SEXUALLY TRANSMITTED DISEASES (STD) continued

Diseases in this Handout:

Syphilis

Chancroid

Genital Herpes

A. T. pallidum has a number of characteristics which are important for diagnosis. 

1. 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.
2. T. pallidum cannot be grown in vitro.

1. Man is the only known host and transmission is virtually always by direct contact with infectious lesions, generally through sexual contact.
2. The incidence is highest in sexually active people (20-29 year old group).
3. The number and rate of 1^o and 2^o (P&S) syphilis cases reported in 1999 were the lowest ever reported in the United States.
4. There are approximately 6,000-7,000 new cases of 1° and 2° or P&S syphilis diagnosed per year
5. Approximately 30% of exposed people contract the disease.
6. 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.
7. The South continues to have the highest rate in the country (rate: 4.5)
8. 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.
9. 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.
10. Nine of the 11 states that have rates above the 2000 objective are in the South.
11. In 1999, of 3115 U.S. counties, 2473 (79.4%) reported no cases of P&S syphilis.
12. 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.
13. 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.
14. 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.
15. 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.

1. Manifestations of primary syphilis: a) hard chancre (lesion on female); and b) regional lymphadenitis.

• 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.
1. Syphilitic chancres are indurated (= hard chancre)
2. They are highly infectious
3. They may occur anywhere on the body
4. They are painless
5. Chancres will heal in 3-6 weeks.
• Regional lymphadenopathy adjacent to the chancre may develop during primary syphilis.
1. The nodes are firm, nonsuppurative
2. It may persist for months, despite healing of the chancre.

• 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.
1. 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.
• Patchy alopecia
• Condyloma lata - moist, flat, confluent plaques
•  Mucous patches
2. 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.

• 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).

• """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
1. Seen within 2 years of infection
2. A lot like other meningitis
3. Headache
4. Vertigo nausea, vomiting
5. Generalized convulsions
6. Cervical rigidity
7. Positive Kernig's and Brudzinski's signs
8. The third cranial nerve is most often affected
• Chronic meningovascular
1. Seen 2-5 years, but no later than 10 years of infection
2. A proliferative endarteritis and perivascular infiltration with lymphocytes (perivascular cuffing)
3. Leads to blocking of blood vessels and necrosis of nerve tissue
4. Gradual intellectual and emotional deterioration
5. Most commonly the middle and posterior arteries are involved. Usually see a weakening in one side.
6. Headache, nausea, vomiting
7. 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
1. 5-20 years after the 1° or 2° stages.
2. 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.
3. Treatment will not help.""""

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:
1. Rhinitis, snuffles followed by skin and mucocutaneous lesions similar to those of adult 2° syphilis
2. Osteochondritis (inflamed bone and cartilage and osteitis (inflammation of bone)
3. Hepatosplenomegaly and lymphadenopathy
4. Immune complex-induced glomerulonephritis
5. Death in first 2 years is due to pulmonary hemorrhage, 2° bacterial infection or hepatitis
• Late congenital syphilis (after 2 years of age) manifestations
1. In 60% of 2-year survivors the infection is subclinical.
2. 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
• Deafness
• Hutchinson's teeth = notched and narrow edged permanent incisors
• Mulberry molars
• Bone abnormalities:
• Saddle nose
• Saber shins
• Rhagades = fissures, cracks or fine linear scars in the skin especially around the mouth and other regions subjected to frequent movement.

1. 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.
2. The most prominent histologic features are vascular changes caused by endarteritis and periarteritis (perivascular cuffing).

E. Diagnosis of syphilis is accomplished via: 

1. Evaluation of presenting signs and symptoms as well as contact history
2. Darkfield examination of exudative material in syphilitic lesions

• Direct fluorescent Ab test for T. pallidum(DFAT-Tp)
1. 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:

1. hepatitis
2. infectious mononucleosis
3. viral infections
4. malaria
5. pregnancy
6. connective tissue disease like SLE
7. disease with Ig abnormalities
8. in some healthy people

False positives in direct treponemal tests are more rare because they are more specific; they are associated with:

1. diseases with Ig abnormalities
2. multiple myeloma
3. SLE

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).

1. 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.
2. Early Latent Syphilis: Benzathine penicillin G 2.4 million units IM in a single dose.
3. 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.
4. Tertiary Syphilis: Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at 1-week intervals.
5. 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.
6. 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.
7. Identify source contact, examine and treat.
8. 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. 

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.

A. Haemophilus ducreyi (= Ducrey's bacillus) is a Gram(-) rod which grows in chains.

B. Epidemiology

1. Transmission of H. ducreyi is almost exclusively by sexual contact.
2. Hygiene and cleanliness are important determinants of contagiousness.
3. The incidence in the U.S. has declined; <1,500 cases/year.
4. 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.
• Initially the lesion is typically solitary but by autoinoculation multiple lesions develop.
• Accompanying chancroid development is an acute, painful inflammatory inguinal lymphadenopathy in > 50% of cases.

D. Pathology and pathogenesis

• The organism enters the body through skin abrasions.
• It induces a papule or vesicle which ulcerates.
• There is a dense inflammatory exudate with PMNs but not mononuclear cells.

E. Diagnosis

• Evaluation of lesion as well as sexual history.
• Specific diagnosis depends upon demonstration of H. ducreyi.
• The ducreyi skin test is an out dated DTH skin test with H. ducreyi antigens.
• Differential diagnosis involves distinguishing
• Primary genital herpes type 2 infection
• Primary syphilis
• Lymphogranuloma venereum
• Granuloma inguinale
• Trauma
G. Prognosis
• Soft chancres may heal quickly and spontaneously (enhanced with improved hygiene).
• They may persist and induce deep scars.

H. Therapy

1. Azithromycin 1 g orally in a single dose, OR Ceftriaxone 250 mg intramuscularly (IM) in a single dose.
2. Aspiration of fluctuant lymph nodes to remove the pus.
3. Patients should be reexamined 3-7 days after initiation of therapy.

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.

• 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.

• 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.

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.

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:

1. 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.
2. 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.