1. George Schmid, M.D., M.Sc. Dept of HIV WHO, Geneva Schmidg@who.int
Developments in (all or so) STDs: Global Epidemiology and Management
George Schmid, M.D., M.Sc.
Dept of HIV
WHO, Geneva

2. Think About Training and Careers in Epidemiology and/or Public Health
The European training programme (Epiet) in epidemiology at the new European CDC, which is focusing on infectious diseases (I think this is correct)
The American training programme (EIS programme) in epidemiology at CDC
World Health Organization
Masters of science or public health degrees

3. STDs: Sex Lust Morality Clinical Medicine Ethics Behaviour (change)
Politics
STDs:
Lust
Economics
Love
Lawsuits
Surveillance
Religion
Lies
Public health
Police
Sex
Education
Clinical Microbiology
Laboratory tests
Divorce
Infectious diseases specialists

4. Risk!

5. 10% Risk

6. 10% Risk
2% Risk
8% Risk
12% Risk
20% Risk

7. I Have Questions for You

8. How many of us in this room have, or have had, an STI?
Question #1
How many of us in this room have, or have had, an STI?
90%
75%
60%
35%
25%

9. What Is a Sexually Transmitted Infection?

10. 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

11. Sexually Transmitted Infection=Sexually Transmitted Disease=Reproductive Tract Infection?

12. "Dear, the doctor says I have bacterial vaginosis and you need to be treated."

13. "My lawyer will contact you tomorrow about the divorce."
"Dear, the doctor says I have bacterial vaginosis and you need to be treated."
"My lawyer will contact you tomorrow about the divorce."

14. RTIs
STIs
STDs

15. Question #2
What proportion of cases of genital herpes are acquired from persons who know they have herpes?
85%
60%
30%
10%

16. Asymptomatic Individuals Are Very Important
With probably every STI, except ????, most people—male and female—are asymptomatic
Asymptomatic people probably are responsible for most disease transmission
We should make people aware of these facts

17. Chancroid Gonorrhea Syphilis Chlamydia Genital herpes Trichomonas
Infection increasingly asymptomatic
Sex practices increasingly risky
Chlamydia
Genital herpes
Trichomonas
Human papillomavirus
Schmid et al. Lancet (in press)

18. Question #3 How Do We Identify Asymptomatic People?
This question applies to people with STIs and persons with any other infection

19. How Do We Identify Asymptomatic People?
1. Screening
2. Partner notification

20. Partner Notification How to do it? Provider referral
Health authorities referral
Contract referral (make a "contract" with the patient to have partners into care in, e.g., 72 hours, or health authorities will contact them)
Alternate approaches
Network approach
Give patient medication for partner (for only certain diseases, e.g., chlamydia, trichomonas)

21. Prevention of STIs is Simple
Abstinence
Mutual monogamy (with an uninfected partner)
Always use a condom
Monogamy
Limit number of sex partners
Limit number of low-quality sex partners
Have lots of sex with whomever you feel like and never use a condom
People’s desire (high to low)
Effectiveness (high to low)

22. There are about 30-50 STIs, or disease syndromes that result from STIs

23. 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)

24. Why Do We Care About STIs?

25. Why Do We Care About STIs?
Acute morbidity
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

26. Why Do We Care About STIs (continued)?
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)
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

27. Why Do We Care About STIs (continued)?
Cofactors for cancer
Cervical cancer (HPV, probably HSV) and anal and penile cancer (HPV)
Hepatic cancer (hepatitis B and hepatitis C)
Enhanced HIV transmission

28. What Characterizes STIs?
Inflammation
Increased numbers of white blood cells, exudates
With some STIs, preferential recruitment of CD4-antigen bearing cells
Breaks in mucosa or skin
Bleeding

29. Evidence for the Enhancement of HIV Infection by STIs
Cross-sectional studies
Cohort studies
Biologic studies

30. Cohort Study, Nairobi 73 HIV-negative men with an STD
All men had had one act of sexual intercourse with a prostitute
The men were counseled, given condoms, told to avoid sex with prostitutes, and followed every 2 weeks for three months for HIV seroconversion
85% of prostitutes were HIV-positive
Cameron WD et al. Lancet 1989;2:403

31. Proportion of Men Developing HIV Infection After a Single Act of Sexual Intercourse
Attributable risk due to lack of circumcision and genital ulcer=98%
Cameron WD et al. Lancet 1989;2:403

32. Presence of HIV in Ulcer Secretions
1 Kreiss J et al. J Infect Dis 1989;160: Plummer FA et al. J Infect Dis 1990;161:810
3 Mertz KJ et al. J Infect Dis 1998;178: Schacker T et al. JAMA 1998;280:61

33. How Common Are STIs Globally?
No one knows

34. Estimated Incidence of STIs, by Continent
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

35. Estimated prevalence (per 1000) of STIs by region in 1999

36. Why Do People Get STIs?

37. Anderson-May Equation
Ro = $ c D
Ro = reproductive rate
$ = infectivity
c = rate of partner change (sex, needle)
D = duration of infectiousness

38. Percentage of population
Core group
Number of partners

39. Diseases and Syndromes
30-50 organisms or syndromes that are sexually transmitted

40. Test!

41. Proportion of Men with Either Gonorrhea or Nongonococcal Urethritis, by Type of Discharge
Swartz SL et al. J Infect Dis 1978;138:445

42. 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

43. STI Syndromes No symptoms or signs
Urethral discharge/discomfort (urethritis) in males
N. gonorrhoeae
C. trachomatis
U. urealyticum
Testicular pain (epididymitis)
Abdominal pain in women (pelvic inflammatory disease)
Flora of bacterial vaginosis
? Mycoplasma genitalium

44. STI Syndromes (con’t) Vaginal discharge/inflammation in women
Trichomonas vaginalis
Candida species (candidiasis)
Bacterial vaginosis
Genital “growths”
Human papillomavirus
Genital ulcers
Herpes simplex virus
Haemophilus ducreyi
Treponema pallidum

45. STI Syndromes (con’t) Inguinal adenopathy Chlamydia trachomatis (LGV)
Haemophilus ducreyi

46. 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

47. Diagnostic Tests for Genital Ulcers
History and physical exam!
Laboratory
Darkfield microscopy (syphilis)
RPR syphilis serology
About 70% sensitive in primary syphilis (if negative today, repeat in one week)
Test for herpes
Culture, antigen tests, PCR
Exclude syphilis!

48. Syphilis
Serology, with the screening RPR and a confirmatory, treponemal test (TPPA), is the mainstay of diagnosis
Works because the average incubation period for primary syphilis is 21 days and the average person waits 7 days before coming in—this 28-day period allows time for antibody to be developed
“Strip” or “dip-stick” rapid tests, all based on treponemal antigen, are available

49. Syphilis Therapy
For early syphilis*, a single dose of benzathine penicillin, 2.4 million units, intramuscularly Or
Procaine penicillin, 600,000 units daily intramuscularly for days
See monthly for 3 months, then at 6 and 12 months for repeat RPR titers to document a four-fold decline, that is, cure.
*Syphilis of one year’s duration or less
All therapy guidance from: European STD Guidelines. Int J STD AIDS 2001;12S3.

50. HPV is a life-long infection True False HSV-2 is a life-long infection
Question #4
HPV is a life-long infection
True
False
HSV-2 is a life-long infection

51. Genital Herpes Genital herpes is common in the Industrialized World
About 20% of the adult population
It is a lifelong infection

52. Prevalence of Antibody to HSV-2, Europe
Smith J, Robinson J. J Infect Dis 2002; 186(S):S3

53. Genital Herpes
Genital herpes is very common in the Industrialized World
About 20% of the adult population
It is a lifelong infection

54. “Facts” About Herpes Simplex Virus
Two types of herpes simplex virus, with about 50% DNA homology between the two. Clinically, they are separated by antibodies to the outer membrane glycoprotein
Type 1, which preferentially infects the oral area
Type 2, which "only" infects the reproductive tract
There is cross-protection between infection with the two types, which protects mostly against disease expression and not infection

55. “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

56. Time Line of Genital Herpes
7 days
7-21 days
5-7 days
One year
Inoculation
First episode
Recurrent episodes
“Shedding” of virus

57. Clinical Differences Between Type 1 and Type 2 Infections
Type 1 infections cause about 15-30% of first-episode reproductive tract infections, but type 2 infections are infrequently acquired except through anogenital sex
Type 1 infections of the reproductive tract are milder than type 2 infections, and are less likely to recur

58. Diagnostic Tests for Possible Genital Herpes
Culture
PCR?
Antigen detection tests
Tzanck smear (about 60% sensitive)

59. Therapy of First-Episode Genital Herpes
Aciclovir, 200 mg, five times a day for 5 days
Famciclovir, 250 mg, three times a day for 5 days
Valaciclovir, 500 mg, twice a day for 5 days

60. 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

61. Recurrent Episodes of Genital Herpes
To treat recurrent episodes, or to suppress episodes?

62. Treatment of Recurrent Episodes
Aciclovir, famaciclovir, or valaciclovir, in varying doses, for 5 days
Therapy must be started within 24 hours of the initial prodrome for there to be clinical effectiveness
So, patients should have either drug on hand, or, a prescription for drug

63. Suppressive Therapy of Recurrent Episodes
Drugs
Aciclovir, 800 mg per day
Famciclovir, 250 mg, twice a day
Valaciclovir, 500 or 1000 mg a day (the lower dose is lnot as effective as the higher dose, particularly for those with high frequencies of recurrence, e.g., >10 recurrences/year)
Reduces frequency of recurrent episodes by 70-80%, and many patients have no episodes
Reduces, but does not eliminate, viral shedding

64. Serologic Tests for Herpes Simplex Virus Type 2
Serology has been available for many years
Does not reliably separate type 1 from type 2 infection, but is very good at identifying antibody to herpes simplex virus
Type 2 specific serology became commercially available in 1999
One test on the market (HerpeSelectTM HSV-1 or HSV-2 IgG ELISA and HerpeSelectTM IgG HSV-1 or HSV-2 Immunoblot)
Sensitivity 80-98% (generally, >90%) but may achieve this 4-6 months after infection
Specificities >96% (Immunoblot may act as confirmation test)

65. Genital Herpes--Management of Sex Partners*
“Sex partners of patients who have genital herpes are likely to benefit from evaluation and counseling.”
Symptomatic partners should be evaluated just as any symptomatic person
Asymptomatic partners should be questioned about a history of lesions, counseled to recognize outbreaks, and offered type-specific serology
*This guidance is CDC guidance. European guidelines: “…it may be appropriate to offer to see partners to help with the counseling process.”

66. Symptoms: a discharge, or discomfort/pain when urinating
Urethritis
Symptoms: a discharge, or discomfort/pain when urinating

67. Question #5
If I have gonorrhea, and I have sex with a woman, the chance of my giving her gonorrhea are about:
80%
60%
40%
15%

68. Urethritis?
Yes No
Test for: Gonorrhea Chlamydia

69. 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

70. Only the Gram Stain Let’s You Separate Gonococcal from Nongonococcal Urethritis
High sensitivity for gonorrhea (>95%)
High specificity for gonorrhea (approaching 100%)

71. 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%

72. Treatment of Gonorrhea
Ceftriaxone, 250 mg, intramuscularly, once, or;
Ciprofloxacin, 500 mg, orally, once *, or;
Ofloxacin, 400 mg, orally, once;
Spectinomycin, 2 gm, intramuscularly, once.
*About 10% of cases in the UK are resistant, and there are known cases in eastern Europe

73. Treatment of Gonorrhea (continued)
Plus, if a chlamydial infection is not excluded:
Azithromycin, 1 gm, orally, once, or;
Doxycycline, 100 mg, orally, twice a day for 7 days

74. Question #6
Three Months After Therapy, What Proportion of Young Women will Again Have:
Bacterial Vaginosis
80%
60%
40%
10%
Chlamydia
50%
25%
10% 5%

75. Chlamydia

76. 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.

77. Treatment of Chlamydia
Recommended
Azithromycin, 1 gm, orally, once, or;
Doxycycline, 100 mg, orally, twice a day, for 7 days.

78. 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 rescreened 3-4 months after treatment.

79. Diseases Characterized by Vaginal Discharge
Candidiasis
Trichomoniasis
Bacterial vaginosis
Others, e.g., desquamative inflammatory vaginitis

80. Diagnosis of Trichomoniasis
Wet mount of vaginal secretions (sensitivity, 50-70%)
Culture (sensitivity approaches 100% if appropriate media/culture conditions)
DNA probe (AffirmVPIIITM) from Becton Dickinson
PCR may be available from local laboratories

81. Therapy of Trichomoniasis
Metronidazole, 2 gm, once, or;
Metronidazole, 500 mg, twice a day for 7 days
No follow-up needed, but there is antimicrobial resistance to metronidazole

82. An increasingly important disease
Bacterial Vaginosis
An increasingly important disease

83. An increasingly important disease
Bacterial Vaginosis
An increasingly important disease
1. Enhances HIV transmission
2. Causes PID
3. Causes post-procedure PID, e.g., after abortion, surgery

84. 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

85. Effectiveness of Therapy
Joesoef et al. Clin Infect Dis Suppl 1995 and 1999.

86. Pelvic Inflammatory Disease (PID)
Diagnosis Remains a Problem

87. What Causes PID? N. gonorrhoeae C. trachomatis Organisms of BV
?Mycoplasma genitalium

88. Why Is PID Bad?

89. Diagnostic Criteria for PID
Minimum Criteria for Instituting Antimicrobial Therapy
Uterine/adnexal tenderness, or;
Cervical motion tenderness
PPV=<65-90% (?)
CDC Guidelines

90. Do We Have Any Vaccines Against STIs?

91. Hepatitis

92. Hepatitis B Virus (HBV)
This IS a sexually transmitted disease
About ½ of cases in the industrialized world are acquired sexually

93. The Happy Young European
Border

94. HBV Immunization Policy
WHO European Region, 2004
Universal infant
Universal newborn
Universal adolescent
No universal HBV immunization

95. HBV-The Major Primary Prevention Strategy
Immunize!
Three dose series with good protection:
One dose--50%
Two doses--85%
Three doses--95%

96. HPV

97. Estimated Prevalence of Genital HPV Among Women and Men, Aged 15-49, U
Estimated Prevalence of Genital HPV Among Women and Men, Aged 15-49, U.S.
Genital Warts
1.4 m 1%
Subclinical HPV by colposcopy or cytology
5 million 4%
Subclinical HPV by amplified NA probes
10%
14 million
Prior infection, detected by antibody
81 million
60%
34 million
No prior or current infection
25%
Koutsky L. Am J Med 1997;102:3

98. 24-month Incidence and Duration of Infection
*High risk
Ho GYF et al. N Engl J Med 1998;338:423

99. Thank you!

100. How many of us in this room have, or have had, an STI?
Question #1
How many of us in this room have, or have had, an STI?
90%
75%
60%
35%
25%

101. Question #2
What proportion of cases of genital herpes are acquired from persons who know they have herpes?
85%
60%
30%
10%

102. Question #3
Screening
Partner notification

103. HPV is a life-long infection True False HSV-2 is a life-long infection
Question #4
HPV is a life-long infection
True
False
HSV-2 is a life-long infection

104. Question #5
If I have gonorrhea, and I have sex with a woman, the chance of my giving her gonorrhea are about:
80%
60%
40%
15%

105. Question #6
Three Months After Therapy, What Proportion of Young Women will Again Have:
Bacterial Vaginosis
80%
60%
40%
10%
Chlamydia
50%
25%
10% 5%