STD Update

Ina Park, MD, MS University of California San Francisco- California Prevention Training Center and California Dept of Public Health

Epi of Bacterial STDs Screening Chlamydia, proctitis Gonorrhea, antibiotic

resistance Syphilis, ocular syphilis PrEP and STIs

ROADMAP

CHLAMYDIA — RATES OF REPORTED CASES BY SEX, UNITED STATES, 1994–2014

N O T E : A s o f J a n u a r y 2 0 0 0 , a l l 5 0 s t a t e s a n d t h e D i s t r i c t o f C o l u m b i a h a v e r e g u l a t i o n s t h a t r e q u i r e t h e r e p o r t i n g o f c h l a m y d i a c a s e s .

2014-Fig 1. SR, Pg 8

GONORRHEA — RATES OF REPORTED CASES BY SEX, UNITED STATES, 1994–

2014

2014-Fig 13. SR, Pg 19

PRIMARY AND SECONDARY SYPHILIS — REPORTED CASES BY SEX AND SEXUAL

BEHAVIOR, 27 AREAS*, 2007–2014

* 2 7 s t a t e s r e p o r t e d s e x o f p a r t n e r d a t a f o r 7 0 % o f r e p o r t e d c a s e s o f p r i m a r y a n d s e c o n d a r y s y p h i l i s f o r e a c h y e a r d u r i n g 2 0 0 7 – 2 0 1 4 . † M S M = m e n w h o h a v e s e x w i t h m e n ; M S W = m e n w h o h a v e s e x w i t h w o m e n o n l y .

2014-Fig 32. SR, Pg 33

SYPHILIS RATES AMONG MSM: A TIMELINE

Peterman, 2015, Expert Rev Anti Infect Ther

Syphilis rates among MSM will soon be similar to those in the early 1980s

0

10

20

30

40

50

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Perc

ent o

f Cas

es

Year

MSM WITH EARLY SYPHILIS* AND VENUES WHERE THEY MEET SEX PARTNERS

CALIFORNIA, 2005–2014

Internet

Bathhouses/ Sex Clubs

Bars/Clubs

Rev. 7/2015 * Includes primary, secondary, and early latent syphilis. California Dept of Public Health

Chew Ng, 2013 AJPH

Location-based Select practice, HIV status, sexual role Rapid / local communication Enormous reach (Grindr-196 countries,10 million downloads)

ANONYMOUS SEX? THERE’S AN APP FOR THAT

SCREENING

thedramadownunder.info

Sexually Active adolescents & adults <25 years old Routine chlamydia and gonorrhea screening* Others STDs and HIV based on risk

Women 25 years of age and older STD/HIV testing based on risk

HIV-positive women CT/GC (vaginal, cervical, or urine) CT/GC (rectal, if exposed) GC (pharyngeal, if exposed) Syphilis serology Trichomoniasis Hepatitis BSAg, Hepatitis C (first visit)

STD SCREENING FOR WOMEN

CDC 2015 STD Tx Guidelines, HIVMA/IDSA 2013 Primary Care Guidelines, USPSTF

Annually

HIV Syphilis Urethral GC and CT Rectal GC and CT (if RAI) Pharyngeal GC (if oral sex)

HSV-2 serology (consider) Hepatitis B (HBsAg, freq not specified)

* At least annually, more frequent (3-6 months) if at high risk (multiple/anonymous partners, drug use, high risk partners)

CDC 2015 STD Treatment Guidelines

*

Anal Cancer in HIV+ MSM: Data insufficient to recommend routine screening, some centers perform anal Pap and HRA

• Hepatitis C (HIV+MSM, at least annually)

N=4217 interviews and chart reviews from Medical Monitoring Project, nationally representative sample of adults in HIV care

SUBOPTIMAL STD SCREENING AMONG MSM IN HIV CARE

Flagg EW, 2015, STD

0

10

20

30

40

50

60

Syphilis Chlamydia Gonorrhea

% of sexually active HIV+ MSM screened for STIs, N=1411

N=21994 MSM in the STD Surveillance Network (SSUN)

% SCREENED BY ANATOMIC SITE AMONG MSM IN STD CLINICS

0

10

20

30

40

50

60

70

80

90

GC CT

UrogenitalPharyngealRectal

Patton et al CID 2014

8% Urogenital CT+ 3% Pharyngeal CT+ 14% Rectal CT+

11% Urogenital GC+ 8% Pharyngeal GC+ 10% Rectal GC+

AMONG MSM, WHAT PERCENT OF GC OR CT INFECTIONS ARE MISSED IF ONLY URINE IS

SCREENED

1. 10-20% 2. 21-50% 3. 51-70% 4. > 70%

HIGH PROPORTION OF EXTRAGENITAL CT/GC ASSOCIATED WITH NEGATIVE URINE TEST, STD SURVEILLANCE NETWORK (N=21994)

Patton et al CID 2014

Between 70-90% of infections would be missed by only screening with urine

Highly acceptable, similar performance compared to clinician-collected specimens Self-collection can be performed at

laboratory along with blood draw/urine collection or in the exam room before/after the provider visit May save patient an office visit May save the provider time

SELF-COLLECTED RECTAL/PHARYNGEAL STI TESTING

Van der helm, 2009, STD; Sexton, 2013 J Fam Pract; Dodge, 2012 Sex Health Freeman 2011, STD; Alexander 2008, STI; Moncada 2009, STD

CHLAMYDIA & GONORRHEA

CHLAMYDIA TREATMENT ADOLESCENTS AND ADULTS

Recommended regimens (non-pregnant): Azithromycin 1 g orally in a single dose Doxycycline 100 mg orally twice daily for 7 days

Recommended regimens (pregnant*): Azithromycin 1 g orally in a single dose Amoxicillin 500 mg po TID x 7 days

* Test of cure at 3-4 weeks only in pregnancy

CDC 2015 STD Treatment Guidelines www.cdc.gov/std/treatment

CHLAMYDIA TREATMENT CHANGES FOR 2015

New Alternative Regimen (non-pregnant): Doxycycline (delayed release) 200 mg QD x 7 d Equally efficacious to doxycycline BID, ↓ GI side effects More $$$

Moved to Alternative Regimen (pregnant*): Amoxicillin 500 mg po TID x 7 days - CT persistence documented in vitro after treatment prompted removal from recommended to alternate

PROCTITIS

No major changes Presumptive treatment of LGV for MSM with

proctitis and rectal CT is recommended: If the patient is HIV-infected OR Bloody discharge, perianal ulcers or mucosal

ulcers are present

GONORRHEA

GONORRHEA DUAL THERAPY UNCOMPLICATED GENITAL, RECTAL,

OR PHARYNGEAL INFECTIONS

Ceftriaxone 250 mg IM in a single dose

Azithromycin 1 g orally

(preferred) or

Doxycycline 100 mg BID x 7 days

CDC 2015 STD Treatment Guidelines www.cdc.gov/std/treatment

PLUS*

• Regardless of CT test result

ALTERNATIVE CEPHALOSPORINS: Cefixime 400 mg orally once

PLUS Azithromycin 1 g (preferred) or doxycycline 100

mg BID x 7 days, regardless of CT

IN CASE OF SEVERE ALLERGY: Azithromycin 2 g orally once

(Caution: GI intolerance, emerging resistance)

Gonorrhea Treatment Alternatives Anogenital Infections

Gentamicin 240 mg IM + azithromycin 2 g PO OR Gemifloxacin 320 mg orally + azithromycin 2 g PO

Doxy removed as co-treatment (unless azithro allergy)

CDC 2015 STD Treatment Guidelines www.cdc.gov/std/treatment

NIH-sponsored non-comparative randomized trial in adults with urethral or cervical gonorrhea

1. gentamicin 240 mg IM + azithromycin 2 g PO, or 2. gemifloxacin 320 mg PO + azithromycin 2 g PO

Per-protocol efficacy: gentamicin + azithromycin = 100% (202/202) gemifloxacin + azithromycin = 99.5% (198/199)

ALTERNATIVE UROGENITAL GC REGIMENS: AVOID MONOTHERAPY

Kirkcaldy, CID 2014;59:1083-91.

ANY DOWNSIDE TO THE ALTERNATIVE REGIMENS?

Gentamicin Regimen

Gemifloxacin Regimen

Route IM or IV Oral Nausea 27% 37% Vomiting (<1 hour)

3% 7%

Availability OK FDA reported shortage in May

2015 Volume Need 6 cc

(40mg/cc)

WHO NEEDS A TEST OF CURE FOR GC?

Patients with pharyngeal GC treated with an alternative regimen Obtain test of cure 14 days after treatment, using

either culture or NAAT

Cases of suspected treatment failure (culture and simultaneous NAAT) Consider if using non-recommended or

monotherapy

ANTIBIOTIC-RESISTANT GONORRHEA

B o l a n e t a l . N e w E n g l a n d J o u r n a l o f M e d i c i n e 2 0 1 2 .

PERCENTAGE OF NEI SSERIA GONORRHOEAE ISOLATES WITH REDUCED

CEFIX IME SUSCEPTIB IL IT Y†

GONOCOCCAL ISOLATE SURVEILLANCE PROJECT (G ISP) , 2006–2015*

0

0.5

1

1.5

2

2006 2007/ 2008††

2009 2010 2011 2012 2013 2014 2015*

†Minimum inhibitory concentration (MICs) ≥0.25 µg/ml *2015 data are preliminary as of March 7, 2016 †† Cefixime susceptibility not tested in 2007 and 2008

Percentage

Dual therapy for GC Increased Ceftriaxone to 250 mg from 125 mg

% OF URETHRAL ISOLATES WITH ELEVATED CEFTRIAXONE MINIMUM INHIBITORY CONCENTRATIONS (MICS) (≥0.125 ΜG/ML) GONOCOCCAL ISOLATE SURVEILLANCE PROJECT

2007–2014

*MSM=men who have sex with men; MSW=men who have sex with women only.

2013-Fig Z. SR. Pg. 75.

Oral cephalosporin treatment failures reported worldwide Japan, Hong Kong, England, Austria,

Norway, France, South Africa, and Canada

Ceftriaxone treatment failures in pharyngeal gonorrhea and a few isolates with high-level ceftriaxone resistance reported

CEPHALOSPORIN TREATMENT FAILURES

The New Yorker 2012

AZITHROMYCIN TREATMENT FAILURE IN CALIFORNIA

Gose et al. STD 2015;42:279-80.

SUSPECTED GC TREATMENT FAILURE

• If GC culture not available, call your local health department

TEST WITH CULTURE AND NAAT:

•Gemifloxacin 320 mg + AZ 2g OR Gentamicin 240 mg IM + AZ 2g • If reinfection suspected, repeat treatment with CTX 250 + AZ 1g

REPEAT TREATMENT:

•To your local health department within 24 hours

REPORT:

•Treat all partners in last 60 days with same regimen

TEST AND TREAT PARTNERS:

•TOC 7-14 days with culture (preferred) and NAAT

TEST OF CURE (TOC):

Partner treatment and Repeat Screening

PREVENTING CT/GC REINFECTION

Clinical evaluation first-line option Concurrent patient-partner therapy can be

effective for for those with one primary partner Offer expedited partner treatment (EPT) CT/GC if

partner cannot be promptly treated Use of prepackaged medication is recommended Dual therapy (cefixime 400 mg + azithromycin 1 g) is crucial

if EPT is used for GC CDC recommends EPT for heterosexuals, CA guidelines do

not discriminate based on gender of sex partners

PARTNER MANAGEMENT: TAKE HOME POINTS

CDC 2015 STD Treatment Guidelines: www.cdc.gov/std/treatment CA EPT Guidelines: www.cdph.ca.gov/pubsforms/Guidelines/Documents/CA-STD-PDPT-Guidelines.pdf

Legal Status of Expedited Partner Therapy, 6/2015

www.cdc.gov/ept

TESTING AFTER AN STD INFECTION

Women who test positive for CT/GC, or trichomonas should be rescreened three months following treatment.

Men who test positive for chlamydia or gonorrhea

should be rescreened at three months after adequate therapy.

All patients with a bacterial STDs or trichomonas

should be tested for other STDs including CT/GC, syphilis, and HIV

CDC 2015 STD Treatment Guidelines www.cdc.gov/std/treatment

Primary, Secondary & Early Latent: Benzathine penicillin G 2.4 million units IM in a

single dose Late Latent and Unknown Duration: Benzathine Penicillin G 7.2 million units total, given

as 3 doses of 2.4 million units each at 1 week intervals

Neurosyphilis: Aqueous Crystalline Penicillin G 18-24 million units

IV daily administered as 3-4 million IV q 4 hr for 10 -14 d

SYPHILIS TREATMENT: NO CHANGE

In pregnancy, benzathine penicillin is the only recommended therapy. No alternatives

•Clinical experience suggests 10-14 days ok for non-

pregnant adults • <9 days is best based on limited pharmacologic data

• In pregnancy, must adhere to strict 7 days between

doses •40% of pregnant women are below treponemicidal

levels after 9 days •If a dose is missed, the entire series must be

restarted

WHAT IS THE MAXIMUM TIME ALLOWED BETWEEN PENICILLIN DOSES?

NEUROSYPHILIS AND OCULAR SYPHILIS

Photo Courtesy: Dr. Kees Rietmeijer, STD Control , Denver PHD

NEUROSYPHILIS: CAN OCCUR AT ANY STAGE OF SYPHILIS

• All patients with syphilis should be evaluated for neurologic symptoms and signs

• CSF examination is recommended for: • Neurologic or ophthalmic symptoms/signs

• Auditory disease, cranial nerve dysfunction, meningitis, stroke, altered mental status, loss of vibration sense, iritis, uveitis

• Evidence of tertiary disease • aortitis, gumma

• Serologic treatment failure

CDC 2015 STD Treatment Guidelines

OCULAR SYPHILIS CLUSTER

OCULAR SYPHILIS

Several cases of ocular syphilis were reported in multiple cities in California and in Seattle, WA Several cases resulted in permanent decline in visual acuity, including

blindness

CLINICAL ADVISORY

CERTAIN T. PALLIDUM STRAINS ARE ASSOCIATED WITH NEUROSYPHILIS

Evaluated in ongoing study of neurosyphilis in Seattle 50% (n=22) of patients with strain type 14d/f had

neurosyphilis, compared to 23% (n=9) of patients with other strain types had

neurosyphilis

Rabbit studies Animals infected with 14a/a strain and 14d/f strain had greatest degree of neuroinvasion

Marra et al. JID 2010 Tantalo et al. JID 2005

OCULAR SYPHILIS IN 2014-2015: SELECT CLINICAL CHARACTERISTICS

Cases both HIV+ and HIV- men and women Clinical presentation of cases has included:

• Red eye • Eye pain • Vision loss, flashing lights, blurry vision • Headache in addition to eye symptoms

• Ophthalmologic exam findings: (Can involve almost any eye structure) • Uveitis (commonly posterior uveitis & panuveitis) • Optic neuritis • Retinal detachment

Photo Courtesy: Dr. Kees Rietmeijer, STD Control , Denver PHD

MMWR October 16, 2015 / 64(40);1150-1

NEW BUGS: MAN WITH A “DRIP”

A 23 yo male presents for evaluation of a urethral discharge without dysuria

He has been seen in clinic 15 times between 5/22/12 and 9/2/14 Sometimes visible discharge, sometimes not On 9 occasions a urethral Gram stain performed 5 times <5PMN/hpf 4 times >5PMN/hpf

GC documented 5/23/13, otherwise, tested for GC and CT at each of the 15 visits and always negative

Most recently treated with 1gm Azithromycin orally once; partner received treatment; GC and CT neg

TODAY HE PRESENTS WITH THICK, WHITE DISCHARGE…NOW WHAT?

Source: Diepgen TL, Yihune G et al. Dermatology Online Atlas

WHAT IS YOUR NEXT STEP?

1) Give up 2) Give him longer course of

azithromycin 3) Get a urine culture 4) Try a different antibiotic 5) Get a consult from ID 6) More than 1 of the above

NEW STI ON THE BLOCK MYCOPLASMA GENITALIUM

Young adults 18-24 yrs1,2

M. genitalium MORE COMMON THAN YOU THINK

1 Miller 2004; 2 Manhart 2007

1.0%

3.8%

0.6%

2.1%

Pre

vale

nce

MG CT GC TV

STD Clinic/ED Attendees3-9

13.4% 12.1%

15.2%

7.0%

22.4% 19.2% 19.2%

Seattle NewOrleans

Cincinnati Baltimore Durham

Men Women

3Totten 2001; 4Mena 2002; 5Manhart 2003; 6Huppert 2008; 7-

8Gaydos 2009a & 2009b; 9Mobley 2012 L. Manhart, with permission

M. GENITALIUM & REPRODUCTIVE TRACT DISEASE

Definitely associated with NGU in men

Study of association with: Cervicitis PID Infertility Preterm delivery

Increased odds of adverse outcomes= ~2.0 fold higher for all conditions Statistically significant for all but infertility

Lis et al., 2015 Clin Infect Dis

DETECTING MG INFECTIONS?

No FDA-approved diagnostic test

Nucleic Acid Amplification Test (Hologic GenProbe) Curently research use only FDA approval being sought

Commercial Laboratories (in house PCR tests) Limited test-performance information

L. Manhart, with permission

MG CURE RATES WITH DOXYCYCLINE AND

AZITHROMYCIN

Randomized Trials

Doxycycline (100mg bid x 7d) vs. Azithromycin (1g)

45% 31% 30%

87%

67%

40%

Mena 2009 Schwebke 2011 Manhart 2013

Doxycycline

Azithromycin

Mic

robi

olog

ic C

ure

L. Manhart, with permission

CONCLUSION: AZM (1g) is superior to DOX (100mg bid x 7d). However, efficacy of AZM is not consistently high and may be declining

Highly effective for treatment failures o 100% cure rates in most cases

Public health 340b pricing available

o Usual price for 7 day course ~ $100+

o Negotiated price to $1.21/pill

Caveat: Moxifloxacin treatment failures emerging (Japan, Seattle, Australia)

Moxifloxacin 400mg po x 7-14d

MG Treatment

L. Manhart, with permission

If azithromycin NOT given for 1st episode: Azithromycin 1 g orally in a single dose

PLUS Metronidazole 2 g orally in a single dose OR Tinidazole 2 g orally in a single dose

If azithromycin given for 1st episode: Moxifloxacin 400 mg orally qd x 7d

PLUS Metronidazole 2 g orally in a single dose OR Tinidazole 2 g orally in a single dose (if having sex with

females)

PERSISTENT NGU TREATMENT

EPILOGUE

Patient takes moxifloxacin 400 mg po x 7 days. Symptoms finally resolve. Take home point: Think about M. genitalium in cases of

cervicitis and urethritis treatment failure.

STIs

BACKGROUND: STDs PREDICT FUTURE HIV RISK

1 in 15 MSM were diagnosed with HIV within 1 year.*

1 in 53 MSM were diagnosed with HIV within 1 year.*

Rectal GC or CT

1 in 18 MSM were diagnosed with HIV within 1 year.**

Primary or Secondary Syphilis

No rectal STD or syphilis infection

*STD Clinic Patients, New York City. Pathela, CID 2013:57; **Matched STD/HIV Surveillance Data, New York City. Pathela, CID 2015:61

50%

33% 33% 28%

5.5% 0%

0%

10%

20%

30%

40%

50%

60%

Any STI Rectal STI Chlamydia Gonorrhea Syphilis HIV

STI Incidence After 12 Months of PrEP Use

HIV PrEP and STIs Kaiser Permanente San Francisco

Volk et al. CID 2015; Slide courtesy J. Volk

HIV incidence = 0.43 cases / 100 py (95% CI 0.05-1.54) STI incidence (90 cases/100 py) high but stable over time (P> 0.1) 50.9% of participants had at least one STI during follow-up >75% of GC and >85% of CT infections were asymptomatic

0

5

10

15

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30

Screening 12 24 36 48

% P

ositi

ve

Visit Week

GC, CT or Syphilis

Rectal GC or CT

Pharyngeal GC orCTUrethral GC or CT

HIV PrEP and STIs-Part II PrEP Demo Project (NIAID), n=557

Liu 2016, JAMA Int Med

% infections for which treatment would have been delayed with q6 month, as opposed to q3 month screening

HIV PrEP and STIs-Part III: Optimal Screening Frequency (n=445)

Cohen # 870 CROI 2016

Pilot RCT of N=30 HIV+ MSM with h/o repeat syphilis Doxycycline 100 mg po daily vs placebo + $50-100 per visit for testing STD-free Outcomes: contracting GC/CT, syphilis, or composite

outcome (any GC/CT/syphilis)

76.7% retention through 48 weeks Less infections seen for syphilis (2 vs 7 infections),

GC/CT (4 vs 8 infections), NS Composite outcome, doxy superior to placebo, OR

0.27 (0.9-0.83), p=0.02

STI PrEP?

Bolan, 2015 STD

LET’S PUT IT IN THE WATER

doxy PreP

Bacterial STIs are all increasing, especially among MSM Serosorting/seroadaptive strategies PrEP Efficient online access to sex

Syphilis and extragenital GC/CT are key as rectal GC/CT infections and syphilis predict future HIV acquisition.

Self-collected GC/CT testing may help overcome provider barriers, is acceptable to MSM and performs well

Ask about ocular/visual symptoms in patients with syphilis

TAKE HOME POINTS

SF Dept of Public Health Stephanie Cohen California Dept of Public Health Jessica Frasure Julie Stoltey

ACKNOWLEDGMENTS

THANK YOU Any burning questions?

Ina.park@cdph.ca.gov