Gonorrhea Christine Wigen, MD, MPH Assistant Medical Director Los Angeles County Department of Pubic Health Sexually Transmitted Diseases Program April 1, 2009

Overview Description of gonorrhea and Transmission Epidemiology Types of Infections Diagnosis, Screening, and Treatment Reporting Partner Management & Patient Delivered Partner Therapy Re-testing

Gonorrhea (GC) Gram-negative diplococcus Second most common bacterial STD Causes a range of clinical syndromes Usually symptomatic in males, often asymptomatic in women Can cause pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and complications in pregnancy in women

Gonorrhea – How do people get it? Transmitted through sexual contact (vaginal, anal, or oral) Ejaculation does not have to occur for GC to be transmitted or acquired Can also be transmitted from mother to baby during delivery People who have been treated for GC can get re-infected if they have sexual contact with a person with GC

Epidemiology of Gonorrhea

Gonorrhea — Rates: United States, 1941–2007 and the Healthy People 2010 target Note: The Healthy People 2010 target for gonorrhea is 19.0 cases per 100,000 population.

Gonorrhea — Rates by state: United States and outlying areas, 2007 Note: The total rate of gonorrhea for the United States and outlying areas (Guam, Puerto Rico and Virgin Islands) was 117.4 per 100,000 population. The Healthy People 2010 target is 19.0 cases per 100,000 population.

Gonorrhea — Rates: Total & by sex: United States, 1988-2007 & the Healthy People 2010 target Note: The Healthy People 2010 target for gonorrhea is 19.0 cases per 100,000 population.

Gonorrhea Rates per 100,000 Population, US, CA, LA County, 2001 - 2007

Reported STD Cases in US, CA and LA, 2006 and 20071,2 Year Chlamydia Gonorrhea P&S Syphilis EL Syphilis 2006[1] US 1,030,911 358,366 9,756 9,186 CA 135,827 33,740 1,835 1,369 LA 42,943 11,162 866 851 % CA 31.6% 33.1% 47.2% 62.1% % US 4.2% 3.1% 8.9% 9.3% 2007[2] 1,108,374 355,991 11,466 10,768 141,928 31,294 2,038 1,460 LA** 44,030 10,063 919 714 31% 32.2% 45.1% 49% 4% 2.8% 8% 7% LAC accounts for slightly more than 1/3 of the state’s STD morbidity and 44% of the early latent syphilis cases. LA County 38,294 cases reported in 2004 CT accounts for 74% of all reported STDs GC accounts for 19% All syphilis accounts for 1.6% [1] Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2006. Atlanta, GA: U.S. Department of Health and Human Services, November 2007. http://www.cdc.gov/std/stats/pdf/Surv2006.pdf [2] Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2007. Atlanta, GA: U.S. Department of Health and Human Services, January 2009

Distribution of Reported STD in Los Angeles County, 2008

Gonorrhea — Rates by race/ethnicity: United States, 1998–2007

Race/Ethnicity Disparity in Reported Gonorrhea Rates per 100,000 Population, LA County 2008 Los Angles Department of Public Health, STD Program

Gonorrhea – Rates by Gender, Los Angeles County, 2003–2007 Male Female 2/2006 Provisional Data - CA DHS STD Control Branch

Gonorrhea — Age- and sex-specific rates: United States, 2007

Males Rate (per 100,000 population) Females Reported Gonorrhea Rates per 100,000 Population, by Gender & Age Group, 2007 Males Rate (per 100,000 population) Females Age 15-19 21-29 35-44 55-64

Gonorrhea Rates, Females, by Race/Ethnicity and Age Group, California, 2007 23 times white rate 13 times white rate 8 times white rate 2/2006 Provisional Data - CA DHS STD Control Branch

Infections Caused by Gonorrhea

Gonococcal Infections in Women Cervicitis Urethritis Proctitis (rectal infection) Pharyngitis (throat infection) Accessory gland infection (Skene, Bartholin) PID/Peri-hepatitis (Fitz-Hugh-Curtis) Conjunctivitis (eye infection) Disseminated Gonococcal Infection (DGI) Many infections asymptomatic

Gonococcal Cervicitis Incubation 3-10 days Symptoms: Vaginal discharge Dysuria (burning pain upon urination) Vaginal bleeding Cervical signs : Redness Friability Purulent discharge STD Atlas, 1997

Gonococcal Infections in Men Urethritis Epididymitis/seminal vesiculitis Proctitis (rectal infection) Conjunctivitis (eye infection) Abscess of Cowper’s/Tyson’s glands Pharyngitis (throat infection) Disseminated gonococcal infection Urethral stricture Penile edema (swelling) Infection may be asymptomatic

Gonococcal Urethritis Incubation 2-7 days Abrupt onset of severe dysuria Purulent urethral discharge (“drip”) Most urethral infections symptomatic STD Atlas, 1997

Complications of GC Infections Disseminated GC infection (DGI) Epididymitis PID

Gonorrhea and HIV Transmission/Acquisition How can syphilis or other STDs increase HIV transmission? Reducing physical barriers Increasing the number of receptor cells Increasing HIV viral load in genital lesions, semen or both Inflammatory STDs2 to 5-fold increased HIV acquisition* Lets now move on to speak about some of the observation studies. Many of these studies were first summarized by Judy Wasserheit. She performed a metaanalysis of ---articles showing that inflammatory STDs were associated with a 2-5 fold increased in HIV acquisition and that genital ulcers were associated with a 3-11 fold increase of HIV acquisition. *Wasserheit STD 19:261; 1992

Diagnosis of Gonorrhea

Gonorrhea - Diagnosis Gram stain: 95% sensitive and >99% specific in symptomatic males Culture: 80 - 95% sensitive and 100% specific DNA probe: 89-97% sensitive 97-99% specific Nucleic acid amplification tests (NAATs): includes LCR, PCR, TMA and SDA; 95-98% sensitive, >98% specific

Gram Stain STD Atlas, 1997

Additional NAAT Capabilities Self-collected vaginal swab Equivalent performance with endocervical and urine specimens and with provider specimens FDA approved for clinic-based testing only Non-genital NAAT testing (Not FDA approved-labs need internal verification) Rectal Pharyngeal Self-collected rectal NAAT

Screening for Gonorrhea

CDC GC Screening Recommendations Women: based on US Preventive Services Task Force (no CDC-specific recommendations) Sexually active women if at increased risk: Women under age 25 Previous GC infection, other STD, new/multiple partners, inconsistent condom use, commercial sex, drug use Screening not recommended in men or in women who are at low risk for infection

California Guidelines for GC Screening, 2005 Routine Screening: Sexually active women <25* annually Over 25: targeted screening based on risk factors History of gonorrhea in past two years >1 partner in past year Partner with other partners African American women up to age 30 * Unless prevalence in patient population known to be <1% From: CA Guidelines for Gonorrhea Screening and Diagnostic Testing Among Women In Family Planning and Primary Care Settings, Dec 2005

STD Screening for Men who have Sex with Men (MSM) STD Screening Site Type of Sex GC/CT urethra or urine oral, anal insertive GC/CT* rectum receptive anal GC/CT* pharynx receptive oral Syphilis blood oral, anal HIV blood oral, anal Note: availability of non-genital NAATs is limited. LAC PHL provides rectal GC/CT and pharyngeal GC testing. CT culture should not be used for screening (unless medico-legal case).

CT & GC Infections among MSM by Anatomic Site, SF STD Clinic San Francisco 2003 Klausner et al, 11th Conf. Retroviruses, 2004

Rectal Gonorrhea in MSM, SF STD Clinic (Kent CK, Chaw JK, Klausner JD, STD Conf. 2004) And 84% of MSM were asymptomatic when infected with gonorrhea.

MSM and GC/CT Rectal CT/GC infections often overlooked due to asymptomatic nature and lack of sensitive test Emerging evidence re: high prevalence Anatomic site-specific screening needed

Gonorrhea Treatment

Gonorrhea Treatment in California Recommended regimens: Ceftriaxone 125 mg IM x 1* Cefixime 400 mg PO x 1† Alternative regimens: Spectinomycin 2 g IM x 1** Cefpodoxime 400 mg po x 1 Co-treat for chlamydia unless ruled out by NAAT *Preferred and only recommended regimen for pharyngeal infection † suspension may be available ** currently not manufactured

Gonorrhea Treatment in Cephalosporin-allergic Patients Urogenital infections Azithromycin 2 g po x 1 with TOC Spectinomycin 2 g IM x 1 * Pharyngeal infections *No longer manufactured!

for patients with gonorrhea in California… CIPRO

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

Gonococcal Isolate Surveillance Project (GISP), Percent of Neisseria Gonorrhoeae Isolates with Decreased Susceptibility or Resistance to Ciprofloxacin in Five California STD Clinics, 1990–2006 Note: Resistant isolates have MICs ≥ 1 μg ciprofloxacin/mL. Isolates with decreased susceptibility have MICs of 0.125 – 0.5 μg ciprofloxacin/mL. STD Clinic Sites: Long Beach, Los Angeles (added in 2003), Orange, San Diego, San Francisco CA DPH STD Control Branch (rev 7/2007)

Gonococcal Isolate Surveillance Project (GISP) — Prevalence of ciprofloxacin resistant Neisseria gonorrhoeae by GISP site, 2004-2007 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, HI

Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance to ciprofloxacin by sexual behavior, 2001–2007

Gonococcal Isolate Surveillance Project (GISP), Percent of Neisseria Gonorrhoeae Isolates Obtained from Men who Have Sex with Men in Five California STD Clinics, 1990–2006 Note: This project began in 1991 for the Orange County STD Clinic, and in 2003 for the Los Angeles County STD Clinic. CA DPH STD Control Branch (rev 7/2007)

Reporting

Non Gonoccocal Urethritis Pelvic Inflammatory Disease Syphilis LGV 7 Diseases Reportable to the STD Program Mandated By California State Law: Chlamydia Chancroid Gonorrhea Non Gonoccocal Urethritis Pelvic Inflammatory Disease Syphilis LGV And now that I’ve discussed the program & it’s activities, let’s discuss the diseases that are reportable to the STD Program which are: The 4 most common in your practice are: CT, GC, PID & Syphilis. These are all bacterial infections which are curable with the appropriate antibiotic therapy and you can refer to your treatment guidelines for those. CT & GC are characterized by discharge ( cervical or urethral); chancroid & syphilis are both characterized by genital lesions however the chancroid lesion is painful whereas the syphilis chancre is painless. PID is an ascending infection of the lower genital tract due to untreated CT, GC or other organism. And NGU or non-gonococcal urethritis is an infection characterized by an abnormal discharge in the absence of CT. AIDS is reportable to the HIV Epidemiology Program. HIV just recently became reportable to the state of California in July of 2002. Other reportable STD’s that can be transmitted sexually are for ex. Hep B & C, and salmonella. These infections are reportable to ACD.

GC Reporting Providers must report syphilis cases within seven calendar days by completing a Confidential Morbidity Report (CMR)

STD Confidential Morbidity Reporting (CMR) Tool used by providers to report STD lab & treatment STD Purpose To determine the extent of STD morbidity in L.A. County To evaluate disease transmission risk Provides a mechanism to target intervention activities Now I have placed a copy of the LA County STD CMR in your packets, which you can review at your leisure. This was recently revised by the program in March of this year with input from county clinicians. As you can see, there is an area to specify the disease, the pt.’s pregnancy status, treatment information as well as any labs or additional tests that were done. All providers, public and private, should use this to report morbidity to the STD Program.

STD CMR: Available via download @ http://lapublichealth.org/std/providers.htm Or call 213-741-8000

Gonorrhea and Chlamydia Partner Management and Patient Delivered Partner Therapy

Patient Delivered Partner Therapy (PDPT) for GC and CT: infection rates at follow-up % Reinfected RCT of expedited partner therapy vs standard 931 patients assigned to SR and 929 to EPT Male and female index cases Rate of reinfection lower in EPT groups P=.02 P=.17 Golden, NEJM, 2005

Rate of CT Re-infection of Women According to Partner Management None= No counseling or attempted partner rx A=Patient counseled to refer partner B= Patient refers partner, compliance monitored C=Patient-delivered Partner Therapy RX 25 years of data. N 372 997 645 167 Ramstedt K, 1991

Gonorrhea & Chlamydia Partner Management All sex partners from 60 days preceding the diagnosis should be evaluated, tested, and treated If no sex partners in previous 60 days, treat the most recent partner

Summary of RCT PDPT Studies Providing treatment for partners of chlamydia or gonorrhea infected heterosexual patients, without provider evaluation, is an effective partner management strategy Decrease in reinfection rates of index cases proves effectiveness (gonorrhea > chlamydia)

Current Options in California for Management of Sex Partners for CT/GC Patient self-referral Provider/clinic referral Patient Delivered Partner Therapy/Expedited Partner Therapy

Status of PDPT/EPT in California Chlamydia PDPT Legal since January 1, 2001(SB 648) Gonorrhea PDPT Became legal January 1, 2007 (AB 2280)

CA Guidelines for PDPT for Chlamydia (1) Diagnosis: Uncomplicated genital chlamydia infection First-line: Attempt to bring partners in for evaluation and treatment Priority patients: Females with male partners Partners: Males who are uninsured or unlikely to seek medical services Medication: Azithromycin (Zithromax*)1 gram (250 mg tablets x 4) orally once

CA Guidelines for PDPT for Chlamydia (2) Number of doses are limited to the number of sex partners in past 60 days Education materials must accompany meds Patient counseling: Abstinence until 7 days after treatment and until 7 days after partners have been treated Evaluation: Recommend re-test patients for chlamydia 3-4 months after treatment Adverse rxns: Report to 1-866-556-3730

Guidelines for PDPT for Gonorrhea Under-development Recommended medication will be cefpodoxime 400mg x 1 plus azithromycin 1g

Re-Testing for Gonorrhea and Chlamydia

Recommendations for Re-testing Recommendation: women and men infected with chlamydia and/or gonorrhea should be re-tested 3-4 months after treatment Rationale: High percent of rapid repeat infection Short time to repeat positive test Re-screening identifies highest risk patients STD Treatment Guidelines, 2006

Gonorrhea Re-infection rates Patients retested at 3-4 months: Women 12-24% infected Men 9% infected Kjaer et al, STI 2000, Golden et al NEJM 2005.

Check List for the Management of Gonorrhea and Chlamydia Cases Ensure timely and appropriate treatment Test for other STDs Patient counseling Ensure that sex partners are treated Schedule 3 month retesting follow-up Report case to the local health department

Harm Reduction Use of condoms consistently and correctly Minimize # of sex partners Avoid sex while under the influence of alcohol or drugs to decrease risky behavior Avoiding abusive relationships

Resources 2006 STD Treatment Guidelines: www.cdc.gov/std Los Angeles County STD Program website: http://publichealth.lacounty.gov/std/index.htm California STD-HIV Prevention Center: www.stdhivtraining.org

Questions? Christine Wigen, MD, MPH Email: cwigen@ph.lacounty.gov Phone #: 213-744-3092