1. Transmission of Chlamydia trachomatis between heterosexual sex partners PRELIMINARY RESULTS FROM A GENOTYPE-SPECIFIC CONCORDANCE STUDY

2. Background Few studies measuring probability of Chlamydia trachomatis (Ct) transmission between sex partners Limitations of transmission studies –Small sample size –Inability to measure directionality of transmission –Limited assessment of Ct infection Estimates of Ct transmission valuable –Mathematical models of disease transmission –Evaluate condom efficacy –Estimate significance of biologic co-factors in transmission –Direct partner notification resources

3. Study Objective To measure crude and genotype- specific concordance for Chlamydia trachomatis infection among heterosexual sex partners

4. Methods Study design Cross sectional study of heterosexual partnerships (dyads) wherein at least one member was Ct-infected Transmission of Incident and Prevalent Ct Infection (‘TIPCI’) study Multi-center study: Indiana University School of Medicine, Boston Medical Center, CDC

5. Methods Study population Sexually active 14-24 year old heterosexual males and females, and their sex partners –Sexually active = intercourse in previous 30 days Recruited in Boston, Indianapolis –Boston: STD clinic, emergency room, adolescent clinics –Indianapolis: STD clinic Ct infection status –Enrollees evaluated for Ct by both culture and nucleic acid amplification testing (NAAT) Sexual partnership (dyad) recruitment –Sex partners to Ct-infected enrollees sought and offered enrollment –Sex partners enrolled together

6. Methods - exclusion criteria Unwilling to name sex partners Used antibiotics previous 30 days Immunocompromising condition Sex partners: –Younger than 14 years old –Used antibiotics previous 30 days

7. Methods – data collection Interview –Calendar recall method Clinical assessment –Full genital exam (speculum and bimanual exam for females) Laboratory assessment –Ct, Neisseria gonorrhoeae, Trichomonas vaginalis, Bacterial Vaginosis

8. Methods Laboratory evaluation for Ct Females –Quantitative Ct culture: endocx, urethra –Ct NAAT: endocx, urethra, urine Males –Quantitative Ct culture: urethra –Ct NAAT: urethra, urine Positive by any test ‘infected’ Results for all tests required for inclusion in this analysis (N=94 dyads)

9. Methods - Ct omp1 genotyping Specimens selected for genotyping –females: endocervical, urethral specimens (then vaginal, urine) –males: urethral specimens (then urine) Full-length omp1 gene amplified and sequenced Mixed infections identified using reverse dot blot, a hybridization technique

10. Methods - analysis Unit of analysis: dyad Concordance: proportion dyads with both members Ct-infected –Crude concordance –Genotype-specific concordance infected uninfected Both infected One infected

11. Estimating crude concordance Numerator: dyads w/ both members Ct-infected Denominator: all dyads (N=94) Does not take genotype into account –maximum estimate

12. Dyads used to estimate crude concordance Concordance (male) 50/(50+25)=67% Concordance (female) 50/(50+19)=73% Concordance 50/94=53% Results

13. Patterns of culture and NAAT results among 94 dyads MalesFemales Dyad PatternCultureNAATCultureNAAT No. dyads 1 ++++ 47 *2 -+++ 3 3 --++ 14 4 ++-- 15 *5 ---+ 5 *6 -+-- 10

14. Estimating genotype-specific concordance Only dyads w/ genotyping completed Numerator: dyads w/ same genotype Classified as discordant: –Dyads w/ mixed infections –Dyads w/ specimens could not be genotyped Denominator: all concordant dyads, and discordant dyads w/ genotyping completed

15. Dyads used to estimate genotype-specific concordance Concordance (male) 35/(35+9+25)=51% *different genotype (n=3); mixed infection (n=3); Omp1 gene could not be sequenced (n=3) Concordance (female) 35/(35+9+19)=56% Results Concordance 35/(35+9+44)=40%

16. Concordance Crude and genotype-specific Concordance: % dyads with both partners Ct-infected 40% 51% 56% 53% 67% 73% CrudeGenotype-specific

17. Limitations Data preliminary; remaining results may change conclusions Probability of infection estimated among partners who enrolled – may differ for those who did not enroll Biologic and behavioral factors not taken into account –Could modify probability of transmission –Could modify measures of infective status Current data cannot be used to ascribe directionality to transmission

18. Conclusions Concordance of Ct infection is high Genotype-specific concordance is lower than crude concordance Low probability of infection among partners to culture-negative, NAAT- positive dyad members suggests risk of transmission from this group may be low

19. Implications Until diagnostic tests differentiate between persons with a higher or lower probability of transmission, sex partners to all persons with Ct infection should be considered to have a high risk for infection High probability of Ct infection in partners to Ct-infected persons confirms the importance of effective partner treatment strategies

20. Acknowledgements Indiana University School of Medicine Byron Batteiger Tim Breen Barry Katz Don Orr Diane Stothard Bobby Van der Pol Boston Medical Center Phillip Braslins Guillermo Madico Peter Rice Lydia Shrier CDC Johanna Chapin Kathleen Hutchins Lauri Markowitz John Papp

22. Results - dyads Characteristic Males (n=96) (%) Females (n=87) (%) P value Age 15-19(24)(49) 20-24(71)(51) 25-29(2)(0) >30(3)(0)<0.01 Race/ethnicity NH-Black(44)(51) NH-White(15)(16) Hispanic(15)(20) NH-Asian(4)(2) NH-Native Am(2)(1) NH-Other(21)(10)0.41

23. Results - dyads Characteristic Males (n=96) (%) Females (n=87) (%) p value Lifetime sex partners 1(3)(13) 2(4)(16) 3(3)(12) 4(3)(10) >5(87)(49)<0.01 Reason for visit Symptoms(16)(17) Sex partner enrolled(3)(7) For STD evaluation(34)(21) Routine genital exam(18)(14) FU to STD diagnosis(5)(10) Other(24)(28)0.36

24. Results-Genotyping Same genotype - 35 of 44 dyads (80%) –E/E (n=16) –F/F (n=5) –D2/D2(n=3) –Ia/Ia(n=4) –E7/E7(n=2) –H/H(n=1) –K/K(n=1) –E4/E4 (n=1) –E6/E6(n=1) –D1/D1(n=1) Different genotypes - 3 dyads Mixed infections - 3 dyads –D6/D,F(n=1) –Ia/I,D(n=1) –F/K,F(n=1) Omp1 gene could not be sequenced - 3 dyads