Chlamydia and pregnancy

Transcription

1 Chlamydia and pregnancy Bertille de Barbeyrac NRC Chlamydia Infections, Bordeaux, France Infectious Diseases in Pregnant Women, Fetuses and Newborns, ESCMID Postgraduate Education Course 3-7 October 2010, Bertinoro, Italy

2 First description 1911 «inclusion conjunctivitis of the newborn» Cervicitis in mother NGU in father Halberstaeder von Prowasek 1907

3 Then Br J Vener Dis Mar;40: GENITAL INFECTION IN ASSOCIATION WITH TRIC VIRUS INFECTION OF THE EYE. III. CLINICAL AND OTHER FINDINGS. PRELIMINARY REPORT. DUNLOP EM, JONES BR, AL-HUSSAINI MK N Engl J Med Feb 10;296(6): Respiratory-tract colonization and a distinctive pneumonia syndrome in infants infected with Chlamydia trachomatis. Beem MO, Saxon EM.

4 Intracellular biology Infection and disease epidemiology Diagnosis Treatment

5 «Chlamydiae» Original bacteria Intracellular cycle «Inclusion» Biphasic developmental cycle: EB and RB

6

7 Cycle - Persistence/Reactivation

8 Cycle - Persistence C. trachomatis Aberrant Rbs IFNγ nutrient starvation AA, iron ct hsp60 ADN MOMP Nondividing RBs Mophologically enlarged Antibiotics Reversible state Microbiol Res 2006, 161, 9-19 ; Antimicro agents Chemother 2005, 49, ; J Infect Dis 2003, 187,

9 Persistence aberrant RB Persistence in vivo? : chronic infection clinical evidences 1 - asymptomatic urethritis and cervicitis 2 - silent PID 3 - Recurrent infection 4 - negative culture/ DNA+

10 Pathogenesis of genital tract disease 1 bacterial factors Virulence factors membrane proteins type III secretion effectors putative large cytotoxin stress response proteins factors produced by the cryptic palsmid 2 Host factors Immune response genetic

11 Envelope structures - C. trachomatis gram(-) Without peptidoglycan EB : cystein-riche proteins MOMP, Omc-A, Omc-B RB : MOMP, Omc-A, Omc-B Rigid Osmotic fragility Permeable J Bacteriol 2004, 186, ; J Bacteriol 2003, 185, ; Clin Microbiol Reviews 2004, 17,

12 Pathogenesis of genital tract disease 1 bacterial factors Virulence factors membrane proteins type III secretion effectors putative large cytotoxin stress response proteins factors produced by the cryptic palsmid 2 Host factors Immune response genetic factors

13 Immune response T-cell response Primary infection repeated infection humoral response Th1 Th2 IFNγ Il6 antibodies + - +

14 Pathogenesis of genital tract disease 1 bacterial factors Virulence factors membrane proteins type III secretion effectors putative large cytotoxin stress response proteins factors produced by the cryptic palsmid 2 Host factors Immune response genetic factors

15 Intracellular biology Infection and disease epidemiology Diagnosis Treatment

16 C. trachomatis human infections Public health problem A-C D-K L1-L3 Trachoma Sexually Transmitted infections LGV

17 C. trachomatis STI (D - K) Current problem Most common STD In the world Young adults cases /year impact on human reproduction

18 C. trachomatis STI (D - K) Asymptomatic infections Uréthritis Epididymitis Cervicitis proctitis Salpingitis...

19 C. trachomatis IST ( D - K) Other clinical forms Conjunctivitis Arthritis : Reiter s syndrom Adverse pregnancy outcome Conjunctivitis Pneumonia

20 Adverse pregnancy outcome Early and late spontaneous abortion Rastogi et a, Detection of Chlamydia trachomatis antigen in spontaneous abortion.is this orgnism a primary or secondary indicator of risk? British Journal of Biomedical Science

21 Adverse pregnancy outcome Early and late spotaneous abortion Post-abortal endometritis and salpingitis QvigstadE, et al, 1983, PID associated with CT infection after therapeutic abortion. A prospective study. Britsih Journal of Veneral Diseases.

22 Adverse pregnancy outcome Early and late spotaneous abortion Post-abortal endometritis and salpingitis Intrauterine infections; stillbirth Gencay et al, CT seropositivity is associated both with stillbirth and preterm delivery. APMIS

23 Adverse pregnancy outcome Early and late spotaneous abortion Post-abortal endometritis and salpingitis Intrauerine infections; stillbirth PROM; premature birth Gravett, et al1986. Independant associations of bacteriel vaginosis and CT infection with adverse pregnancy outcome. American Journal of Obstetrics and gynecology

24 Adverse pregnancy outcome Early and late spotaneous abortion Post-abortal endometritis and salpingitis Intrauerine infections; stillbirth PROM; premature birth Postpartum infections Mardh PA, Endometritis caused by CT. British Journal of Veneral Diseases

25 Adverse pregnancy outcome Early and late spotaneous abortion Post-abortal endometritis and salpingitis Intrauerine infections; stillbirth PROM; premature birth Postpartum infections Ectopic pregnancy Svenson et al Ectopic pregnancy and antibodies to CT. Fertility and Sterility.

26 Neonatal infections Neonatal Conjunctivitis incubation 5-14days mid to severe gonococcal ophthalmia Neonatal pneumonia = benign 3 weeks to 3 months tachypnea, staccato cough afebrile + conjunctivitis, otitis RSV

27

28 Number of STI cases in EU/EEA countries in 2007 C. trachomatis N. gonorrhoeae Syphilis cases cases cases HIV cases

29

30

31 Review of prevalence of C. trachomatis infection in pregnant women

32 Epidemiology NeoNat Infection genitale Infection USA exposed 4M F infected France? 200 à F general pop 3% < 25years CT repiratory infection in Dutch infants. high Archrisk Dis Child, pop 5 15% 2009, Rours pregnant et al women: Bx 7% < 25 years 2% 30 years Hollande 7%

33 Intracellular biology Infection and disease epidemiology Laboratory diagnosis Treatment

34 Laboratory diagnosis Direct : Specimen types Neonates :conjunctival, pharyngeal swabs Mother :endocervix or non invasive samples (urine, vaginal samples) Transport :dry or transport medium Methods : culture or non culture (DFA, EIA, Probe, NAATs) Indirect : serology IgG + IgM

35

36 Direct diagnosis of C. trachomatis Nucleic Acid amplification tests > other methods NAATs Cell culture DFA organism / sample probes EIA

37 Alarming poor performance in Chlamydia trachomatis point of care testing Van Dommelen, J. et al. STI, 2010, sensitivity Biorapid chlamydia AG test 17% QuickVue Chlamydia 27% Handilab-C 12%

38 Treatment Prognosis Prevention

39 Antibiotic susceptibility Intrinsic susceptibility and resistance Few antibiotics are effective (host cell membrane, inclusion, bacterial wall) Potentially active Abs : rifampin, macrolides, Fluoroquinolones, cyclines intrinsic resistance : aminoglycosides, vancomycin, colimycin paradoxical activity of penicillin

40 Antibiotic susceptibility Acquired Résistance Not a problem in C.trachomatis In vivo résistance: in clinical isolates Treatment failure Heterotypic resistance In vitro résistance: selection of mutants described for FQ, rifampin

41 Treatment uncomplicated urogenital CT infections - azithromycin 1g single dose - doxycycline 100mg x2 7-day course - josamycin mg x2 7-day course therapy in pregnancy - azithromycin 1g single dose - erythromycin is not recommended Conjunctivitis and pneumonia - erythromycin 50mg/kg/d in 4 divided doses for 14d - azithromycin 20mg/kg/d one dose daily for 3 days

42 Prognosis Conjunctivitis : untreated, persists for many weeks and resolves spontaneously without complications Pneumonia: untreated, ill for several weeks Follow up Failure in 20% of cases: second course is needed Parents treatment

43 Prevention No isolation Ocular prophylaxis not effective Treatment infected pregnant women : screening (age < 25 ans,high risk factors) Azithromycin 1g orally as a single dose

44 Conclusion Practice points Perform screening for C. trachomatis in pregnant women Test for C. trachomatis in cases of adverse pregnancy outcome Do not forget partner notification Test for C. trachomatis infections in infants as a differential diagnosis in cases of conjunctivitis and pneumonia