姜占青

Q热是由贝纳柯克斯体（Coxiella burnetii）引起的全球性人兽共患病，其流行病学特征复杂、病理机制独特且临床诊断与治疗存在诸多挑战。流行病学研究显示，Q热在全球广泛分布，除新西兰外几乎覆盖所有地区，其传播途径以气溶胶传播为主，动物宿主包括牛、羊、骆驼等，人类感染风险与职业暴露、动物接触密切相关。病理机制方面，贝氏柯克斯体通过IV型分泌系统（T4SS）分泌效应蛋白，如CaeA、AnkG等，抑制宿主细胞凋亡并调控自噬通路，形成独特的含菌空泡（CCV）以利于自身复制。临床特征上，急性Q热常表现为非特异性流感样症状，慢性Q热则易累及心脏瓣膜和血管系统，导致心内膜炎、动脉瘤等严重并发症。治疗上，多西环素联合羟氯喹是慢性Q热的标准方案，但耐药性问题及治疗效果评估仍需深入研究。本文报道1例以慢性心肺疾病为基础，合并Q热感染的病例，结合临床资料进行分析，为临床诊疗提供参考。

Q热；贝纳柯克斯体；临床特征；诊断与治疗

[1] Boarbi S,Fretin D,Mori M.Coxiella burnetii,agent de la fièvre Q.Can J Microbiol.2016 Feb;62(2):102-22.French. [2] Leulmi H,Aouadi A,Bitam I,Bessas A,Benakhla A,Raoult D,Parola P.Detection of Bartonella tamiae,Coxiella burnetii and rickettsiae in arthropods and tissues from wild and domestic animals in northeastern Algeria.Parasit Vectors.2016 Jan 20;9:27. [3] Shabbir MZ,Akram S,Hassan ZU,Hanif K,Rabbani M,Muhammad J,Chaudhary MH,Abbas T,Ghori MT,Rashid H,Jamil T,Islam ZU, Rasool H,Bano A,Ahmad A,Ali MA,Yaqub T,McVey W,Jayarao BM.Evidence of Coxiella burnetii in Punjab province,Pakistan.Acta Trop.2016 Nov;163:61-9. [4] van Leuken JP,Swart AN,Droogers P,van Pul A,Heederik D,Havelaar AH.Climate change effects on airborne pathogenic bioaerosol concentrations:a scenario analysis.Aerobiologia(Bologna).2016;32(4):607-617. [5] Bisle S,Klingenbeck L,Borges V,Sobotta K,Schulze-Luehrmann J,Menge C,Heydel C,Gomes JP,Lührmann A.The inhibition of the apoptosis pathway by the Coxiella burnetii effector protein CaeA requires the EK repetition motif,but is independent of survivin. Virulence. 2016 May 18;7(4):400-12. [6] Schäfer W,Eckart RA,Schmid B,CagköylüH,Hof K,Muller YA,Amin B,Lührmann A.Nuclear trafficking of the anti-apoptotic Coxiella burnetii effector protein AnkG requires binding to p32 and Importin-α1.Cell Microbiol.2017 Jan;19(1). [7] Kohler LJ,Reed ShC,Sarraf SA,Arteaga DD,Newton HJ,Roy CR.Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the Coxiella-Containing Vacuole.mBio.2016 Jul 19;7(4):e01127-16. [8] Jansen AFM,Schoffelen T,Textoris J,Mege JL,Bleeker-Rovers CP,Roest HIJ,Wever PC,Joosten LAB,Netea MG,van de Vosse E,van Deuren M.Involvement of matrix metalloproteinases in chronic Q fever.Clin Microbiol Infect.2017 Jul;23(7):487.e7-487.e13. [9] Mulye M,Samanta D,Winfree S,Heinzen RA,Gilk SD.Elevated Cholesterol in the Coxiella burnetii Intracellular Niche Is Bacteriolytic. mBio.2017 Feb 28;8(1):e02313-16. [10] Larson CL,Heinzen RA.High-Content Imaging Reveals Expansion of the Endosomal Compartment during Coxiella burnetii Parasitophorous Vacuole Maturation.Front Cell Infect Microbiol.2017 Feb 28;7:48. [11] Bastos RG,Howard ZP,Hiroyasu A,Goodman AG.Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to Coxiella burnetii Infection.Infect Immun.2017 Jun 20;85(7):e00218-17. [12] Luedtke BE,Mahapatra S,Lutter EI,Shaw EI.The Coxiella Burnetii type IVB secretion system(T4BSS)component DotA is released/ secreted during infection of host cells and during in vitro growth in a T4BSS-dependent manner.Pathog Dis.2017 Jun 1;75(4):ftx047. [13] Leahey PA,Tahan SR,Kasper EM,Albrecht M.Chronic Q-Fever(Coxiella burnetii)Causing Abdominal Aortic Aneurysm and Lumbar Osteomyelitis:A Case Report.Open Forum Infect Dis.2015 Dec 9;3(1):ofv185. [14] Raizada A,Apte N,Pham S.Q Fever Endocarditis Presenting with Superior Mesenteric Artery Embolism and Renal Infarction.Tex Heart Inst J.2016 Feb 1;43(1):91-3. [15] Graves SR,Islam A.Endemic Q Fever in New South Wales,Australia:A Case Series(2005-2013).Am J Trop Med Hyg.2016 Jul 6;95(1):55-9. [16] Biecker A,Bitzer M,Biecker E.Q Fever Pneumonia in Southwest Germany:Radiographic and Clinical Findings.Rofo.2017 Feb; 189(2):146-151.English. [17] Robinson WP,Schuksz M.Surgical and Antimicrobial Management of a Thoracic Aortic Aneurysm Due to Q Fever:A Case Report and Brief Review.Vasc Endovascular Surg.2016 May;50(4):290-4. [18] Sachs N,Atiya-Nasagi Y,Beth-Din A,Levy I,Ben-Shimol S,Tasher D,Grisaru-Soen G,Dabaja H,Kassis I,Spilman S,Bilavsky E.Chronic Q Fever Infections in Israeli Children:A 25-year Nationwide Study.Pediatr Infect Dis J.2018 Mar;37(3):212-217. [19] Chang K,Lee NY,Ko WC,Lin WR,Chen YH,Tsai JJ,Chen TC,Lin CY,Chang YT,Lu PL.Characteristics of scrub typhus,murine typhus,and Q fever among elderly patients:Prolonged prothrombin time as a predictor for severity.J Microbiol Immunol Infect.2019 Feb;52(1):54-61. [20] Shah SY,Kovacs C,Tan CD,Pettersson G,Shrestha NK,Lutwick L,Gordon SM.Delayed diagnosis of Q fever endocarditis in a rheumatoid arthritis patient.IDCases.2015 Sep 26;2(4):94-6. [21] Shaikh K,Travers H,Anuwatworn A,Potu K,Pownell B,Stys M,Stys A,Kumar A.A Case of Silent Q Fever Endocarditis.S D Med.2016 Dec;69(12):550-551.PMID:28810106. [22] Edouard S,Raoult D.Lyophilization to improve the sensitivity of qPCR for bacterial DNA detection in serum:the Q fever paradigm.J Med Microbiol.2016 Jun;65(6):462-467. [23] Hagenaars JC,Wever PC,Vlake AW,Renders NH,van Petersen AS,Hilbink M,de Jager-Leclercq MG,Moll FL,Koning OH,Hoekstra CJ.Value of 18F-FDG PET/CT in diagnosing chronic Q fever in patients with central vascular disease.Neth J Med.2016 Aug;74(7):301- 8.PMID:27571945. [24] Stokes W,Janvier J,Vaughan S.Chronic Q Fever in Alberta:A Case of Coxiella burnetii Mycotic Aneurysm and Concomitant Vertebral Osteomyelitis.Can J Infect Dis Med Microbiol.2016;2016:7456157. [25] Shishido AA,Letizia AG,Hartzell JD.Q Fever.US Army Med Dep J.2016 Jan-Mar;2016 Jan-Mar:68-70.PMID:26874100. [26] Steffen J,Bogner J,Huber BC.Q-Fieber–seltene Ursache einer Myokarditis[Q-fever-a rare cause for myocarditis].Dtsch Med Wochenschr.2020 Apr;145(7):484-487.German. [27] Robinson WP,Schuksz M.Surgical and Antimicrobial Management of a Thoracic Aortic Aneurysm Due to Q Fever:A Case Report and Brief Review.Vasc Endovascular Surg.2016 May;50(4):290-4. [28] van Roeden SE,Bleeker-Rovers CP,de Regt MJA,Kampschreur LM,Hoepelman AIM,Wever PC,Oosterheert JJ.Treatment of Chronic Q Fever:Clinical Efficacy and Toxicity of Antibiotic Regimens.Clin Infect Dis.2018 Feb 10;66(5):719-726. [29] Fratzke AP,van Schaik EJ,Samuel JE.Immunogenicity and Reactogenicity in Q Fever Vaccine Development.Front Immunol.2022 May 26;13:886810. [30] Xiong X,Jiao J,Gregory AE,Wang P,Bi Y,Wang X,Jiang Y,Wen B,Portnoy DA,Samuel JE,Chen C.Identification of Coxiella burnetii CD8+T-Cell Epitopes and Delivery by Attenuated Listeria monocytogenes as a Vaccine Vector in a C57BL/6 Mouse Model.J Infect Dis.2017 May 15;215(10):1580-1589. [31] Keijmel SP,Raijmakers RP,Bleeker-Rovers CP,van der Meer JW,Netea MG,Schoffelen T,van Deuren M.Altered interferon-γresponse in patients with Q-fever fatigue syndrome.J Infect.2016 Apr;72(4):478-85. [32] Keijmel SP,Delsing CE,Bleijenberg G,van der Meer JWM,Donders RT,Leclercq M,Kampschreur LM,van den Berg M,Sprong T,Nabuurs-Franssen MH,Knoop H,Bleeker-Rovers CP.Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome(Qure Study):A Randomized Controlled Trial.Clin Infect Dis.2017 Apr 15;64(8):998-1005. [33] Shishido AA,Letizia AG,Hartzell JD.Q Fever.US Army Med Dep J.2016 Jan-Mar;2016 Jan-Mar:68-70.PMID:26874100. [34] Sabourin E,Podglajen I,Fournier PE,Mainardi JL.Clinical and biological diagnosis and follow-up of patients treated for endovascular infections due to Coxiellaburnetii.J Infect Chemother.2023 Mar;29(3):371-374. [35] Keijmel SP,Delsing CE,Bleijenberg G,van der Meer JWM,Donders RT,Leclercq M,Kampschreur LM,van den Berg M,Sprong T,Nabuurs-Franssen MH,Knoop H,Bleeker-Rovers CP.Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome(Qure Study):A Randomized Controlled Trial.Clin Infect Dis.2017 Apr 15;64(8):998-1005. [36] Islam MM,Farag E,Hassan MM,Enan KA,Mohammad Sabeel KV,Alhaddad MM,Smatti MK,Al-Marri AM,Al-Zeyara AA,Al-Romaihi H,Yassine HM,Sultan AA,Bansal D,Mkhize-Kwitshana Z.Diversity of bacterial pathogens and their antimicrobial resistance profile among commensal rodents in Qatar.Vet Res Commun.2022 Jun;46(2):487-498. [37] Fratzke AP,van Schaik EJ,Samuel JE.Immunogenicity and Reactogenicity in Q Fever Vaccine Development.Front Immunol.2022 May 26;13:886810. [38] Xiong X,Jiao J,Gregory AE,Wang P,Bi Y,Wang X,Jiang Y,Wen B,Portnoy DA,Samuel JE,Chen C.Identification of Coxiella burnetii CD8+T-Cell Epitopes and Delivery by Attenuated Listeria monocytogenes as a Vaccine Vector in a C57BL/6 Mouse Model.J Infect Dis.2017 May 15;215(10):1580-1589. [39] Huang C,Ding H,Lin Y,Zhang Z,Fang X,Chen Y,Chen Y,Zhang C,Li W,Zhang W,Huang Z.Diagnosis of Coxiella burnetii Prosthetic Joint Infection Using mNGS and ptNGS:A Case Report and Literature Review.Orthop Surg.2023 Jan;15(1):371-376. [40] Islam MM,Farag E,Hassan MM,Enan KA,Mohammad Sabeel KV,Alhaddad MM,Smatti MK,Al-Marri AM,Al-Zeyara AA,Al-Romaihi H,Yassine HM,Sultan AA,Bansal D,Mkhize-Kwitshana Z.Diversity of bacterial pathogens and their antimicrobial resistance profile among commensal rodents in Qatar.Vet Res Commun.2022 Jun;46(2):487-498. [41] Sandoz KM,Beare PA,Cockrell DC,Heinzen RA.Complementation of Arginine Auxotrophy for Genetic Transformation of Coxiella burnetii by Use of a Defined Axenic Medium.Appl Environ Microbiol.2016 May 2;82(10):3042-51. [42] Martinez E,Allombert J,Cantet F,Lakhani A,Yandrapalli N,Neyret A,Norville IH,Favard C,Muriaux D,Bonazzi M.Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development.Proc Natl Acad Sci U S A.2016 Jun 7; 113(23):E3260-9. [43] Sam G,Plain K,Chen S,Islam A,Westman ME,Marsh I,Stenos J,Graves SR,Rehm BHA.Synthetic Particulate Subunit Vaccines for the Prevention of Q Fever.Adv Healthc Mater.2024 Mar;13(7):e2302351.

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