Download Genital Herpes

Developments in (all 30-50 or so)
STDs: Global Epidemiology and
Management
George Schmid, M.D., M.Sc.
Dept of HIV
WHO, Geneva
[email protected]
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 www.epiet.org (I
think this is correct)
• The American training programme (EIS
programme) in epidemiology at CDC www.cdc.gov
• World Health Organization www.who.org
• Masters of science or public health degrees
Behaviour (change)
Lust
STDs:
Religion
Public health
Sex
Divorce
Infectious diseases specialists
Risk!
10% Risk
10% Risk
2% Risk
8% Risk
12% Risk
20% Risk
I Have Questions for You
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?
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."
"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 ????, 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
Genital herpes
Human papillomavirus
Chlamydia
Trichomonas
Schmid et al. Lancet (in press)
Question #3
How Do We Identify Asymptomatic
People?
This question applies to people with STIs
and persons with any other infection
How Do We Identify Asymptomatic
People?
1. Screening
2. Partner notification
Partner Notification
•
•
How to do it?
1. Provider referral
2. Health authorities referral
3. 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)
Prevention of STIs is Simple
Effectiveness (high to low)
1. Abstinence
2. Mutual monogamy (with an
uninfected partner)
3. Always use a condom
4. Monogamy
5. Limit number of sex partners
6. Limit number of low-quality
sex partners
7. Have lots of sex with
whomever you feel like and
never use a condom
STIs
There are about 30-50 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)
Why Do We Care About STIs?
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
What Characterizes STIs?
• Inflammation
• Increased numbers of white blood cells, exudates
• With some STIs, preferential recruitment of CD4antigen bearing cells
• Breaks in mucosa or skin
• Bleeding
Evidence for the Enhancement of HIV
Infection by STIs
1 Cross-sectional studies
2 Cohort studies
3 Biologic studies
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
Proportion of Men Developing HIV
Infection After a Single Act of Sexual
Intercourse
Circumcised
Uncircumcised
Unstratified
Urethritis
Ulcer
Urethritis
Ulcer
13%
0%
7% (6*)
0%
43% (15)
*Standard Error
Attributable risk due to lack of circumcision and genital ulcer=98%
Cameron WD et al. Lancet 1989;2:403
Presence of HIV in Ulcer Secretions
Culture for HIV
(Pos./Tested)
4/35 (11%)
PCR for HIV
(Pos./Tested)
NT
2
2/7 (30%)
6/7 (86%)
Chancroid
3
NT
2/6 (33%)
Syphilis
NT
1/2 (50%)
Unknown
NT
2/3 (67%)
Genital herpes
NT
1/3 (33%)
0/8 (0%)
25/26 (96%)
Disease
1
Chancroid
Chancroid
Genital herpes
4
1 Kreiss J et al. J Infect Dis 1989;160:380 2 Plummer FA et al. J Infect Dis 1990;161:810
3 Mertz KJ et al. J Infect Dis 1998;178:1795 4 Schacker T et al. JAMA 1998;280:61
How Common Are STIs Globally?
No one knows
Estimated Incidence of 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
Estimated prevalence (per 1000) of
STIs by region in 1999
Region
27
Australia and New Zealand
7
East Asia and Pacific
50
South and South East Asia
119
Sub-Saharan Africa
21
North Africa and Middle East
71
Latin America and Caribbean
19
North America
20
Western Europe
29
CEE and NIS
0
20
40
60
80
100
120
Estimated prevalence (per 1000)
140
Why Do People Get STIs?
Anderson-May Equation
Ro = $ c D
Ro = reproductive rate
$ = infectivity
c = rate of partner change (sex, needle)
D = duration of infectiousness
Core group
Number of partners
Diseases and Syndromes
30-50 organisms or syndromes that are
sexually transmitted
Test!
Proportion of Men with Either
Gonorrhea or Nongonococcal
Urethritis, by Type of Discharge
80
70
60
50
GC
NGU
40
30
20
10
0
None
Clear
White
Swartz SL et al. J Infect Dis 1978;138:445
Yellow
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
STI Syndromes
• No symptoms or signs
• Urethral discharge/discomfort (urethritis) in males
• N. gonorrhoeae
• C. trachomatis
• U. urealyticum
• Testicular pain (epididymitis)
• N. gonorrhoeae
• C. trachomatis
• Abdominal pain in women (pelvic inflammatory disease)
• N. gonorrhoeae
• C. trachomatis
• Flora of bacterial vaginosis
• ? Mycoplasma genitalium
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
STI Syndromes (con’t)
• Inguinal adenopathy
• Chlamydia trachomatis (LGV)
• Haemophilus ducreyi
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
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 28day period allows time for antibody to be
developed
• “Strip” or “dip-stick” rapid tests, all based on
treponemal antigen, are available
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 10-14 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.
Question #4
HPV is a life-long infection
True
False
HSV-2 is a life-long infection
True
False
Genital Herpes
• Genital herpes is common in the Industrialized
World
• About 20% of the adult population
• It is a lifelong infection
Prevalence of Antibody to HSV-2, Europe
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
• 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
“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
Inoculation First episode
5-7 days
Recurrent episodes
“Shedding” of virus
One year
Clinical Differences Between Type 1
and Type 2 Infections
• Type 1 infections cause about 15-30% of firstepisode 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
Diagnostic Tests for Possible Genital
Herpes
• Culture
• PCR?
• Antigen detection tests
• Tzanck smear (about 60% sensitive)
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
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
Recurrent Episodes of Genital Herpes
To treat recurrent episodes, or to suppress
episodes?
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
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
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)
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.”
Urethritis
Symptoms: a discharge, or discomfort/pain
when urinating
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%
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%
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
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
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%
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 rescreened 3-4 months after
treatment.
Diseases Characterized by Vaginal
Discharge
•
•
•
•
Candidiasis
Trichomoniasis
Bacterial vaginosis
Others, e.g., desquamative inflammatory vaginitis
Diagnosis of Trichomoniasis
• Wet mount of vaginal secretions (sensitivity, 5070%)
• Culture (sensitivity approaches 100% if appropriate
media/culture conditions)
• DNA probe (AffirmVPIIITM) from Becton Dickinson
• PCR may be available from local laboratories
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
Bacterial Vaginosis
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
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
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 et al. 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 Guidelines
Do We Have Any Vaccines Against
STIs?
Hepatitis
Hepatitis B Virus (HBV)
• This IS a sexually transmitted disease
• About ½ of cases in the industrialized world are
acquired sexually
The Happy Young European
Border
HBV Immunization Policy
WHO European Region, 2004
Universal infant
Universal newborn
Universal adolescent
No universal HBV
immunization
HBV-The Major Primary Prevention
Strategy
Immunize!
Three dose series with good protection:
One dose--50%
Two doses--85%
Three doses--95%
HPV
Estimated Prevalence of Genital HPV
Among Women and Men, Aged 15-49,
U.S.
Genital Warts
1%
1.4 m
Subclinical HPV by
4%
colposcopy or cytology
10%
14 million
Prior infection, detected
by antibody
34 million
Koutsky L. Am J
Med 1997;102:3
60%
25%
5 million
Subclinical HPV by
amplified NA probes
81 million
No prior or current
infection
24-month Incidence and Duration of
Infection
HPV
type
51*
Incidence
Median
(%)
duration (mo)
8
7
# resolved/
#infected (%)
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
Thank you!
Question #1
How many of us in this room have, or have
had, an STI?
90%
75%
60%
35%
25%
Question #2
What proportion of cases of genital herpes
are acquired from persons who know they
have herpes?
85%
60%
30%
10%
Question #3
1. Screening
2. Partner notification
Question #4
HPV is a life-long infection
True
False
HSV-2 is a life-long infection
True
False
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%
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%