimmunofluorescence test.     

1例Q热肺炎诊治报告北大核心CSCD

Q热是一种重要的人兽共患病,病原体为贝氏柯克斯体(Coxiella burnetii),其经呼吸道吸入进入体内,引起急性Q热,严重急性Q热可出现肺炎、肝炎或心肌炎并发症。部分患者治疗不彻底转为慢性Q热。慢性Q热为贝氏柯克斯体在机体局部持续感染,常需要外科手术及数年抗感染治疗,其严重危害患者身体健康及加重家庭经济负担;。追其原因是临床医生对该病认识不足,导致延误治疗所致。本文旨在报告1例Q热肺炎的诊治和体会,以提高临床医生对该病认识。     

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.     

Acute and chronic Q fever in patients with cancer.

Q fever is caused by Coxiella burnetii, a strictly intracellular bacterium that lives within the phagolysosome of infected cells. We report here five cases of Q fever in patients with cancer. Three of them had a solid tumor, one had a B cell lymphoma, and one had chronic myeloid leukemia. One patient had acute Q fever, and the four others had chronic Q fever endocarditis. Two patients with endocarditis had no previous history of valvulopathy. C. burnetii was isolated from the valves of two patients. One of the patients with endocarditis died. Patients with cancer who have unexplained fever and live in areas in which C. burnetii is endemic should undergo serological testing for infection with this microorganism.     

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.     

Cynomolgus monkey model for experimental Q fever infection.

A subhuman primate model was developed for study of the pathogenesis of infection with Coxiella burnetii. Cynomolgus monkeys (Macaca fascicularis) that were exposed to 10(5) mouse median infectious intraperitoneal doses of C. burnetii in a small-particle aerosol developed clinical signs of illness and pathologic changes characteristic of Q fever infection in humans. All monkeys had radiologic evidence of pneumonia by day 9. Antibodies to C. burnetii were detectable by the indirect fluorescent antibody test by day 7. These data indicate that the cynomolgus monkey is a suitable model for study of the pathogenesis of Q fever infection and may prove valuable in the evaluation of C. burnetii vaccines.     

Repeated pregnancies in BALB/c mice infected with Coxiella burnetii cause disseminated infection, resulting in stillbirth and endocarditis

Q fever is a widespread zoonosis caused by the obligate intracellular bacterium Coxiella burnetii. Although this highly virulent organism is most concentrated in mammals during parturition, there are few reports on the manifestations of perinatal Q fever in the human and animal host. The affinity of C. burnetii to pregnancy and its abortifacient potential were investigated in a murine animal model. Intraperitoneal infection of female BALB/c mice with C. burnetii, followed by repeated pregnancies over a 2-year period, resulted in persistent infection associated with abortion and perinatal death, with a statistically significant decrease in viable offspring. In addition, endocarditis occurred in 2 of the adult animals, and C. burnetii antigen and DNA were detected in their heart valves. Taken together, these results demonstrate the abortifacient potential of C. burnetii and the increased risk of persistent infection and endocarditis in pregnant mice, probably related to a decline in cellular immunity during pregnancy.     

Q fever in acute exacerbation of chronic lower respiratory tract infection]

We studied the effect of Q fever in acute exacerbation of chronic lower respiratory tract infection. The subjects consisted of 80 cases with acute exacerbation of chronic lower respiratory tract infection treated during the period from March 2002 till October 2004. Q fever was diagnosed using a PanBio Coxiella burnetii ELISA test kit. Two cases (2.5%) were positive for IgM in the acute stage, and were diagnosed as having acute infection by C. burnetii. They were elderly women with bronchiectasis, aged 76 and 82. They had no history of keeping cats or dogs, but the onset of acute exacerbation of chronic lower respiratory tract infection was June and March which is the breeding seasons for cats and dogs. Acute exacerbation of chronic lower respiratory tract infection were considerd to be a mixed infection with Pseudomonas aeruginosa (the 76-year-case) and Haemophilus influenzae (the 82-year-case). It is concluded that C. burnetii can induce exacerbation of chronic lower respiratory tract infection, their cases were considerd to be mixed infection with C. burnetii and other bacteria.     

Clinical manifestation of Q fever and tuberculosis, similarly caused by intracellular parasites

Q fever is a generic term for pneumonia, bronchitis, etc. caused by infection with Coxiella burnetii, a rickettsia-related species of bacteria, in humans. Q-fever is a transient and acute febrile illness that takes a course similar to influenza, and its clinical picture greatly differs from that of tuberculosis that takes a chronic course. The reason for this is thought to be because the generation time of C. burnetii is extremely short (several tens of minutes) compared with Mycobacterium tuberculosis, though those are similar intracellular parasites. Q fever is fourth- or fifth-ranked among the community-acquired pneumonias in the United States and Europe but has a good prognosis with 1-2% of mortality even in the cases that follow a natural course without treatment. Meanwhile, there is a chronic type that follows a protracted course or has a poor prognosis. Therefore, cases definitely diagnosed with Q fever or strongly suspected of Q fever should seek aggressive treatment. Q fever is definitely diagnosed by confirming significant increase in serum antibody titer, but the patients should be followed because in many cases it takes a long time before serum antibody titer increases. Beta-lactams are ineffective against C. burnetii, an obligate intracellular parasite. Although tetracyclines, macrolides, quinolones, rifampicin, etc. are used effectively in the treatment of Q fever, many cases appear to improve by beta-lactam administration because the illness often takes a natural course.     

Chronic sternal wound infection and endocarditis with Coxiella burnetii.

Chronic Q fever is most commonly associated with culture-negative endocarditis and less frequently with infection of vascular grafts, infection of aneurysms, hepatitis, pulmonary disease, osteomyelitis, and neurological abnormalities. We report a case of chronic sternal wound infection, polyclonal gammopathy, and mixed cryoglobulinemia in which Q fever endocarditis was subsequently diagnosed. Polymerase chain reaction analysis of the wound tissue was positive for Coxiella burnetii DNA, and treatment of the endocarditis resulted in prompt healing of the wound. Chronic Q fever can occur without epidemiological risk factors for C. burnetii exposure and can produce multisystem inflammatory dysfunction, aberrations of the immune system, and persistent wound infections.     

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.     

Diffuse abdominal uptake mimicking peritonitis in gallium inflammatory scan: an unusual feature of acute Q fever

The clinical features in patients with acute Q fever are variable. We present a patient with fever, abdominal distension, pericardial effusion, and diffuse gallium uptake in the abdominal cavity, mimicking peritonitis or peritoneum carcinomatosis. Serologic surveys revealed acute infection by Coxiella burnetii. The patient responded poorly to doxycycline and improved with oral levofloxacin. During the afebrile period, gallium inflammatory scan showed resolution of previous diffuse uptake in the abdomen, and cardiac echo resolution of pericardial effusion, which was suggestive of peritoneal inflammation related to acute C. burnetii infection. Therefore, clinicians in Taiwan should be alert to the possibility of acute Q fever in patients with fever of unknown cause, especially with clinical evidence of peritoneal and/or pericardial inflammation.     

Natural history of Q fever in goats

During the spring of 1999, an outbreak of Q fever resulted in 30 abortions among 174 (17%) goats in a caprine cooperative in Newfoundland. The intent of this study was to determine the natural history of Coxiella burnetii infection in goats. Twenty-four goats on one farm were followed through the next two kidding seasons following the Q fever outbreak. Antibodies to phases I and II C. burnetii were determined using an indirect immunofluorescence assay and samples of placentas were cultured for C. burnetii and polymerase chain reaction was used to identify C. burnetii DNA. Phase I antibody was present in high levels and was maintained over the study period, while phase II antibody levels declined to the seronegative range in 60% of the infected goats. Molecular studies suggest that excretion of C. burnetii in the placenta of infected goats seems to be limited to the next kidding season following an outbreak. We therefore conclude that C. burnetii infection in goats seems to be limited to two kidding seasons. Phase I antibody levels are maintained, while phase II antibody levels decline.