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2,434 cases of Q fever From the French National reference center 1991-2016 Dr Cléa Melenotte Marseille IHU Méditerranée Infection
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Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Jun 25, 2020

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Page 1: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

2,434 cases of Q fever From the French National reference center

1991-2016

Dr Cléa Melenotte

Marseille

IHU Méditerranée Infection

Page 2: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Q fever

Coxiella burnetii, gram negative intracellular bacteria

Worldwide zoonosis (excepted in New Zealand)

Endemic: French Guiana, Netherlands, Africa, France

Acute Q fever (hepatitis and pneumonia) and persistent C. burnetii infection (cardio-vascular infection)

Peacock, Infect Imm, 1983 Raoult, Clin infect Dis, 2017 Melenotte, Int J infect dis, 2018

Persistent C. burnetii infection: a changing paradigm Organic lesion + Microbiological evidence (serology, PCR, culture)

Phase I: 100, IgM, 0, IgA 0 Phase II: 200, IgM, 0, IgA, 0

Page 3: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

National reference Center for Q fever Marseille

Page 4: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Questionnaire

Page 5: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Patients included

Primary (acute) C. burnetii infection -acute clinical symptoms -IgG titers II ≥ 200 and IgM II ≥ 50 - or seroconversion within three months of the primary symptoms.

Persistent C. burnetii focal infection -Persistence of clinical symptoms >3 months - Identification of an infectious focus

Page 6: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

C. burnetii persistent infection

SystematicTTEproposed

SystematicPET-scanproposed

Page 7: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Q fever clinical presentation

Page 8: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Acute Q fever

Page 9: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Acute Q fever complication and anticardiolipins

French Guiana Metropolitan France0

500

1000

1500

2000

IgG

an

ticard

iolip

in a

nti

bo

die

s (

GP

LU

)

*

Page 10: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Acute Q fever endocarditis

50 cases of acute Q fever endocarditis

28 % had a preexisting valvulopathy

70% had positive IgG aCL (>22GPLU) OR=2.4; 95 confidence interval [1.2-4.9]; p=0.011

3 positive culture from blood

Page 11: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Persistent C. burnetii complications

Page 12: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

C. burnetii persistent infection

Page 13: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Q fever the hidden pathogen of

interstitial lung diseases

Melenotte, Clin infect dis, 2018

Page 14: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Lymphadenitis

IgA

97 lymphadenitis 44% isolated with PET-scanner associated with a risk of lymphoma HR=77.4, 95% CI [21.2-281.8], p<.001

Page 15: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Q fever and lymphoma

C. burnetii vascular infection Follicular lymphoma C. burnetii in the tumoral microenvironment

18 months

Melenotte, Lancet, 2012 Melenotte, Blood, 2016

Patients with Q fever had a 25-fold increased risk of NHL C. burnetii identified in macrophages and plasmacytoid dendritic cells Gradiant IL-10 in patients with persistent C. burnetii infection, lymphadenitis and lymphoma

Page 16: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Q fever and lymphoma

Anatomicalsiteoflymphoma Coxiellaburnetiiinfectiousfoci

N=8-Lymphnodes

3-Cervical:1DLBCL,1T-celllymphoma,1Marginallymphoma2-Abdominal:1DLBCL1&FL1-Inguinal:1DLBCL1-Mediastinal:DLBCL1-Axillar:Lymphoplasmocyticlymphoma

N=1-Lung1-DLBCL

N=2-Gastric1-MALT1-NHLgastriclymphoma

N=1-Spleen1-Marginalzonelymphoma

N=3-Osteomedullar

1-Mantlecelllymphoma1-Marginalzonelymphoma1-Tcelllymphoma

N=1-Pectoralmass1-DLBCL

N=4acuteQfever N=13persistentfocalizedinfection

N=1acuteevolvingtopersistentC.burnetiiinfection

Page 17: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Mortality rate

58 patients died C. burnetii persistent focal infections HR=10.9, 95% CI [3.2-37.1], p<.001 endocarditis (HR=2.4, 95% CI [1.1-5.1], p<.01 vascular infection (HR=3.1, 95% CI [1.7-5.7], p<.01

Page 18: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Limitations

¼ patients with acute Q fever were lost follow-up

C. burnetii cardio-vascular infections were probably over-represented

Conversely, the mortality rate might be underestimated because of potential loss to follow-up.

Page 19: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Conclusion

Cardio-vascular : fatal complication

Anticardiolipin antibodies associated with acute complications

Neglected rare foci Alithiasic cholecystitis

Haemophagocytic syndrome

Acute Q fever endocarditis

Lymphadenitis

Lymphoma

Interstitial lung disease

Use TTE and PET !

Page 20: Q fever From - Accueil - SPILF - Infectiologie · 2018-07-02 · Q fever Coxiella burnetii, gram negative intracellular bacteria Worldwide zoonosis (excepted in New Zealand) Endemic:

Thank you

Marseille Didier Raoult

Camélia Protopopescu

Patrizia Carrieri

Matthieu Million

Sophie Edouard

Jean-Louis Mège

Philippe Parola

Cayenne Félix Djossou

Loïc Epelboin

Aba Mahamat

You