Hiroshi Takahashi, Yutaka Tokue, Toru Kikuchi, Takao Kobayashi, Kazuhiro Gomi, Ikuo Goto, Hiroyuki Shiraishi, Hideto Fukushi, Katuya Hirai, Toshihiro Nukiwa, Akira Watanabe
Prevalence of community-acquired respiratory tract infections associated with Q fever in Japan.
Diagn Microbiol Infect Dis. 2004 Apr;48(4):247-52. doi: 10.1016/j.diagmicrobio.2003.11.002.
Abstract/Text
A multicenter prospective cohort study to assess the occurrence and characteristics of acute Q fever associated with community acquired respiratory infections was performed. Among the 400 patients enrolled for the study, 10 (2.50%) patients (5 out of 120 cases of pneumonia, 3 out of 131 cases of acute bronchitis, and 2 out of 149 cases of upper respiratory infections) were diagnosed as having acute Q fever. Contact with dogs or cats before the onset of the disease was confirmed in most of the patients. The clinical profiles of these 10 patients were generally similar to those reported from other countries, such as fever, general fatigue and liver dysfunction, except for the predominance of sporadic cases among the urban population. Our study demonstrates that Q fever is not uncommon cause of community-acquired respiratory infections even in Japan.
Niro Okimoto, Naoko Asaoka, Kohichi Osaki, Takeyuki Kurihara, Kenji Yamato, Takako Sunagawa, Kazue Fujita, Hideo Ohba, Junichi Nakamura, Keiichi Nakada
Clinical features of Q fever pneumonia.
Respirology. 2004 Jun;9(2):278-82. doi: 10.1111/j.1440-1843.2004.00586.x.
Abstract/Text
The aim of the study was to assess the clinical features of Q fever pneumonia in Japan. Four cases of Q fever pneumonia (a female aged 21 and males aged 53, 74 and 87 years) who were diagnosed using the PanBio ELISA test kit, were assessed and their clinical features are described. The frequency of Q fever pneumonia among our cases of community-acquired pneumonia was 1.4% (4/284). A 21-year-old female had a typical case of the disease with (i) a history of owning a cat, (ii) onset with fever and dry cough, (iii) multiple soft infiltrative shadows on CXR, (iv) a normal white blood cell count, and (v) good response to clarithromycin. The pneumonias in the other three cases were considered mixed infections with bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Their clinical features included the following: (i) an elderly person with an underlying disease, (ii) onset with fever and purulent sputum, (iii) coarse crackles on auscultation, (iv) infiltrative shadows and pleural effusion on CXR, (v) increased white blood cells with elevated BUN and hyponatraemia, and (vi) modest responses to combined therapy with carbapenem and minocycline. Our observations suggest that two types of pneumonia caused by Coxiella burnetti exist; one with the usual features of atypical pneumonia, and the other presenting with the clinical features of bacterial pneumonia in the elderly due to mixed bacterial infection.
Yasuo Takiguchi, Satoru Ishikawa, Yukiko Shinbo
[Clinical features of Q-fever pneumonia].
Nihon Kokyuki Gakkai Zasshi. 2008 Dec;46(12):967-71.
Abstract/Text
A retrospective study was undertaken to investigate the clinical aspects of Q-fever pneumonia. Six sporadic cases, 5 men and 1 woman, aged between 36 and 81 years were diagnosed by testing paired serum samples using an indirect immunofluorescence assay from July 2004 to June 2007. Of these, 5 suffered from concomitant or chronic disease. The predominant clinical features were fever, cough, sputum, and chest pain. The WBC count was within normal values in half of the patients. C-reactive protein was elevated in all patients. Liver dysfunction was noted in 2 patients. Chest computed tomography revealed air space consolidation and small nodules in all patients and pleural effusion in 1 patient. Anti-phase II IgG titers of paired serum samples were elevated, but anti-phase II IgM titers were within normal limits in all the patients. Antibiotics were given to all the patients, and, beta-lactum agents were prescribed for 3 patients. The outcome was favorable in all the patients. These patients demonstrated nonspecific clinical, radiological, and laboratory manifestations, and we were able to distinguish Q-type pneumonia from other forms of community-acquired pneumonia only by testing anti-phase II IgG titers of paired serum samples.
A Stein, D Raoult
Pigeon pneumonia in provence: a bird-borne Q fever outbreak.
Clin Infect Dis. 1999 Sep;29(3):617-20.
Abstract/Text
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.
M Maurin, D Raoult
Q fever.
Clin Microbiol Rev. 1999 Oct;12(4):518-53.
Abstract/Text
Q fever is a zoonosis with a worldwide distribution with the exception of New Zealand. The disease is caused by Coxiella burnetii, a strictly intracellular, gram-negative bacterium. Many species of mammals, birds, and ticks are reservoirs of C. burnetii in nature. C. burnetii infection is most often latent in animals, with persistent shedding of bacteria into the environment. However, in females intermittent high-level shedding occurs at the time of parturition, with millions of bacteria being released per gram of placenta. Humans are usually infected by contaminated aerosols from domestic animals, particularly after contact with parturient females and their birth products. Although often asymptomatic, Q fever may manifest in humans as an acute disease (mainly as a self-limited febrile illness, pneumonia, or hepatitis) or as a chronic disease (mainly endocarditis), especially in patients with previous valvulopathy and to a lesser extent in immunocompromised hosts and in pregnant women. Specific diagnosis of Q fever remains based upon serology. Immunoglobulin M (IgM) and IgG antiphase II antibodies are detected 2 to 3 weeks after infection with C. burnetii, whereas the presence of IgG antiphase I C. burnetii antibodies at titers of >/=1:800 by microimmunofluorescence is indicative of chronic Q fever. The tetracyclines are still considered the mainstay of antibiotic therapy of acute Q fever, whereas antibiotic combinations administered over prolonged periods are necessary to prevent relapses in Q fever endocarditis patients. Although the protective role of Q fever vaccination with whole-cell extracts has been established, the population which should be primarily vaccinated remains to be clearly identified. Vaccination should probably be considered in the population at high risk for Q fever endocarditis.
K Hirai, H To
Advances in the understanding of Coxiella burnetii infection in Japan.
J Vet Med Sci. 1998 Jul;60(7):781-90.
Abstract/Text
Q fever is a zoonotic disease caused by a rickettsia Coxiella burnetii. Since its first description in 1937, the disease has been found to be present in most countries of the world. Serological evidences of Q fever in humans and coxiellosis in animals were reported in Japan in the 1950s, however, systematic studies of the disease did not begin until the report of isolation of C. burnetii from an acute Q fever patient in 1989. In addition to the extensive information about epidemiology of the disease, the understanding of Japanese isolates of C. burnetii is increasing rapidly in recent years. In this review, the epidemiology of the disease along with some characteristics of isolates of C. burnetii in Japan is summarized in five sections, i.e., coxiellosis, Q fever, modes of spread of the infection, laboratory diagnosis of the infection and some characteristics of Japanese isolates. This review includes some recent, unpublished data from our and other groups.
Joris Af van Loenhout, W John Paget, Jan H Vercoulen, Clementine J Wijkmans, Jeannine L A Hautvast, Koos van der Velden
Assessing the long-term health impact of Q-fever in the Netherlands: a prospective cohort study started in 2007 on the largest documented Q-fever outbreak to date.
BMC Infect Dis. 2012 Oct 30;12:280. doi: 10.1186/1471-2334-12-280. Epub 2012 Oct 30.
Abstract/Text
BACKGROUND: Between 2007 and 2011, the Netherlands experienced the largest documented Q-fever outbreak to date with a total of 4108 notified acute Q-fever patients. Previous studies have indicated that Q-fever patients may suffer from long-lasting health effects, such as fatigue and reduced quality of life. Our study aims to determine the long-term health impact of Q-fever. It will also compare the health status of Q-fever patients with three reference groups: 1) healthy controls, 2) patients with Legionnaires' disease and 3) persons with a Q-fever infection but a-specific symptoms.
METHODS/DESIGN: Two groups of Q-fever patients were included in a prospective cohort study. In the first group the onset of illness was in 2007-2008 and participation was at 12 and 48 months. In the second group the onset of illness was in 2010-2011 and participation was at 6 time intervals, from 3 to 24 months. The reference groups were included at only one time interval. The subjective health status, fatigue status and quality of life of patients will be assessed using two validated quality of life questionnaires.
DISCUSSION: This study is the largest prospective cohort study to date that focuses on the effects of acute Q-fever. It will determine the long-term (up to 4 years) health impact of Q-fever on patients and compare this to three different reference groups so that we can present a comprehensive assessment of disease progression over time.
Linda M Kampschreur, Sandra Dekker, Julia C J P Hagenaars, Peter J Lestrade, Nicole H M Renders, Monique G L de Jager-Leclercq, Mirjam H A Hermans, Cornelis A R Groot, Rolf H H Groenwold, Andy I M Hoepelman, Peter C Wever, Jan Jelrik Oosterheert
Identification of risk factors for chronic Q fever, the Netherlands.
Emerg Infect Dis. 2012 Apr;18(4):563-70. doi: 10.3201/eid1804.111478.
Abstract/Text
Since 2007, the Netherlands has experienced a large Q fever outbreak. To identify and quantify risk factors for development of chronic Q fever after Coxiella burnetii infection, we performed a case-control study. Comorbidity, cardiovascular risk factors, medications, and demographic characteristics from 105 patients with proven (n = 44), probable (n = 28), or possible (n = 33) chronic Q fever were compared with 201 patients who had acute Q fever in 2009 but in whom chronic Q fever did not develop (controls). Independent risk factors for development of proven chronic Q fever were valvular surgery, vascular prosthesis, aneurysm, renal insufficiency, and older age.
Matthieu Million, Franck Thuny, Hervé Richet, Didier Raoult
Long-term outcome of Q fever endocarditis: a 26-year personal survey.
Lancet Infect Dis. 2010 Aug;10(8):527-35. doi: 10.1016/S1473-3099(10)70135-3. Epub 2010 Jul 14.
Abstract/Text
BACKGROUND: Q fever endocarditis caused by Coxiella burnetii is a potentially fatal disease characterised by a chronic evolution. To assess the long-term outcome and identify prognostic factors for mortality, surgical treatment, and serological changes in Q fever endocarditis, we did a retrospective study in the French National Referral Centre.
METHODS: Patients included were diagnosed with Q fever endocarditis at our centre from May, 1983, to June, 2006, and followed up for a minimum of 3 years for each patient, history and clinical characteristics were recorded with a standardised questionnaire. Prognostic factors associated with death, surgery, serological cure, and serological relapse were assessed by Cox regression analysis. Excised heart valve analysis was assessed according to duration of treatment.
FINDINGS: 104 patients were identified for inclusion in the study, although one was lost to follow-up; median follow-up was 100 months (range 37-310 months). 18 months of treatment was sufficient to sterilise the valves of all the patients except three, and 2 years of treatment sterilised all valves except one. In a multivariate Cox regression analysis, the major determinants associated with mortality were age (hazard ratio 1.11, 95% CI 1.05-1.18, p=0.003), stroke at diagnosis (7.09, 2.00-25.10, p=0.001), endocarditis on a prosthetic valve (6.04, 1.47-24.80, p=0.044), an absence of a four-times decrease of phase I IgG and IgA at 1 year (5.69, 1.00-32.22, p=0.049), or the presence of phase II IgM at 1 year (12.08, 3.11-46.85, p=0.005). Surgery was associated with heart failure (2.68, 1.21-5.94, p=0.015) or a cardiac abscess (4.71, 1.64-13.50, p=0.004). The determinants of poor serological outcome were male sex (0.47, 0.26-0.86, p=0.014), a high level of phase I IgG (0.65, 0.45-0.95, p=0.027), and a delay in the start of treatment with hydroxychloroquine (0.20, 0.04-0.91, p=0.037). Factors associated with relapse were endocarditis on a prosthetic valve (21.3, 2.05-221.86, p=0.01) or treatment duration less than 18 months (9.69, 1.08-86.72, p=0.042).
INTERPRETATION: The optimum duration of treatment with doxycycline and hydroxychloroquine in Q fever endocarditis is 18 months for native valves and 24 months for prosthetic valves. This duration should be extended only in the absence of favourable serological outcomes. Patients should be serologically monitored for at least 5 years because of the risk of relapse.
FUNDING: French National Referral Centre for Q Fever.
2010 Elsevier Ltd. All rights reserved.
高橋 洋他 Q熱 病原菌の今日的意味 改訂4版 726～738 医薬ジャーナル社 2011.
G Q Zhang, S V Nguyen, H To, M Ogawa, A Hotta, T Yamaguchi, H J Kim, H Fukushi, K Hirai
Clinical evaluation of a new PCR assay for detection of Coxiella burnetii in human serum samples.
J Clin Microbiol. 1998 Jan;36(1):77-80.
Abstract/Text
A nested PCR method was developed for the detection of Coxiella burnetii in human serum samples. Two pairs of oligonucleotide primers were designed to amplify a 438-bp fragment of the com1 gene encoding a 27-kDa outer membrane protein of C. burnetii. The primers amplified the predicted fragments of 21 various strains of C. burnetii but did not react with DNA samples from other microorganisms. The 438-bp amplification products could be digested with restriction enzymes SspI and SalI. The utility of the nested PCR was evaluated by testing human serum samples. The com1 gene fragment was amplified from 135 (87%) of 155 indirect immunofluorescence test (IF)-positive serum samples and from 11 (11%) of 100 IF-negative serum samples. The nested PCR with primers targeted to the com1 gene appeared to be a sensitive, specific, and useful method for the detection of C. burnetii in serum samples.
T Abe, K Yamaki, T Hayakawa, H Fukuda, Y Ito, H Kume, T Komiya, K Ishihara, K Hirai
A seroepidemiological study of the risks of Q fever infection in Japanese veterinarians.
Eur J Epidemiol. 2001;17(11):1029-32.
Abstract/Text
The causative agent of Q fever, a widespread zoonotic disease, is the bacteria Coxiella burnetii. Although cases of Q fever have been documented in countries throughout the world, the prevalence of the disease in Japan is not yet known. Q fever is a demonstrated occupational hazard to those employed in zoological professions, but the risk to Japanese veterinarians has not yet been quantified. In order to evaluate the risk to Japanese veterinarians, we performed a serological survey using serum samples from 267 veterinarians. Two control groups consisting of 352 medical workers and 2003 healthy blood donors were also evaluated. The antibody titers of the serum samples were measured by indirect immunofluorescence assay (IFA) using phase II C. burnetii Nine Mile strain as the antigen. The positive rate of IgG antibody was 13.5% in the veterinarians, which was higher than in the blood donors (3.6%, p < 0.001) and medical workers (5.1 %,p < 0.001). These findings suggest that Japanese veterinarians have a higher risk of infection by C. burnetii than other members of the Japanese population. An interesting finding of this study was that positive rates of IgG and IgM antibodies in the blood donor group were higher in younger individuals. The IgM antibody positive rate was the highest in females under 30 years old.
F E Pickworth, M el-Soussi, I P Wells, C R McGavin, S Reilly
The radiological appearances of 'Q' fever pneumonia.
Clin Radiol. 1991 Sep;44(3):150-3.
Abstract/Text
The chest film findings in a series of 21 cases of serologically proven 'Q' fever with radiological evidence of pneumonia were reviewed retrospectively. Segmental opacities which were slow to clear, often with loss of volume and sometimes lobar consolidation, were the most usual findings. Lesions were occasionally multiple and sometimes became rounded during resolution. The appearances were not considered sufficiently distinctive to allow the diagnosis to be made in the acute phase of the illness, although the appearance of round pneumonias which are slow to resolve should alert the radiologist to this possible diagnosis. The findings are discussed in relation to previously reported series.
J K Millar
The chest film findings in 'Q' fever--a series of 35 cases.
Clin Radiol. 1978 Jul;29(4):371-5.
Abstract/Text
Thirty-five cases of 'Q' fever have been admitted and confirmed serologically over the past 20 years. Thirty-two of these cases had chest films on admission, and lung changes were present in 87%. The lung changes were: 1. Multiple round segmental consolidations, 5--10 cm in diameter, of ground glass density and usually situated in the lower lobes. 2. Linear atelectasis. 3. Lobar or partial lobar consolidation, with some loss of volume in the affected lobe. 4. A slight pleural reaction in a few cases. 5. Some cases had background emphysema of the lungs. All the lesions tended to be slow to clear. The resolution time was from 10 to 70 days, with an average time fo 30 days. Some of the segmental lesions became small, round and dense during resolution. The 35 cases were almost exclusively in males. The finding of a single or multiple round segmental opacities of ground glass density, as described, especially with linear atelectasis, was found to be good evidence that the patient had 'Q' fever. The point is made that the admission chest film is in some cases a very useful early pointer to the diagnosis. This allows specific chemotherapy to be started before the serological results have come back. Plate atelectasis was helpful as a distinguishing feature from primary atypical pneumonia.
高橋 洋、渡辺 彰：Q熱の画像診断および臨床診断 肺炎の画像診断と最新の診療 235～242 医薬ジャーナル社 2008.
D Raoult, H Tissot-Dupont, C Foucault, J Gouvernet, P E Fournier, E Bernit, A Stein, M Nesri, J R Harle, P J Weiller
Q fever 1985-1998. Clinical and epidemiologic features of 1,383 infections.
Medicine (Baltimore). 2000 Mar;79(2):109-23.
Abstract/Text
In order to describe the clinical features and the epidemiologic findings of 1,383 patients hospitalized in France for acute or chronic Q fever, we conducted a retrospective analysis based on 74,702 sera tested in our diagnostic center, National Reference Center and World Health Organization Collaborative Center for Rickettsial Diseases. The physicians in charge of all patients with evidence of acute Q fever (seroconversion and/or presence of IgM) or chronic Q fever (prolonged disease and/or IgG antibody titer to phase I of Coxiella burnetii > or = 800) were asked to complete a questionnaire, which was computerized. A total of 1,070 cases of acute Q fever was recorded. Males were more frequently diagnosed, and most cases were identified in the spring. Cases were observed more frequently in patients between the ages of 30 and 69 years. We classified patients according to the different clinical forms of acute Q fever, hepatitis (40%), pneumonia and hepatitis (20%), pneumonia (17%), isolated fever (17%), meningoencephalitis (1%), myocarditis (1%), pericarditis (1%), and meningitis (0.7%). We showed for the first time, to our knowledge, that different clinical forms of acute Q fever are associated with significantly different patient status. Hepatitis occurred in younger patients, pneumonia in older and more immunocompromised patients, and isolated fever was more common in female patients. Risk factors were not specifically associated with a clinical form except meningoencephalitis and contact with animals. The prognosis was usually good except for those with myocarditis or meningoencephalitis as 13 patients died who were significantly older than others. For chronic Q fever, antibody titers to C. burnetii phase I above 800 and IgA above 50 were predictive in 94% of cases. Among 313 patients with chronic Q fever, 259 had endocarditis, mainly patients with previous valvulopathy; 25 had an infection of vascular aneurysm or prosthesis. Patients with endocarditis or vascular infection were more frequently immunocompromised and older than those with acute Q fever. Fifteen women were infected during pregnancy; they were significantly more exposed to animals and gave birth to only 5 babies, only 2 with a normal birth weight. More rare manifestations observed were chronic hepatitis (8 cases), osteoarticular infection (7 cases), and chronic pericarditis (3 cases). Nineteen patients were observed who experienced first a documented acute infection, then, due to underlying conditions, a chronic infection. To our knowledge, we report the largest series of Q fever to date. Our results indicate that Q fever is a protean disease, grossly underestimated, with some of the clinical manifestations being only recently reported, such as Q fever during pregnancy, chronic vascular infection, osteomyelitis, pericarditis, and myocarditis. Our data confirm that chronic Q fever is mainly determined by host factors and demonstrate for the first time that host factors may also play a role in the clinical expression of acute Q fever.
Xavier Carcopino, Didier Raoult, Florence Bretelle, Léon Boubli, Andreas Stein
Managing Q fever during pregnancy: the benefits of long-term cotrimoxazole therapy.
Clin Infect Dis. 2007 Sep 1;45(5):548-55. doi: 10.1086/520661. Epub 2007 Jul 17.
Abstract/Text
BACKGROUND: Q fever is a zoonosis caused by Coxiella burnetii. During pregnancy, it may result in obstetric complications, such as spontaneous abortion, intrauterine growth retardation, intrauterine fetal death, and premature delivery. Pregnant women are exposed to the risk of chronic Q fever.
METHODS: We included 53 pregnant women who received a diagnosis of Q fever. We compared the incidence of obstetric and maternal Q fever complications for women who received long-term cotrimoxazole treatment (n=16) with that for women who did not receive long-term cotrimoxazole treatment (n=37); long-term cotrimoxazole treatment was defined as oral administration of trimethoprim-sulfamethoxazole during at least 5 weeks of pregnancy.
RESULTS: Obstetric complications were observed in 81.1% of pregnant women who did not receive long-term cotrimoxazole therapy: 5 (13.5%) women experienced spontaneous abortions, 10 (27%) experienced intrauterine growth retardation, 10 (27%) experienced intrauterine fetal death, and 10 (27%) experienced premature delivery. Oligoamnios was observed in 4 patients (10.8%). Obstetric complications were found to occur significantly more often in patients infected during their first trimester of pregnancy than in those infected later (P=.032). The outcome of the pregnancy was found to depend on placental infection by C. burnetii (P=.013). Long-term cotrimoxazole treatment protected against maternal chronic Q fever (P=.001), placental infection (P=.038), and obstetric complications (P=.009), especially intrauterine fetal death (P=.018), which was found to be related to placental infection (P=.008).
CONCLUSIONS: Q fever during pregnancy results in severe obstetric complications, including oligoamnios. Because of its ability to protect against placental infection, intrauterine fetal death, and maternal chronic Q fever, long-term cotrimoxazole treatment should be used to treat pregnant women with Q fever.
A Milazzo, R Hall, P A Storm, R J Harris, W Winslow, B P Marmion
Sexually transmitted Q fever.
Clin Infect Dis. 2001 Aug 1;33(3):399-402. doi: 10.1086/321878. Epub 2001 Jul 5.
Abstract/Text
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.
D Raoult, T Marrie
Q fever.
Clin Infect Dis. 1995 Mar;20(3):489-95; quiz 496.
Abstract/Text
