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STI Update 2009

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STI Update 2009 Powered By Docstoc
					Alice C. Thornton, MD Program Director Kentucky Local Performance Site
Southeast AIDS Training and Education Center May 4, 2009

Objectives



Participant will be able to . . .

 Discuss STI Treatment Guidelines  Demonstrate a knowledge of signs and symptoms
of STI’s  Describe recent events in the world of STI’s

Which is true regarding syphilis?
 (A) Since 2000, syphilis in the US has been    

increasing in men & women (B) Up to 5% of strains of Treponema pallidum are resistant to penicillin (0.1 ug/mL) (C) The recommended alternative treatment for early infectious syphilis in patients allergic to penicillin is doxycycline (D) The alternative treatment for early infectious syphilis in pregnancy is erythromycin (E) To avoid a Jarisch-Herxheimer reaction, treatment should be initiated with serial doses of an antimicrobial

ABIM, 2008

Syphilis Rates are Increasing in men, Especially those who have Sex with Men but not Women

Http://www.cdc.gov/std/stats07/trends.htm

Primary and Secondary Syphilis — Rates: Total and by sex: United States, 1988–2007 and the Healthy People 2010 Target

Rate (per 100,000 population) 25 20 15 10 5 0 1988 90 92 94 96 98 2000 02 04 06 Male Female Total 2010 Target

Note: The Healthy People 2010 target for P&S syphilis is 0.2 case per 100,000 population.

http://www.cdc.gov/std/stats07/slides.htm

Primary and secondary syphilis — Rates among 15 -19-year-old Males by race/ethnicity: United States, 1998–2007

Rate (per 100,000 population) 20 16 12 8 4 0 1998 99 2000 01 02 03 04 05 06 07
American Indian/AK Native Asian/Pacific Islander Black Hispanic White

Http://www.cdc.gov/std/stats07/slides.htm

Primary and Secondary Syphilis — Reported cases* by stage and sexual orientation, 2007
Cases 5000 Primary Secondary

3750

2500

1250

0 Heterosexual Men Women MSM
†

*21.0% †MSM

of reported male cases with P&S syphilis were missing sex of sex partner information. denotes men who have sex with men.

Http://www.cdc.gov/std/stats07/slides.htm

Syphilis …Definitions
 

Primary
 Ulcer/chancre (painless)



Latent
 Seroreactivity without

Secondary
 Skin rash,mucous

evidence of disease  Early latent
○ Acquired within 1yr

patches,alopecia, etc.


 Late latent or syphilis of

Tertiary
 Cardiac,ophthalmic,


unknown duration

Neurosyphilis

auditory,etc.

STD Treatment Guidelines.MMWR.2006; 55:1-92

Latent : Asymptomatic


Early latent
 <1 YR of Infection  Documented seroconversion/unequivocal sx/sex

partner dx with 1o or 2o or early latent


Late Latent (>1 yr ) or Unknown Duration

STD Treatment Guidelines.MMWR.2006; 55:1-92

Neurosyphilis
Serology  Can occur at any stage  CSF

 WBC( >5) / protein  +VDRL-CSF=diagnostic (very specific ..

watch for false -)  Some feel a negative CSF FTA-ABS rules out neurosyphilis (highly sensitive)

STD Treatment Guidelines.MMWR.2006; 55:1-92

Primary, Secondary, Early Latent Recommended Regimen
Benzathine Penicillin G, 2.4 million units IM Penicillin Allergy* Doxycycline 100 mg twice daily x 14 days or  Ceftriaxone 1 gm IM/IV daily x 8-10 days (limited studies)


or


Azithromycin 2 gm single oral dose (preliminary data).  *Use in HIV-infection has not been studied  Reports of resistance (First noted in San Francisco, 2002)

STD Treatment Guidelines.MMWR.2006; 55:1-92
Katz, KA .Azithromycin resistance in T. Pallidum.. Curr Opin Infect Dis; 21:83-91

Treatment of Syphilis
Penicillin G is the DOC for all stages  Consider desensitization for pregnant penicillin allergic patients (any stage) (NEW)


STD Treatment Guidelines.MMWR.2006; 55:1-92

Latent Syphilis Recommended Regimen






Benzathine penicillin G 2.4 million units IM at one week intervals x 3 doses Penicillin allergy* Doxycycline 100 mg orally twice daily or Tetracycline 500 mg orally four times daily Duration of therapy 28 days; close clinical and serologic follow-up; Data to support alternatives to pcn are limited
STD Treatment Guidelines.MMWR.2006; 55:1-92

Neurosyphilis Penicillin Allergy
Ceftriaxone 2 gm daily IM/IV for 10-14 days  Consideration of cross-reactivity  Pregnant patients should undergo penicillin desensitization  Other regimens have not been evaluated


STD Treatment Guidelines.MMWR.2006; 55:1-92

―So who is perfect? Washington had false teeth…Mussolini had syphilis and Lincoln was constipated.‖ O’Hara


All strains of T. pallidum are very susceptible to PCN Tx of Jarisch Herxheimer: antipyrectics



http://www.cdc.gov/std/training/clinicalslides/slides-dl.htm

Syphilis in HIV infected


P/S
 Single Dose PCN G 2.4 mu  Some recommend 3 treatments in 1-week intervals  “The use of alternative therapies in HIV-infected has

not been well studied; the use of doxy, ceftriaxone and azithromycin among such persons must be undertaken with caution”


F/U
 Evalulate clinically and serologically at 3,6,9,12 and

24 mo  Some recommend a CSF at 6mo but unproven benefit
STD Treatment Guidelines.MMWR.2006; 55:1-92

Syphilis in HIV infected


Latent
 Early Latent: Same as P/S  Late/Latent or Unknown Duration ○ CSF b/f treatment ○ F/U: 6,12,18 and 24 mo ○ Be prepared to repeat CSF if sx develop or titers rise 4-fold; if no 4-fold decline in 12-24mo, Repeat CSF and tx if indicated



Neurosyphilis
 Tx same as HIV uninfected

STD Treatment Guidelines.MMWR.2006; 55:1-92

18 year old woman consults you regarding genital HSV type 2
Which of the following is true?
 A. Asymptomatic viral shedding occurs on less than

1% of days in women with documented infection clinically apparent infection

 B. Most transmission occurs when one partner has  C. Acyclovir reduces the duration of symptomatic &

asymptomatic viral shedding

 D. Acyclovir is non or minimally toxic because it does

not penetrate into uninfected cells type-specific serology

 E. The best way of diagnosing active infection is by

ABIM, 2007

“Vinnie, when you get married you realize that a wife is like herpes…She comes and goes when and where she pleases.” Ari Gold of Entourage


Active infection is best dx by culture/PCR Acyclovir penetrates uninfected cells but is activated only in viral-infected cells



ABIM, 2007

http://www.cdc.gov/std/training/clinicalslides/slides-dl.htm

Shedding/Reactivation
  

Subclinical shedding of HSV-2 can occur in ~ 20-25% of all days Recurrence in first year: HSV-1 (60%) /HSV-2 (90%) Risk of shedding decreases with time after the primary infection


After 10yrs, it is ~70% lower than during 1st 6mo of acquisition

Sacks, 2004

Shedding (Information Gleaned from PCR Data)
Shedding occurs at many anatomical sites (urethra, vulva, cervico-vagina, rectum)  Mucosal reactivation is 4-5 times more frequent than thought  All HSV-2 seropositive people are infectious  PCR is 3-4 times more sensitive in detecting HSV on mucosa than culture


Sacks, 2004

Valacyclovir Transmission Study








1,484 immunocompetent, heterosexual couples Clinical severity of HSV-2 was not associated with transmission (OR: 0.89) (CI: 95%) There was no association btwn freq of recurrence and risk of transmission. Both symptomatic and asymptomatic shed virus intermittently. Most transmissions appear to occur during episodes of subclinical viral reactivation. Kim, 2008

HSV…Type-specific Serologic Tests
HSV-2 antibody indicates anogenital infection  Must be based on HSV-specific glycoprotein G1 for HSV-1 and G2 for HSV-2

 Request type specific gG-based tests  Focus Technology (HerpeSelect 1 and 2

Immunoblot IgG and HerpeSelect-1 ELISA IgG or HerpeSelect -2 ELISA IgG)

STD Treatment Guidelines.MMWR.2006; 55:1-92

Not Mexico
A 22 year old man comes to the student health clinic because of dysuria and purulent urethral discharge.  He recently returned from Spring Break in Hawaii.  Staining of the urethral exudate reveals gram-negative diplococci with neutrophils.




ABIM, 2005

Which of the following is the best treatment approach for the organism seen?
○ (A) a single dose of ceftriaxone
○ (B) a single dose of ofloxacin ○ (C) oral linazolid

○ (D) oral single dose of azithromycin

ABIM, 2005

Quinolone Resistant N. Gonorrhea
CDC’s Gonococcal Isolate Surveillance Project (GISP);started in 1986 (26-30 sites)  ~6000 isolates: 4.2% QRNG  19/5,461 isolates (0.4%) MIC >1.0ug/ml to ciprofloxacin

 Resistant isolates comprised 14.3% of the

Honolulu GISP sample

Gonococcal Isolate Surveillance Project (GISP) — Prevalence of ciprofloxacin resistant Neisseria gonorrhoeae by GISP site, 20042007
SEA POR MIN DTR CHI SFO LVG LAX LBC ORA ALB PHX DAL SDG HON TRP NOR MIA OKC BHM ATL DEN KCY NYC CLE CIN GRB BAL RIC
QR N G P revalence 50%

PHI

25%

0%

' 0 40 50 60 7 ' ' '

Note: Not all clinics participated in GISP for the last 4 years. Sites include: ALB=Albuquerque, NM; ATL=Atlanta, GA; BAL=Baltimore, MD; BHM=Birmingham, AL; CHI=Chicago, IL; CIN=Cincinnati, OH; CLE=Cleveland, OH; DAL=Dallas, TX; DEN=Denver, CO; DTR=Detroit, MI; GRB=Greensboro, NC; HON=Honolulu, HI; KCY=Kansas City, MO; LAX=Los Angeles, CA; LBC=Long Beach, CA; LVG=Las Vegas, NV; MIA=Miami, FL; MIN=Minneapolis, MN; NOR=New Orleans, LA; NYC=New York City, NY; OKC=Oklahoma City, OK; ORA=Orange County, CA; PHI=Philadelphia, PA; PHX=Phoenix, AZ; POR=Portland, OR; SDG=San Diego, CA; SEA=Seattle, WA; SFO=San Francisco, CA; and TRP=Tripler Army Medical Center, Http://www.cdc.gov/std/stats07/slides.htm

Ciprofloxacin Resistance
 <1%

in 1990; 0.4% in 2000

 Fluroquinolones not recommended in

Asia/Pacific Island acquisition

in 2002: rec. extended to Calif.  4.1% in 2003  6.8% in 2004: no use in MSM  9.4% in 2005; 13.3% in 2006  14.8% in 2007

 2.2%

MMWR; April 13, 2007
Increasing prevalence of QRNG in heterosexual males and MSM  “The CDC no longer recommends fluroqinolones for the treatment of GN or conditions such as PID caused by GN.”  2gm azithromycin of concern as rapid emergence of resistance has been seen


Treatment Recommendations
Gonorrhea Cefixime 400 mg  Ceftriaxone 125 mg IM  Ceftizoxime 500mg  Cefoxitin 2g with probenecid 1 g orally  ?cefpodoxime 400 or cefuroxime 1 g?  PLUS treatment of CT if CT is not ruled out  Persistent sx

 Reevaluate by cx and do

Chlamydia
    

Azithromycin 1 gm Doxycyline 100mg BID for 7 days Erthromycin 500mg or 800mg QID x 7d Ofloxacin 300 mg BID for 7 days Levo 500mg QD x 7d

susceptibility testing

PCN or Cephalosporin Allergies
Spectinomycin 2g (not available in US)  ? Azithromycin


MMWR, 2007

Gonococcal Isolate Surveillance Project (GISP) — Penicillin, tetracycline, and ciprofloxacin resistance among GISP isolates, 2007

Note: PenR=penicillinase producing N. gonorrhoeae and chromosomally mediated penicillin-resistant N. gonorrhoeae; TetR=chromosomally and plasmid mediated tetracycline-resistant N. gonorrhoeae; QRNG=ciprofloxacin resistant N. gonorrhoeae. Http://www.cdc.gov/std/stats07/slides.htm

Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance or intermediate resistance to ciprofloxacin, 1990–2007

Percent 16 Resistance Intermediate resistance

12

8

4

0
1990 91 92 93 94 95 96 97 98 99 2000 01 02 03 04 05 06 07

Note: Resistant isolates have ciprofloxacin MICs ≥ 1 µg/ml. Isolates with intermediate resistance have ciprofloxacin MICs of 0.125 - 0.5 µg/ml. Susceptibility to ciprofloxacin was first measured in GISP in 1990. Http://www.cdc.gov/std/stats07/slides.htm

Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance to ciprofloxacin by sexual behavior, 2001–2007
Percent 40 32 24 16 8 0 2001 2002 2003 2004 2005 2006 2007 Heterosexual men Men who have sex with men (MSM)

Http://www.cdc.gov/std/stats07/slides.htm

http://www.cdc.gov/std/gisp2007/GISPSurvSupp2007Complete.pdf

http://www.cdc.gov/std/gisp2007/GISPSurvSupp2007Complete.pdf

Scenario #9
 (D)

Which of the following is true regarding Human Papillomavirus (HPV) infection?
 (A) Cervical cancer is caused by only HPV



 



types 6 & 11 (B) Anogenital HPV infection is a sexually transmitted infection with low incidence in the United States (C) Most HPV infections persist for many years (D) The recently approved recombinant HPV vaccine is highly effective in preventing cervical cancer & its precursors (E) Current evidence indicates that HPV recurrent respiratory papillomatosis is a precancerous condition
ABIM, 2007

Epidemiology
6.2 million new US HPV infections occur yearly; most common STI in US  More than 120 different types  20 million (15 to 49 yrs) currently infected  5 - 30% are infected with multiple types  Sexual behavior is the most constant predictor of acquiring infection  Found in heterosexuals, WSW and MSM

Trottier, 2005

HPV 101
 Cutaneous or mucosa  Mucosa: Anogenital epithelium (cervix, vagina, vulva,

rectum, urethra, penis and anus)  Low Risk Types
○ Benign associated with genital warts (6, 11,40 etc.)

 High Risk Types

Associated with cervical, vulvar, penile and anal cancer(16, 18, 31, etc) ○ 16 and 18 are associated with 99% of cervical cancers, LSIL,HSIL and abnormal Pap tests
○
MMWR, 2007 56(No. RR-2)

Transmission
Skin to skin contact  Most HPV infections are asymptomatic and resolve without treatment • 70% spontaneously clear within 1st year ○ 90% within 2 years  No evidence that treatment prevents transmission  Persistant infection with high-risk types is impt risk for cervical cancer

MMWR, 2007 56(No. RR-2)

Recurrent Respiratory Papillomatosis


Most common benign neoplasm of larynx in children
 Exposure of neonatal larynx to infected

cervical tissue ?

Tends to recur and spread throughout the respiratory tract  Possesses the potential for airway compromise and a 3-7% risk of malignant conversion  Mostly caused by HPV types 6 and 11

Gallagher, 2008

HPV Vaccines
Merck and GSK  Noninfectious recombinant HPV capsid proteins that form VLPs  Prophylactic .. Administer before onset of sexual activity  Appears to have high efficacy in preventing HPV 16

 91% effective in preventing infection

Vaccination
Confers protection against both high/low-risk HPV  Bivalent Vaccine

 Most common high-risk (16 and 18)



Quadrivalent Vaccine
 High risk (16 and 18)  Most common low-risk (6 and 11)

Gardasil
Quadrivalent HPV Vaccine  Protects against 6,11,16, 18 (responsible for 70% of cervical cancer and 90% of genital warts)  Made from non-infectious HPV-like particles (VLP)  No thimersol or mercury

MMWR 2007;56(No. RR-2) http://www.canada.com/calgaryherald/

Human Papillomavirus (HPV) Vaccine Schedule

Females 9 through 26 years of age  Routine schedule is 0, 2, and 6 months  Minimum intervals:

 4 weeks between doses 1 and 2  12 weeks between doses 2 and 3

Source: MMWR 2007;56(No. RR-2)

HPV Vaccination ACIP (Advisory Committee on Immunization Practices) Recommendations
Routine vaccination of females 11-12 years of age with three doses of quadrivalent HPV vaccine  The vaccination series can be started as young as 9 years of age at the clinician’s discretion


Source: MMWR 2007;56(No. RR-2)

HPV Vaccination ACIP Recommendations
Vaccination is recommended for females 13 - 26 years of age not previously vaccinated  Vaccine should be administered before onset of sexual activity, if possible  Females who are sexually active should be vaccinated


Source: MMWR 2007;56(No. RR-2)

HPV Vaccine Special Situations
Females 26 years of age or younger with equivocal or abnormal Pap test, positive HPV DNA, or genital warts may be vaccinated  Vaccine will have no effect on existing disease or infection


Source: MMWR 2007;56(No. RR-2)

Safety, Efficacy and Duration


In studies of over 11,000 females: no serious side effects
 Mainly, mild infections site pain

100% efficacy in prevention of cervical pre-cancers  Nearly 100% prevention of vulvar and vaginal pre-cancers and genital warts  Duration is unclear: 5 yr follow-up data

http://www.cdc.gov/std/hpv/common-clinicians/ClinicianBro-br.pdf

Which of the following does NOT decrease transmission of HIV from a positive to a negative heterosexual partner?
 (A) Circumcision  (B) Vaginal microbicides containing

nonxynol-9  (C) Treatment of HIV in the infected partner  (D) Treatment of herpes simplex virus in the infected partner

ABIM, 2008

Discussion
Circumcision has been show in several studies to decrease the transmission rate of HIV by ~50%  After viral load, co-infection with HSV is the second most impt risk factor for HIV transmission  Although nonoxynol-9 effectively kills HIV in-vitro, use is associated with increased transmission (? Local irritation?).

ABIM, 2008

Resources
Self-Evaluation Process – Infectious Disease. Module A6-F. Version 08-1. American Board of Internal Medicine. 2008.  Sexually Transmitted Diseases Treatment Guidelines.MMWR.2006; 55:1-92  http://www.cdc.gov/std/training/clinicalslide s/slides-dl.htm



Azithromycin resistance in T. Pallidum. Katz, KA.Curr Opin Infect Dis 21:83-91



Self-Evaluation Process – Infectious Disease. Module A6-E. Version 07-01. American Board of Internal Medicine. 2007

Resources
 

    



HSV Shedding. Antiviral Research; 2004:S19-S26. Kim, HN. Does Frequency of Genital Herpes Recurrences Predict Risk of Transmission? Furhter Analysis of the Valacyclovir Transmission Study. STDs; 2008:124-128. Self-Evaluation Process – Infectious Disease. Module 06-B. Version 05-1. American Board of Internal Medicine. 2006. Http://www.cdc.gov/std/stats07/trends.htm http://www.cdc.gov/std/gisp2007/GISPSurvSupp2007Complete. pdf http://www.cdc.gov/std/treatment/2006/GonUpdateApril2007.pdf Update to CDC’s STDs Treatment Guidelines, 2006: Furoquinolones No Longer Recommended for Treatment of Gonococcal Infections. MMWR. 2007;56:332-336. Self-Evaluation Process – Infectious Disease. Module 26-R. Version 05-1. American Board of Internal Medicine. 2005.

Resources


 



Trottier H and Franco E. The Epidemiology of Genital Human Papillomavirus Infection. Vaccine 24S1 2006;24S1:S1/4-1/15. Quadrivalent HPV Vaccine;MMWR 2007; 56(No. RR-2) Gallagher,T and Derkay, C. Recurrent Respiratroy Papillomatosis:Update 2008. Current Opionon In Otolaryngolgoy, Head and Neck Surgery. 2008;16:536-542. http://www.cdc.gov/std/hpv/commonclinicians/ClinicianBro-br.pdf


				
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