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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