Developments in (all 30 or so) STIs: Global Epidemiology and Management with an emphasis on asymptomatic infections
George Schmid, M.D., M.Sc. Dept. HIV/AIDS WHO [email protected] "Asymptomatic" Infections
Signs = objective evidence of disease
Symptoms = Signs that persons notice
"Inapparent infection" = Persons with symptoms but the persons do not think they represent an STI The Happy Young European 10% Risk 10% Risk 2% Risk
8% Risk
12% Risk
20% Risk Question #1
How many of us in this room have, or have had, an STI? 90% 75% 60% 35% 25% What Is a Sexually Transmitted Infection?
An infection which is transmitted from one person to another through acts of sex and an infection for which we want to contact the sex partner to prevent transmission to other people Sexually Transmitted Infection=Sexually Transmitted Disease=Reproductive Tract Infection? "Dear, the doctor says I have bacterial vaginosis and you need to be treated."
"My lawyer will contact you tomorrow about the divorce." RTIs
STIs
STDs Question #2
What proportion of cases of genital herpes are acquired from persons who know they have herpes? 85% 60% 30% 10% Asymptomatic Individuals Are Very Important
• With probably every STI, except… .(Question #3), most people— male and female— are asymptomatic • Asymptomatic people probably are responsible for most disease transmission • We should make people aware of these facts Gonorrhea Chancroid
Syphilis
Infection increasingly asymptomatic
Chlamydia Genital herpes Trichomonas Human papillomavirus
Sex practices increasingly risky increasingly practices Sex Glasier A et al. Lancet 2006;268:1-12 Question #4 How Do We Identify Asymptomatic People? Partner Notification
• How to do it? •Tell the patient to have partners examined? •Give the patient referral papers to give to partners? •Have the health authorities contact partners? • Alternate approaches •Network approach •Give patient medication for partner (for only certain diseases, e.g., chlamydia, trichomonas) STIs
There are about 30 STIs or disease syndromes that result from STIs STDs Bacteria • Gonorrhea (Neisseria gonorrhoeae) • Chlamydia (Chlamydia trachomatis) • Syphilis (Treponema pallidum) • Chancroid (Haemophilus ducreyi) Viruses • Genital warts and cervical— mainly--cancer (human papillomavirus) • Genital herpes (herpes simplex virus) • Hepatitis B (hepatitis B virus) Parasites • Trichomoniasis (Trichomonas vaginalis) STI Syndromes 1. Urethral discharge/discomfort (urethritis) in males • N. gonorrhoeae • C. trachomatis • U. urealyticum 2. Testicular pain (epididymitis) • N. gonorrhoeae • C. trachomatis 3. Abdominal pain in women (pelvic inflammatory disease) • N. gonorrhoeae • C. trachomatis • Flora of bacterial vaginosis • ? Mycoplasma genitalium STI Syndromes (continued)
4. Vaginal discharge/inflammation in women • Trichomonas vaginalis • Candida species (candidiasis) • Bacterial vaginosis 5. Genital “growths” • Human papillomavirus 6. Genital ulcers • Herpes simplex virus • Haemophilus ducreyi • Treponema pallidum STI Syndromes (continued)
7. Inguinal adenopathy • Chlamydia trachomatis (LGV) • Haemophilus ducreyi 8. Itchy/crawly things 9. Asymptomatic Why Do We Care About STIs?
1. Acute morbidity 2. Late morbidity • Spread locally, e.g., • 10-40% of women with a gonococcal or chlamydial infection develop PID. Of women with one episode of PID: – 20% are infertile – Of those who become pregnant, 9% will have an ectopic pregnancy Why Do We Care About STIs (continued)?
2. Late morbidity (continued) • Spread in body, e.g., • 30% of individuals with untreated syphilis develop neurosyphilis, cardiovascular syphilis, or late benign syphilis • Disseminated gonococcal infection (DGI) 3. Adverse outcomes of pregnancy, i.e., • Infertility • Affect the pregnancy, i.e., miscarriage, congenital infection • Affect the baby at delivery, e.g., genital herpes, chlamydia Why Do We Care About STIs (continued)?
4. Cofactors for cancer • Cervical cancer (HPV, probably HSV) and anal and penile cancer (HPV) • Hepatic cancer (hepatitis B and hepatitis C) 5. Enhanced HIV transmission How Common Are STIs Globally?
No one knows
Estimated Incidence of Four Curable STIs, by Continent
Continent Estimated Incidence
Western Europe 1-2%
United States 2-3%
Latin America 7-14%
Southeast Asia 9-17%
Sub-Saharan Africa 11-35%
Delebatta G et al. Family Health International Why Do People Get STIs? Anderson-May Equation
R c D o = β
Ro = reproductive rate β = infectivity c = rate of partner change (sex, needle) D = duration of infectiousness Core group
Percentage of population Percentage
Number of partners Diseases and Syndromes
~30 organisms or syndromes that are sexually transmitted
Ability of Clinicians to Diagnose the Cause of a Genital Ulcer
Disease Diagnostic Accuracy
Chancroid 80%
Syphilis 55%
Genital herpes 22%
Dangor Y et al. Sex Transm Dis 1990;17:184 Syndromes
• Genital ulcer • Urethritis (men) • Epididymitis • Vaginal discharge • Abdominal pain • Warts • Inguinal adenopathy • Itching/crawling creatures (lice, scabies) • Asymptomatic Diseases Characterized by Genital Ulcers
• Chancroid • Syphilis • Genital herpes • Other infectious causes of ulcers: • Epstein-Barr virus • Cytomegalovirus • Noninfectious causes, e.g. • Fixed drug eruption (tetracycline, laxatives commonly cause) • Trauma
Diagnostic Tests for Genital Ulcers
• History and physical exam • Laboratory •Darkfield microscopy (syphilis) Exclude syphilis! •RPR syphilis serology •About 70% sensitive in primary syphilis (if negative today, repeat in one week) •Test for herpes •Culture, antigen tests, PCR Question #5
HSV-2 is a life-long infection True False
HPV is a life-long infection True False Genital Herpes
• Genital herpes is common in the Industrialized World •About 20% of the adult population Prevalence of Antibody to HSV-2, Europe
Swiss Female Male
Smith J, Robinson J. J Infect Dis 2002; 186(S):S3 Genital Herpes
• Genital herpes is very common in the Industrialized World •About 20% of the adult population • It is a lifelong infection “Facts”About Herpes Simplex Virus (continued)
• Terminology •Primary infection--the first time someone is infected with a herpes simplex virus •First-episode genital herpes— the first time someone has a recognized genital infection Time Line of Genital Herpes
7 days 7-21 days 5-7 days One year
Inoculation First episode Recurrent episodes
“Shedding”of virus
Diagnostic Tests for Possible Genital Herpes
• Culture • PCR • Antigen detection tests Counseling of First-Episode Genital Herpes
• Patients should be counseled about: • The recurring nature of genital herpes • That many recurrent episodes are mild • That most cases of genital herpes are acquired from asymptomatic, or minimally symptomatic, cases • That sex should be avoided during prodromes or episodes, and that consistent condom use likely decreases transmission • That relatively normal lives can be led • That women who are infected may become pregnant and have children just as easily as women without a history of genital herpes Urethritis
Symptoms: a discharge, or discomfort/pain when urinating Question #6
If I have gonorrhea, and I have sex with a woman one time, the chance of my giving her gonorrhea are about: 80% 60% 40% 15% Urethritis?
Yes No
Test for: Gonorrhea Chlamydia Diagnosis of Urethritis
• Objective evidence of a discharge, or evidence of inflammation; •>5 WBC/oil immersion field on a Gram stain of urethral secretions, or; •A positive leukocyte esterase test on first-voided urine or; •>10 WBC per high power field on centrifuged, first-voided urine
Only the Gram Stain Let’s You Separate Gonococcal from Nongonococcal Urethritis
• High sensitivity for gonorrhea (>95%) • High specificity for gonorrhea (approaching 100%) Pathogenesis of Gonorrhea
• Incubation period 3-5 days (in men); often uncertain in women • A single act of intercourse will result in transmission: •Infected male infects female, 40% •Infected female infects male, 25% Question #7
Three Months After Therapy, What Proportion of Young Women Will Again Have:
Bacterial Vaginosis Chlamydia • 80% • 50% • 60% • 25% • 40% • 10% • 10% • 5% Chlamydia Pathogenesis of Chlamydia
• 48-hour life cycle, so that it grows very slowly in comparison to other bacteria (N. gonorrhoeae grows in 15 minutes) • The incubation period is, therefore, long (about two weeks) • How often a partner infects the other is uncertain, but if one person has chlamydia, the “typical” partner is infected in 40% of the time. Treatment of Chlamydia
Recommended • Azithromycin, 1 gm, orally, once, or; • Doxycycline, 100 mg, orally, twice a day, for 7 days. Follow-up of Patients with Chlamydia (continued)
• High rates of subsequent infection (up to 40%) occur in adolescent females •Consider advising all women with chlamydia infection to be re-screened 3-4 months after treatment. Diseases Characterized by Vaginal Discharge
• Candidiasis • Trichomoniasis • Bacterial vaginosis • Others, e.g., desquamative inflammatory vaginitis Bacterial Vaginosis
An increasingly important disease
1. Enhances HIV transmission 2. Causes PID 3. Causes post-procedure PID, e.g., after abortion, surgery
Therapy of Bacterial Vaginosis
• Metronidazole, 500 mg, orally, twice a day for 7 days, or; • Metronidazole gel, 0.75%, one applicator (5 gm), intravaginally, once a day for 5 days, or; • Clindamycin cream, 2%, one applicator (5 gm), intravaginally, once a day at bedtime for 7 days
European STD Guidelines. Int J STD AIDS 2001;12S3. Effectiveness of Therapy
5-10 days 3-4 weeks
Metronidazole, 2 g, once 84% 62%
Metronidazole, 500 mg bid for 7 days 93 82
Clindamycin, 300 mg bid for 7 days 94
Metronidazole* gel bid for 5 days 81 71
Clindamycin cream qhs for 7 days 85 82
*qhs dose approved
Joesoef R, Schmid G. Clin Infect Dis Suppl 1995 and 1999. Pelvic Inflammatory Disease (PID)
Diagnosis Remains a Problem What Causes PID?
• N. gonorrhoeae • C. trachomatis • Organisms of BV • ?Mycoplasma genitalium Why Is PID Bad?
Diagnostic Criteria for PID
Minimum Criteria for Instituting Antimicrobial Therapy
• Uterine/adnexal tenderness, or; • Cervical motion tenderness
PPV=<65-90% (?)
CDC STD Treatment Guidelines, MMWR, 2002 Do We Have Any Vaccines Against STIs?
Hepatitis viruses A and B HPV
HPV Estimated Prevalence of Genital HPV Among Women and Men, Aged 15-49, U.S. 1.4 m 1% Genital Warts Subclinical HPV by 5 million colposcopy or cytology 4% 10% Subclinical HPV by 14 million amplified NA probes Prior infection, detected by antibody 60% 81 million
34 million No prior or current 25% Koutsky L. Am J infection Med 1997;102:3 24-month Incidence and Duration of Infection
HPV Incidence Median # resolved/ type (%) duration (mo) #infected (%) 51* 8 7 29/36 (81) 66 7 6 26/28 (93) 16* 7 11 18/25 (72) 6 5 6 22/23 (96) 18* 4 12 11/17 (65)
*High risk
Ho GYF et al. N Engl J Med 1998;338:423 The Happy Young European?? Thank you!