Abstract
Q fever is an ubiquitous zoonosis caused by Coxiella burneti, an intracellular bacterium that can produce acute or chronic infections in humans. These forms are characterized by different evolution, serological profile and treatment that must be very long to achieve a cure in chronic forms. However, the serological profile for diagnosis and the real value of serology for predicting outcome are controversial, and management dilemmas for many patients with Q fever infection are continuously emerging. In this article, we describe in a comprehensive manner the different clinical presentations of the disease, making a critical overview of the evidence for serological predictions. We also take a broad view of new available diagnostic techniques and finally, we give recommendations for treatment.
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Derrick EH. “Q” fever, a new fever entity: clinical features, diagnosis and laboratory investigations. Med J Aust. 1937;2:821–99.
Burnet FM, Freeman M. Experimental studies on the virus of “Q” fever. Med J Aust. 1937;2:299–305.
Davis GE, Cox HR. A filter-passing infectious agent isolated from ticks.I. Isolation from Dermacentor andersonii, reactions with animals, and filtration experiments. Publ Health Rep. 1938;53:2259–76.
Dyer RE. Similarity of Australian “Q” fever and a disease caused by an infectious agent isolated from ticks in Montana. Publ Health Rep. 1939;54:1229–37.
Dijkstra F, Hoek W, Wijers N, et al. The 2007–2010 Q fever epidemic in the Netherlands: characteristics of notified acute Q fever patients and the association with dairy goat farming. FEMS Immunol Med Microbiol 2011, in press
Raoult D, Marrie T, Mege J. Natural history and pathophysiology of Q fever. Lancet Infect Dis. 2005;5:219–26.
McCaul TF, Williams JC. Development cycle of Coxiella burnetii: structure and morphogenesis of vegetative and sporogenic differentiations. J Bacteriol. 1981;147:1063–76.
McCaul TF. The developmental cycle of Coxiella burnetii. In: Williams JC, Thompson HA, editors. Q fever: the biology of Coxiella burnetii. Boca Raton: CRC; 1991. p. 224–58.
Baca OG, Paretsky D. Q fever and Coxiella burnetii: a model for host-parasite interactions. Microbiol Rev. 1983;47:127–49.
Gonder JC, Kishimoto RA, Kastello MD, et al. Cynomolgus monkey model for experimental Q fever infection. J Infect Dis. 1979;139:191–6.
• Angelakis E, Raoult D. Q fever. Vet Microbiol. 2010;140:297–309. These authors provide a good review of many aspects of this entity and its consequences in humans and animals.
Johnson III JE, Kadu PJ. Laboratory acquired Q fever. A report of fifty cases. Am J Med. 1966;41:391–403.
Raoult D, Brouqui P, Marchou B, Gastaut JA. Acute and chronic Q fever in patients with cancer. Clin Infect Dis. 1992;14:127–30.
Raoult D, Levy PY, Dupont HT, et al. Q fever and HIV infection. AIDS. 1993;7:81–6.
Boschini A, Di Perri G, Legnani D, et al. Consecutive epidemics of Q fever in a residential facility for drug abusers: impact on persons with human immunodeficiency virus infection. Clin Infect Dis. 1999;28:866–72.
Montes M, Cilla G, Marimon JM, et al. Coxiella burnetii infection in subjects with HIV infection and HIV infection in patients with Q fever. Scand J Infect Dis. 1995;27:344–6.
Sidwell RW, Thorpe BD, Gebhardt LP. Studies of latent Q fever infections. I. Efects of whole boy X-irradiation on latently infected guinea pigs, white mice and deer mice. Am J Hyg. 1964;79:113–24.
Sidwell RW, Thorpe BD, Gebhardt LP. Studies of latent Q fever infections. II. Efects of multiple cortisone injection. Am J Hyg. 1964;79:320–7.
Samuel JE, Frazier ME, Mallavia LP. Correlation of plasmid type and disease caused by Coxiella burnetii. Infect Immun. 1985;49:775–9.
Stein A, Raoult D. Lack of pathotype specific gene in human Coxiella burnetii isolates. Microb Pathog. 1993;15:177–85.
de Alarcón A, Villanueva JL, Viciana P, et al. Q fever: epidemiology, clinical features and prognosis. A study from 1983 to 1999 in the South of Spain. J Infect. 2003;47:110–6.
Raoult D, Tissot-Dupont H, Foucault C, et al. Q fever 1985–1998. Clinical an epidemiologic features of 1,383 infections. Medicine. 2000;79:109–23.
Spelman DW. Q fever: a stuy of 111 consecutive cases. Med J Austral. 1982;1:547–53.
Pebody RG, Wall PG, Ryan ML, Fairley C. Epidemiological features of Coxiella burnetii infection in England and Wales: 1984 to 1994. Commun Dis Rep. 1996;6:128–32.
Marrie TJ. Coxiella burnetii (Q fever) pneumonia. Clin Infect Dis. 1995;21 suppl 3:S253–64.
Tselentis Y, Gikas A, Kofteridis D, et al. Q fever in the Greek Island of Crete: epidemiologic, clinical, and therapeutic data from 98 cases. Clin Infect Dis. 1995;20:1311–6.
Ergas D, Keysari A, Edelstein V, Sthoeger ZM. Acute Q fever in Israel: Clinical and laboratory study of 100 hospitalized patients. Isr Med Assoc J. 2008;8(5):337–41.
Clark WH, Lennete EH, Railsback OC, Romer MS. Q fever in California. Arch Intern Med. 1951;58:155–61.
Vellend H, Salit IE, Spence L. Q fever-Ontario. Can Dis Wkly Rep. 1982;8:171.
Marrie TJ. Q fever, 1979–1987-Nova Scotia. Can Dis Wkly Rep. 1988;14:69–70.
Montejo-Baranda M, Corral-Carranceja J, Aguirre-Errasti C. Q fever in the Basque country: 1981–1984. Rev Infect Dis. 1985;7:700–1.
Sobradillo V, Ansola P, Baranda F, Corral C. Q fever pneumonia: a review of 164 community acquired cases in the Basque country. Eur Respir J. 1989;2:263–6.
Javier Alvarez Gutiérrez F, del Castillo Otero D, García Fernández A, et al. Prospective study of 221 community acquired pneumonias followed up in an outpatient clinic. Etiology and clinical-radiological progression. Med Clin (Barc). 2001;116(5):161–6.
Fournier PE, Etienne J, Harle JR, et al. Myocarditis, a rare but severe manifestation of Q fever: report of 8 cases and review of the literature. Clin Infect Dis. 2001;32:1440–7.
Bernit E, Puget J, Janbon F, et al. Neurological involvement in acute Q fever. A report of 29 cases and review of the literature. Arch Intern Med. 2002;162:693–700.
• Fournier PE, Thuny F, Richet H, et al. Comprehensive diagnostic strategy for blood culture-negative endocarditis: a prospective study of 819 new cases. Clin Infect Dis. 2010;51(2):131–40. The authors describe a diagnostic strategy that lead to a high percentage of aetiologic identification in blood culture-negative endocarditis. Coxiella burnetii was in this study one of the main causes.
Turk WP, Howitt G, Turnberg LA, et al. Chronic Q fever. Q J Med. 1976;45:193–217.
Brouqui P, Dupont HT, Drancourt M, et al. Chronic Q fever. Ninety-two cases from France, including 27 cases without endocarditis. Arch Intern Med. 1993;153:642–8.
Haldane EV, Marrie TJ, Faulkner RS, et al. Endocarditis due to Q fever in Nova Scottia: experience with five patients in 1981–1982. J Infect Dis. 1983;148:978–85.
Wilson HG, Neilson GH, Galea EG, et al. Q fever endocarditis in Queensland. Circulation. 1976;53:680–4.
Karakousis PC, Trucksis M, Dumler S. Chronic Q fever in the United States. J Clin Microbiol. 2006;44:2283–7.
Tobin MJ, Cahill N, Gearty G, et al. Q fever endocarditis. Am J Med. 1982;72:396–400.
Siegman-Igra Y, Kaufman O, Keysary A, et al. Q fever endocarditis in Israel and a worldwide review. Scand J Infect Dis. 1997;29:41–9.
•• Mogollón MV, Anguita MP, Aguado JM, et al. Q fever endocarditis in Spain. Clinical characteristics and outcome. Enferm Infecc Microbiol Clin. 2011;29(2):109–16. This article reports a large cohort of patient with endocarditis. The utility of serology for predicting the outcome is largely questioned.
Perez-Fontan M, Huarte E, Tellez A, et al. Glomerular nephropathy associated with chronic Q fever. Am J Kidney Dis. 1988;11(4):298–306.
Leipidi H, Houpikian P, Liang Z, Raoult D. Cardiac valves in patients with Q fever endocarditis:microbiological, molecular and histologic studies. J Infect Dis. 2003;187:1097–106.
•• Million M, Thuny F, Richet H, Raoult D. Long-term outcome of Q fever endocarditis: a 26-year personal survey. Lancet Infect Dis. 2010;10(8):527–35. The authors from the French National Reference Center for Rickettsial Diseases describe their experience with the largest serie of the world. Considerations about the optimun duration of treatment are provided with special consideration to serology.
Botelho-Nevers E, Fournier PE, Richet H, et al. Coxiella burnetii infection of aortic aneurysms or vascular grafts: report 30new cases and evaluation of outcome. Eur Clin Microbiol Infect Dis. 2007;26(9):635–40.
Wegdam-Blans MCA, Vainas T, van Sambeek MR, et al. Vascular complications of Q-fever infections. Eur J Vasc Endovasc Surg. 2011;42:384–92.
Nourse C, Allworth A, Jones A, et al. Three cases of Q fever osteomyelitis in children and a review of the literature. Clin Infect Dis. 2004;39:e61–6.
Landais C, Fenollar F, Constantin A, et al. Q fever osteoarticular infection: four new cases and a review of the literature. Eur J Clin Microbiol Infect. 2007;26:341–7.
Delsol G, Pellegrini M, Familiades J, Auvergnat C. Bone marrow lesions in Q fever. Blood. 1978;52:637–8.
Zoutman DE, Ralph ED, Frei JV. Hepatic fibrin-ring granulomas in granulomatous hepatitis: report of four cases and review of the literature. Acta Clin Belg. 2001;56(6):341–8.
Stein A, Raoult D. Q fever during pregnancy: a public health problem in southern France. Clin Infect Dis. 1998;27(3):592–6.
• Carcopino X, Raoult D, Bretelle F, Boubli L, Stein A. Q fever during pregnancy:a cause of poor fetal and maternal outcome. Ann N Y Acad Sci. 2009;116:79–8956. In this article the authors recommend to treat pregnant women with Q fever to avoid obstetric complications and maternal chronic Q fever.
Rey D, Obadia Y, Tissot-Dupont H, Raoult D. Seroprevalence of antibodies to Coxiella burnetii among pregnant women in South Eastern France. Eur J Obstet Gynecol Reproduc Biol. 2009;93(2):57–61.
Baud D, Peter O, Langel C, Regan L, Greub G. Seroprevalence of Coxiella burnetii and Brucella abortus among pregnant women. Clin Microbiol Infect. 2009;15(5):499–501.
• van der Hoek W, Meekelenkamp JC, Leenders AC, et al. Antibodies against Coxiella burnetii and pregnancy outcome during the 2007–2008 Q fever outbreaks in The Netherlands. BMC Infect Dis. 2011;11:44. In this article, the authors conclude that there is no evidence of adverse pregnancy outcome among women who had antibodies to C. burnetii during early pregnancy.
Munster JM, Leenders AC, van der Hoek W, et al. Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial. BMC Womens Health. 2010;10:32.
Houpikian P, Raoult D. Diagnostic methods, current best practices and guidelines for identification of difficult-to-culture pathogens in infective endocarditis. Infect Dis Clin North Am. 2002;16(2):377–92.
•• Omsland A, Heinzen RA. Life on the outside: the rescue of Coxiella burnetii from its host cell. Annu Rev Microbiol. 2011;65:111–28. Excellent article in wich the long way to the isolation of Coxiella burnetii in an axenic medium is thoughtfully described.
Peacock MG, Phillip RN, Williams JC, Faulkner R. Serological evaluation of Q fever in humans: enhanced phase I titers of Immunoglobulins G and A are diagnostic for Q fever endocarditis. Infect Immun. 1983;41:1089–98.
Musso D, Raoult D. Serological cross-reactions between Coxiella burnetii and Legionella micdadei. Clin Diagn Lab Immunol. 1997;4(2):208–12.
Schramek S, Kazár J, Sádecký E. Serological cross-reactions of lipid A components of lipopolysaccharides isolated from Chlamydia psittaci and Coxiella burnetii. Acta Virol. 1980;24(3):224.
La Scola B, Raoult D. Serological cross-reactions between Bartonella quintana, Bartonella henselae, and Coxiella burnetii. J Clin Microbiol. 1996;34(9):2270–4.
Raoult D, Tissot-Dupont H, Foucault C, et al. Q fever 1985–1998. Clinical and epidemiologic features of 1,383 infections. Medicine (Baltimore). 2000;79(2):109–23.
Fournier PE, Casalta JP, Habib G, et al. Modification of the diagnostic criteria proposed by the Duke Endocarditis Service to permit improved diagnosis of Q fever endocarditis. Am J Med. 1996 Jun;100(6):629–33.
• van der Hoek W, Versteeg B, Meekelenkamp JC, Renders NH, Leenders AC, Weers-Pothoff I, Hermans MH, Zaaijer HL, Wever PC, Schneeberger PM. Follow-up of 686 patients with acute Q fever and detection of chronic infection. Clin Infect Dis. 2011;52(12):1431–6. In this study, a considerable number of patients with acute Q fever exhibited high antibodies titers to phase I antigens, but no evolution to chronic form was observed.
• Hung MN, Lin LJ, Hou MY, et al. Serologic assessment of the risk of developing chronic Q fever in cohorts of acutely infected individuals. J Infect. 2011;62(1):39–44. High titers of phase I IgG and even progressive elevation of them ater an acute Q fever infection do not indicate or predict the development of chronic Q fever in this report.
Frankel D, Richet H, Renvoisé A, Raoult D. Q fever in France, 1985–2009. Emerg Infect Dis. 2011;17(3):350–6.
Fenollar F, Fournier PE, Carrieri MP, et al. Risk factors and prevention of Q fever endocarditis. Clin Infect Dis. 2001;33:312–6.
Fenollar F, Thuny F, Xeridat B, et al. Endocarditis after acute Q fever in patients with previously undiagnosed valvulopathies. Clin Infect Dis. 2006;42(6):818–21.
•• Healy B, van Woerden H, Raoult D, et al. Chronic Q fever: different serological results in three countries--results of a follow-up study 6 years after a point source outbreak. Clin Infect Dis. 2011;52(8):1013–9. In this study, concordance in immnunofluorescence result interpretation from 3 international reference laboratories was only 35 %. The interpretation o chronic serological profiles must be done with caution and always in accordance with the clinical picture.
Meekelenkamp JC, Schneeberger PM, Wever PC, Leenders AC. Comparison of ELISA and indirect immunofluorescent antibody assay detecting Coxiella burnetii IgM phase II for the diagnosis of acute Q fever. Eur J Clin Microbiol Infect Dis. 2011 Oct 14 (in press)
• Jager MM, Weers-Pothoff G, Hermans MH, et al. Evaluation of a diagnostic algorithm for acute Q fever in an outbreak setting. Clin Vaccine Immunol. 2011;18(6):963–8. In this article the authors reported their experience with serology (ELISA), immunofluorescece and PCR for acute Q fever diagnosis during the large outbreak in the Netherlands.A simple and effective algorithmis proposed.
Limonard GJ, Thijsen SF, Bossink AW, et al. Developing a new clinical tool for diagnosing chronic Q fever: the Coxiella ELISPOT. FEMS Immunol Med Microbiol. 2012;64(1):57–60.
Schneeberger PM, Hermans MH, van Hannen EJ, et al. Real-time PCR with serum samples is indispensable for early diagnosis of acute Q fever. Clin Vaccine Immunol. 2010;17(2):286–90.
•• Fenollar F, Fournier PE, Raoult D. Molecular detection of Coxiella burnetii in the sera of patients with Q fever endocarditis or vascular infection. J Clin Microbiol. 2004;42(11)):4919–24. In this study, the efficacy of PCR in blood samples for the diagnosis of chronic forms (mainly endocarditis) is analysed.
• Landais C, Fenollar F, Thuny F, Raoult D. From acute Q fever to endocarditis: serological follow-up strategy. Clin Infect Dis. 2007;44(10):1337–40. French authors propose in this study an algorithm based in serology and genomic amplification for preventing the development of chronic forms.
Raoult D. Treatment of Q fever. Antimicrob Agents Chemother. 1993;37:1733–6.
Yeaman MR, Mitscher LA, Baca OG. In vitro susceptibility of Coxiella burnetii to antibiotics, including several quinolones. Antimicrob Agents Chemother. 1987;31(7):1079–84.
Ormsbee RA, Parker RA, Picens EG. The comparative effectiveness of aureomycin, terramycin, chloramphenicol erythromycin, and thiocymetin in suppressing experimental rickettsial infections in chick embryos. J Infect Dis. 1955;96(2):162–7.
Raoult D, Marrie T. Q fever. Clin Infect Dis. 1995;20:489–96.
Lai CH, Lin JN, Chang LL, Chen YH, Lin HH. Circulating cytokines and procalcitonin in acute Q fever granulomatous hepatitis with poor response to antibiotic and short-course steroid therapy: a case report. BMC Infect Dis. 2010;10:193.
Crespo M, Sopeña B, Bordón J, et al. Steroids treatment of granulomatous hepatitis complicating Coxiella burnetii acute infection. Infection. 1999;27(2):132–3.
Garcia-Alfranca F, Clemente-Rodriguez C, Pigrau-Serrallach C, et al. Q fever associated with persistent fever: an immunologic disorder? Clin Infect Dis. 1994;18(1):122–3.
Stein A, Raoult D. Q fever endocarditis. Eur Heart J. 1995;16:19–23.
Levy PY, Drancourt M, Etienne J. Comparison of different antibiotic regimens for therapy of 32 cases of Q fever endocarditis. Antimicrob Agents Chemother. 1991;35(3):533–7.
Maurin M, Benoliel AM, Bongrand P, Raoult D. Phagolysosomes of Coxiella burnetii-infected cells lines maintains an acidic pH during persistant infection. Infect Immun. 1992;60:5013–6.
Maurin M, Benoliel AM, Bongrand P, Raoult D. Phagolysosomal alkalinization and the bactericidal effect of antibiotics: the Coxiella burnetii paradigm. J Infect Dis. 1992;33:428–31.
Raoult D, Houpikian P, Tissot-Dupont H, Riss JM, Arditi-Djiane J, Brouqui P. Treatment of Q fever endocarditis. Comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med. 1999;159:167–73.
Abril V, Ortega E, Segarra P, Fraile T. Late recurrence of endocarditis caused by Coxiella burnetii folowing prosthetic valve substitution and prolonged antibiotic treatment. Enferm Infecc Microbiol Clin. 1999;17:478–9.
Morguet AJ, Jansen A, Raoult D, Schneider T. Late relapse of Q fever endocarditis. Clin Res Cardiol. 2007;96:519–21.
Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009;30(19):2369–413.
Rolain JM, Mallet MN, Raoult D. Correlation between serum doxycycline concentrations and serologic evolution in patients with Coxiella burnetii endocarditis. J Infect Dis. 2003;188:1322–5.
Lecaillet A, Mallet MN, Raoult D, Rolain JM. Therapeutic impact of the correlation of doxycycline serum concentrations and the decline of phase I antibodies in Q fever endocarditis. J Antimicrob Chemother. 2009;63(4):771–4.
Sánchez-Recalde A, Maté I, López E, et al. Coxiella burnetii endocarditis: long term follow up of 20 patients. Rev Esp Cardiol. 2000;53:940–6.
Houpikian P, Habib G, Mesana T, Raoult D. Changing clinical presentation of Q fever endocarditis. Clin Infect Dis. 2002;34:e28–31.
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de Alarcón, A. Q Fever Endocarditis: Does Serology Predict Outcome?. Curr Infect Dis Rep 14, 350–358 (2012). https://doi.org/10.1007/s11908-012-0264-6
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DOI: https://doi.org/10.1007/s11908-012-0264-6