1. U.S. Food and Drug Administration Notice: Archived Document The content in this document is provided on the FDA’s website for reference purposes only. It was current when produced, but is no longer maintained and may be outdated.

2. Overview of the Infectivity and Epidemiology of Chlamydia trachomatis and Neisseria gonorrhoeae John R Papp, Ph.D. Team Lead, Chlamydia and Gonorrhea Laboratory Laboratory Reference and Research Branch Division of STD Prevention Centers for Disease Control and Prevention The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention

3. Comparison Chlamydia and Gonorrhea Life Cycles  Chlamydia  Obligate intracellular pathogens  Gonorrhea  Fastidious pathogens  Both infect columnar epithelial cells

4. Comparison Chlamydia and Gonorrhea Life Cycles  Chlamydia  Life cycle that involves a change in the organism  Elementary Body (EB)  form that is outside the host cell  infects the host cell  Reticulate Body (RB)  form that is inside the cell  replicates to produce more chlamydia  Gonorrhea  Diplococci with adjacent sides flattened  Cells divide in 2 planes at right angles

5. Chlamydia Growth Cycle

6. Chlamydia Persistence In vitro studies 7000 X CONTROL PERSISTENT  Large inclusions with enlarged, aberrant RBs  RBs do not divide and mature to EBs  Different set of proteins measured in persistent state

7. Chlamydia Persistence In vitro studies  Persistent chlamydia (viable, nonculturable) can be induced by:  β-lactam antibiotics (PCN)  IFN-gamma  Iron / amino acid / nutrient deprivation  Natural occurrence with eukaryotic cell differentiation  Other organisms (e.g. HSV)  Persistent chlamydia is reversible leading to active replication  All persistence mechanisms are not the same – there may be different markers for persistence

8. Alteration of Chlamydia Growth in Association with Hormonal Modulation  In vitro studies:  enhanced infection of HeLa cells grown in estrogen enriched me dium  Non-human animal studies:  increased chlamydial shedding near ovulation in sheep  progesterone pretreatment required before vaginal infection of mice  increased disease severity in guinea pigs pretreated with estrogen

9. Alteration of Chlamydia Growth in Association with Hormonal Modulation  Non-human animal studies:  increased chlamydial shedding near ovulation in sheep

10. Alteration of Chlamydia Growth in Association with Hormonal Modulation  Pathologic consequence of chlamydial infection in sheep  Chlamydiophila abortus (Chlamydia psittaci)  Detectable infection in the placenta as early as 60 days gestation (normal term gestation in sheep is ~140 days)  Macroscopic pathologic changes observed in the placenta at ~90 days gestation  Coincides with increased progesterone production from the placenta and with the development of fetal immunocompetence

11. Alteration of Chlamydia Growth in Association with Hormonal Modulation  Pathologic consequence of chlamydial infection in sheep  Chlamydiophila abortus (Chlamydia psittaci)  Detectable infection in the placenta as early as 60 days gestation (normal term gestation in sheep is ~140 days)  Macroscopic pathologic changes observed in the placenta at ~90 days gestation  Coincides with increased progesterone production from the placenta and with the development of fetal immunocompetence  Leads to placental insufficiency

12. Chlamydia trachomatis Epidemiology in the US Rates: Total and by sex: United States, 1988–2007 Note: As of January 2000, all 50 states and the District of Columbia had regulations requiring the reporting of chlamydia cases.

13. Chlamydia trachomatis Epidemiology in the US Age- and sex-specific rates: United States, 2007

14. Chlamydia trachomatis Epidemiology in the US Trends in positivity among 15- to 24-year-old women tested in family planning clinics by HHS region, 2003–2007

15. Chlamydia trachomatis Epidemiology in the US Positivity in 15- to 24-year-old women tested in prenatal clinics by state: United States and outlying areas, 2007

16. Neisseria gonorrhoeae Epidemiology in the US Age- and sex-specific rates: United States, 2007

17. Neisseria gonorrhoeae Epidemiology in the US Cases by reporting source and sex: United States, 1998–2007

18. Neisseria gonorrhoeae Epidemiology in the US Positivity in 15- to 24-year-old women tested in prenatal clinics by state: United States and outlying areas, 2007

19. CDC recommendations  All pregnant women should routinely tested for Chlamydia trachomatis at the first prenatal visit  Women aged <25 years and those at increased risk for chlamydia (i.e., women who have a new or more than one sex partner) also should be retested during the third trimester to prevent maternal postnatal complications and chlamydial infection in the infant  All pregnant women at risk for gonorrhea or living in an area in which the prevalence of Neisseria gonorrhoeae is high should be tested at the first prenatal visit for N. gonorrhoeae  repeat test should be performed during the third trimester for those at continued risk

20. Summary  Chlamydia developmental cycle may be influenced by host factors  Viability may be compromised by harsh treatment but actual data regarding survivability in placental tissues are lacking  Primary chlamydia infections in ruminants result placental infection  Chlamydia trachomatis infections are the most frequently reported bacterial STD in the US  Neisseria gonorrhoeae prevalence is much lower than C. trachomatis  Viability may be compromised by harsh treatment but actual data regarding survivability in placental tissues are lacking

21. Acknowledgements Dr Stuart Berman Chief, Epidemiology and Surveillance Branch Division of STD Prevention National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention Centers for Disease Control and Prevention Atlanta, GA