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。     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Serological diagnosis of Q fever endocarditis

The diagnosis of Q fever endocarditis cannot be made by bacterialcultures and necessitates serological identification of specificantibodies to Coxiella burnetii which stimulates mainly theproduction of anti-phase II antibodies during the acute diséase,but primarily anti-phase I antibodies in endocarditis. Indirectmicro-immunofluorescence allows rapid detection of specificIgA, IgG and IgM. The results of serological analyses of 191acute cases of Q fever were compared with those of 8 cases ofCoxiella burnetii endocarditis. All sera were evaluated by complementfixation and microimmunofluorescence tests. The highest titredifferences between primary Q fever and Q fever endocarditiswere observed with anti-phase IIgA and IgG antibodies measuredby microimmunofluorescence followed by anti-phase I antibodiesmeasured by complement fixation tests. Anti-phase IIgG and IgMtitres were consistently higher than anti-phase II titres inendocarditis. The reverse is true in acute Q fever. In addition,anti-phase I Ig A appeared to be diagnostic for Coxiella burnetiiendocarditis. Accordingly we recommend the testing of thesespecific IgA, IgG, and IgM by microimmunofluorescence in casesof culture-negative endocarditis. These tests could also proveuseful for following the development of Coxiella burnetii endocarditisin patients under treatment.     

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.     

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.     

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.     

Pigeon pneumonia in provence: a bird-borne Q fever outbreak.

Q fever is a widespread zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium, which humans usually acquire through the inhalation of infected dust from subclinically infected mammals. Human infection commonly takes place when an infected mammal gives birth, since high concentrations of the organism are found in the products of conception. Worldwide, cattle, sheep, and goats are the most common reservoirs for C. burnetii. A few investigators have also reported parturient cats and dogs as the sources of human outbreaks of Q fever. During a 10-day period in May 1996, all five members of one family living on a farm in Provence, in the south of France, became ill with fever, general malaise, and cough. All of them had acute Q fever. An epidemiological investigation suggested that this outbreak resulted from exposure to contaminated pigeon feces and ticks.     

Cardiac valves in patients with Q fever endocarditis: microbiological,molecular, and histologic studies

The pathologic features of Q fever endocarditis, which is caused by Coxiella burnetii, were histologically evaluated in cardiac valves from 28 patients. We used quantitative image analysis to compare valvular fibrosis, calcifications, vegetations, inflammation, and vascularization due to Q fever endocarditis with that due to non-Q fever endocarditis and valvular degeneration. We also studied the presence of C. burnetii in valves by immunohistochemical analysis, culture, and polymerase chain reaction (PCR). Histologically, Q fever endocarditis was characterized by significant fibrosis and calcifications, slight inflammation and vascularization, and small or absent vegetations. Despite antibiotic treatment, non-statistically significant variations at the histologic level were observed. These pathologic features could be confused with noninfectious valvular degenerative damage. We found that the detection of C. burnetii in cardiac valves by immunohistochemical analysis, culture, and PCR decreased significantly only after 1 year of antibiotic treatment, which emphasizes the long persistence of this organism in valve tissues. Pathologic and immunohistochemical analyses may contribute to the diagnosis of Q fever endocarditis.     

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.     

Bichat guidelines for the clinical management of Q fever and bioterrorism-related Q fever

Q fever is a zoonotic disease caused by Coxiella burnetii. Its interest as a potential biological weapon stems from the fact that an aerosol of very few organisms could infect humans. Another route of transmission of C. burnetii could be through adding it to the food supply. Nevertheless, C. burnetii is considered to be one of the less suitable candidate agents for use in a bioterrorist attack; the incubation is long, many infections are inapparent and the mortality is low. In the case of an intentional release of C. burnetii by a terrorist, clinical presentation would be similar to naturally occurring disease. It may be asymptomatic, acute, normally accompanied by pneumonia or hepatitis, or chronic, usually manifested as endocarditis. Most cases of acute Q fever are asymptomatic and resolve spontaneously without specific treatment. Nevertheless, treatment can shorten the duration of illness and decrease the risk of complications such as endocarditis. Post-exposure prophylaxis is recommended after the exposure in the case of a bioterrorist attack.