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Sexually Transmitted Infections (STI): Biomedical and Public Health Aspects Vijay Kandula, MD MPH AAHIVS Adjunct Assistant Professor Division of Public Health, Department of Family and Preventive Medicine University of Utah, Salt Lake City 1 RESOURCES • • • • • www.health.nih.gov www.cdc.gov www.clinicaltrials.gov www.ashastd.org WHO: http://whqlibdoc.who.int/publications/200 7/9789241563475_eng.pdf 2 Current Issues with Sexually Transmitted Infection Management John F. Toney, MD, FACP, FIDSA Professor of Medicine Division of Infectious Disease and International Medicine University of South Florida College of Medicine Director, Southeast Region STD/HIV Prevention Training Center CDC National Network of STD/HIV Prevention Training Centers Director of Healthcare Epidemiology and Infectious Disease Clinical Research James A. Haley Veterans’ Hospital 3 Overview • • • • • Epidemiology of HIV Interaction between HIV and STIs Overview of Common STIs Public Health Approach Syndrome Management 4 Why STIs are important? • HIV infection is mainly a STI • STI s increase the spread of HIV • Treatment of STIs ↓ HIV transmission • HIV care / STI care: Integrated approach • HIV can alter the manifestations of STIs 5 HIV-1 and STIs • Genital ulcerConcentration disease increases HIVinTransmission of virus semen 14 • HIV increases asymptomatic shedding of Herpes 12 10 8 6 4 2 0 • HSV increase viral replication • HIV RNA can be detected in HIV person from ulcers secretions Without urethritis With urethritis After treatment (1 week) After treatment (2 weeks) • HIV RNA from genital fluid do not correlate with HIV RNA in blood 6 What’s in a Name? Sexually Transmitted Infections (STIs) Sexually Transmitted Diseases (STDs) Reproductive Tract Infections (RTIs) Venereal Diseases (VD) 7 Biological evidence of STI as cofactor for HIV transmission Presence of STD : • Increases HIV viral load in genital secretion of HIV infected partner • Increases HIV susceptibility: – disruption of epithelium cells, and – increased inflammatory cells in HIV uninfected partner 8 Relative risk: STI as risk factor for HIV transmission through Heterosexual route Study population STI Relative risk Men, Kenya Genital ulcer 4.7 Men, USA Syphilis 1.5-2.2 Men, USA Herpes 4.4 Women, Zaire Gonorrhoea 3.5 Chlamydia 3.2 Trichomonas 2.7 Herpes 3.3-8.5 Syphilis 8.4-8.5 Men, USA 9 The Hidden Epidemic: An Urgent Reality Still With Us “STDs are hidden epidemics of tremendous health and economic consequences in the U.S. They are hidden from public view because many Americans are reluctant to address sexual health issues in an open way and because of the biological and social factors associated with these diseases. In addition, the scope, impact, and consequences of STDs are under recognized by the public and health care professionals. ” 10 Global Overview • > 340 million new cases of STI Globally/yr – bacterial and protozoan infections • In pregnancy, untreated early syphilis – – – – 25% stillbirth rate responsible for 14% of neonatal deaths 40% overall perinatal mortality 4% - 15% of pregnant women in Africa Syphilis + • ~ 50 million new STIs/yr in USA 11 Recent Concerns Over STIs USA Today 25 February, 2004 12 Text 13 Deja Vu “All Over Again” Jack Wroten 1996 14 Primary and secondary syphilis — Reported cases* by Sexual Orientation and Race/Ethnicity†, 2007 *21% of reported male cases with P&S syphilis cases were missing sex of sex partner information; 3% of reported male cases with sex of partner data were missing race/ethnicity data. † No imputation was done for race/ethnicity. ‡MSM denotes men who have sex with men. Primary and secondary syphilis — Reported cases* by stage and sexual orientation, 2007 *21.0% of reported male cases with P&S syphilis were missing sex of sex partner information. †MSM denotes men who have sex with men. Division of STD Prevention (DSTDP), CDC 15 Primary and Secondary Syphilis—Rates by Sex and Male-to-Female Rate Ratios, United States, 1990–2009 Rate (per 100,000 population) Rate Ratio (log scale) 16:1 25 Male Rate Female Rate Total Rate Male-to-Female Rate Ratio 20 8:1 15 4:1 10 2:1 5 0 1:1 1990 1992 1994 1996 1998 2000 Year 2002 2004 2006 2008 Primary and Secondary Syphilis—Rates by State, United States and Outlying Areas, 2009 2.1 0.4 0.6 1.4 1.5 0.2 0.8 0.0 Guam 1.1 0.6 0.8 0.3 2.7 5.8 1.1 2.1 3.6 6.1 2.3 3.5 5.2 VT NH MA RI CT NJ DE MD DC 0.3 1.1 2.7 3.1 2.5 2.9 2.2 0.4 3.8 6.3 6.5 9.6 2.7 8.1 6.8 3.1 16.8 8.9 9.8 Rate per 100,000 population 0.0 2.6 Puerto Rico 5.7 0.0 1.1 3.7 1.9 1.9 2.4 3.1 5.6 27.5 Virgin Islands 0.0 5.7 NOTE: The total rate of primary and secondary syphilis for the United States and outlying areas (Guam, Puerto Rico, and Virgin Islands) was 4.6 per 100,000 population. <0.2 (n = 5) 0.21–2.2 (n = 19) >2.2 (n = 30) Primary and Secondary Syphilis—Rates by Race/Ethnicity, United States, 2000–2009 Rate (per 100,000 population) 25 20 American Indians/Alaska Natives Asians/Pacific Islanders Blacks Hispanics Whites 15 10 5 0 2000 2001 2002 2003 2004 Year 2005 2006 2007 2008 2009 Syphilis cause by Bacteria: Treponema pallidum • Primary lesion • Highly infectious • Heals spontaneously within 1 to 6 weeks • 25% present with multiple lesions • Secondary • 3 to 6 weeks after the primary chancre • may persist for weeks to months • Tertiary: • A year after primary infection • Heart, brain, eyes, almost all part of the body 19 Syphilis cause by Bacteria: Treponema pallidum • Primary lesion or "chancre" develops at the site of inoculation Chancre: • Highly infectious • Heals spontaneously within 1 to 6 weeks • 25% present with multiple lesions Serologic tests for syphilis may not be positive during early primary syphilis Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides 20 Source: Southeast Region STD/HIV Prevention Training Center Primary Syphilis – Labial Chancre Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides Source: CDC/ NCHSTP/ Division of STD Prevention /STD Clinical Slides 21 2. Secondary Syphilis • 3-6 wks after the primary chancre: may persist for wks-mths • May overlap with primary stages • Mucocutaneous lesions common • Manifestations: – Rash (75%-100%) – Lymphadenopathy (50%-86%) • Serologic tests (VDRL, RPR) are usually highest in titer during this stage 22 Secondary Syphilis: Palmar/Plantar Rash Source: Southeast Region STD/HIV Prevention Training Center Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 23 Secondary Syphilis: Generalized Body Rash Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides Source: Gower Medical Slides 24 Secondary Syphilis - Condylomata lata Source: Southeast Region STD/HIV Prevention Training Center 25 Secondary Syphilis - Alopecia Source: Southeast Region STD/HIV Prevention Training Center 26 Secondary Syphilis – Mucous Patches Source: Dermatology On-line Atlas (http://www.dermis.net) 27 Latent Syphilis and Tertiary • Host suppresses the infection enough so that no lesions are clinically apparent • Only evidence is positive serologic test for syphilis • May occur between primary and secondary stages, between secondary relapses, and after secondary stage • Categories: – Early latent: < 1 year duration – Late latent: 1 year duration 28 Gonorrhea • Etiologic agent: Neisseria gonorrhoeae • Gram-negative bacteria • Infects mucus-secreting epithelial cells Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 29 Gonorrhea—Rates, United States, 1941–2009 Rate (per 100,000 population) 500 400 300 200 100 0 1941 1946 1951 1956 1961 1966 1971 Year 1976 1981 1986 1991 1996 2001 2006 Male • Urethritis – Typically purulent or mucopurulent urethral discharge • Asymptomatic in 10% of cases • Incubation period: usually 1-14 days for symptomatic disease, but may be longer Source: Southeast Region STD/HIV Prevention Training Center 31 Gonococcal Periurethral Abscess Epididymitis Source: Southeast Region STD/HIV Prevention Training Center 32 Genital Infection in Women • Most infections are asymptomatic – Cervicitis – Urethritis 33 Cervicitis • Non-specific symptoms: – abnormal vaginal discharge, intermenstrual bleeding, dysuria, lower abdominal pain, or dyspareunia • Clinical findings: mucopurulent or purulent cervical discharge, easily induced cervical bleeding • 50% of women with clinical cervicitis have no symptoms • Incubation period unclear, but symptoms may occur within 10 days of infection 34 Gonococcal Urethritis in Women • Symptoms: dysuria, however, most women are asymptomatic • 40%-60% of women with cervical gonococcal infection may have urethral infection 36 Bartholin’s Abscess Source: Cincinnati STD/HIV PTC and CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides 37 39 MMWR 2007;56:332-336 40 Chlamydia Screening Among Sexually Active Young Female Enrollees of Health Plans, 2000-2007 (MMWR, April 17, 2009) 41 Chlamydia—Rates by Sex, United States, 1990–2009 Rate (per 100,000 population) 600 Men Women Total 500 400 300 200 100 0 1990 1992 1994 1996 1998 2000 2002 2004 2006 Year NOTE: As of January 2000, all 50 states and the District of Columbia had regulations that required chlamydia cases to be reported. 2008 C. trachomatis Infection Men – 50% - no symptoms Women • Cervicitis – 70%-80%- no symptoms – Symptoms/signs if present: mucoid or clear urethral discharge, dysuria • Urethritis – Usually asymptomatic 43 Non-Gonococcal Urethritis: Mucoid Discharge Source: Seattle STD/HIV Prevention Training Center at the University of Washington 44 Swollen or tender testicles (epididymitis) Source: Seattle STD/HIV Prevention Training Center at the University of Washington 45 Normal Cervix Chlamydia Cervicitis Source: STD/HIV Prevention Training Center at the University of Washington/Claire E. Stevens 46 HERPES: Herpevirdae • • • • • • • • • HSV-1 HSV-2 VARICALLA ZOSTER VIRUS EPSTEIN-BARR VIRUS CYTOMEGALOVIRUS HUMAN HERPESVIRUS 6 (CASTLEMAN’S) HUMAN HERPESVIRUS 7 HUMAN HERPESVIRUS 8 (KS) HERPES B VIRUS 47 EPIDEMIOLOGY • US > $1 Billion medical cost (direct and indirect) 2000 • 500,000 Cases annually • >50 Million people have Genital HSV • Seroprevalence 22% (> 12 Y/O) • HSV-1 and -2 CAN can caues genital herpes 49 50 52 Prevalence of HCV/HIV Co-infection 100 90% Percentage 80 IVDU MSM All HIV+ US Pop 60 40 20 33% 10% 1.9% 0 Population Sulkowski MS et al Clin Infect Dis 2000;Apr30Suppl 1:S77-84. 53 STRATEGIES IN COMMUNITY • • • • • Sexual behavior change and condom promotion Education of the public regarding the s/s Improve the health seeking behavior Training of health workers to screen STI Training of GPs to treat STIs 57 Operational model of the role of health services in STD case management Population with STD Aware and worried Seeking care Correct diagnosis Correct treatment Treatment completed Cure 58 Where STD control is likely to have a maximum impact • In settings with high prevalence of “relevant” STD (GUD, urethritis and cervicitis) • Low quality of STD services • At the earlier stages of the HIV epidemic It is NOT A MAGIC BULLET, but an essential component of a package of multiple HIV prevention strategies 59 Objectives of STI control • To interrupt the transmission of STD (acquired infection) • To prevent complication and sequelae • To reduce HIV infection risk 60 •Why Bother Screening? Percent of Persons with STIs Who Are Asymptomatic Men Women 100 90 80 70 60 50 40 30 20 10 Urethra Any 0 Rectum Gonorrhea Division of STD Prevention (DSTDP), CDC Pharynx Cervix Rectum Chlamydia Urethra Genital HSV 61 Management of STIs 1. Etiological (diagnostic) approach 2. Clinical diagnosis approach 3. Syndromic approach 62 Problems with etiological (diagnostic) management • • • • • • Delay in treatment Compliance with treatment Partner management Follow up Referral Maintenance of case records 63 Problems with etiological (diagnostic) management • • • • • Lab facility Interpretation of results Quality control Expensive (Chlamydia) Sophisticated tests 64 2. Clinical Diagnosis Approach Identify the STD causing symptoms based on clinical experience • even experienced providers often misdiagnose STDs • miss mixed infections • difficult for surveillance 67 Disease Agent Clinical features Chancroid Haemophilus Multiple painful irregular, ducreyi undermined edges, soft ulcerUnilateral Bubo Donovanosis Calmeto Painless progressive ulcer Herpes HSV 2&1 Multiple painful grouped vescicles- ulcerate coalase Reccurence b/L adenopathy I primary LGV Chlamidia trachomatis L1 L2 L3 Transient ulcer Unilateral tender adenopathy, grove sign Syphilis Treponema pallidum Painless single ulcer, indurated 68 clean base, Firm b/L adenopathy bacterium granulomatis No regional adenopathy 3. Syndromic Approach • Identify all possible STDs that could cause the syndrome Symptom • recommended treatment based on epidemiological and laboratory data Decision Action action action action 69 Syndromic Diagnosis Approach : Advantages Disadvantages • • • • Treat at first visit Cost saving No loss to follow up Effective in mixed infection • Minimal lab necessary • Reduce HIV& STI spread • Can be done by paramedics • Over treatment • False positive diagnosis • Social problems due to over diagnosis • Over treatment of partners 70 Syndromic Diagnosis Approach Principles of treatment • • • • • Medical treatment Follow up-return after 7 days if symptoms persists Partner notification Rule out other STDs - counsel HIV test Counseling & education – safe sex – risk reduction – behavior modification etc • Condom promotion and provision 71 Syndromic approach- Rationale • It is the diagnosis and treatment of selected STDs based on the identification of a syndrome through a clinical flowchart • Delivers effective STD treatment quickly to people when they first come for care • Ideal- “user friendly” 72 Syndromic approach- STDs • Focuses on the most common STDs that can be cured. • Complete STD care = - education - condom promotion - follow up - partner treatment - VCTC linkage 73 STD syndromes Syndrome Treat For Urethral discharge Gonorrhoea and chlamydia Genital ulcers Syphilis and chancroid Vaginal discharge Gonorrhoea, chlamydia and trichomonas Lower abdominal pain Gonorrhoea, chlamydia and anaerobes Inguinal bubo as for chlamydia Scrotal swelling Gonorrhoea and chlamydia Neonatal eye discharge Gonorrhoea and chlamydia 74 Remember 6 Cs for STIs management • Cure with treatment • Compliance to treatment • Contact tracing for partner management • Counseling & education • Condom promotion & provision • Come back for clinical follow up 75 Condom & ART • Continue condom use even in concordant couples. Why? – Different strains – Viral resistance – STIs – Effective ART programs may lead to increase in STI prevalence 79 HIV/AIDS • Which public health interventions can prevent the spread of HIV? – Examples from some countries in Asia • The 100% condom program • Harm reduction in injecting drug users 80 100% condom programme Annual new HIV infections, Thailand 100% condom program begins 120,000 100,000 80,000 60,000 40,000 20,000 0 1985 Thai Working Group on AIDS projections 2000 1990 1995 Male 2000 2005 Female 2010 2015 2020 Child 81 Incidence of STDs in Thailand (1982-2001) 5 4.5 4 3.5 3 First case of AIDS in 1984 100% condom initiated in 1989 gonorrhoea N.S.U. chancroid LGV syphilis 2.5 2 1.5 1 100% condom completed in 1992 0.5 0 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 2000 822001 Intervention studies: STD case finding strategies among CSW in Abidjan Intervention HIV incidence/100 py Before intervention 16.5 Basic strategy : monthly case finding 7.9 Intensive strategy : monthly case finding using pelvic exam, and lab 5.5 83 Mwanza trial • • • • • STD reference centre Syndromic approach Regular supply of effective STD drugs supervisory visits promote prompt attendance A 42% reduction in the incidence of HIV was noted in the intervention group as compared to the control group over 2 years of this intervention From Grosskurth et al., Lancet, 1995 84