IV. Syphilis Syphilis is a sexually transmitted infectious disease caused by the
bacteriumTreponema pallidum.
A. T. pallidum has a number of characteristics
which are important for diagnosis.
The spiral shaped morphology and characteristic motility pattern (they
spin around their longitudinal axis in a corkscrew type manner) are important
for diagnosis via darkfield microscopy. Here is a picture
of the cross section of the organism.
Man is the only known host and transmission is virtually always by direct
contact with infectious lesions, generally through sexual contact.
The incidence is highest in sexually active people (20-29 year old group).
The number and rate of 1o and 2o (P&S) syphilis
cases reported in 1999 were the lowest ever reported in the United States.
There are approximately 6,000-7,000 new cases of 1° and 2° or P&S
syphilis diagnosed per year
Approximately 30% of exposed people contract the disease.
In 1999, 6657 cases of P&S syphilis were reported in the United States
(2.5 per 100,000 population), a 5.4% decrease from the 7035 cases (rate:
2.6) reported in 1998 and a 22% decrease from the 8556 cases (rate: 3.2)
reported in 1997.
The South continues to have the highest rate in the country (rate: 4.5)
From 1998 to 1999, rates declined 10% in the South (from 5.0 to 4.5) and
12.5% in the Northeast (0.8 to 0.7). The rate for the West remained unchanged
(1.0), and the rate for the Midwest increased from 1.9 in 1998 to 2.2 in
1999.
P&S syphilis rates have declined in 28 states since 1998, and 39 states
have rates below the national health objective for 2000 of 4.0.
Nine of the 11 states that have rates above the 2000 objective are in the
South.
In 1999, of 3115 U.S. counties, 2473 (79.4%) reported no cases of P&S
syphilis.
In 1999, 22 counties and Baltimore, Maryland; Danville, Virginia; and St.
Louis, Missouri, accounted for 50% of all reported P&S syphilis cases
in the United States.
Syphilis continues to disproportionately affect minority populations despite
progress in reducing this racial disparity. P&S syphilis rates for
African Americans have remained substantially higher than those for Caucasians.
However, the magnitude of this difference has decreased 30% since 1997.
The persistence of racial disparities in syphilis incidence is, in part,
attributable to differences between African Americans and Caucasians regarding
poverty and in access to and use of health-care services, especially in
the rural South.
Historically, rates of syphilis have been higher for men than women. The
male-to-female rate ratio peaked at 3.5:1 in 1980 during the height of
syphilis transmission among men who have sex with men (MSM) and decreased
to 1:1 in 1994; since then, it has increased gradually.
C. The manifestations of syphilis depend on
the stage of disease the patient is in.
Following an incubation period of approximately 3 weeks (10-90 days, referred
to as the incubation phase of syphilis), the principal lesion, a hard chancre,
develops.
Syphilitic chancres are indurated (= hard chancre)
They are highly infectious
They may occur anywhere on the body
They are painless
Chancres will heal in 3-6 weeks.
Regional lymphadenopathy adjacent to the chancre may develop during primary
syphilis.
The nodes are firm, nonsuppurative
It may persist for months, despite healing of the chancre.
2. Manifestations of secondary syphilis
Lesions generally begin 6-8 weeks after the appearance of the initial chancre
and may overlap the time when the chancre is still present.
The principal manifestations of 2° syphilis are skin and mucous membrane
lesions, as well as manifestations of systemic disease.
Skin and mucous membrane lesions include
Skin lesions vary from macular, papular,
or occasional pustular and nodular type rashes. Can occur on the
palms
and the soles.
Manifestations of systemic disease during 2° syphilis include
Malaise
Anorexia
Headache
Sore throat
Arthralgia
Low grade fever
Generalized lymphadenopathy
2° syphilis lasts 2-6 weeks before the patient enters the latent phase.
There is a high bacteremia during secondary syphilis.
3. Latent syphilis is by definition the stage in which there is a positive
serological test for syphilis in the absence of any clinical disease symptoms.
Its duration is highly variable.
Approximately 25% of patients experience a relapse of 2° syphilis.
Only about 1/3 of latent cases progress to 3° syphilis.
4. Tertiary or late syphilis is a noncontagious but highly destructive
phase of syphilis which may take many years to develop; it may manifest
itself in several forms:
Late benign or gummatous syphilis is the most common form of 3° syphilis.
It develops in 15% of untreated cases within 1-10 years after infection.
Gummas are nodular lesions characterized
by a granulomatous inflammation.
Gummas may be in any organ.
Cardiovascular syphilis
10% of untreated syphilis cases develop this 10-40 years after initial
infection.
The basic lesion is an aortitis consisting of necrosis resulting from thickening
and hardening of the vasa vasorum. -- The elastic tissue is replaced by
fibrous tissue -- This is manifested by:
Aortic regurgitation because of altered aortic valve function
Aneurysm because of weakened vessel walls
Obstruction of the coronary ostia
Neurosyphilis
Symptoms of neurosyphilis are expressed only in approximately 8% of untreated
cases and then only 5-35 years after infection. Invasion of the CNS occurs
early when generalized dissemination occurs (2° syphilis).
YOU DO NOT NEED TO KNOW THE TEXT THAT IS BETWEEN THE """ """
"""Neurosyphilis is categorized into 4 forms:
Asymptomatic neurosyphilis in which there are no
symptoms of CNS involvement but the CSF is abnormal:
Elevated lymphocytes
Elevated protein
Positive CSF VDRL tests
Approximately 20% of these patients progress to symptomatic
neurosyphilis
Forms of symptomatic neurosyphilis
Acute meningitis
Seen within 2 years of infection
A lot like other meningitis
Headache
Vertigo nausea, vomiting
Generalized convulsions
Cervical rigidity
Positive Kernig's and Brudzinski's signs
The third cranial nerve is most often affected
Chronic meningovascular
Seen 2-5 years, but no later than 10 years of infection
A proliferative endarteritis and perivascular infiltration
with lymphocytes (perivascular cuffing)
Leads to blocking of blood vessels and necrosis of
nerve tissue
Gradual intellectual and emotional deterioration
Most commonly the middle and posterior arteries are
involved. Usually see a weakening in one side.
Headache, nausea, vomiting
3rd, 4th, 6th cranial nerves are affected most often.
General paresis
About 5% of patients experience general paresis
Seen 20 or more years after untreated infection
Symptoms:
Personality changes: neurosis, euphoria, depression,
over activity, paranoia
Affect: Reaction to a problem is inappropriate
to the problem. Often act in an "all-out" type of reaction much like a
child.
Reflexes: Hyperactive
Eyes: Argyll Robertson pupils
Sensorium: Delusions, illusions, hallucinations,
and paranoid ideas
Intellect: Reduction in mental capacity, orientation,
retention and recall, calculations, judgment, and insight
Speech: Slurred speech, S & L pronounced
slowly, tremors of lips and tongue, repeats last few words, face often
smooth and mask like
Several forms of general paresis
Early stage
Simple dementia
Euphoric or expansive paretic
Agitated paretic
Depressed paretic
Tabes dorsalis
5-20 years after the 1° or 2° stages.
3 stages
preataxic - lightning like pain radiating from the
gluteal region to the heel or foot paresthesia of the soles of the feet;
feels like walking on carpet or wood, also patient develops a loss of sense
of position and passive motion. Poor control of the extremities.
Atoxic - loss of deep sensory abilities, difficulty
in maintaining balance, sways side to side when eyes are closed, holds
body stiffly.
Paralytic - requires one or 2 canes to walk, cannot
feel feet touching surfaces.
Treatment will not help.""""
YOU DO NEED TO KNOW ABOUT CONGENITAL SYPHILIS.
5. Congenital syphilis results when maternal syphilis spreads in
utero to the fetus after the 4th month of gestation.
If the mother is highly infective, the baby will be stillborn or present
with a fulminating case of syphilis manifested initially (during first
2 years of life) by:
Rhinitis, snuffles followed by skin and
mucocutaneous lesions similar to those of adult 2° syphilis
Osteochondritis (inflamed bone and cartilage and osteitis (inflammation
of bone)
Hepatosplenomegaly and lymphadenopathy
Immune complex-induced glomerulonephritis
Death in first 2 years is due to pulmonary hemorrhage, 2° bacterial
infection or hepatitis
Late congenital syphilis (after 2 years of age) manifestations
In 60% of 2-year survivors the infection is subclinical.
The remainder develop manifestations similar to those of adults with 3°
syphilis, as well as the following:
Clutton's joints = painless symmetrical
hydrarthrosis of the knee joint
Rhagades = fissures, cracks or fine linear scars in the skin especially
around the mouth and other regions subjected to frequent movement.
D. Pathology and Pathogenesis of Syphilis
The organisms enter the body via minute abrasions of epithelial cell linings,
by penetrating mucous membranes or via hair follicles, and then there is
a rapid systemic spread via the blood and lymphatics.
The most prominent histologic features are vascular changes caused by endarteritis
and periarteritis (perivascular cuffing).
E. Diagnosis of syphilis is accomplished via:
Evaluation of presenting signs and symptoms as well as contact history
Darkfield examination of exudative material in syphilitic lesions
Direct fluorescent Ab test for T. pallidum(DFAT-Tp)
Serological approaches using treponemal or nontreponemal tests
Nontreponemal tests measure anti-treponemal antibody using a cross reactive
cardiolipin lecithin as an antigen rather than the actual bacterial antigens.
VDRL slide test (Venereal Disease Research Laboratories)
USR - (Unheated Serum Reagin)
RPR 18 mm circle card (Rapid Plasma Reagin)
TRUST (Toluidine Red Unheated Serum Test)
RST (Reagin Screen Test)
Treponemal antigen tests rely upon antigens derived directly from T.
pallidum.
Examples include:
FTA-ABS or fluorescent treponemal antibody-absorption test where you mix
spirochetes with the patient's serum, add FITC-tagged anti-human globulin
and look for fluorescence in a fluorescent microscope.
FTA-ABS double staining - same as FTA-ABS except also add anti-human antibody
with a red fluorescent dye.
MHATP T. pallidum hemagglutination test where you mix formalinized, tanned
sheep erythrocytes coated with T. pallidum antigens with the patient's
serum and look for agglutination.
False + serological reactions in non-treponemal antigen tests are quite
common and may occur in patients with:
hepatitis
infectious mononucleosis
viral infections
malaria
pregnancy
connective tissue disease like SLE
disease with Ig abnormalities
in some healthy people
False positives in direct treponemal tests are more rare because they are
more specific; they are associated with:
diseases with Ig abnormalities
multiple myeloma
SLE
F. Prognosis of Syphilis
1. In untreated cases:
25% of people experience one or more relapses with the development of mucocutaneous
lesions during the first four years.
Approximately 33% will develop manifestations of late syphilis.
The remaining 66% do not develop manifestations of late syphilis but signs
are present at autopsy.
2. Treatment during 1° and 2° syphilis aborts the process but the
changes associated with 3° syphilis are irreversible for the most part
(except for gummas).
G. Therapy of syphilis
Patients who have primary or secondary syphilis should be treated with
the following regimen: Benzathine penicillin G 2.4 million units IM in
a single dose.
Early Latent Syphilis: Benzathine penicillin G 2.4 million units IM in
a single dose.
Late Latent Syphilis or Latent Syphilis of Unknown Duration: Benzathine
penicillin G 7.2 million units total, administered as three doses of 2.4
million units IM each at 1-week ntervals.
Tertiary Syphilis: Benzathine penicillin G 7.2 million units total, administered
as three doses of 2.4 million units IM at 1-week intervals.
Recommended Regimen for Children: Benzathine penicillin G 50,000 units/kg
IM, up to the adult dose of 2.4 million units in a single dose.
Congenital Syphilis: Aqueous crystalline penicillin G 100,000-150,000 units/kg/day,
administered as 50,000 units/kg/dose IV every 12 hours during the first
7 days of life, and every 8 hours thereafter for a total of 10 days; OR
Procaine penicillin G 50,000 units/kg/dose IM a day in a single dose for
10 days.
Identify source contact, examine and treat.
Treatment of congenital syphilis.
Treatment of mother before 16th week of pregnancy prevents congenital syphilis.
Treatment after the 16th week also helps fetus but may not alleviate all
of the future manifestations. Treat child if maternal treatment is inadequate,
unknown, with drugs other than penicillin, or if follow-up is not ensured,
treat child with penicillin.
POST TREATMENT FOLLOW-UP IS IMPORTANT.Jarisch-Herxheimer Reaction: Intensification of existing syphilitic
lesions and/or exacerbation of old ones following administration of penicillin;
the reaction subsides in 24 hours and you should simply warn the patient
to expect it. H. Prevention of Syphilis
In October 1999, CDC, in collaboration with other federal partners,
launched the National Plan to Eliminate Syphilis in the United States.
In 1998, Congress initiated funding for the syphilis elimination effort.
Syphilis elimination is defined as the absence of sustained transmission
(i.e., no transmission after 90 days of the report of an imported index
case). The national goal for syphilis elimination is to reduce primary
and secondary (P&S) syphilis to <1000 cases (rate: 0.4 per 100,000
population) and to increase the number of syphilis-free counties to 90%
by 2005.
To sustain progress toward syphilis elimination, communities must understand
local patterns of syphilis transmission and develop intervention strategies,
including education, risk reduction, and screening of persons at risk for
this disease.
V. Chancroid or soft chancre disease
is an acute sexually transmitted disease characterized by genital ulceration
and suppuration caused by the organism Haemophilus ducreyi.
A. Haemophilus ducreyi
(=
Ducrey's bacillus) is a Gram(-) rod which grows in chains.
B. Epidemiology
Transmission of H. ducreyi is almost exclusively by sexual contact.
Hygiene and cleanliness are important determinants of contagiousness.
The incidence in the U.S. has declined; <1,500 cases/year.
Prostitution is a major cause of spread (seen a lot during Korean and Vietnam
wars).
C. Clinical manifestations
There is an incubation period of 1-14 days after exposure before you get
the development of the characteristic lesion, the soft chancre.
Chancre development begins as a small inflammatory papule.
The lesion is a true ulcer.
In contrast to the syphilis chancre, the chancroid is extremely painful.
The chancroid lacks induration and is referred to as a
soft
chancre.
Patients should be reexamined 3-7 days after initiation of therapy.
VI. Genital herpes (= herpes genitalis)
is an acute inflammatory disease of the male and female genital tract due
to infection with Herpes simplex virus
(HSV).
A. Etiology
Herpes simplex exists as two closely related forms which are antigenically
and biologically distinct. Five percent to 30% of first-episode cases of
genital herpes are caused by HSV-1, but clinical recurrences are much less
frequent for HSV-1
than HSV-2 genital infection. Therefore, identification of the type
of the infecting strain has prognostic importance and may be useful for
counseling purposes.
HSV-1 is primarily transmitted by nonvenereal routes, particularly following
contact with infected saliva and is responsible for facial and oropharyngeal
infections like herpetic gingivostomatitis and the common cold sore or
fever blister.
HSV-2 is usually transmitted venereally or maternally to newborn infants
and is responsible for genital herpes and neonatal infections. -- also
it has been linked epidemiologically with carcinoma of the cervix
This rough rule of HSV-1 above the waist and HSV-2 below the waist is no
longer strictly true:
approximately 20% of genital herpes cases are due to HSV-1
HSV-2 may induce oropharyngeal infections
B. Epidemiology
HSV is an extremely successful and ubiquitous parasite of man; it is estimated
that 10% of adult U.S. population experiences symptomatic genital herpes
and the incidence is increasing.
Acquisition of HSV-2 either by sexual contact with a symptomatic person
or transfer to a fetus/newborn from an infected mother.
Risk of infection is approximately 75% following contact with a symptomatic
case.
C. Manifestations
1. Primary genital herpes acquired following sexual contact with symptomatic
partner
Incubation period of 2-7 days (2-21 days)
Initial manifestations include local pain, tenderness, itching sensation,
dysuria, and in females, a profuse, watery vaginal discharge.
Initial lesions are papules on a red erythematous base but they rapidly
develop into vesicles and later ulcers
covered with a grayish exudate.
In females the vesicles develop on labia majora
and minora, vaginal mucosa, cervix, and perineal region.
In males the lesions typically appear on the glans penis, the prepuce,
and the shaft of the penis.
Of course the vesicles are full of infectious virus, so contact via scratching
can spread the infection anywhere, including extra genital regions.
These lesions are self-limiting and heal in about 3 weeks.
75% of patients present with a painful, nonsuppurative inguinal, pelvic
and/or femoral lymphadenopathy.
Constitutional symptoms:
headache
malaise
myalgias
approximately 15% of cases also have herpetic pharyngitis
2. The manifestations of recurrent genital herpes are similar but less
severe, and resolve faster.
Recurrence is generally at about 4 months after the first episode and then
at approximately 6-8 week intervals and may be hormonally triggered during
menses.
3. Newborns who pick up the virus during passage through the birth
canal of a symptomatic female usually develop disseminated infection with
a 60- 70% fatality rate.
It is estimated that 1 in 20,000 deliveries is potentially involved.
There is a 50% chance of infection.
The virus can also cross the placenta and result in stillbirth or extreme
teratogenic effects.
D. Pathology
The virus is introduced into the genital mucosa by sexual contact with
an HSV infected partner. Symptomatic AND asymptomatic HSV infected sexual
partners can spread the infection to an uninfected partner.
Viral replication induces an erythematous papule that swells into a fluid-filled
vesicle. -- This fluid has much infectious virus and degenerating cells
containing eosinophilic intranuclear inclusion bodies and multinucleated
giant cells. -- Eventually these vesicles rupture to leave small ulcers
covered with a grayish exudate. -- The lesions heal in about 3 weeks.
During primary infections you have extensive viremia and regional lymphadenopathy.
Eventually local interferon as well as specific antibody and CMI will curtail
virus replication.
The virus invades local nerve endings, ascends the axons, and establishes
latency in the sacral ganglia, however.
This is the usual source of recurrence because the virus reactivates, travels
down the axon, and causes new lesions in the epidermis.
E. Diagnosis
A clinical diagnosis based upon presence of vesicular lesions in genital
area and sexual history is important and highly suggestive.
other disease may cause similar lesions so laboratory backup is important.
Laboratory approaches for the diagnosis of genital herpes include:
Virus isolation, demonstration of characteristic CPE in target cells, and
inhibition of CPE with type specific antisera.
Cytologic examination -- Scrape off cells from the base of the ulcer and
look for eosinophilic intra nuclear inclusion bodies and
multi-nucleated
giant cells.
Direct immune fluorescent staining of cells scraped off the base of the
ulcer.
F. Therapy
First clinical episode:
Acyclovir 400 mg orally three times a day for 10 days, OR
Acyclovir 200 mg orally five times a day for 10 days, OR
Famciclovir 250 mg orally three times a day for 5-10 days, OR
Valacyclovir 1 g orally twice a day for 10 days.
Recommended Regimens for Episodic Recurrent Infection:
Acyclovir 400 mg orally three times a day for 5 days, OR
Acyclovir 200 mg orally five times a day for 5 days, OR
Acyclovir 800 mg orally twice a day for 5 days, OR
Famciclovir 125 mg orally twice a day for 5 days, OR
Valacyclovir 500 mg orally twice a day for 5 days.
Recommended Regimens for Daily Suppressive Therapy
Acyclovir 400 mg orally twice a day, OR
Famciclovir 250 mg orally twice a day, OR
Valacyclovir 250 mg orally twice a day, OR
Valacyclovir 500 mg orally once a day, OR
Valacyclovir 1,000 mg orally once a day.
Counseling of these patients should include the following:
Patients who have genital herpes should be told about the natural history
of the disease, with emphasis on the potential for recurrent episodes,
asymptomatic viral shedding, and sexual transmission.
Patients should be advised to abstain from sexual activity when lesions
or prodromal symptoms are present and encouraged to inform their sex partners
that they have genital herpes. The use of condoms during all sexual exposures
with new or uninfected sex partners should be encouraged.
Sexual transmission of HSV can occur during asymptomatic periods. Asymptomatic
viral shedding occurs more frequently in patients who have genital HSV-2
infection than HSV-1 infection and in patients who have had genital herpes
for less than 12 months. Such patients should be counseled to prevent spread
of the infection.
The risk for neonatal infection should be explained to all patients, including
men. Childbearing-aged women who have genital herpes should be advised
to inform health-care providers who care for them during pregnancy about
the HSV infection.
Patients having a first episode of genital herpes should be advised that
episodic antiviral therapy during recurrent episodes might shorten the
duration of lesions and suppressive antiviral therapy can ameliorate or
prevent recurrent outbreaks.
Treatment does not cure.
Recurrent Episodes of HSV Disease:
When treatment is started during the prodrome or within 1 day after onset
of lesions, many patients who have recurrent disease benefit from episodic
therapy.
Daily suppressive therapy reduces the frequency of genital herpes recurrences
by greater than or equal to 75% among patients who have frequent recurrences
(i.e., six or more recurrences per year). Suppressive treatment with acyclovir
reduces but does not eliminate asymptomatic viral shedding.
These antiviral compounds have NO effect on establishment of latency
and subsequent recurrences can and do occur. However, the recurrences maybe
less numerous and less severe.
Severe Disease IV therapy should be provided for patients who have severe disease
or complications necessitating hospitalization, such as disseminated infection,
pneumonitis, hepatitis, or complications of the central nervous system
(e.g., meningitis or encephalitis). Acyclovir 5-10 mg/kg body weight IV
every 8 hours for 5-7 days or until clinical resolution is attained.
G. Prognosis
The primary lesions heal spontaneously and it is usually a self-limiting
disease.
The patient must be educated as to the clinical course of the disease,
the likelihood of reccurrence, and the potential for infecting others.