The document discusses sexually transmitted infections (STIs), including rates of different STIs in the US and Colorado. It covers topics like diagnosis of STIs, treatment and antibiotic resistance, the role of human papillomavirus (HPV) in cancers, HPV vaccination programs, and the emergence of Mycoplasma genitalium as an STI pathogen. It also addresses issues like higher STI rates among minorities and challenges in detecting and treating infections caused by M. genitalium.

1. Sexually Transmitted Infections:
All you ever wanted to know
… and more
Lisa E. Manhart, PhD
Associate Professor, Epidemiology & Global Health
University of Washington

2. Where are we going…
Who gets STIs
Diagnosis
Cases, treatment scenarios
Treatment, antibiotic resistance
The future

3. Chlamydia – inclusion bodies

4. STI Rates – Nationwide & Colorado
Colorado 2012 Sexually Transmitted Infections Annual Report
Gonorrhea—Rates by Sex, U.S., 1992–2012
Chlamydia—Rates by Sex, U.S., 1992–2012
CDC STD Surveillance Report 2012

5. Gonorrhea Incidence Rates by County,
Colorado (per 100,000), 2012
14.9
14.7
Colorado 2012 Sexually Transmitted Infections Annual Report

6. Chlamydia Incidence Rates by County,
Colorado (per 100,000), 2012
429.5
198.9
Colorado 2012 Sexually Transmitted Infections Annual Report

8. Most young women acquire HPV
soon after sexual debut
Cumulative Incidence of HPV Infection
College women 18-20 years
(Winer et al, Am J Epidemiol 2003)

9. Role of HPV in Cancers
100
80
60
40
20
0
Cx Anal Vulva/Vaginal Penile Oral
% HPV-positive
Slide Courtesy of Rachel Winer
Trottier H et al, Public Health Genomics 2009

10. Number of new HPV-associated cancers
overall, and by sex, in the United States 2009
Slide courtesy of Rachel Winer
Jemal A et al. JNCI J Natl © The Author 2013. Published by Oxford University Press. Cancer Inst 2013;105:175-201
Reused with permission.

11. Oral HPV
 Predominantly sexually transmitted
o 8-fold higher prevalence in sexually experienced individuals1
o Associated with lifetime number of sex partners1
 Linked to oropharyngeal squamous cell carcinomas
(OSCC)
o ~90% due to HPV162
 Incidence of OSCC is increasing
o Expected to surpass incidence of cervical cancer by 20203
Slide Courtesy of Rachel Winer
1Gillison et al. JAMA 2012; 307(7):693-703
2D’Souza et al. N Engl J Med 2007;356(19):1944-56
3Chaturvedi et al. J Clin Oncol 2011;29(32):4294-301

12. HPV Vaccination Works
Australia
Urban Clinic Records 2004-2010
(Ali et al, IUSTI,2012)

13. But only if people get vaccinated
Genital Warts - Initial Visits to
Physician Offices
U.S. 1966-2012
(CDC STD Surveillance 2012)
Only ~35% vaccination
coverage rate

14. gonococcus

15. MSM get STDs
Syphilis (P&S)
US 2008-2012
Syphilis (P&S)
Colorado 2012
Colorado 2012 Sexually Transmitted
Infections Annual Report
CDC STD Surveillance Report
2012

16. Minorities get STDs
Gonorrhea-Rates by Race/Ethnicity
US 2008-2012

17. Why do minorities get more STDs?
30
20
10
0
STI/HIV prevalence - Add Health
Low risk Few
p's/low
ATOD
Multiple
partners
Sex for
money
IDU
Whites
Blacks
Adapted from Hallfors et al, AJPH 2007
STI/HIV Prevalence

18. Whites consistently use condoms
less!
National Survey of Sexual Health and Behavior - 2009
100
80
60
40
20
0
Condom use
14-17 18-24 25-29 30-39 40-49
Whites
Blacks
Adapted from Reece et al., J Sex Med 2010
Proportion

19. Sexual Networks –
connectedness

21. Antibiotic Resistance in Gonorrhea
Bolan, Sparling, Wasserheit, NEJM 2012

22. DRAFT - Sexually Transmitted Diseases
Treatment Guidelines, 2014
(Distributed solely for the purpose of pre-dissemination peer review)
Uncomplicated Gonococcal Infections of the
Cervix, Urethra, & Rectum
Recommended Regimen
Ceftriaxone 250 mg in a single intramuscular dose
(Cefixime 400mg single oral dose if Ceftriaxone not available)
PLUS
Azithromycin 1 g orally in a single dose

23. Alternate therapies
 Matt’s data
 Bob Kirkcaldy’s trial
 Other drugs in the pipeline

25. STD Syndromes
Organisms detected in
men with NGU
in Seattle STD Clinic
(2007-2010)
Organisms detected in
women with cervicitis
in Seattle STD Clinic
(1984-1986)

26. Sexually Transmitted Diseases Treatment
Guidelines
Syndromic Therapy for Female Cervicitis and
Male Urethritis
Recommended Regimen
Doxycycline 100 mg bid x 7 days
OR
Azithromycin 1 g orally in a single dose

27. How well do standard therapies
work?
45%
31% 30%
87%
67%
40%
Mena
2009
Schwebke
2011
Manhart
2013
DOX
AZM
90% 95%
90%
83% 86%
77%
Stamm
1995
Schwebke
2011
Manhart
2013
Chlamydia trachomatis
DOX
AZM
Mycoplasma genitalium
Eradication
Eradication

29. M. genitalium
More common than you think
Young adults 18-24 yrs1,2
1.0%
3.8%
0.6%
1 Miller 2004; 2 Manhart 2007
2.1%
Prevalence
MG CT GC TV
STD Clinic/ED Attendees3-9
13.4% 12.1%
15.2%
7.0%
22.4%
19.2% 19.2%
Men Women
3Totten 2001; 4Mena 2002; 5Manhart 2003; 6Huppert
2008; 7-8Gaydos 2009a & 2009b; 9Mobley 2012

30. Patients are concerned
“My persistent NGU began after a sexual encounter and lacks other
explanations (I have tested negative for everything else), and the
symptoms persist even after 1G azithromycin and 5 day
metronidazole regimens, which were essentially done as
experiments by my doctor to see if symptoms remained. I am in
<STATE> and unfortunately neither the local STD clinic nor my
doctor seem to know much about M. genitalium as a cause, and I'm
not confident about the local ability to accurately test for it…..”
-email received 11-11-13
(Permission to share granted)

31. Detecting MG infections?
No FDA-approved diagnostic test
 Culture extremely difficult
 Not reliable
 Hologic Gen-Probe TMA assay
 Research use only (currently)
 Anticipated commercial release early 2015
 Commercial Laboratories & NAAT tests
 Limited test-performance information
 Assays licensed in Europe
 Bio-Rad Dx/CT/NG/MG Assay®
 Sacace Biotechnologies

32. Persistent NGU Treatment
Recommended regimens:
 Metronidazole 2 g orally in a single dose
OR
 Tinidazole 2 g orally in a single dose
PLUS
 Azithromycin 1 g orally in a single dose (if not used for
initial episode)
Moxifloxacin 400 mg PO x 7d effective for NGU
treatment failures due to M. genitalium

34. M. genitalium:
a pathogen emerged
Syndrome Summary risk estimate
NGU 5.5 (4.3 – 7.0)
Cervicitis 1.7 (1.4 – 2.0)
PID/Endometritis 2.1 (1.3 – 3.5)
Infertility
2.4 (0.9 – 6.3)
3.5 (1.5 – 7.9)*
Preterm Delivery 1.9 (1.4 – 2.6)
*Excluding one outlying study
~2.0
Meta-analysis; Lis et al, submitted

35. Therapy for PID (outpatient)1
Ceftriaxone 250 mg IM in a single dose
Cefoxitin PLUS Doxycycline: 57% MG+ persistent endometritis2
Moxifloxacin 400mg PO x 14 days effective against
M. genitalium-associated PID3
1 CDC STD Treatment Guidelines 2010; 2 Haggerty 2008; 3Ross 2006
PLUS
Doxycycline 100 mg orally twice daily for 14 days
WITH or WITHOUT
Metronidazole 500 mg orally twice a day for 14 days

37. Slide with data on candida and
BV

38. Broad Range 16S rDNA gene
PCR

39. Vaginal Bacterial Communities
Srinivasan PLoS One 2012;7(6):e37818

40. Now, let’s hear from you.
Questions? Discussion?

41. THANK YOU!
University of Washington
 Rebecca Lis
 Patricia Totten
 King Holmes
 David Fredricks
 Sujatha Srinivasan
 Rachel Winer
Disclosures
 Pfizer, Inc. – study drugs
 Hologic Gen-Probe –
reagents & test kits
 Qiagen – consultation
Funding
 National Institutes of
Health (GRANT
NUMBERS)