Sexually Transmitted Pathogens Average Risk per Episode from Known Positive Source

Sexually Transmitted
Pathogens
• Bacteria
Neisseria gonorrhoeae
Chlamydia trachomatis
Mycoplasma hominis
Ureaplasma urealyticum
Treponema pallidum
Gardnerella vaginalis
Hemophilus ducreyi
Calymmatobacterium
granulomatis
Shigella spp.
Salmonella spp.
Campylobacter spp.
Streptococcus agalactiae
• Viruses
Herpes simplex
Hepatitis A, B, C
Cytomegalovirus
Papillomavirus
Adenovirus
Molluscum contagiosum
HIV
• Fungi
Candida albicans
• Protozoa
Trichomonas vaginalis
Entamoeba histolytica
Giardia lamblia
• Ectoparasites
Phthirus pubis
Sarcoptes scabei
Average Risk per Episode
from Known Positive Source
Percut Blood
Mucocutan
Blood
Recept Anal
Recept Vag
Insertive Vag
Fellator
HIV
HCV
HBV eAg+
HBV eAg -
0.3%
1.8%
40%
1.5-10%
.09%
0.1-5%
0.1-0.2%
0.03-0.14%
.06%
?; low
?; low
?; low
?; low
“Safe”r Sex
• Condoms
– effective only when used all the time; otherwise,
failure rate is in 10% range
– effective for HIV prevention, but unproven in HSV
prevention
• Nonoxynol-9
– may increase risk of HIV transmission when used
alone as contraceptive gel
– unknown if any increased risk when used as
condom lubricant
Contraception Failure Rates
Method
Actual Rate
Chance
Spermacide
Periodic Abstinence
Coitus interruptus
Cervical cap
Diaphragm
Condom
85%
21%
20%
18%
18%
18%
12%
Theoretical Rate
85%
3%
2-9%
4%
6%
6%
2%
-adapted from Trussel, et al., Obstet Gynecol 76:558-67, 1990.
STD’s Transmissible without
Intromission
•
•
•
•
•
•
•
•
•
Syphilis
Herpes
Chancroid
Lymphogranuloma venereum
Human papillomavirus
Bacterial vaginosis
Molluscum contagiosum
Phthiris pubis
Sarcoptes scabei
1
Sexually Transmitted
Diseases
Prevention: Abstinence
Neisseria gonorrheae Virulence Factors
•
•
•
•
•
IgA protease
Pilins
Opa (PII)
PI
LipoOligoSaccharide
•Antigenic variation makes immunity
difficult
•Attachment proteins can be varied to be
most suited to the tissue being colonized
Asymptomatic Infection
urethra, endocervix, rectum, pharynx
Symptomatic Infection
urethritis, cervicitis, proctitis,
pharyngitis, bartholinitis,
conjunctivitis
Local Complications
salpingitis, epididymitis,
Bartholin’s abscess,
lymphangitis, penile edema,
periurethral abscess,
prostatitis
DGI
Neisseria gonorrheae Clinical
• Males
– incubation 2-6 days
– purulent discharge, dysuria - 90% symptomatic
• 10% never develop Sx
– these may be responsible for the spread of disease
– homosexual males: anal, pharyngeal infection
• pharyngeal seen in 20% of fellators of men with GC
• fellator’s partner = irrumator
• “The Clap” - gonococcal urethritis
– O.F. clapoir - bubo, an illness of debauchery;
– first use in English 1587 meaning gonorrhea
2
Neisseria gonorrheae Clinical
• Females
– dysuria, urinary frequency, exudative cervicitis
– ASx infection - endocervix, urethra, anal, pharynx
• high prevalence - screening Cx in active female
– extension to Fallopian tubes in 15-20% causing
acute salpingitis
– misdiagnosed as UTI; Sx may resolve with
suboptimal Rx
• Children
– ophthalmic infection via birth canal
– infancy through puberty: vulvovaginitis = child abuse
Ophthalmia neonatorum
gonococcal
chlamydial
Neisseria gonorrheae Clinical
• Disseminated GC - 3%
– tends to disseminate during menses
– resistant to C’-mediated ‘cidal activity of serum
– patients deficient in C’6-C’8 have increased susceptibility to
disseminated gonococcal and meningococcal infection
– Sx: fever, polyarthralgia, skin lesions (distal extremities)
• tenosynovitis - wrists-ankles-knees
• Sx may resolve spontaneously or proceed to purulent arthritis
• Diagnosis:
– Gram’s stain, culture, rapid antigen tests
Neisseria gonorrheae Treatment
N.B.: 50% have co-infection with chlamydia
• ceftriaxone 125 mg IM plus azithromycin 1 gm PO
• ceftriaxone 125 mg IM plus doxycycline 100 BID x 7
days
• cefixime 400 md PO plus azithro or doxy
• ciprofloxacin 500 mg PO plus azithro or doxy
• levofloxacin 500 mg PO plus azithro or doxy
Disseminated GC
• ceftriaxone 1 gm IM/IV until ASx, then F/U with PO -orcefixime or a FQ
• spectinomycin 2 gm IM q 12h
3
Comparison of N. gonorrheae and
C. trachomatis Genital Infections
Site
Men
urethra
epididymidis
rectum
conjunctiva
systemic
N. gonorrheae
C. trachomatis
urethritis
epididymitis
proctitis
conjunctivitis
DGI
NGU, PGU
epididymitis
proctitis
conjunctivitis
Acute
Urethral
bartholinitis
conjunctivitis
perihepatitis
DGI - arthritis/dermatitis
Syndrome
bartholinitis
conjunctivitis
perihepatitis
Women
urethra
Bartholin’s gland
conjunctiva
liver capsule
systemic
Chlamydia trachomatis
• Obligate intracellular parasite that can be
grown on artificial media
• Life Cycle
– Elementary Body- endocytosed into a phagosome;
inhibits phagosomal-lysosomal fusion
– Reticulate body-metabolically active (8 hour
incubation)
• reproduces by binary fission within phagosome
– ruptures and releases infectious elementary bodies
• cell-to-cell infection ensues
4
Chlamydia trachomatisClinical
• Serotypes D-K
• Males - 30% NGU in men
– fewer Asx (5-10%) than GC
– Dx: PCR (urine, swab), culture
– serology unreliable except for LGV
• Women
– cervix - mucopurulent discharge
– salpingitis(major cause), TOA (with other flora)
• major cause of infertility and ectopic pregnancies
– urethritis
– Dx: PCR (urine, swab), culture
• Reiter’s Syndrome - 70% follow chlamydial infection
Chlamydia trachomatis - LGV
• Lymphogranuloma venereum - L serotypes
• Primary
– painful genital lesion - papule - 3-30 days after exposure
• Secondary (days to weeks)
– multilocular suppurative adenopathy
• “groove sign”: division of inguinal nodes by Poupart’s ligament
– proctocolitis if primary site was anal canal
• Late (months to years)
– draining sinus tracts, urethral/rectal strictures, lymphatic
obstruction
5
Chlamydia trachomatis Treatment
NGU, cervicitis, urethritis, etc.
NB: Chlamydia 50%, M. hominis, U. urealyticum
•
•
•
•
azithromycin 1 gm PO (98% effective)
doxycycline 100 mg PO bid x 7 days
levofloxacin 500 PO qd x 7 days
erythromycin base 500 mg po QID x 7 days (in pregnancy)
LGV
• doxycycline 100 mg PO bid x 21 days
• erythromycin base 500 mg PO bid x 21 days
Herpes Simplex
• Icosahedral DS DNA virus
• replication in nucleus
• Primary Infection
–
–
–
–
break in mucous membranes
epithelial cell invasion to sensory nerves to ganglia
also may spread from primary site to nodes to blood
mild primary infection may be due to cross-reacting HSV I
immunity
• Only a relatively small percentage of people with HSV II Ab’s
report a memorable primary infection, so ASx infection may be
fairly common
• Reactivation
– ganglia to axon to skin
Comparison of HSV1 and HSV2
Characteristics
urogenital infections
nongenital infections
labialis
keratitis
whitlow
encephalitis (adult)
meningitis
neonatal
primary transmission mode
genital
physical properties
40o sensitive
heparin sensitive
plaques
HSV1
- (10-30%)
+(80-90%)
+
+
+
+
- (~30%)
nongenital
HSV2
+ (70-90%)
- (10-20%)
+
+
+ (~70%)
+
+
small
large
6
Comparison of HSV1 and HSV2
Clinical
Characteristics
Primary Infection Usual Site
pharyngitis
gingivostomatitis
keratoconjunctivitis
encephalitis
vulvovaginitis
neonatal herpes
meningitis
Recurrent Infection Usual Site
labialis
keratitis
encephalitis
vulvovaginitis
HSV1
HSV2
+
+
+
+
-
+
+
+
+
+
+
-
+
Herpes Simplex - Clinical
• Females
– painful vulvovaginitis, cervicitis (80%), urethritis
• Males
– balanitis - painful
• Duration of primary stage is 21 days
• 75% have at least 1 recurrence
• Complications
– congenital (primary only)
– meningoencephalitis
Pathogenesis of Reactivated
Genital HSV Infection
Primary HSV Infection Clinical Course
VIRAL SHEDDING
VESICLE
WET ULCER
HEALING ULCER
CRUST
Symptoms
PUSTULE
Systemic Sx
Local Sx
-6 -4 -2
SEXUAL
CONTACT
0
2
LESIONS
NOTED
4
6
8 10 12 14 16 18 20
Days
M.D.
MORE
LESIONS
HEALING
Sx GONE
BEGINS
HEALED
Recurrence Rates of Genital
HSV Infection
1. Reactivated HSV in
ganglionic nerve
cells produces
recurrent disease
via peripheral
migration along
axons to skin and
mucous
membranes
2. Reactivation
results in recurrent
mucocutaneous
lesions and
potential for
transmission.
Clinical Course of Recurrent
Genital HSV
7
Herpes simplex
• Diagnosis
–
–
–
–
Tzanck preparation
Direct immunofluorescence
Viral culture - cells and fluid
Serology
• older generation ELISA unreliable because of multiple
cross-reacting antigens, making differentiation between
HSV1 and HSV2 difficult
• new immunodot assays and antigen capture ELISA
based on gG1 and gG2 highly sensitive and specific
8
Tzanck Smear: multinucleate giant cell
Herpes simplex - Treatment
Primary genital
• acyclovir 400 mg PO tid x 10 days
• famciclovir 250-500 mg PO tid x 10 days
• valacyclovir 1000 mg PO bid x 10 days
Recurrent genital
• acyclovir 400 mg PO bid x 5 days
• famciclovir 125 mg PO bid x 5 days
• valacyclovir 500 mg PO bid x 5 days
Suppression
• acyclovir 200-600 mg PO qd
• famciclovir 125-500 mg PO qd
• valacyclovir 500 mg PO qd
Treponema pallidum - Syphilis
Old World vs. New World Hypothesis
• “Great Pox” arrived/ravaged Europe at the time of
Columbus’ return
– sailors had disease immediately on their return in 1493
– it seems to have been a very virulent disease as compared
with today’s disease - Was this the same disease?
• John Hunter self-inoculated with both GC and syphilis, thus
muddied the waters for years longer
Treponema pallidum - Syphilis
•
•
•
•
•
•
Slender spirochaete 5-15 µm long with regular spirals
Trilaminer cytoplasmic membrane
Peptidoglycan layer
Lipopolysaccharide layer
Fibrils at each end
Not able to be cultivated
.
• mercurials were used from medieval times on - this is
a marker for the existence of syphilis
9
Primary Syphilis
• Chancre: single, indurated, non-tender
– 10-90 days post contact (average 14-21 days)
– painless regional adenopathy
– spontaneous healing in 3 weeks
• Site
– Males: coronal sulcus
– Females: labia
– anal intercourse: anus/anal canal
10
Secondary Syphilis
•
•
•
•
2-6 weeks after primary chancre
Flu-like illness - headache, malaise, adenopathy
Rash - salmon-colored; palms and soles
Mucous patches
• Condylomata lata
11
Tertiary Syphilis
• Neurosyphilis:
–
–
–
–
Meningovascular (early)
Parenchymatous (later)
Tabes dorsalis
General Paresis of the Insane
• Asymptomatic neurological (+ CSF)
• Cardiovascular:
– aneurysms, aortic insufficiency
• Late Benign:
– gumma (bone, soft tissue, liver, etc)
Benign Tertiary Syphilis
gummatous
12
Congenital Syphilis
•
•
•
•
•
•
•
Skin rash
Rhinitis (“snuffles”)
Periostitis
Spontaneous fractures
VIII deafness
Optic atrophy
Skeletal deformities - saddle nose, saber shins,
Hutchinson’s incisors, mulberry molars
• Juvenile paresis
.
Syphilis and HIV Infection
• HIV transmision is enhanced by genital ulcer disease
• Syphilis in HIV infection may be more protracted and
more severe
–
–
–
–
enhanced constitutional Sx
more organ involvement
more severe rashes
predisposition to neurosyphilis and uveitis
• Syphilis in HIV infection may require more vigorous
treatment, and bacteriostatic drugs (e.d. doxyctcline)
should be avoided in favor of bactericidal agents
Syphilis - Diagnosis
• Serologic testing is the mainstay of diagnosis
– 2 types of serology
• non-specific reagins directed against cardiolipin-type antigens, e.g.
RPR, VDRL, ART, STS, Hinton, Wasserman
– often reverts to negative with effective treatment, making it a
good screening test and useful for tracking therapy
» however, those treated in late stages may be “sero-fast”,
I.e., retaining low-titer positivity after Rx
• specific anti-treponemal antibodies
– FTA, FTAabs, MHA-TP, HATS
– remains positive for life, making it a poor screening test for new
disease, or for tracking therapy, but its specificity makes it a
good confirmatory test
– positive in 85% of primary syphilis and 95-99% in later forms
13
Syphilis - Diagnosis
• False negative reagin-based tests
– too soon after sexual exposure
– treated or untreated late syphilis
– AIDS
• False-positive reagin-based tests
– infections (mono, measles, hepatitis, leprosy)
– immunizations (smallpox)
– sarcoid, SLE, etc
• False-positive treponemal tests
– Lyme Disease
– non-syphilitic treponematoses (yaws, pinta, bejel)
Syphilis - Treatment
Early: primary, secondary, late latent < 1 year
• benzathine PCN G (LA Bicillin) 2.4 x 106 U IM - or • doxycycline 100 mg PO bid x 14 days -or• ceftriaxone 125 mg IM qd x 10 days or 250 mg IM qod x 5 doses
-or- 1000 mg IM qod x 4 doses
Late: latent > 1 year, cardiac
• benzathine PCN G (LA Bicillin) 2.4 x 106 U IM q week x 3 -or• doxycycline 100 mg PO bid x 28 days
Neurological
• Aq PCN G 12-24 x 106 U IV qd x 10-14 days -or• ceftriaxone 1 gm IV or IM qd x 14 days
REPEAT SEROLOGIC TESTS AFTER TREATMENT!
There was a young man from Back Bay
Who thought syphilis just went away
He believed that a chancre
Was only a canker
That healed in a week and a day.
But now he has "acne vulgaris"(Or whatever they call it in Paris);
On his skin it has spread
From his feet to his head,
And his friends want to know his hair is.
There's more to his terrible plight:
His pupils won't close in the light
His heart is cavorting,
His wife is aborting,
And he squints through his gun-barrel
sight.
Arthralgia cuts into his slumber;
His aorta is in need of a plumber;
But now he has tabes,
And saber-shinned babies,
While of gummas he has quite a
number.
He's been treated in every known
way,
But his spirochaetes grow day by day;
He's developed paresis,
Has long talks with Jesus,
And thinks he's the Queen of the
May.
-Anonymous, ca. 1920
Infectious Vaginitis
•
•
•
•
Bacterial vaginosis (40-50%)
Vulvovaginal candidiasis (20-25%)
Trichomoniasis (15-20%)
uncommon causes
–
–
–
–
group A streptococcal
ulcerative TSS-related (S. aureus)
atrophic vaginitis with 2o bacterial infection
FB vaginitis with 2o bacterial infection
Sobel, JD, NEJM 237(26):1896-1903, 1997.
14
Bacterial Vaginosis
• change in bacterial flora
– reduction of H2O2-positive lactobacilli
– increase of Gardnerella vaginalis, Mycoplasma hominis, Mobiuncus
spp, Prevotella spp, Bacteroides spp, Peptostreptococcus spp
• bacteria possibly sexually transmitted
• other factors
– non-white race, IUD, prior pregnancy
• “fishy-smelling”, thin, off-white discharge
• pruritus, inflammation absent: frequently asymptomatic
• Dx: wet mount, gram’s stain : “clue cells” (epithelial cells with
adherent bacteria)
– release of aromatic amines after treatment of secretions with 10%20% KOH
Sobel, JD, NEJM 237(26):1896-1903, 1997.
Candida Vulvovaginitis
• Candida albicans 80-90%
• Candida glabrata increasing in frequency
– thinner discharge
• not really an STD, but ping-pong effect may
occur
• Dx: wet mount, KOH preparation
• Rx: topicals, single-dose fluconazole
– may need prolonged therapy, other agents if C.
glabrata
Trichomoniasis
• Trichomonas vaginalis may be present in 30-40% of
male sexual partners
• associated with other STD’s
• may facilitate HIV transmission
• ASx carrier
severe, acute inflammation
• Dx: smears (wet mounts, PAP); culture possible
• Rx: metronidazole (single 2-gm dose vs 500 bid X 7)
15
Human Papilloma Virus
• Major risk factors in women
–
–
–
–
earlier age at onset of sexual activity
higher lifetime number of sexual partners
younger age
other STIs such as HIV or HSV-2
• Most are infected at a young age, soon after
becoming sexually active
• Most infections are transient (90% resolve in 5 years)
• Multiple sequential/concurrent infections with different
oncogenic strains common in sexually active women
• Vertical transmission (respiratory papillomatosis of
the newborn (especially types 6, 11)
HPV
• Causes a variety of lesions of the skin and
mucous membranes
–
–
–
–
–
common warts of the skin
plantar warts
genital warts (or condyloma acuminatum)
squamous intraepithelial lesions
invasive anogenital carcinoma including cervical,
vaginal, vulvar, perineal, penile and anal cancers
(especially in anal revceptive intercourse)
www.hafmc.org/ resources/hpv.html
HPV
HPV
• >100 types of HPV
– ~30 infect the anogenital area
• spread principally through skin-skin contact
• high-risk* (associated with anogenital
malignancies):16, 18, 31, 33, 35, 39, 45, 51,
52, 56, 58, 59, 68, 73, 82
• “probably carcinogenic”*: 26, 53, 66
• low-risk (associated with condyloma only) Most
HPV infections are subclinical, and can be
either transient or persistent
All photos copyright 1998-2000 David Reznik,DDS
*Munoz, N, et al., Epidemiologic Classification of Human Papillomavirus Types
Associated with Cervical Cancer. NEJM 2003; 348(6): 518-527.
16
HPV - Diagnosis
HPV- Natural History
• Papanicolaou (cervical or anal)
• Molecular screening for HPV DNA in positives
highly reliable to predict women with high risk
of progressing to high-grade lesions*
– molecular screening can be overdone especially in
young women, who may be only transiently
infected with oncogenic strains
• misclassification, anxiety, overtreatment
*Wright, TC, et al., 2001 Consensus Guidelines for the Management of Women with Cervical
Cytological Abnormalities. JAMA 2002; 287:2120-9.
HPV - Treatment
• Imiquimod cream
• 20 % podophyllin antimitotic solution
• 0.5 % podofilox solution
• 5 % 5-fluorouracil cream
• Trichloroacetic acid (TCA)
• cryosurgery
• electrocautery
• laser treatment
• Investigational Vaccine
Wright TC and Schiffman M, NEJM 348(6):489-490, 2003
Granuloma Inguinale
(Donovanosis)
• Calymmatobacterium granulomatis (donovani)
– a gram-negative rod related to Klebsiella
• begins as a small subcutaneos nodule in the genital
area that breaks through to the surface
• uncommon in USA
• Diagnosis:
– smear
– histopathology: mononuclear cells, PMN, no giant cells,
Donovan bodies
• Treatment:
– doxycycline 100 mg PO bid until lesions heal
– TMP-SMX I DS PO bid until lesions heal
17
Hemophilus ducreyi - Chancroid
• common in Africa, uncommon in USA
– major risk for acquisition of HIV
• most cases in males
• small friable papule develops in 2-5 days
– penis, vagina, anus
• later, development of regional lymphadenopathy
– buboes, draining sinuses
– Dx: “boxcars” on touch prep
– fastidious (chocolate agar or fetal calf serum)
• Treatment:
–
–
–
–
ceftriaxone 250 mg IM -orazithromycin 1 gm PO -oramox/clav 500 PO tid x 7 days -orciprofloxacin 500 mg PO bid x 3 days
Before Rx
After Rx
18
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