今日の臨床サポート

Q熱

著者: 高橋洋 坂総合病院 呼吸器科・感染症科

監修: 細川直登 亀田総合病院

著者校正済:2022/03/16
現在監修レビュー中
参考ガイドライン:
  1. 米国疾病管理予防センター(Centers for Disease Control and Prevention:CDC):Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group
  1. オーストラリア保健省:Q fever - CDNA National Guidelines for Public Health Units
患者向け説明資料

概要・推奨   

  1. Q熱コクシエラ肺炎症例の胸部X線所見は典型例では多発性の肺野斑状影を呈する。
  1. 市中肺炎としてのコクシエラ肺炎の頻度は1~4%程度とする報告が多い。
  1. 急性Q熱国内発症例の臨床像
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
高橋洋 : 未申告[2022年]
監修:細川直登 : 未申告[2022年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. Q熱は病原菌Coxiella burnetiiによる動物由来感染症であり、家畜、ペット、野生動物など多様な動物種が無症候性に本菌を保菌してヒトへの潜在的な感染源となる。国内では市中肺炎の原因のうち2~4%程度を占める疾患と考えられている。
  1. 市中肺炎としてのコクシエラ肺炎の頻度は1~4%程度とする報告が多い(エビデンスレベルO)。(参考文献:[1][2][3]
  1. 市中肺炎中に占めるQ熱コクシエラ肺炎の頻度に関しては報告によるばらつきも多いが、スペインやアフリカの一部などの多発地域を除けば積極的に検索して1~4%程度だったとするものが多い。
  1. 国内での検討成績をみると、われわれが宮城で行ったprospective studyでは市中発症呼吸器感染症400例中で2.5%、市中肺炎120例中で4.2%が急性Q熱と診断されている。また沖本らの岡山での検討では市中肺炎中の1.4%、瀧口らの千葉での検討では市中肺炎中の約2%がそれぞれ急性Q熱肺炎であったことが報告されている。
 
病原体Coxiellaのヒトへの感染経路

保菌動物の分泌物や排泄物中に存在する病原菌を直接経気道的に吸入することがCoxiellaのヒトへの主要な感染ルートとなる。

出典

img1:  著者提供
 
 
 
  1. コクシエラのヒトへの感染源として最重要なのは、ウシやヤギ、ヒツジなどの家畜であるが、イヌやネコなどの愛玩動物やハトやカラス、ニワトリなども、ときに本菌を保菌してヒトへの感染源となることが知られている。また、コクシエラは感染力が強く、保菌動物周囲でのアウトブレイクがしばしば報告されている。
  1. コクシエラの感染宿主域は広汎であり多様な動物種が潜在的なヒトへの感染源となり得る(エビデンスレベルO)。(参考文献:[4][5][6]
  1. コクシエラのヒトへの感染源として最重要なのは、ウシやヤギ、ヒツジなどの家畜であるが、イヌやネコなどの愛玩動物もときに本菌を保菌してヒトへの感染源となる、保菌動物の出産時には周囲環境への大量の曝露が成立するため感染の危険性が高い。
  1. またハトやカラス、ニワトリなどの鳥類、あるいはアザラシなどの海生動物も本菌を保菌することがあり、ハトを推定感染源としたアウトブレイクなども報告されている。
  1. 国内でも家畜、イヌ、ネコ、シカ、ウサギ、ネズミ、ハト、カラスなどの動物種においてコクシエラの抗体保有あるいは菌の分離が報告されていることから、わが国においても自然環境中にはコクシエラは広汎に分布していることがうかがえる。
  1. コクシエラは感染力が強く、保菌動物周囲でのアウトブレイクがしばしば報告されている。(参考文献:[7]
  1. コクシエラは感染力が非常に強く、また自然環境中でも長期生存が可能なことから保菌動物の周囲での限局的なアウトブレイクが多数報告されている。
  1. 病原体は風にのって周囲に広汎に飛散するため畜舎などから距離があっても感染が成立する場合がある。
  1. また動物自体だけでなく動物が敷いていた麦藁などが感染源になる場合もあり得る。
  1. 近年では2007年から数シーズンにわたってオランダにおいて農場のヤギやヒツジを感染源とした史上最大規模のアウトブレイクが発生しており、患者数は4,000人を超えたこと、農場の周囲2km程度までが感染拡大のハイリスクゾーンであることなどが報告されている。
  1. 国内では4類感染症であり診断時には届出が必要である。
  1. 急性Q熱は予後良好の疾患である。Coxiella burnetiiに曝露された症例のうちで半数は不顕性感染、4割がインフルエンザ様の一過性の発熱、残る数%が肺炎や肝炎、不明熱など比較的重症な病型を呈する。最も多くみられるのはインフルエンザ様症状で発症し自然治癒するタイプである。病像はおおむね非特異的であり、その臨床像や一般検査所見のみから本症を診断することは困難である[5]
  1. 慢性Q熱は主として心内膜炎の病型をとるが、急性Q熱とは違って治療抵抗性で予後不良である。急性感染例のうち数%が後に慢性Q熱に移行するが、その機序はいまだ十分には解明されていない[8][9]
 
Q熱の発症経過と諸病型

病原体に曝露された症例のうちで半数は不顕性感染、4割がインフルエンザ様の一過性の発熱、残る数%が肺炎や肝炎など比較的重症な病型を呈する。

出典

img1:  著者提供
 
 
問診、診察のポイント  
  1. 診察所見は非特異的であり、ほかの動物由来感染症で認められるような皮疹、刺し口、リンパ節腫大などの特徴的な診断指標は存在しない。

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文献 

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.

PMID 15062916
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.

PMID 15182283
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.

PMID 19195195
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.

PMID 10530457
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.

PMID 10515901
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.

PMID 9713803
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.

PMID 23110336
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.

PMID 22469535
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.
PMID 20637694
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.

PMID 9431924
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.

PMID 12380717
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.

PMID 1914387
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.

PMID 679610
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.

PMID 10771709
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.

PMID 17682987
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.

PMID 11438911
D Raoult, T Marrie
Q fever.
Clin Infect Dis. 1995 Mar;20(3):489-95; quiz 496.
Abstract/Text
PMID 7756465

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