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TATOIU ALEXANDRA

Universitatea Ovidius Constanta


Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
http://dictionary.cambridge.org/dictionary/british/osteoporosis

Sexually Transmitted Diseases


The term sexually transmitted diseases (STDs) refers to many diseases and the number
keeps expanding with the discovery of newer pathogens (e.g., HIV) or a new route of acquisition
of a known pathogen (e.g., hepatitis C). The terminology can be confusing as well. Historically,
the term venereal disease was used for the class of diseases known to be transmitted by sexual
intercourse. Other terminology includes sexually transmitted infections, because some infections
may be asymptomatic and not cause disease, sexually transmissible diseases and infections,
because some diseases such as hepatitis C may be transmitted predominantly by a nonsexual
route, and reproductive tract infections, because the sexual transmission of some diseases such as
bacterial vaginosis are still debated. In this chapter, STD is used to encompass all these diseases.
Although there is a vast number of STDs, only a few important ones that are classically
associated with sexual transmission will be discussed. HIV infection is not discussed in this
chapter.
STDs have complex social, political, and public health implications, in addition to their
medical significance. Even with the introduction of effective treatments such as penicillin for
syphilis more than 60 years ago, syphilis continues to remain an important disease. In fact, the
rate of syphilis in men who have sex with men (MSM) is on the rise in some areas in the United
States. STDs remain among the most common infectious diseases in developed and developing
countries. The fact that diseases for which there are effective therapies that can be prevented by
changing behavior are still rampant illustrates the complex nature of these diseases and the
enormous challenges faced by the medical and public health communities in dealing with them.
The STDs discussed in this chapter can be categorized into two main categories: diseases
characterized by genital ulcers and those characterized by genital discharge.
Sexually transmitted diseases with ulcers:
Herpes simplex virus (HSV) infections, syphilis, and chancroid account for almost all the
STDs characterized by genital ulcers in the United States. More than one may be present in a
patient who presents with genital ulcers and each of these diseases has been associated with an
increased risk of HIV infection. A diagnosis based only on the patient's medical history and
examination is often inaccurate and laboratory confirmation should be sought. Often, the
clinician must treat the patient before laboratory results are available. In this case, the clinician
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
should treat based on the clinical presentation or epidemiologic circumstances. Even after a
complete diagnostic evaluation, at least 25% of patients who have genital ulcers have no
laboratory-confirmed diagnosis. Noninfectious causes of genital ulcers, including Crohn's
disease, Behet's disease, and traumatic ulcers, should be considered.
Herpes Simplex Virus Infections:
Genital HSV infection prevalence has markedly increased over the past two decades. About
50 million persons in the United States have genital HSV infection based on seroprevalence
studies and most of them remain undiagnosed. Most infections are transmitted by those who are
asymptomatic. Two serotypes, HSV-1 and HSV-2 have been identified, and both have been
implicated as the pathogen in genital HSV infection. Although genital HSV infections are
usually caused by HSV-2, up to 50% of first episodes of genital herpes are caused by HSV-1.
However, recurrences are much less frequent for HSV-1; thus, distinction of the serotypes
influences prognosis and counseling. HSV-2 infections are almost always sexually acquired,
whereas HSV-1 infections may be caused by anogenital or orolabial infections.
Laboratory diagnosis of HSV infections consists of virologic and serologic tests. Viral culture
is the preferred test for patients with mucocutaneous lesions. However, the sensitivity is low and
declines rapidly as lesions begin to heal. Antigen detection by direct fluorescent antibody (DFA)
and polymerase chain reaction (PCR) assays to detect viral DNA are other methods. The PCR
assay is not widely available and has not been well studied for genital lesions but is the preferred
method of diagnosis in spinal fluid specimens. Type-specific serologic tests are useful for the
diagnosis of patients who are asymptomatic or for whom virologic test results are negative.
Cytologic detection of cellular changes from lesions (using the Tzanck test) is insensitive and
nonspecific and should not be relied on for diagnosis.
The clinical manifestations of first-episode genital HSV infections differ greatly from
recurrent episodes and will be discussed separately.
First-Episode Genital Herpes I nfection :
Primary genital HSV infection is one in which the patient has not had prior infection by any
HSV serotype. Patients with primary infection are more likely to have a symptomatic and more
severe infection.
First-episode infections often are associated with prolonged systemic and local symptoms.
Systemic symptoms include fever, headache, malaise, and myalgias. These appear in the first 3
to 4 days after the onset of lesions and gradually recede over the next 3 to 4 days. Local
symptoms are characterized by papules or vesicular lesions that coalesce to form painful ulcers
and can also include itching, urethral discharge, dysuria, vaginal discharge, and painful inguinal
adenopathy. Cervicitis manifesting with ulcerative lesions in the exocervix and purulent or
bloody vaginal discharge may be present. Local symptoms often last 3 weeks and peak at about
the end of the first week. Pharyngitis and proctitis can also occur, depending on the site of
inoculation of the virus. Complications of first-episode genital HSV infection include aseptic
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
meningitis (usually with HSV-2), urinary retention (because of autonomic dysfunction),
transverse myelitis, and extragenital lesions, usually on the buttocks and caused by
autoinoculation, disseminated infection with both cutaneous or visceral involvement and pelvic
inflammatory disease. Women may also be superinfected by yeast vaginitis during the course of
the illness.
Most patients with primary genital herpes should receive antiviral therapy because they may
have mild symptoms early but could develop severe disease later. The recommended therapy is
acyclovir, 200 mg five times daily or 400 mg three times daily, or famciclovir, 250 mg three
times daily, or valacyclovir, 1 g twice daily. The recommended duration of therapy is 7 to 10
days.
Recurrent Genital Herpes :
Almost all persons infected with HSV-2 have the infection reactivated in the genital region.
About 60% of episodes are preceded by prodromal symptoms, such as a mild tingling sensation
or shooting pains in the buttocks or hips. The lesions tend to be more severe in women. As with
the primary episode, the lesions are classically described as painful vesicles that ulcerate and
later crust, without leaving a scar. However, compared with the primary episode, the lesions are
less painful, heal faster, and are not associated with systemic symptoms. Also, the lesions may
not be typical, and all genital ulcers should be evaluated for HSV. The frequency of recurrences
decreases over time.
The strategy for managing recurrent episodes consists of episodic treatment to ameliorate or
shorten the duration of illness or suppressive treatment to reduce the frequency of recurrences.
Recommended regimens for episodic treatment include acyclovir, 400 mg three times daily or
800 mg twice daily, famciclovir, 125 mg twice daily, or valacyclovir, 500 mg twice daily or 1 g
daily. The recommended duration of therapy is 5 days, except for valacyclovir, 500 mg twice
daily, which has been shown to be as effective with 3-day therapy as 5-day therapy. Treatment
should be started within 1 day of onset of lesions; hence, the patient should be provided with a
prescription for of the relevant drug(s) so that therapy can be self-initiated when symptoms arise.
Suppressive treatment has been shown to reduce the frequency of genital herpes by 70% to
80% in patients who have more than six recurrent episodes per year. Recommendations for
suppressive therapy include acyclovir, 400 mg twice daily, famciclovir, 250 mg twice daily, or
valacyclovir, 1 g daily. Because the frequency of recurrences decreases over time, continuation
of suppressive therapy should be reassessed periodically.
Other Considerations
Severe Disease.
In patients with severe disease or with disseminated infection such as meningitis, IV acyclovir
should be given. The recommended regimen is acyclovir, 5 to 10 mg/kg body weight every 8
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
hours for 2 to 7 days, or until clinical improvement is observed, followed by oral therapy for a
total of 10 days.
Herpes Simplex Virus in Pregnancy.
The risk of neonatal herpes in an infant born to a mother who has primary HSV infection is
30% to 50% and is less than 1% in mothers with a history of recurrent herpes or those who
acquire herpes in the first half of pregnancy. Prevention of neonatal herpes depends both on
preventing the acquisition of HSV during late pregnancy and avoiding exposure of the infant to
herpetic lesions during delivery. It is recommended that mothers with a history of recurrent
genital HSV infection who have prodromal symptoms or herpetic lesions on examination
undergo cesarean section to lessen the chance of neonatal herpes infection.
Herpes Simplex Virus in HI V infection.
HSV infection increases the risk of HIV infection. In addition, HIV patients may have more
severe and prolonged episodes of recurrent herpes. The recommendations for episodic and
suppressive therapy differ from those for immunocompetent patients. Recommended therapy for
episodic treatment is oral therapy for 5 to 10 days with acyclovir, 400 mg three times daily or
200 mg five times daily, famciclovir, 500 mg twice daily, or valacyclovir, 1 g twice daily.
Recommended therapy for suppressive therapy is oral therapy as follows: acyclovir, 400 to
800 mg two or three times daily, famciclovir, 500 mg twice daily, or valacyclovir, 500 mg twice
daily.
Counseling Discordant Couples.
Transmission of HSV from the patient to a seronegative partner can occur during
asymptomatic shedding. Hence, discordant couples should be advised to abstain from sexual
activity when active lesions are present and encouraged to use condoms consistently at other
times. However, condoms do not fully prevent transmission because there can be asymptomatic
shedding from areas such as the perineum, which are not protected by condoms.
Syphilis:
Syphilis is a systemic disease caused by the spirochete Treponema pallidum. The natural
history of syphilis consists of different stages with distinctive clinical stages: primary, secondary,
latent, and tertiary syphilis. Neurosyphilis, often considered part of tertiary syphilis, can occur
with any of the different stages and requires special attention because of its therapeutic
implications. Syphilis and its complications were common in medical practice in the earlier part
of the 20th century. After the introduction of penicillin and public health efforts to control the
disease, its prevalence has declined. Advanced stages of syphilis are now rare and clinicians are
often unfamiliar with its various manifestations. However, outbreaks have occurred in several
groups and, in the presence of HIV infection, may manifest different signs and symptoms. Thus,
there is renewed interest in this disease.
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
Because it has not been possible to grow the organisms in vitro, definitive diagnosis depends
on visualizing the organisms by dark field microscopy or DFA tests of lesion exudates or tissue.
A presumptive diagnosis can be made based on two types of serologic tests: nontreponemal tests
(e.g., Venereal Diseases Research Laboratory [VDRL]) and rapid plasma reagin [RPR]); and
treponemal tests, such as fluorescent treponemal antibody adsorption (FTA-ABS) and T.
pallidum particle agglutination (TP-PA) assays. Nontreponemal test titers correlate with disease
activity and therefore should be quantitative. Treatment can be considered effective if follow-up
titers at 6 months have fallen at least fourfold. They usually become negative after treatment. If
the titer has dropped at least fourfold, but remains positive, the patient is considered serofast
(usually in the 1 : 2 to 1 : 4 range). Sequential tests in individual patients should be performed
using the same test because the two tests (VDRL and RPR) cannot be compared. Patients who
have positive treponemal test results generally remain positive for the rest of their lives.
The incubation period of syphilis is 10 to 90 days (average, 2 weeks). Clinical manifestations
depend on the stage of the disease, which are discussed here.
Primary Syphilis
The lesion of primary syphilis starts as a painless papule at the site of inoculation, which
subsequently develops into an ulcer (chancre). The chancre is a painless, slightly elongated ulcer
1 to 2 cm across, with a clean base and an indurated margin. Moderate painless, bilateral,
inguinal lymphadenopathy is usually present. Lesions are usually solitary and can be missed if
they are not in visible regions because of their painless nature. Untreated, they spontaneously
heal in 3 to 6 weeks. Treatment is with benzathine penicillin, 2.4 million units IM, in a single
dose.
Secondary Syphilis
Secondary syphilis develops 4 to 10 weeks after the initial appearance of primary lesions. It
starts as an evanescent macular rash followed in a few days by a symmetrical papular eruption
involving the entire trunk and extremities. Characteristically, it involves the palms and soles. The
papules are reddish brown and generally scaly, and may be mistaken for psoriasis. Other
manifestations could be a patchy alopecia (moth-eaten alopecia), mucosal lesions (painless
aphthous ulcers or gray plaques), condyloma latum (raised, moist whitish lesions in warm moist
areas such as the axilla or groin region), and lymphadenopathy. It is a systemic disease with
possible symptoms of low-grade fever, sore throat, headache, malaise, and weight loss. The
lesions of primary and secondary syphilis are highly infectious. Treatment, as for primary
syphilis, is benzathine penicillin, 2.4 million units IM in a single dose.
Latent Syphilis
If secondary syphilis is untreated, there is a spontaneous resolution of symptoms in 3 to 12
weeks. The patient then enters into the latent phase, during which the patient is asymptomatic but
has serologic evidence of ongoing infection. During the first year of latent syphilis, the patient
may have relapses of secondary syphilis. This phase is early latent syphilis. After the first year,
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
during the late latent phase, it is highly unlikely that the patient will have any recurrences of
secondary syphilis. Often, the duration of infection cannot be determined to classify the infection
as early or late.
These patients, with latent syphilis of unknown duration, should be treated as if they had late
latent syphilis. Recommended treatment for early latent syphilis is benzathine penicillin, 2.4
million units IM in a single dose. The recommended treatment for late latent syphilis is
benzathine penicillin, 2.4 million units IM given weekly for 3 weeks consecutively.
Tertiary Syphilis :
About one third of patients with late latent disease go on to develop tertiary syphilis if left
untreated. This includes gummatous disease (benign late syphilis), cardiovascular syphilis, and
neurosyphilis.
Gummatous disease, now uncommon, can manifest as recurrent nodular lesions in the skin that
ulcerate and heal leaving an atrophic scar. In addition to the skin, skeletal and upper respiratory
tract areas are the more common sites involved.
Cardiovascular syphilis consists mainly of an aortitis of the ascending aorta. The aortic valve
and coronary ostia may also be involved. Gummatous disease and cardiovascular syphilis are
treated with benzathine penicillin, 2.4 million units IM given weekly for 3 weeks consecutively.
Neurosyphilis is classically described as a part of tertiary syphilis. There may be several forms
with overlap, among them; these forms include asymptomatic, meningeal, meningovascular,
parenchymatous (general paresis and tabes dorsalis), and gummatous disease. Asymptomatic
syphilis is manifest by cerebrospinal fluid (CSF) findings suggestive of meningitis. Usually,
there is a CSF pleocytosis, predominantly lymphocytic, with more than 5 cells/mm
3
. The protein
level is elevated and there may be decreased glucose levels. The VDRL test result is positive in
most cases; this is specific but not very sensitive. The FTA-ABS test result on the CSF is
sensitive but not specific and may be used to exclude a diagnosis of central nervous system
(CNS) syphilis when the CSF VDRL test result is negative. Syphilitic meningitis manifests as
cranial nerve palsies and hearing loss caused by basilar meningitis. There may also be signs of
uveitis. Meningovascular syphilis can result in cerebrovascular accidents.
The recommended treatment regimen for neurosyphilis is aqueous penicillin G, 18 to 24
million units daily, given as 3 to 4 million units IV every 4 hours or as a continuous infusion for
10 to 14 days. Alternatively, procaine penicillin, 2.4 million units IM once daily, plus
probenecid, 500 mg PO four times daily, may be given, both for 10 to 14 days. A CSF
examination should be repeated every 6 months until the cell count is normal. If the cell count
has not decreased after 6 months or the CSF is not normal after 2 years, re-treatment should be
considered.
Other Considerations
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
J arisch-Herxheimer Reaction.
After treatment for primary or secondary syphilis patients may have a febrile reaction because
of the release of treponemal constituents. It starts 4 to 6 hours after treatment, subsides in 24
hours, and is characterized by fever, chills, headache, arthralgias, and a transient increase in
prominence of the lesions. Patients should be managed with an anti-inflammatory agent such as
ibuprofen.
Penicillin Allergy.
For patients with primary or secondary syphilis or early latent syphilis, other options include
doxycycline, 100 mg PO twice daily for 14 days, or tetracycline, 500 mg PO four times daily for
14 days. Ceftriaxone, 1 g IM or IV daily for 8 to 10 days, is another option. Some reports have
suggested that azithromycin, 2 g PO as a single dose is effective. However, other reports have
suggested that there may be substantial resistance to azithromycin, based on molecular studies,
so caution should be used with this approach. For patients with late latent syphilis, doxycycline
or tetracycline may be used for 28 days. For patients with neurosyphilis, ceftriaxone, 2 g IV or
IM for 10 to 14 days, may be used. Pregnant women who are allergic to penicillin should be
desensitized and treated with penicillin.
Follow-up.
Because any therapy could fail, follow-up is extremely important. In patients without HIV, 6-
month and 1- and 2-year follow-ups are recommended. Patients who have continued signs and
symptoms or a fourfold increase in titer during follow-up are considered to be therapeutic
failures. Also, if patients do not achieve a fourfold decrease in nontreponemal titers in 6 months,
they are considered therapeutic failures. In this case, the patient should be checked for HIV and
neurosyphilis. For therapeutic failures, the patient should receive three weekly doses of
benzathine penicillin.
Syphilis in HI V-I nfected Persons.
Patients with HIV infection have an increased risk of developing neurosyphilis, even if they are
not severely immunocompromised, and the disease may progress more rapidly. In addition, they
may have higher rates of treatment failure. Some specialists have recommended treatment for
primary syphilis, secondary syphilis, and early latent syphilis in HIV-infected patients with 2.4
million units of benzathine penicillin every week for 3 weeks. In addition, many specialists
would do a CSF examination to rule out neurosyphilis before starting treatment. Follow-up is
recommended at 3-month intervals in HIV-infected patients for the first year of follow-up.
Syphilis in Pregnancy.
Infants born to mothers at any stage of syphilis are at risk of becoming infected with congenital
syphilis. The mode of transmission is transplacental. The risk, however, decreases with later
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
stages of disease. Syphilis during pregnancy is associated with increased risk of miscarriage. All
pregnant women should be screened serologically for syphilis at their first prenatal visit.
Treatment should consist of the penicillin regimen appropriate for the stage of syphilis.
Penicillin-allergic patients should be desensitized and treated with penicillin.
Chancroid
Chancroid is an ulcerative disease caused by Haemophilus ducreyi. The U.S. incidence of
chancroid has declined since 1987, with less than 100 cases per year reported to the Centers for
Disease Control and Prevention (CDC). It usually occurs in discrete outbreaks, although it is
endemic in some U.S. regions. About 10% of persons in the United States who acquire chancroid
are coinfected with T. pallidum or HSV.
Clinically, it manifests as a tender erythematous papule that may develop at the site of
inoculation after 4 to 7 days. This then progresses to form a pustule that may rupture after 2 to 3
more days to form painful shallow ulcers. These ulcers typically have a granulomatous base,
with purulent exudates and overhanging margins. Painful tender lymphadenopathy is seen in up
to 50% of cases and is usually unilateral; this may become fluctuant and drain spontaneously
unless aspirated or drained by incision.
Chancroid ulcers take several weeks or months to resolve in the absence of effective therapy.
As with other ulcerative diseases, chancroid is a cofactor in the transmission of HIV.
The definitive microbiologic diagnosis of chancroid is challenging, so chancroid is usually
diagnosed clinically. A special medium is required to isolate H. ducreyi in culture, and is not
widely available. Even using this medium, the sensitivity is less than 80%. Several commercial
laboratories offer DNA amplification assays for H. ducreyi but these are not widely available.
For treatment purposes, a probable diagnosis can be made if the following criteria are met: the
patient has one or more painful genital ulcers; the patient has no evidence of T. pallidum
infection by dark field examination of ulcer exudates or by serologic testing for syphilis
performed at least 7 days after the onset of ulcers; the clinical presentation, appearance of genital
ulcers and, if present, regional lymphadenopathy are typical of chancroid; and a test for HSV
performed on the ulcer exudates is negative. It must be remembered that such a definition
excludes coinfections.
Treatment
Recommended regimens are as follows:
Azithromycin, 1 g PO single dose, or
Ceftriaxone, 250 mg IM single dose, or
Ciprofloxacin, 500 mg PO twice daily for 3 days, or
Erythromycin base, 500 mg PO three times daily for 7 days
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
Patients with HIV and uncircumcised men do not respond well to therapy, compared to those
who are HIV negative and circumcised. These patients should be carefully followed. Some
specialists recommend using the erythromycin 7-day regimen for HIV-positive patients. Patients
should be tested for HIV when chancroid is diagnosed. Patients who test negative for HIV and
syphilis when chancroid is diagnosed should be retested again for these diseases after 3 months.
Patients should be re-examined within 3 to 7 days; they should have symptomatic improvement
within 3 days and objective improvement within 7 days after therapy is initiated. If no clinical
improvement is apparent, consideration should be given to the possibility of an incorrect
diagnosis, coinfection with another STD such as HSV or syphilis, HIV coinfection,
noncompliance, or resistance of the organism. Complete healing of the ulcer may take longer
than 2 weeks. Resolution of fluctuant lymphadenopathy is slower than ulcers. These buboes
should be drained to provide symptomatic relief to the patient and avoid spontaneous rupture.
Sexual partners of patients with chancroid should be treated regardless of symptoms if they have
had sexual contact with the patient within 10 days preceding the patient's onset of symptoms.
Lymphogranuloma Venereum
Lymphogranuloma venereum (LGV) is caused by the L1, L2, and L3 serovars of Chlamydia
trachomatis. These serovars are more invasive than other C. trachomatis serovars. The disease is
rare in the United States and other industrialized nations but is endemic in Africa, southeast Asia,
Central and South America, and the Caribbean islands.
The clinical manifestations of LGV can be divided into three stages. After an incubation period
of 3 to 30 days at the site of inoculation, the patient may develop a painless papule that may
ulcerate (primary stage). The lesion is self limited and often may go unnoticed. After several
weeks of the primary lesion, the patients may have involvement of the inguinal lymph nodes or
the anus and rectum (secondary stage). Inguinal lymph nodes are usually involved in men. The
lymphadenopathy is typically unilateral, tender, and firm. It may manifest on both sides of the
inguinal ligament, which forms a groove, called the groove sign. Stellate abscesses that are
present in the lymph nodes coalesce and form discharging sinuses. Many patients present with
systemic complaints such as fever, myalgias, and headache.
Anorectal involvement manifests as an acute hemorrhagic proctitis. Patients present with
rectal pain and bleeding and often with pronounced systemic complains. A recent outbreak in
the Netherlands in MSM highlights the importance of awareness of this manifestation of LGV.
In untreated LGV, fibrosis caused by chronic inflammation is present (tertiary stage). Fibrosis
can lead to lymphatic obstruction and elephantiasis of the genitalia in either gender. Rectal
involvement may cause strictures and fistulas. These conditions are more common in women and
can lead to widespread destruction of the genitalia, a condition known as esthiomene (from the
Greek, eating away).
Diagnosis may be made by serologic testing or detection of the organism. Because the disease
is invasive, antibody titers to Chlamydia are high. Laboratory criteria consistent with a diagnosis
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
of LGV include a complement fixation titer for Chlamydia of 1 : 64 or higher, or a
microimmunofluorescence test for C. trachomatis titer of 1 : 128 or higher. C. trachomatis may
also be identified in buboes by tissue culture or by DFA staining on a bubo or ulcer smear. A
PCR diagnostic assay has been described.
Treatment
Treatment cures infection and prevents ongoing tissue scarring. The recommended regimen is
doxycycline, 100 mg PO twice daily for 21 days. An alternative regimen is erythromycin base,
500 mg PO four times daily for 21 days. Some specialists believe that azithromycin, 1 g PO once
weekly for 3 weeks is effective, but clinical data are lacking.
Patients should be followed until signs and symptoms have resolved. Sexual partners of the
patient within the last 60 days should be evaluated. In the absence of symptoms, sexual partners
should be treated with azithromycin, 1 g PO as a single dose, or doxycycline, 100 mg PO twice
daily for 7 days.
Granuloma Inguinale (Donovanosis)
Granuloma inguinale is caused by the bacterium Calymmatobacterium granulomatis, which
has been seldom isolated on culture. The disease is rare in the United States but endemic in
Papua, New Guinea, parts of South Africa and India, Brazil, and among aborigines in Australia.
In addition to sexual transmission, the disease may also be transmitted during birth and to
children, probably when sitting on the laps of infected persons.
The incubation period is uncertain, with estimates ranging from 1 to 360 days. Experimental
lesions in humans appear after 50 days of inoculation. The lesions of donovanosis start as a firm
papule that ulcerates. Lymphadenopathy is typically absent. Classically, four types of lesions are
described: ulcerogranulomatous (nontender beefy red lesions that bleed easily on touch);
hypertrophic or verrucous ulcer, with irregular margins; necrotic, foul-smelling deep ulcers
causing tissue destruction; and sclerotic or cicatricial lesions, with fibrous or scar tissue. Lesions
generally occur in the genital areas or inguinal region. Lesions may also occur in the cervix or
upper genital tract of women. Occasionally, lesions may appear in the oral cavity or pharynx.
Rarely, disseminated infection is present, which may involve the bone and liver, and is usually
associated with pregnancy and cervical infection.
Diagnosis requires visualization of dark-staining Donovan bodies on tissue crush section or
biopsy. Other methods of preparation of the specimen have been described. One technique is to
firmly roll a cotton-tipped swab across the surface of the lesion after removing debris from the
surface of the wound. The swab is then rolled over a glass slide and stained by a rapid Giemsa
method. If multiple samples for different tests are taken at the same time, the sample for
Donovan bodies should be taken first so that enough cells are obtained.
The treatment regimen recommended by the CDC is as follows:
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
Doxycycline, 100 mg PO twice daily for at least 3 weeks, or
Alternative regimens include the following:
Ciprofloxacin, 750 mg twice daily for at least 3 weeks, or
Erythromycin, base 500 mg PO twice daily for at least 3 weeks, or
Azithromycin, 1 g PO once/week for at least 3 weeks
Trimethoprim-sulfamethoxazole, one double-strength tablet PO twice daily for at least 3
weeks
Three weeks of the above-recommended therapy is generally sufficient, although the addition
of an aminoglycoside such as gentamicin, 1 mg/kg IV every 8 hours, to these regimens may be
considered if improvement is not evident in the first few days of therapy.
Despite optimal therapy, relapse can occur after 6 to 18 months. Persons who have had sexual
contact with the patient within 60 days before onset of the patient's symptoms should be
examined and offered therapy, although the value of treating asymptomatic contacts has not been
established.
Sexually transmitted diseases with genital discharge:
Pelvic Inflammatory Disease
Pelvic inflammatory disease (PID) is the term used to describe any single infection or
combination of infections of the upper female genital tract such as endometritis, salpingitis, tubo-
ovarian abscess and pelvic peritonitis. In the United States alone, approximately 1,200,000
women and girls acquire PID annually; of these, 100,000 are likely to become infertile as a result
of the infection, and more than 150 will die as a result of PID or its complications. Even mild to
moderate or asymptomatic disease could result in long-term morbidity, such as infertility, ectopic
pregnancy, and chronic pelvic pain.
PID is caused by various organisms. The sexually transmitted organisms C. trachomatis and
Neisseria gonorrhoeae are believed to be important in the pathogenesis. Gonococcus infection
generally causes a more acute illness, whereas that caused by Chlamydia tends to be mild or
subtle. Other organisms generally found in the vaginal flora have also been implicated: namely
anaerobes, facultative gram-negative organisms, and streptococci. In addition, cytomegalovirus,
Mycoplasma hominis, and Ureaplasma urealyticum may be causative agents. Immunologic
mechanisms seem to be important, especially in Chlamydia infection, in which recurrent
episodes tend to be more severe than the first. Risk factors for PID include younger age
(teenagers), STDs (Chlamydia, gonococcus, and bacterial vaginosis), intrauterine contraceptive
devices, and douching. Oral contraceptives have been associated with a decreased severity of
PID caused by Chlamydia, probably by modifying the immune response of the body.
The diagnosis of PID is difficult and a combination of signs, symptoms, and tests may be
used. The clinical diagnosis of PID has a positive predictive value of 65% to 90% compared with
that for laparoscopy. Some cases are asymptomatic and many cases go undiagnosed because of
mild or nonspecific symptoms. In addition, a delay in initiating treatment has been shown to
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increase the risk of long-term gynecologic complications. It is therefore recommended that
health care providers have a low threshold for the diagnosis of PID and that empirical therapy be
initiated promptly. The minimum criteria in women at risk of STDs for the diagnosis of PID,
when no other cause of illness can be identified, include uterine or adnexal tenderness and
cervical motion tenderness.
Additional criteria used to increase diagnostic specificity, especially in low-risk women,
include the following:
Oral temperature higher than 101 F (38.3 C)
Abnormal vaginal or uterine mucopurulent discharge
Presence of white blood cells on saline microscopy of vaginal secretions
Elevated erythrocyte sedimentation rate
Elevated C-reactive protein level
Laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis
If the cervical discharge appears normal and no white cells are seen on a vaginal wet
preparation, the diagnosis of PID is unlikely and alternative causes of pain should be considered.
More specific criteria for the diagnosis of PID include an endometrial biopsy showing
endometritis, transvaginal ultrasound or magnetic resonance imaging showing a fluid-filled
salpinx (or salpinges), or laparoscopic findings consistent with PID.
PID may occasionally manifest more acutely with peritonitis and frank vaginal discharge.
Acute complications of PID include periappendicitis and perihepatitis (Fitz-HughCurtis
syndrome).
Treatment
In the past, many specialists recommended that all patients with PID be hospitalized so that
bed rest and parenteral antibiotics could be initiated. However, outpatient therapy is being
increasingly used, based on the important PEACH trial data. This randomized clinical trial (PID
evaluation and clinical health [PEACH]) compared short- and long-term outcomes of parenteral
(cefoxitin-doxycycline) with oral (cefoxitin-probenecid or ceftriaxone plus doxycycline) for mild
to moderate symptomatic PID in several U.S. centers showed no difference in short-term and
long-term outcomes.
The treatment regimen generally consists of antibiotics that will be effective against N.
gonorrhoeae, C. trachomatis, anaerobes, facultative gram-negative bacilli, and streptococci.
Recommended Parenteral Treatment.
Parenteral treatment regimens include the following:
Cefoxitin, 2 g IV every 6 hours (or cefotetan, 2 g IV every 12 hours) plus doxycycline,
100 mg PO or IV every 12 hours. IV therapy is continued for 24 hours after clinical
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improvement. The patient can then take oral doxycycline to complete 14 days of therapy.
If the patient has a tubo-ovarian abscess, metronidazole or clindamycin may be added for
better anaerobic coverage.
Clindamycin, 900 mg IV every 8 hours, plus gentamicin, 2-mg/kg IV loading dose
followed by 1.5 mg/kg every 8 hours (single daily dosing may be substituted). Parenteral
therapy can be discontinued after 24 hours of clinical improvement and the patient can be
switched to oral therapy with clindamycin, 450 mg PO four times daily, or doxycycline,
100 mg PO twice daily, to complete 14 days of therapy.
Alternative, less-preferred regimens include the following:
Ofloxacin, 400 mg IV every 12 hours (or levofloxacin, 500 mg IV every 24 hours), with
or without metronidazole
Ampicillin-sulbactam, 3 g IV every 6 hours, plus doxycycline, 100 mg PO or IV every 12
hours
These regimens can be switched to oral therapy when clinical improvement is apparent.

Oral and intramuscular treatments:
Oral or intramuscular treatments can be given to patients who do not appear very ill, are not
pregnant, do not have a tubo-ovarian abscess, can tolerate oral therapy, and for whom surgical
emergencies such as appendicitis is unlikely. Patients who do not improve despite 72 hours of
oral therapy should be admitted for parenteral therapy.
The recommended oral and IM regimens are as follows:
Ofloxacin, 400 mg PO once daily (or levofloxacin, 500 mg PO once daily), with or
without metronidazole, 500 mg PO twice daily, administered for 14 days
Ceftriaxone, 250 mg IM single dose, or cefoxitin, 2 g IM single dose, and probenecid, 1 g
PO administered concurrently or another third-generation cephalosporin administered
parenterally, plus doxycycline, 100 mg PO twice daily (with or without metronidazole,
500 mg PO twice daily), administered for 14 days.
Follow-up is necessary, especially for oral therapy. Clinical improvement should be apparent
in 72 hours. Some specialists have recommend rescreening for N. gonorrhoeae and C.
trachomatis 4 to 6 weeks after completion of therapy. Male sexual partners of women with PID
should be treated empirically, even if they are asymptomatic, with a regimen that covers both N.
gonorrhoeae and C. trachomatis to prevent reinfection.
Bacterial Vaginosis:
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Bacterial vaginosis (BV) is a clinical syndrome resulting from the replacement of normal
hydrogen peroxideproducing Lactobacillus in the vagina with high concentrations of anaerobic
bacteria, Gardnerella vaginalis, and Mycoplasma hominis. It does not appear to be a sexually
transmitted disease, although it has been associated with having multiple sex partners. However,
it is the most common cause of vaginal discharge or malodor and is commonly encountered in
the context of STDs. This syndrome will be summarized here.
The clinical diagnosis of BV requires three of the following four symptoms or signs: a
homogeneous, white, noninflammatory discharge that smoothly coats the vaginal walls; the
presence of clue cells on microscopic examination (clue cells are squamous epithelial cells
covered with many vaginal bacteria, giving the cells a stippled appearance); a vaginal fluid pH
higher than 4.5; and a fishy odor of vaginal discharge before or after the addition of 10% KOH
(positive whiff test).
A diagnosis can also be made based on Gram staining criteria. Scoring for the absence of large
gram-positive rods (Lactobacillus), and the presence of small gram-negative or variable rods
(Gardnerella) and curved gram-negative rods (Mobiluncus) provides evidence for BV.
Commercially available tests such as Affirm VP III (Becton-Dickinson, Sparks, Md), FemExam
test card (Cooper Surgical, Shelton, Conn), and QuickVue Advance (Quidel, San Diego, Calif)
can also be used.
Treatment
BV has been associated with endometritis, PID, and vaginal cuff cellulitis after invasive
procedures. It has also been associated with postabortion PID. Thus, treatment of BV is aimed at
relieving symptoms as well as preventing complications after invasive procedures.
Recommended regimens are as follows:
Metronidazole, 500 mg PO twice daily for 7 days, or
Metronidazole 0.75% cream, one full applicator (5 g) intravaginally once daily for 5
days, or
Clindamycin 2% cream, one full applicator (5 g) intravaginally at bedtime for 7 days
Alternative regimens are less efficacious and include the following:
Clindamycin, 300 mg PO twice daily for 7 days, or
Clindamycin ovules, 100 g intravaginally, once at bedtime for 3 days
BV occurring during pregnancy has been associated with adverse pregnancy outcomes,
including preterm labor, premature rupture of membranes, chorioamnionitis, preterm birth,
postpartum endometritis, and postcesarean wound infection. All symptomatic pregnant women
should be tested and treated for BV. It is also recommended that all asymptomatic pregnant
women at high risk for preterm delivery (i.e., those who have previously delivered a preterm
infant) be screened for BV during their first antenatal visit and be treated if positive. Currently,
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there is no recommendation to do the same for mothers at low risk. Intravaginal therapy is not
recommended for pregnant patients.
The regimens recommended for pregnant women are the following:
Metronidazole, 500 mg PO twice daily for 7 days, or
Metronidazole, 250 mg PO three times daily for 7 days, or
Clindamycin, 300 mg PO twice daily for 7 days
No teratogenic of mutagenic effects of metronidazole have been demonstrated despite concerns
about this possibility.
Follow-up visits are unnecessary if symptoms resolve, except in pregnant women who have
been treated for asymptomatic BV, for whom a 1-month follow-up is recommended. There has
been no benefit shown in treating sexual partners of patients with BV.
Trichomoniasis
Trichomoniasis is caused by the protozoan Trichomonas vaginalis. An estimated 3 million
American women contract trichomoniasis each year. They usually have a diffuse, malodorous,
sometimes frothy, yellow-green discharge with vulvar pruritis, but some women may have no
symptoms. On colposcopy, a strawberry cervix may be seen. In men, trichomoniasis may be
asymptomatic or may manifest as a nongonococcal urethritis.
Diagnosis of vaginal trichomoniasis is by microscopic examination of a wet mount, which is
60% to 70% sensitive. It is important to obtain a fresh specimen because the organism is
identified by its motility and hence must be viable when it arrives in the laboratory. Culture is a
more sensitive method.
Recommended treatment for trichomoniasis is metronidazole, 2 g PO in a single dose.
Alternatively, metronidazole, 500 mg twice daily for 7 days, is recommended.
Certain strains of Trichomonas have diminished susceptibility to metronidazole and respond to
higher doses of metronidazole. In case of treatment failure with either regimen, patients should
be re-treated with metronidazole, 500 mg twice daily for 7 days. If this fails, patients should be
treated with 2 g daily for 3 to 5 days. Tinidazole in a single dose of 2 g has recently been
approved for treatment of trichomoniasis.
Sexual partners of patients should be treated to avoid reinfection. Pregnant patients with
trichomoniasis should be treated if symptomatic with metronidazole, 2 g PO. Although
trichomoniasis has been associated with adverse pregnancy outcomes such as premature rupture
of membranes, preterm delivery, and low neonatal birth weight, data have not indicated that
treating asymptomatic patients reduces this risk.
Gonococcal Infections
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In the United States, nearly 340,000 new cases of gonococcal were reported to the CDC in
2005. Although gonococcal infection is a notifiable disease in the United States, it is estimated
that about 50% of these infections go unreported. N. gonorrhoeae, the causative agent of
gonorrhea, is a gram-negative diplococcus. In clinical specimens, a smear is considered positive
for gonorrhea when gram-negative diplococci with typical morphology are identified in or
closely associated with polymorphonuclear leukocytes. A smear is considered equivocal if the
organisms are not cell-associated or intracellular organisms do not have the typical morphology.
Gonococcal infections have a wide variety of clinical manifestations and can manifest as
asymptomatic or symptomatic local infections in men and women. It may also manifest as a
complicated local infection with systemic dissemination.
Local infections may manifest as urethritis, proctitis, pharyngitis, or cervicitis. Acute anterior
urethritis is the most common manifestation in men. Most men are symptomatic after infection.
It manifest after an incubation period of 1 to 14 days, usually 2 to 5 days, with purulent discharge
and dysuria. Varying degrees of meatal erythema and edema accompany the infection.
Untreated, the infection tends to resolve in most patients. Local complications include
epididymitis, prostatitis, and seminal vesiculitis. Periurethral abscess, urethral stricture, and
fistulas are rare in the era of antibiotic therapy.
Urogenital infection in women has a nonspecific presentation and includes increased vaginal
discharge, dysuria, intermenstrual bleeding, and menorrhagia. Many patients have purulent to
mucopurulent cervicitis on examination. Purulent exudates may occasionally be expressed from
the urethra, periurethral glands, or Bartholin's gland (duct).
Rectal infection is common in women with gonococcal cervicitis and infection is probably
from perineal contamination of infected cervical secretions. It is usually asymptomatic. Rectal
infection in MSM is caused by direct inoculation. Symptoms range from minimal anal pruritis,
mucopurulent discharge, or scant rectal bleeding to overt proctitis, with severe rectal pain and
tenesmus.
Orogenital sexual contact can result in pharyngeal infection. Most of these cases are
asymptomatic but may occasionally cause acute pharyngitis or tonsillitis associated with cervical
lymphadenopathy. Pharyngeal infection may also be a source of gonococcal urethritis in MSM.
Rarely, adults may present with conjunctivitis from autoinoculation.
Systemic Complications
Disseminated gonococcal infection (DGI) is the most common systemic complication of acute
gonorrhea. DGI manifests with fever accompanied by joint pain and skin lesions: arthritis-
dermatitis syndrome. Joint pain is polyarticular in more than 50% of cases, but monoarticular
arthritis in a young, sexually active person should have gonococcus (GC) in the differential. Joint
pain may be caused by arthralgias or tenosynovitis or possible by frank arthritis with effusion.
Joints involved are usually the wrists, metacarpophalangeal joints, ankles, or knees but any joint
may be involved. The classic skin lesion is a necrotic pustule on an erythematous base. The skin
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lesions, however, may manifest as macules, papules, pustules, petechiae, bullae, or ecchymoses.
They generally occur in the distal extremities and are sparse. Diagnosis is made by
demonstrating the presence of the organism from clinical specimens. The likelihood of recovery
of the organism is best from mucosal surfaces (e.g., urethra, pharynx, rectum) when this
syndrome is suspected. Other systemic complications are rare and include endocarditis and
meningitis.
Diagnosis
Culture and Gram staining of urethral, rectal, or pharyngeal swabs have been the methods
traditionally used for diagnosis. A Gram stain showing intracellular diplococci resembling
gonococci is highly specific and sensitive in the presence of urethral discharge. However, Gram
staining is not sensitive for screening asymptomatic patients. Newer tests include
nonamplification tests such as DNA probes or amplification tests such as PCR assay and
transcription-mediated amplification. These tests are highly sensitive and specific and can also
be used to screen patients for N. gonorrhoeae and Chlamydia from urine samples. However, they
should not be used to test for N. gonorrhoeae in pharyngeal or rectal specimens because of the
presence of commensal Neisseria, which can yield a false-positive result.
Treatment
N. gonorrhoeae was initially sensitive to penicillin, but the 1970s saw the emergence of
plasmid-mediated resistance to penicillin (penicillinase-producing N. gonorrhoeae [PPNG]).
Also, the emergence of chromosomally mediated resistant N. gonorrhoeae (CMRNG), resistant
to penicillin as well as tetracycline, emerged in the 1970s. In 2003, 16.4% of isolates were
penicillin resistant, tetracycline resistant, or both. Quinolones have been increasingly used for
oral therapy, but recently there have been reports of strains of increasing quinolone-resistant N.
gonorrhoeae (QRNG) from different states, especially in MSM. It was recommended that
patients who acquired gonorrhea in Asia, the Pacific Islands, Hawaii, or California not be treated
with a quinolone because of a high prevalence of resistance in these areas. With the emergence
of resistance in MSM, it is now recommended that quinolones not be used for the treatment of
MSM with gonorrhea.
Patients infected with N. gonorrhoeae are frequently coinfected with C. trachomatis. This has
led to the recommendation that patients with gonococcal infection be routinely treated with a
regimen effective for Chlamydia as well. Routine dual therapy without testing for Chlamydia is
cost-effective for patients in whom coinfection occurs more than 10% to 30% of the time.
Recommended treatment regimens for uncomplicated gonococcal infections of the cervix,
urethra, and rectum are as follows:
Ceftriaxone, 125 mg IM single dose, or
Cefixime, 400 mg PO single dose, or
Ciprofloxacin, 500 mg PO single dose, or
Ofloxacin, 400 mg PO single dose, or
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Levofloxacin, 250 mg PO single dose
In addition, treatment for C. trachomatis with azithromycin 1 g PO in a single dose, or
doxycycline 100 mg PO twice daily for 7 days, may be initiated. Note that cefixime is currently
not available in the United States after its manufacturer discontinued making the medication.
Alternative regimens include the following:
Spectinomycin, 2 g IM single dose, or
Other single-dose third-generation cephalosporins: ceftizoxime, 500 mg IM, cefoxitin,
2 g IM plus 1 g probenecid, cefotaxime, 500 mg IM
Other single-dose quinolones: gatifloxacin, 400 mg PO, norfloxacin, 800 mg PO, or
lomefloxacin, 400 mg PO
Azithromycin, 2 g PO single dose, has been shown to be effective but may have high
rates of gastrointestinal intolerance.
Uncomplicated gonococcal infections of the pharynx are more difficult to eradicate. The
following is recommended:
Ceftriaxone, 125 mg IM single dose, or
Ciprofloxacin, 500 mg PO single dose
In addition, treatment for C. trachomatis with azithromycin, 1 g PO in a single dose, or
doxycycline, 100 mg PO twice daily for 7 days, may be initiated.
Other Considerations
Persons who have persistent symptoms should be evaluated by culture and for antimicrobial
susceptibility. Persistent symptoms may be caused by untreated coinfection with Chlamydia or
other infections, such as trichomoniasis.
Patient should abstain from sexual activity for 7 days after therapy is started. All sex partners
within 60 days before onset of symptoms or diagnosis should be treated. If the last sexual
encounter was more than 60 days before the onset of symptoms or diagnosis, the patient's most
recent sex partner should be treated. Pregnant women should be treated with a cephalosporin or
spectinomycin; avoid quinolone.
For complicated infections, higher doses of antibiotics are recommended:
Gonococcal conjunctivitis: ceftriaxone, 1 g IM, single dose
Disseminated gonococcal infection: ceftriaxone, 1 g IV or IM every 24 hours. Alternative
treatment regimens for DGI include the following:
o Equivalent third-generation cephalosporin, or
o Ciprofloxacin, 400 mg IV every 12 hours (or equivalent quinolone), or
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o Spectinomycin, 2 g IM every 12 hours, until 24 to 48 hours of clinical
improvement
Therapy can then be completed with oral cefixime, 400 mg twice daily, ciprofloxacin 500 mg
twice daily, levofloxacin 500 mg daily, or ofloxacin, 400 mg twice daily, to complete at least 1
week of antimicrobial therapy.
Gonococcal meningitis or endocarditis, ceftriaxone, 1 to 2 g IV every 12 hours. Therapy
is continued for 10 to 14 days for meningitis and at least 4 weeks for endocarditis.
Chlamydia Infection
C. trachomatis infection of the genital tract, a reportable disease in the United States, has been
increasing in prevalence probably to the result of an actual increase in prevalence and also
increased screening and more sensitive tests. In 2004, there were approximately 930,000 cases
reported to the CDC. Underreporting is a major problem because most patients are
asymptomatic.
An estimated 2,800,000 Americans are infected each year. Genital infections caused by
Chlamydia are similar to those of N. gonorrhoeae in that similar syndromes develop: urethritis,
epididymitis, cervicitis, PID, and proctitis. However, the symptoms tend to be less abrupt in
onset and tend to be milder or asymptomatic. The incubation period for chlamydial infection is 1
to 3 weeks, longer than that of gonococcus. Some syndromes are discussed here.
Symptoms of urethritis include dysuria and a mild to moderate whitish to clear urethral
discharge. Because coinfection with gonococcus is common, patients may present after being
treated for gonococcal urethritis with a persistent discharge, although milder. Urethritis may be
asymptomatic, although even these patients will exhibit signs of ongoing inflammation
manifested by the presence of urethral leukocytes.
In male patients, chlamydial infection has also been implicated as a common pathogen in
epididymitis in sexually active young men. Non-LGV serotypes of Chlamydia may cause
proctitis. This organism has also been associated with nonbacterial prostatitis and Reiter's
syndrome: urethritis, conjunctivitis, arthritis, and skin lesions.
In female patients, chlamydia is frequently isolated from the cervix. Infection is often silent
and symptoms such as discharge, if present, are nonspecific. Findings on examination suggestive
of chlamydial infection include easily induced endocervical bleeding, mucopurulent endocervical
discharge, and edema within an area of ectopy. Mucopurulent discharge from the cervix may
have other causes, such as gonococcal cervicitis, endometritis, or PID.
In addition to cervicitis, female patients may also have an acute urethritis, bartholinitis, and
PID caused by Chlamydia. Fitz-HughCurtis syndrome, perihepatitis as a result of PID, although
once considered to be a complication of only gonococcal infection, has been shown to be more
often associated with Chlamydia.
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Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
Diagnosis
The preferred methods of diagnostic testing are molecular. Both DNA probes and
amplification assays are available, with the latter being more sensitive. Amplification assays
include PCR assay and transcription-mediated amplification. Using these assays may be
inhibited in clinical specimens, sometimes yielding a false-negative result. The ligase chain
reaction, another amplification assay that was once widely used, is no longer available. Other
diagnostic methods include culture, antigen tests (e.g., DFA), enzyme immunoassay (EIA), and
serologic assays. Culture needs special precautions during collection and cell culture systems
may not be available in many centers. Antigen assays are not very sensitive and serologic assays
are difficult to interpret because of the high prevalence of infection in the population and largely
asymptomatic infection in women.
Empirical therapy is started in symptomatic patients and often in contacts. However, where
possible, a confirmatory test should be done because it helps in tracing contacts and controlling
the epidemic.
Treatment
Recommended regimens include the following:
Azithromycin, 1 g PO single dose, or
Doxycycline, 100 mg PO twice daily for 7 days
Alternative regimens include the following:
Erythromycin base, 500 mg PO four times daily for 7 days, or
Erythromycin ethylsuccinate, 800 mg four times daily for 7 days, or
Ofloxacin 300, mg twice daily for 7 days, or
Levofloxacin, 500 mg PO daily for 7 days
It is recommended that a test for cure be done at 3 weeks for pregnant women when
amplification tests are used. This is not recommended in others unless there is a suspicion of
noncompliance. However, because of a high rate of reinfection caused by C. trachomatis in
patients who have received therapy, and because a second infection confers a higher risk for PID,
health care providers should consider rescreening all female patients who have received
treatment 3 to 4 months after completion of therapy.
Patients should abstain from sexual activity for 7 days after therapy is started. All sex partners
within 60 days before the onset of symptoms or diagnosis should be treated. If the last sexual
encounter was more than 60 days before the onset of symptoms or diagnosis, the patient's most
recent sex partner should be treated.
In pregnancy, doxycycline and quinolones are contraindicated. Thus, the recommended
regimens are as follows:
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Azithromycin, 1 g PO in a single dose, or
Amoxicillin, 500 mg three times daily for 7 days
Alternative regimens during pregnancy are erythromycin base or erythromycin ethylsuccinate
for 7 days or 14 days, depending on the dose.
Chlamydial infections and gonococcal infections are frequent in women but often
asymptomatic. Even asymptomatic infections can have serious long-term consequences, mainly
infertility and ectopic pregnancy. Hence, it is recommended that all sexually active adolescent
women and women aged 20 to 25 years be screened for chlamydial infection annually, even if
they are asymptomatic. Older women with risk factors (e.g., new sexual partner and those with
multiple sexual partners) should also be screened annually.
Urethritis
Urethritis is a syndrome characterized by urethral discharge of mucopurulent or purulent
material and sometimes by dysuria or urethral pruritis. Infected patients may also be
asymptomatic. It is a syndrome mainly found in men. The principal bacterial pathogens
implicated are N. gonorrhoeae and C. trachomatis. Gonococcal urethritis is diagnosed if
intracellular gram-negative diplococci with characteristic morphology are identified on urethral
smears. Otherwise, it is classified as nongonococcal urethritis (NGU). C. trachomatis is a
frequent cause (15%-55%) of NGU. The cause of most cases of nonchlamydial NGU is
unknown. Ureaplasma urealyticum and Mycoplasma hominis have been implicated in some
studies. However, detection of these organisms is often difficult and specific diagnostic tests for
these organisms are not indicated. T. vaginalis and HSV sometimes cause NGU, and diagnosis
should be pursued if these infections are suspected (e.g., nonresponse to therapy or history of
exposure).
Diagnosis
A diagnosis of urethritis is made if any of the following are present:
Mucopurulent or purulent discharge
Gram staining of urethral discharge demonstrating more than 5 white blood cells
(WBCs)/oil immersion field
This is the preferred method for rapid diagnostic testing because it is highly sensitive and
specific for documenting urethritis as well as the presence or absence of gonococcal infection.
Positive leukocyte esterase test on first-void urine or microscopic examination of first-
void urine demonstrating 10 WBCs or more per high-power field
If none of these conditions is met, treatment should be deferred and the patient should be
tested for N. gonorrhoeae and C. trachomatis and followed closely if results are negative.
Empirical treatment of symptoms without documentation is recommended only for patients at
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high risk for infection and who are unlikely to return for follow-up. Such patients should be
treated for both gonorrhea and chlamydia. Their partners should be also evaluated and treated.
Treatment
Treatment for gonococcal urethritis has been discussed earlier (see Gonococcal Infections).
For NGU, treatment should begin as soon as possible after diagnosis. Recommended regimens,
aimed at treating mainly C. trachomatis (but also effective against Mycoplasma and
Ureaplasma), include the following:
Azithromycin, 1 g PO in a single dose (this regimen has the advantage of compliance and
directly observed therapy), or
Doxycycline, 100 mg PO twice daily for 7 days
Alternative regimens include the following:
Erythromycin base, 500 mg PO four times daily for 7 days, or
Erythromycin ethylsuccinate, 800 mg PO four times daily for 7 days, or
Ofloxacin, 300 mg PO twice daily for 7 days, or
Levofloxacin, 500 mg PO once daily for 7 days
Patients should be instructed to abstain from sexual intercourse for 7 days after therapy is
initiated. They should be retested if symptoms persist or recur after completion of therapy. All
sex partners within the last 60 days should be evaluated.
For patients with objective signs of recurrent or persistent urethritis, patients should be
evaluated for noncompliance or re-exposure to an untreated sex partner. After this has been
excluded, patients should have a culture of an intraurethral swab as well as a first-void urine
specimen tested for T. vaginalis. Also, some cases of recurrent urethritis may be caused by
tetracycline-resistant U. urealyticum. Thus, the recommended regimen for these patients is
metronidazole, 2 g PO in a single dose, plus erythromycin base, 500 mg PO four times daily, or
erythromycin ethylsuccinate, 800 mg PO four times daily for 7 days.
Mucopurulent Cervicitis
Mucopurulent cervicitis (MPC) is characterized by purulent or mucopurulent endocervical
exudate visible in the endocervical canal or in an endocervical swab specimen. It is often
asymptomatic, but some patients may have an abnormal vaginal discharge or vaginal bleeding
after intercourse. MPC can be caused by N. gonorrhoeae or C. trachomatis, but in most cases
neither organism is isolated. This may be the result of nonmicrobiologic causes (e.g.,
inflammation of the zone of ectopy).
Patients with MPC should be tested for N. gonorrhoeae and C. trachomatis using sensitive and
specific tests and therapy should be based on these results. Empirical therapy may be given for
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patients in whom the likelihood of infection is high and who are unlikely to return for follow-up.
In patients with MPC, signs of PID should be sought because this may manifest as MPC.
Human Papilloma Virus
Human papilloma virus (HPV) infections of the genital tract can be asymptomatic or can
manifest as genital warts or as intraepithelial neoplasia or carcinoma of the vulva, cervix, penis,
or anus. About 1% of the sexually active population in the United States has genital warts. There
are more than 100 different types of HPV. Types 6 and 11 are the most common types associated
with genital warts. Intraepithelial neoplasia is most commonly associated with types 16, 18, 31,
32, and 34 (also called high-risk types). Types 6 and 11 also cause respiratory papillomatosis in
infants and children and it is believed that transmission occurs perinatally.
Genital Warts
These commonly manifest as flesh-colored, painless, cauliflower-like lesions (condyloma
acuminata), but may also manifest as smooth, dome-shaped papules (papular warts), flat crusty
papules resembling seborrheic keratosis (keratotic warts), or macular or slightly raised flat-
topped papules. They occur on the penis, scrotum, perianal area, vulva, or perineum. Less often,
they may appear on the crural folds, thighs, or pubic area. They may also appear on the vaginal
wall, on the cervix, or in the anus. Occasionally, patients report itching, burning, pain, or
bleeding. Perianal warts may appear, even in the absence of anal intercourse. Application of 5%
acetic acid to genital warts turns the lesion a whitish color, a property sometimes used to
differentiate a wart from other lesions.
Genital warts may resolve spontaneously,
grow in size or number, or remain the same.
Warts that have been present for less than 1 year
respond better to therapy. Treatment of genital
warts reduces viral DNA and probably reduces
infectivity. Response to therapy is variable and
recurrences can occur, usually in the first 3
months after therapy. Therapy is usually
undertaken to remove aesthetically unpleasant
lesions.
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
Treatment for External Genital Warts.
Therapy can be divided into patient-applied or provider-administered therapy. The choice of
therapy depends on the patient and provider. Generally, if there is no significant improvement
after three provider-administered therapies, or if warts have not completely cleared after six
treatments, the treatment modality should be changed. Hypo- or hyperpigmentation or scars can
occur at sites of treatment.
Patient-Applied Treatment.
Podofilox, 0.5% solution, should be applied with a cotton swab, and podofilox gel should be
applied with a finger to visible warts twice daily for 3 days, followed by 4 days of no therapy.
This cycle should be repeated for up to four cycles as necessary. No more than 0.5 mL/day
should be applied and the total wart area treated should not exceed 10 cm
2
.
The patient should apply imiquimod 5% cream once daily at bedtime three times a week for
up to 16 weeks. The treatment area should be washed with soap and water 6 to 10 hours after the
application.
Provider-Administered Treatment.
A small amount of podophyllin resin, 10% to 25%, in a compounded tincture of benzoin,
should be applied to each wart and allowed to dry. Because systemic absorption can lead to
complications such as bone marrow suppression and neuropathy, less than 0.5 mL of the resin
should be applied to a wart area smaller than 10 cm
2
per session. Some experts recommend
washing off the area 1 to 4 hours after application to reduce local irritation. The treatment can be
repeated weekly if necessary.
A small amount of trichloroacetic acid (TCA) or bicholoroacetic acid (BCA), 80% to 90%,
should be applied only to the warts and allowed to dry so that a white frosting develops. Excess
acid can be removed by applying powdered talc, sodium bicarbonate (baking soda), or liquid
soap to the area. The treatment may be repeated weekly if necessary. Some centers apply a
repellent such as petroleum jelly (Vaseline) to the skin area surrounding the warts before
applying podophyllin or TCA to prevent application to unaffected areas.
Cryotherapy using liquid nitrogen or cryoprobe and surgical removal by excision, curettage, or
electrosurgery are other recommended modalities. Alternative modalities include intralesional
interferon and laser surgery.
Treatment for Other Genital Warts.
For vaginal warts, recommended treatment includes cryotherapy or TCA or BCA. Urethral
meatus warts can be treated with cryotherapy or podophyllin resin. Anal warts can be treated
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
with cryotherapy, TCA or BCA, or surgical excision. For cervical warts, squamous
intraepithelial lesions should be excluded from treatment.
Cervical Cancer Screening
It is believed that cervical intraepithelial neoplasia is an early lesion in the continuum of
changes leading to cervical cancer after HPV infection. This concept has remained the principle
behind cervical cancer screening using the Papanicolaou (Pap) test, which has helped reduce the
incidence of cervical cancer in developed countries. Cervical cancer can occur in young, sexually
active women as well as in older women, and it is important to ensure that all women presenting
with STDs be screened for cervical cancer using the Pap test. It is recommended that women
who are sexually active be screened every year for cervical cancer, but can be screened less
frequently if three consecutive Pap tests show no abnormality. A thin-preparation medium is
widely available in developed countries that allows for Pap smear and HPV testing to be
performed on the same sample.
Results are reported as the presence or absence of a low- or high-risk HPV type. High-risk
HPV types (16, 18, 31, 32, 34) predict those women who are at greater risk of progressing to
high-grade SIL or cervical cancer. Patients with atypical squamous cells of undetermined
significance (ASCUS) or low-grade SIL who also have high-risk HPV types as determined by
the Pap smear should be referred for colposcopy.
Other Considerations
No evidence exists to suggest that the presence of genital warts (low-risk HPV types) or their
treatment is associated with the development of cervical cancer. Thus, HPV typing of patients
with genital warts is not recommended, nor is colposcopy or increased frequency of Pap smear
recommended.
Genital warts can proliferate and become friable during pregnancy and many experts advocate
their removal during pregnancy. Imiquimod, podofilox, or podophyllin should not be used during
pregnancy. Although HPV types 6 and 11, which can also cause genital warts, cause respiratory
papillomatosis, their transmission is not well understood. Cesarean section is not recommended
as a preventive measure in patients with genital warts. A Pap smear is recommended during
pregnancy.
The use of latex condoms has been associated with a lower rate of cervical cancer, an HPV-
associated disease. However, they are not effective in preventing the transmission of genital
warts, because condoms cannot cover all the affected skin.
In June 2006, the U.S. Food and Drug Administration approved a quadrivalent vaccine for
HPV. Two low-risk types that cause most genital warts, HPV 6 and 8, are targeted, as well as the
two high-risk types that cause 70% of U.S. cervical cancer cases, HPV types 16 and 18. The
vaccine is most effective when given before the initiation of sexual intercourse, so
recommendations are for girls and young women between the ages of 9 and 26. Approval will
TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV
eventually be sought for boys and young men because they can develop genital warts and penile
or anal cancer from HPV as well. The vaccine is generally well tolerated and is given as a series
of three vaccines at 0, 1, and 6 months. Several states have already recommended making HPV
vaccination mandatory for middle schoolaged girls.


Summary
STDs are still a major cause of morbidity in the United States and worldwide.
Pelvic inflammatory disease can lead to devastating long-term sequelae, even when
symptoms are mild. If PID is suspected, it should be treated.
Neisseria gonorrhoeae is becoming more quinolone resistant. Thus, quinolone should not
be used as first-line treatment for the MSM population, and all other populations should
be carefully monitored, because recommendations may change.
HPV vaccine is available for use in girls and young women aged 9 to 26 years. It is
highly effective in preventing genital warts and, most importantly, in preventing cervical
cancer.




TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV



TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV











TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV















TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV







TATOIU ALEXANDRA
Universitatea Ovidius Constanta
Facultatea de Medicina-Asistenta medicala generala
Anul I,grupa IV