Trichom vagin

Background
Trichomoniasis is a sexually transmitted infection (STI) caused by the motile parasitic protozoan
Trichomonas vaginalis. It is one of the most common STIs, both in the United States and worldwide. [1, 2]
The high prevalence of T vaginalis infection worldwide and the frequency of coinfection with other STIs
make trichomoniasis a compelling public health concern. Notably, research has shown that infection with
T vaginalis increases the risk of HIV transmission in both men and women. [1, 3] Trichomoniasis is also
associated with adverse pregnancy outcomes, infertility, postoperative infections, and cervical neoplasia.
[4]

Humans are the only known host of T vaginalis. Transmission occurs predominantly via sexual
intercourse. The organism is most commonly isolated from vaginal secretions in women and urethral
secretions in men. It has not been isolated from oral sites, and rectal prevalence appears to be low in men
who have sex with men.[5]
Women with trichomoniasis may be asymptomatic or may experience various symptoms, including a
frothy yellow-green vaginal discharge and vulvar irritation. Men with trichomoniasis may experience
nongonococcal urethritis but are frequently asymptomatic. [6]
Trichomoniasis is thought to be widely underdiagnosed due to a variety of factors, including a lack of
routine testing,[2] the low sensitivity of a commonly used diagnostic technique (wet mount microscopy), [6,
7, 8]
and nonspecific symptomatology. Self-diagnosis and self-treatment or diagnosis by practitioners
without adequate laboratory testing may also contribute to misdiagnosis.
Testing is recommended for T vaginalis in all women seeking care for vaginal discharge and screening for
T vaginalis in women at high risk of STI.[9]
Sex partners of infected women should also be treated. Both patient and partner should abstain from sex
until pharmacological treatment has been completed and they have no symptoms. Infected women who
are sexually active have a high rate of reinfection; thus, rescreening at 3 months post treatment should be
considered.[9] Currently, no data are available on rescreening men.
Oral metronidazole (Flagyl) remains the treatment of choice for trichomoniasis. In cases in which the
first-line agent is ineffective, other nitroimidazoles or high doses of metronidazole may be used. Topical
metronidazole and other antimicrobials are not efficacious and should not be used to treat trichomoniasis.
Pathophysiology
T vaginalis is approximately the size of a white blood cell (WBC)about 10-20 m long and 2-14 m
widethough its size may vary with physical conditions (see the image below). It has 4 flagella
projecting from the anterior portion of the cell and 1 flagellum extending backward to the middle of the
organism, forming an undulating membrane. An axostyle, a rigid structure, extends from the posterior
aspect of the organism.[10, 11]

Trichomonas vaginalis. (A) Two trophozoites of T vaginalis obtained

from in vitro culture, stained with Giemsa. (B) Trophozoite of T vaginalis in vaginal smear, stained with
Giemsa. Images courtesy of Centers for Disease Control and Prevention.
In women, T vaginalis is isolated from the vagina, cervix, urethra, bladder, and Bartholin and Skene
glands. In men, the organism is found in the anterior urethra, external genitalia, prostate, epididymis, and
semen (see the image below). It resides both in the lumen and on the mucosal surfaces of the urogenital
tract.[11] The flagella allow the trophozoite to move around vaginal and urethral tissues.

Life cycle of Trichomonas vaginalis. T vaginalis trophozoite resides in

female lower genital tract and in male urethra and prostate (1), where it replicates by binary fission (2).
The parasite does not appear to have a cyst form and does not survive well in the external environment. T
vaginalis is transmitted among humans, the only known host, primarily via sexual intercourse (3). Image
courtesy of Centers for Disease Control and Prevention.
During infection with T vaginalis, jerky motile trichomonads may be observed on wet mount microscopy.
T vaginalis destroys epithelial cells by direct cell contact and by release of cytotoxic substances. It also
binds to host plasma proteins, thereby preventing recognition by the alternative complement pathway and
by host proteinases.[1] During infection, the vaginal pH increases, as does the number of
polymorphonuclear leukocytes (PMNs). PMNs, a type of white blood cell, are the predominant host
defense mechanism. These cells respond to chemotactic substances released by trichomonads. There is
also evidence that lymphocyte priming occurs, as shown by the presence of antigen-specific peripheral
blood mononuclear cells.[11] An antibody response has been detected both locally and in serum. However,
infection produces an immunity that is only partially protective, at best.
Despite the interaction the human immune system has with T vaginalis, there is little evidence that a
healthy immune system prevents infection. One study showed no association between trichomoniasis and
the use of protease inhibitors or immune status in HIV-infected women. [12] Another study showed that HIV
seropositivity did not alter the rate of infection in males. [13]
Symptoms of trichomoniasis typically occur after an incubation period of 4-28 days. [11, 14] Infection may
persist for long periods in women but generally persists for fewer than 10 days in males. Anecdotal
evidence suggests that asymptomatic infection may persist for months or even years in women. [15]
Etiology
The risk of acquiring T vaginalis infection is based on the type of sexual activity. Women who engage in
higher-risk sexual activity are at a greater risk of infection. Risk factors for T vaginalis infection include:
New or multiple partners
A history of STIs
Current STIs
Sexual contact with an infected partner
Exchanging sex for money or drugs
Using injection drugs
Not using barrier contraception (eg, because of oral contraceptives)
In a study that considered risk factors for prevalent trichomoniasis, drug use in the preceding 30 days was
the one most strongly associated with infection and with incident infection (new infection observed
during the study).[16] The most significant risk factor was sexual activity in the preceding 30 days (with 1
or more partners). Women with 1 or more sexual partners in the preceding 30 days were 4 times more
likely to have T vaginalis infection.[16]
Epidemiology
United States statistics

Trichomoniasis is one of the most common STIs in the United States, with a prevalence estimated at 8
million cases annually.[17, 18, 19, 20] Exact numbers are difficult to obtain because the infection is not
nationally reportable and many infections are asymptomatic. Prevalence is also thought to be
underestimated due to the low sensitivity of diagnostic tests, particularly the commonly used wet mount
technique.
Research done among high-risk populations shows that the prevalence varies widely. The prevalence of T
vaginalis infection at STI clinics ranges from 15% to 54%. [21] The reported prevalence from a different
study done among inner-city STI clinics approached 25%. [11] In 2 samples of female prison inmates, the
prevalence was 31.2-46.9%.[22, 23] In men, trichomoniasis accounts for 10-21% of urethritis cases not
attributable to gonorrheal or chlamydial infection. [21] Multiple studies have found that T vaginalis
infection is less prevalent in men than in women. [24, 25, 26]
International statistics
Estimates of the worldwide prevalence of trichomoniasis range from 170-180 million cases annually. The
World Health Organization estimates the worldwide incidence of trichomonas infection at over 170
million cases annually.[27]
The incidence of trichomoniasis in Europe is similar to that in the United States. In Africa, the prevalence
of trichomoniasis may be much higher. The prevalence of vaginal T vaginalis infection was estimated to
be 11-25% among African study populations.[28, 29, 30]
Age-related demographics
Trichomoniasis is an STI. As such, it is typically found in sexually active adolescents and adults. In
female adolescents, trichomoniasis is more common than gonorrhea; this is particularly disconcerting in
that it increases susceptibility to other infections. [31]
Vertical transmission of T vaginalis during birth is possible and may persist up to 1 year. From 2-17% of
female offspring of infected women acquire infection. [32]
Unlike other STIs, trichomoniasis generally becomes more common with age and lifetime number of
sexual partners.[33] The National Longitudinal Study of Adolescent Health Study[34] found a prevalence of
2.3% among adolescents aged 18-24 years and 4% among adults 25 years and older. A prevalence of
3.1% in females aged 14-49 years was observed based on a nationally representative sample of women in
the National Health and Nutrition Examination Survey (NHANES) 2001-2004 study.[33]
In a study of men attending an STI clinic in Denver, the prevalence of trichomonal infection was 0.8% in
men younger than 30 years and 5.1% in men 30 years and older. The increase in prevalence was thought
to be due to age-related enlargement of the prostate gland. [24]
Sex-related demographics
Symptomatic trichomoniasis is more common in women than in men. Trichomoniasis infection in men
tends to be less clinically apparent. However, women can also frequently be asymptomatic carriers. The
NHANES 2001-2004 study conducted on a nationally representative sample of women aged 14-49 years
found that 85% of women found to have trichomoniasis reported no symptoms. [33]
The reported incidence of trichomoniasis among men in various populations has ranged from 2.8-17%. [24,
25]
This incidence may be underestimated, depending on the method of detection and the site of specimen
collection. The use of multiple sites in the genitourinary tract (urine, urethral swab, and semen) in male
patients has been shown to increase sensitivity.[35]
In one study, T vaginalis was detected in 72% of male sexual partners of women with trichomoniasis. [36]
Of these, 77% patients were asymptomatic.
Race-related demographics
In the National Longitudinal Study of Adolescent Health Study, significant differences in the prevalence
of trichomoniasis among adolescents were noted by race: white, 1.2%; Asian, 1.8%; Latino, 2.1%; Native
American, 4.1%; and African American, 6.9%. [34] Considerable differences were also observed in the
national NHANES 2001-2004 study conducted among women ages 14-49: non-Hispanic whites, 1.2%;
Mexican Americans, 1.5%; and non-Hispanic blacks, 13.5%. [33]
Evidence suggests that T vaginalis infection likely increases HIV transmission. Thus, the observed higher
prevalence of T vaginalis infection among African American women is cause for great concern. Control

of T vaginalis may represent an important means of slowing HIV transmission, particularly among
African Americans.[37]
Prognosis
Recommended metronidazole therapy regimens have produced a 90-95% cure rate in randomized clinical
trials.[9] The recommended tinidazole regimens have produced cure rates of 86-100%. [9] Cure rates may be
even higher with concurrent treatment of a patients sexual partners.
Recurrent infections are common in sexually active patients. One study found that 17% of sexually active
patients with T vaginalis infection were reinfected at 3-month follow-up. [38]
T vaginalis infection is strongly associated with the presence of other STIs, including gonorrhea,[39]
chlamydia, and sexually transmitted viruses. T vaginalis infection increases the susceptibility to other
viruses, including herpes, human papillomavirus (HPV), and HIV.[31] Persons with trichomoniasis are
twice as likely to develop HIV infection as the general population. [29] There are 2 explanations for the
association between T vaginalis and HIV, as follows:
Disruption of the epithelial monolayer leads to increased passage of the HIV virus
T vaginalis induces immune activation, specifically lymphocyte activation and replication and
cytokine production, leading to increased viral replication in HIV-infected cells
Pregnant women with T vaginalis infection are more likely than uninfected women to deliver preterm or
to have other adverse pregnancy outcomes, including low birth weight, premature rupture of membranes,
and intrauterine infection.[1] Respiratory or genital infection in the newborn may also occur.[6] T vaginalis
infection may also increase the vertical transmission of HIV due to a disruption of the vaginal mucosa.
One study reported a higher risk of pelvic inflammatory disease (PID) in women with trichomoniasis.[40]
Other studies have reported a 1.9-fold risk of tubal infertility in women with trichomoniasis. [41]
Trichomoniasis may also play a role in cervical neoplasia and postoperative infections. [4]
Patient Education
Education concerning STI treatment and prevention is vital (see Prevention). Because T vaginalis
infection is strongly associated with the presence of other STIs (gonorrhea,[39] chlamydia, and sexually
transmitted viruses such as HIV), providers should provide appropriate counseling, testing, and treatment.
Upon diagnosis of trichomoniasis, healthcare providers should discuss treatment, including the adverse
effects and interactions encountered with metronidazole and other nitroimidazole drugs, and should
address the treatment of sexual partners. Persons with trichomoniasis who notify partners of their
infection help disrupt the transmission of trichomoniasis and other STIs. [6] Providers should also discuss
methods of preventing T vaginalis reinfection. It may be important to explain that the infection may have
been longstanding and not due to a recent sexual encounter. Lastly, the US Centers for Disease Control
and Prevention (CDC) advises providers to consider rescreening sexually active women at 3 months after
the completion of treatment.[9]
History
Trichomoniasis is typically found in sexually active patients. Transmission occurs predominantly via
sexual intercourse. The organism is most commonly isolated from vaginal secretions in women and
urethral secretions in men. It has not been isolated from oral sites, and rectal prevalence appears to be low
in men who have sex with men.[5] While it is possible to contract trichomoniasis without engaging in
sexual intercourse, it is less common. In the NHANES 2001-2004 study conducted among females aged
14-49 years, 1% of women with trichomoniasis had no history of sexual intercourse. [33]
Nearly half of infected females and nearly all infected males are asymptomatic. [14, 42] One third of
asymptomatic women become symptomatic within 6 months. [14]
Women
Trichomoniasis symptoms in women range from none to severe pelvic inflammatory disease (PID).
Women with trichomoniasis frequently report an abnormal vaginal discharge, which may be purulent,
frothy, or bloody. Frothy vaginal discharge, which is thought to be the classic presentation of
trichomoniasis, may be observed in only 12% of patients with this infection.
Women with trichomoniasis also commonly report abnormal vaginal odor (often described as musty);
vulvovaginal itching, burning, or soreness; dyspareunia (pain during sexual intercourse), which is often

the major complaint; and dysuria (pain during urination). [11, 43] Patients may also complain of postcoital
bleeding and lower abdominal pain.
Cervicitis due to trichomoniasis is characterized by 2 major signs: purulent discharge in the endocervical
canal and easily induced endocervical bleeding. [6] However, it may also be asymptomatic.
T vaginalis infection is one of the top 3 causes of vaginitis. [6] Vaginitis is usually characterized by vaginal
discharge, which may be accompanied by vulvar itching, irritation, and odor. The two other most common
causes of vaginal discharge are anaerobic bacterial overgrowth of normal flora and candidiasis (infection
with Candida albicans).[6]
Men
Men with trichomoniasis may be divided into the following 3 groups on the basis of their symptoms [14] :
Asymptomatic carrier state (comprising the majority of patients)
Mild symptomatic disease
Acute trichomoniasis
Trichomoniasis symptoms in men range from none to urethritis complicated by prostatitis.
Nongonococcal nonchlamydial urethritis is the most common symptom reported by men with
trichomoniasis. Symptoms of urethritis include discharge (purulent to mucoid in character), dysuria, and
urethral pruritus.[6] Some patients report pain in the urethra, testicular pain, or lower abdominal pain.
Most symptomatic infections are intermittent and self-limiting.
Physical Examination
Women
Vaginal discharge is found in 42% of infected women.[11] The discharge is classically described as thin and
frothy; however, this is only seen in about 10% of patients. [11] The discharge is often yellow and
sometimes is thick enough to be confused with that seen in candidiasis. Abnormal vaginal odor was found
in 50% of infected women, and edema or erythema was found in 22-37%. [11] Vaginal pH is often elevated
(>4.5).[44]
Colpitis macularis, or strawberry cervix, describes a diffuse or patchy macular erythematous lesion of the
cervix. This is a specific sign for trichomoniasis but is visible in only 1-2% of cases without the aid of
colposcopy; with colposcopy, colpitis macularis is detected in up to 45% of cases. [39] Together, colpitis
macularis and frothy vaginal discharge have a specificity of 99%; individually, they have positive
predictive values of 90% and 62%, respectively.
Lower-abdominal tenderness may be present; however, this is described in fewer than 10% of patients. If
this occurs, coexisting salpingitis or an intra-abdominal pathology is possible.
Coexisting Neisseria gonorrhoeae infection, candidiasis, and bacterial vaginosis are common and may
produce a mixed clinical picture.
Most of the symptoms described above are not specific for trichomoniasis and can occur in other vaginal
or cervical infections. In one study, the clinicians ability to accurately diagnose Tvaginalis infection on
the basis of physical findings alone had a positive predictive value of only 47%. [45] Relying on physical
examination findings alone misses the diagnosis of most patients with trichomoniasis. Definitive
diagnosis requires appropriate laboratory testing.
Men
Most men with trichomoniasis have no physical findings. Infrequently, infected men have abnormal
penile discharge. However, the discharge usually is only scant and thin. Trichomoniasis in men may be
associated with local inflammatory states, including balanitis and balanoposthitis. Physical findings of
epididymitis and prostatitis may also occur.
Children
In female newborns, T vaginalis acquired during birth may cause vaginal discharge during the first week
of life. Respiratory infection of the newborn is also possible. [9] An infected infant may present with fever.
Prepubertal children with trichomoniasis may present with symptoms similar to those seen in the
adolescent and adult patient. T vaginalis infection in prepubertal children is suggestive of sexual abuse.
Complications

In women, vaginitis is the most common manifestation of infection. Other complications include infection
of the adnexa, endometrium, and Skene and Bartholin glands. Pelvic inflammatory disease and tuboovarian abscess may also occur.
Research has shown that infection with T vaginalis increases the risk of HIV transmission in both men
and women.[1, 3] It is estimated that in women alone, 747 new HIV cases per year are a result of the
facilitative effects of T vaginalis on the transmission of HIV.[46] Overall, persons with trichomoniasis are
twice as likely to develop HIV infection as the general population. [29] Treatment of trichomoniasis has
been shown to decrease the rate of viral shedding in HIV patients. [3, 47]
In addition to HIV, T vaginalis infection also increases the susceptibility to other viruses, including herpes
and human papillomavirus (HPV). T vaginalis may increase the rate of infection or reactivation of HPV,
although it may shorten the duration of infection.[48]
An association with cervical intraepithelial neoplasia has also been demonstrated. [49] Trichomoniasis has
also been associated with postoperative infections.
An increased risk of posthysterectomy infection, including cuff cellulitis, cuff abscess, and wound
infection, has been documented.[50] Rare cases of trichomonal peritonitis have been reported. [51]
In pregnant women, T vaginalis infection has been associated with an increased risk of low birth weight,
preterm delivery, and intrauterine infection.[1, 52] Systemic immune response has been demonstrated in
pregnant women infected with T vaginalis; a significant increase in granulocyte-macrophage colonystimulating factor (GM-CSF) and C-reactive protein (CRP) was noted. [43]
Neonatal trichomoniasis has been described. [53] Respiratory or genital infection in the newborn may also
occur.[6]
In men, when symptoms occur, T vaginalis infection usually manifests as urethritis. As many as 11% of
nongonococcal urethritis cases in men are caused by T vaginalis.[54] Complications of untreated
trichomoniasis in men include prostatitis, epididymitis, urethral stricture disease, and infertility,
potentially resulting from decreased sperm motility and viability.[4, 55] Symptomatic men with comorbid T
vaginalis and HIV infections have been found to have significantly higher numbers of HIV RNA particles
in their seminal fluid.[3]
GO
Practice Essentials
Gonorrhea is a purulent infection of the mucous membrane surfaces caused by Neisseria gonorrhoeae. N
gonorrhoeae is spread by sexual contact or through transmission during childbirth. The Centers for
Disease Control (CDC) recommends that all patients with gonorrheal infection also be treated for
presumed co-infection with Chlamydia trachomatis.[1]
Signs and symptoms
History
In women, the major genitourinary symptoms of gonorrhea include the following:
Vaginal discharge : The most common presenting symptom of gonorrhea, vaginal discharge from
endocervicitis is usually described as thin, purulent, and mildly odorous; however, many patients
have minimal or no symptoms from gonococcal cervicitis
Dysuria
Intermenstrual bleeding
Dyspareunia (painful intercourse)
Mild lower abdominal pain
If the infection progresses to pelvic inflammatory disease (PID), symptoms may include the following:
Lower abdominal pain: Most consistent symptom of PID
Increased vaginal discharge or mucopurulent urethral discharge
Dysuria: Usually without urgency or frequency
Cervical motion tenderness
Adnexal tenderness (usually bilateral) or adnexal mass

Intermenstrual bleeding
Fever, chills, nausea, and vomiting (less common)
In males, the major genitourinary symptoms of gonorrhea include the following:
Urethritis: The major manifestation of gonococcal infection in men; initial characteristics include
burning upon urination and a serous discharge; a few days later, the discharge usually becomes
more profuse, purulent, and, at times, tinged with blood
Acute epididymitis: Usually unilateral and often occurs in conjunction with a urethral exudate
Urethral strictures: Have become uncommon in the antibiotic era, but they can present with a
decreased and abnormal urine stream, as well as with the secondary complications of prostatitis
and cystitis
Rectal infection: May present with pain, pruritus, discharge, or tenesmus
In males and females, the classic presentation of disseminated gonococcal infection (DGI) is an arthritisdermatitis syndrome. Joint or tendon pain is the most common presenting complaint in the early stage of
infection. The second stage of DGI is characterized by septic arthritis. The knee is the most common site
of purulent gonococcal arthritis.
In neonates, in whom bilateral conjunctivitis (ophthalmia neonatorum) often follows vaginal delivery
from an untreated mother with a gonococcal infection, symptoms of gonococcal conjunctivitis include the
following:
Eye pain
Redness
Purulent discharge
Physical examination
Look for the following genitourinary symptoms during physical examination in females:
Mucopurulent or purulent vaginal, urethral, or cervical discharge
Vaginal bleeding; vulvovaginitis in children
Cervical friability - Tendency to bleed upon manipulation
Cervical motion tenderness during bimanual pelvic examination
Fullness and/or tenderness of the adnexa, unilateral or bilateral (eg, ovaries, fallopian tubes)
Lower abdominal pain/tenderness, with or without rebound tenderness
Possible low back pain - More common in progression to PID
Upper right abdominal tenderness (with perihepatitis)
Look for the following genitourinary symptoms during physical examination in males:
Mucopurulent or purulent urethral discharge: Obtained by milking the urethra along the shaft of
the penis
Possible epididymitis: Unilateral epididymal tenderness and edema, with or without penile
discharge or dysuria
Penile edema without other overt inflammatory signs
Urethral stricture: Uncommon; more often seen in the preantibiotic era with urethral irrigation
using caustic liquids
See Clinical Presentation for more detail.
Diagnosis
Culture is the most common diagnostic test for gonorrhea, followed by the deoxyribonucleic acid (DNA)
probe and then the polymerase chain reaction (PCR) assay and ligand chain reaction (LCR). The DNA
probe is an antigen detection test that uses a probe to detect gonorrhea DNA in specimens.
Specific culture of a swab from the site of infection is a criterion standard for diagnosis at all potential
sites of gonococcal infection. Cultures are particularly useful when the clinical diagnosis is unclear, when
a failure of treatment has occurred, when contact tracing is problematic, and when legal questions arise.
In patients who may have DGI, all possible mucosal sites should be cultured (eg, pharynx, cervix, urethra,
rectum), as should blood and synovial fluid (in cases of septic arthritis). Three sets of blood cultures
should also be obtained.

See Workup for more detail.

Management
For uncomplicated urogenital, anorectal, and pharyngeal gonococcal infection, a drug regimen using
ceftriaxone plus either azithromycin or doxycycline may be used. Antimicrobial drugs used alone or in
various combinations in other gonococcal infections include the following:
Gonococcal arthritis: Ceftriaxone
Gonococcal conjunctivitis: Ceftriaxone
Gonorrhea contributing to PID: Cefoxitin, ceftriaxone, doxycycline, metronidazole, cefotetan,
clindamycin, gentamicin
Gonococcal epididymitis: Ceftriaxone, doxycycline
DGI: Ceftriaxone, cefotaxime, ceftizoxime
Gonococcal meningitis and endocarditis: Ceftriaxone
See Treatment and Medication for more detail.
Image library

This patient presented with gonococcal urethritis, which became

systemically disseminated, leading to gonococcal conjunctivitis of the right eye. Courtesy of the CDC/Joe
Miller, VD.
Background
Gonorrhea, an important public health problem and the second most common notifiable disease in the
United States, is a purulent infection of mucous membrane surfaces caused by the gram-negative
diplococcus Neisseria gonorrhoeae. Although gonorrhea (known colloquially as the clap and the drip) is
most frequently spread during sexual contact, it can also be transmitted from the mother's genital tract to
the newborn during birth, causing ophthalmia neonatorum and systemic neonatal infection. (See
Etiology.)
In women, the cervix is the most common site of gonorrhea, resulting in endocervicitis and urethritis,
which can be complicated by pelvic inflammatory disease (PID). In men, gonorrhea causes anterior
urethritis. Gonorrhea can also spread throughout the body to cause localized and disseminated disease.
Complications also include ectopic pregnancy and increased susceptibility to human immunodeficiency
virus (HIV) infection. Most commonly, the term gonorrhea refers to urethritis and/or cervicitis in a
sexually active person. (See Pathophysiology, Prognosis, Presentation, and Workup.)
Gonococcal infections following sexual and perinatal transmission are a major source of morbidity
worldwide. In the developed world, where prophylaxis for neonatal eye infection is standard, the vast
majority of infections follow genitourinary mucosal exposure. (See Pathophysiology, Etiology, and
Prognosis, and Treatment.]
In the pediatric population, the importance of gonorrhea is 3-fold, as follows:
As a common and preventable sexually transmitted disease (STD) in the sexually active teenage
population
As a perinatal infection at childbirth
As a forensic aid in investigating sexual abuse
Gonococcemia
Gonococcemia is defined as the presence of N gonorrhoeae in the bloodstream, which can lead to the
development of disseminated gonococcal infection (DGI). Gonococcemia occurs in about 0.5-3% of
patients with gonorrhea (see the image below). (See Pathophysiology and Prognosis.)

This patient presented with gonococcal urethritis, which became

systemically disseminated, leading to gonococcal conjunctivitis of the right eye. Courtesy of the CDC/Joe
Miller, VD.
The clinical manifestations of this process are biphasic, with an early bacteremic phase consisting of
tenosynovitis, arthralgias,[2] and dermatitis, followed by a localized phase consisting of localized septic
arthritis. Other potentially severe clinical complications include osteomyelitis, meningitis, endocarditis,
adult respiratory distress syndrome (ARDS),[3, 4] and fatal septic shock.[5] Polymyositis is also a rare
complication of gonococcemia. (See Pathophysiology, Prognosis, and Presentation.)
Patients who are pregnant or menstruating may be particularly prone to gonococcemia. Other populations
at risk of infection include women and individuals with complement deficiencies, HIV disease, or
systemic lupus erythematosus (SLE). DGI is an important, potentially life-threatening, and easily
treatable clinical entity that remains the most common cause of acute septic arthritis in young, sexually
active adults.
Pathophysiology
The pathophysiology of N gonorrhoeae and the relative virulence of different subtypes depend on the
antigenic characteristics of the respective surface proteins. Certain subtypes are able to evade serum
immune responses and are more likely to lead to disseminated (systemic) infection.
Well-characterized plasmids commonly carry antibiotic-resistance genes, most notably penicillinase.
Plasmid and nonplasmid genes are transmitted freely between different subtypes. The ensuing exchange
of surface protein genes results in high host susceptibility to reinfection. The exchange of antibiotic
resistance genes has led to extremely high levels of resistance to beta-lactam antibiotics. Fluoroquinolone
resistance has also been documented on multiple continents and in widespread populations within the
United States.[6]
Infection of the lower genital tract, the most common clinical presentation, primarily manifests as male
urethritis and female endocervicitis. Infection of the pharynx, rectum, and female urethra occur frequently
but are more likely to be asymptomatic or minimally symptomatic. Retrograde spread of the organisms
occurs in as many as 20% of women with cervicitis, often resulting in pelvic inflammatory disease (PID),
with salpingitis, endometritis, and/or tubo-ovarian abscess. Retrograde spread can lead to frank abdominal
peritonitis and to a perihepatitis known as Fitz-Hugh-Curtis syndrome.
Long-term sequelae of PID, such as tubal factor infertility, ectopic pregnancy, and chronic pain, may
occur in up to 25% of affected patients. Epididymitis or epididymo-orchitis may occur in men after
gonococcal urethritis. Lower genital infection is a risk factor for the presence of other sexually
transmitted diseases (STDs), including human immunodeficiency virus (HIV).
Conjunctivitis can occur in adults, as well as children, following direct inoculation of organisms (usually
as a result of hand-eye inoculation in adults) and can lead to blindness.
Disseminated gonococcal infection
Disseminated gonococcal infection (DGI) occurs following approximately 1% of genital infections.
Patients with DGI may present with symptoms of rash, fever, arthralgias, migratory polyarthritis, septic
arthritis, tendonitis, tenosynovitis, endocarditis, or meningitis.
N gonorrhoeae organisms spread from a primary site, such as the endocervix, the urethra, the pharynx, or
the rectum, and disseminate to the blood to infect other end organs. Usually, multiple sites, such as the
skin and the joints, are infected. Neisserial organisms disseminate to the blood due to a variety of
predisposing factors, such as host physiologic changes, virulence factors of the organism itself, and
failures of the host's immune defenses.[7]

For example, changes in the vaginal pH that occur during menses and pregnancy and the puerperium
period make the vaginal environment more suitable for the growth of the organism and provide increased
access to the bloodstream. (Three fourths of the cases of DGI occur in women; susceptibility is increased
if the primary mucosal infection occurs during menstruation or pregnancy.) [8, 9]
Defects in the host's immune defenses are also involved in the pathophysiology, with certain patients
more likely to develop bacteremia. Specifically, patients with deficiency in terminal complement
components are less able to combat infection, as complement plays an important role in the killing of
neisserial organisms. As many as 13% of patients with DGI have a complement deficiency.
A study of 22 patients with DGI revealed that total serum complement activity was greater than 25%
below the normal mean. Other causes of immunocompromise (eg, HIV, SLE) also predispose to
dissemination of infection.
In addition, certain strains of gonorrhea causing asymptomatic genital infections are seen in association
with DGI.[10]
Etiology
N gonorrhoeae is a gram-negative, intracellular, aerobic diplococcus; more specifically, it is a form of
diplococcus known as the gonococcus. N gonorrhoeae is spread by sexual contact or through vertical
transmission during childbirth. It mainly affects the hosts columnar or cuboidal epithelium. Virtually any
mucous membrane can be infected by this microorganism. The physiologic ectopy of the
squamocolumnar junction onto the ectocervix in the adolescent female is one factor that causes particular
susceptibility to this infection.
Many factors influence the manner in which gonococci mediate their virulence and pathogenicity. Pili
help in attachment of gonococci to mucosal surfaces and contribute to resistance by preventing ingestion
and destruction by neutrophils. Opacity-associated (Opa) proteins increase adherence between gonococci
and phagocytes, promote invasion into host cells, and possibly down-regulate the immune response.
Porin channels (porA, porB) in the outer membrane play key roles in virulence. Gonococcal strains with
porA may have inherent resistance to normal human serum and an increased ability to invade epithelial
cells, explaining their association with bacteremia.
Certain acquired plasmids and genetic mutations enhance virulence. TEM-1type beta-lactamase
(penicillinase) affects penicillin binding and efflux pumps and confers resistance to penicillin. [11, 12] TetM
protects the ribosome and confers resistance to tetracycline. Alterations in gyrA and parC genes result in
fluoroquinolone resistance by efflux activation and decreased antibiotic cell permeation. [11]
Gonococci attach to the host mucosal cell (pili and Opa proteins play major roles) and, within 24-48
hours, penetrate through and between cells into the subepithelial space. A typical host response is
characterized by invasion with neutrophils, followed by epithelial sloughing, formation of submucosal
microabscesses, and purulent discharge. If left untreated, macrophage and lymphocyte infiltration
replaces the neutrophils. Some gonococcal strains cause an asymptomatic infection, leading to an
asymptomatic carrier state in persons of either sex.
The ability to grow anaerobically allows gonococci, when mixed with refluxed menstrual blood or
attached to sperm, to secondarily invade lower genital structures (vagina and cervix) and progress to
upper genital organs (endometrium, salpinx, ovaries).
Gonococcal infection usually follows mucosal inoculation during vaginal, anal, or oral sexual contact or
perinatally.
Sexually transmitted infection
Gonococcal infection usually follows mucosal inoculation during vaginal, anal, or oral sexual contact. It
also may be caused by inoculation of mucosa by contaminated fingers or other objects. Transmission
through penile-rectal contact is fairly efficient.
The risk of transmission of N gonorrhoeae from an infected woman to the urethra of her male partner is
approximately 20% per episode of vaginal intercourse and rises to 60-80% after 4 or more exposures. In
contrast, the risk of male-to-female transmission approximates 50-70% per contact, with little evidence of
increased risk with more sexual exposures.

Persons who have unprotected intercourse with new partners frequently enough to sustain the infection in
a community are defined as core transmitters.
Neonatal and pediatric gonococcal infection
Neonatal gonococcal infection may follow conjunctival infection, which is obtained during passage
through the birth canal. In addition, direct infection may occur through the scalp at the sites of fetal
monitoring electrodes.
In children, infection may occur from sexual abuse by an infected individual or possibly nonsexual
contact in the child's household or in institutional settings.
Autoinoculation
Autoinoculation can occur when a person touches an infected site (genital organ) and contacts skin or
mucosa.
Risk factors
Risk factors for gonorrhea include the following:
Sexual exposure to an infected partner without barrier protection (eg, failure to use a condom or
condom failure)[13]
Multiple sex partners
Male homosexuality
Low socioeconomic status
Minority status - Blacks, Hispanics, and Native Americans have the highest rates in the United
States
History of concurrent or past STDs
Exchange of sex for drugs or money
Use of crack cocaine
Early age of onset of sexual activity
Pelvic inflammatory disease (PID) - Use of an intrauterine device (IUD)
Epidemiology
Occurrence in the United States
An estimated 700,000 new gonococcal infections occur annually in the United States, with less than half
being reported.[14, 15, 16] In 2009, 301,174 cases of gonorrhea were reported to the US Centers for Disease
Control and Prevention (CDC).[17, 18, 19, 16] The national average in 2009 was 99.1 cases per 100,000
population, a 10.5% decrease from 2008, with considerable state-to-state variation (see the figure below).
[18, 16]
Some experts estimate the annual cost of gonorrhea and its complications to be $1.1 billion.

Gonorrhea rates, United States, 1941-2009. Centers for Disease Control

and Prevention.
In the United States, the number of gonococcal infections peaked in the 1970s, the era of the sexual
revolution. With the onset of the HIV epidemic and the practicing of safe sex techniques, the incidence
dramatically decreased from 468 cases per 100,000 population in 1975 to 100-150 cases per 100,000
population at the turn of the century. The incidence of disseminated gonococcal infection (DGI) naturally
parallels the incidence of gonococcal infection. [20]
Within the United States, carriage rates highly depend on the geographic area, the racial and ethnic group,
and sexual preferences. The rate of gonorrhea is much higher in African Americans than in other racial
groups[21] and is much higher in the rural southeastern United States and in inner cities, presumably
because of an association with socioeconomic and behavioral factors, as well as with social networks.
Rates of infection range from about 246.4 cases per 100,000 population in Mississippi to 8 cases per
100,000 population in Vermont. The CDC began a campaign (Healthy People 2010:
http://www.cdc.gov/nchs/healthy_people.htm) that targeted an incidence rate of 19 cases per 100,000

population. According to 2009 data from the CDC, the only states with incidences below that target were
Utah, Montana, Idaho, Wyoming, Maine, Vermont, and New Hampshire, along with Puerto Rico (see the
image below).[18, 16] Healthy People 2020 is in the process of being developed
(http://healthypeople.gov/2020/default.aspx).

Rates of gonococcal infection per 100,000 by state and outlying regions

(2009). Data from the Centers for Disease Control and Prevention (CDC):
In children who have been sexually abused, rates of recovery of gonorrhea range from 1% to 30%. In
female adolescents who are sexually active, asymptomatic carriage of gonorrhea occurs in 1-5%.
The incidence of antibiotic-resistant strains of N gonorrhoeae has been rising since the late 1940s. Of
greatest concern is the rise in the percentage of cases due to penicillinase-producing N gonorrhoeae.
International occurrence
An estimated 200 million new cases of gonorrhea occur annually. In 1999, the number of new cases of
gonococcal infection diagnosed in North America was 1.56 million; in Western Europe, 1.11 million; in
South and Southeast Asia, 27.2 million; and in Latin America and the Caribbean, 7.27 million.
Gonorrhea was the most common STD worldwide for at least most of the 20th century, although since the
mid-1970s, public health initiatives in the industrialized world have resulted in declining incidence of the
disease. As noted earlier, however, gonococcal infection is still the second most common notifiable
disease in the United States, and Western European rates approximate those in the United States. [22, 23, 24]
Although the frequency data are unknown in most developing nations, these countries are considered to
have the highest rates of gonorrhea and its complications. Gonococcal infection rates in pregnant women
in the Central African Republic and South Africa were found to be 3.1% and 7.8%, respectively.
The incidence of antibiotic-resistant strains has been rising since the late 1940s. Of greatest concern
historically has been the high percentage of cases due to penicillinase-producing N gonorrhoeae.
However, fluoroquinolone resistance has increased rapidly over the past decade on most continents and
within the United States. The CDC reported fluoroquinolone resistance in 6.8% of 2004 isolates, 9.4% of
2005 isolates, and 13.3% of 2006 isolates.[6]
Race-related demographics
All sexually active populations are at risk for gonococcal infection, and the level of risk rises with the
number of sexual partners and the presence of other STDs.
Although race has no intrinsic effect on susceptibility to gonorrhea, the frequency of gonorrhea in the
United States is increased among urban dwellers, individuals of lower socioeconomic status, and
minorities of any population. This may be due to decreased access to diagnosis and treatment; lack of
adequate care (ie, education, diagnosis, and treatment), leading to increased transmission rates; and/or
reflection bias due to data collection site preference (eg, urban emergency departments [EDs] and STD
clinics), as well as true differences in prevalence.
Overall, the African Americantowhite ratio of gonococcal infections declined from 23:1 in 2002 to 18:1
in 2006. Infection rates have been trending downward since 1998. However, between 2005 and 2006, the
CDC noted a 6.3% increase in the rate of gonococcal infections in African Americans. Subsequently, rates
have begun to downtrend once again. (See the figure below.)

Gonorrhea rates by race/ethnicity, United States, 2000-2009. Centers

for Disease Control and Prevention.

Similarly, in other ethnic groups, rates increased from 2002 to 2006, including by 22.8% in American
Indian/Alaskan Natives, by 17.7% in whites, and by 11.8% in Hispanics. On the other hand, the rate
decreased by 1.4% in Asian/Pacific Islanders.
Sex-related demographics
The male-to-female ratio for gonorrhea is approximately 1:1.2; however, females may be asymptomatic,
whereas males are rarely asymptomatic. Women younger than 25 years are at the highest risk for
gonococcal infection.
Men who have sex with men are much more likely to acquire and carry gonorrhea and have far higher
rates of antibiotic-resistant bacteria.
Serious sequelae are much more common in women, in whom pelvic inflammatory disease (PID) may
lead to ectopic pregnancy or infertility and in whom DGI is more likely, owing to menstruation,
pregnancy, and a higher incidence in occult infection.
Age-related demographics
The highest incidence of gonococcal infection in the United States is among persons aged 15-24 years. [18,
16]
This is likely due to the following (see the figure below):
Increased numbers of sexual partners
Decreased access to or use of health care
Physiologic ectopy of the squamocolumnar junction in females

Decreased use of barrier contraceptives

Gonorrhea rates by age
and sex, United States, 2009. Centers for Disease Control and Prevention.
Infection in children is a marker for child sexual abuse and should be reported as such, although a 2007
review provided some support for nonsexual transmission between children and for transmission from
adults to children related to poor hand hygiene.[25, 26]
Gonococcemia remains an important disease in the adolescent and young adult population, with a peak
incidence in males aged 20-24 years and in females aged 15-19 years.
Prognosis
With adequate early therapy, complete cure and return to normal function are the rule. Most gonococcal
infections respond quickly to cephalosporin therapy. Late, delayed, or inappropriate therapy may lead to
significant morbidity or, on rare occasions, death.
Complications in males
Urethral strictures secondary to gonococcal infection in men are less common than previously thought.
Some strictures in the preantibiotic era likely resulted from treatment by urethral irrigation using caustic
compounds rather than from the gonorrhea itself.
Other complications, such as penile lymphangitis, periurethral abscess, acute prostatitis, seminal
vesiculitis, and infection of the Tyson and Cowper glands, are now rare.
Complications in females
Tubal scarring and infertility are the major complications of gonococcal infection in females. The
incidence of involuntary infertility is estimated at 15% after one attack of pelvic inflammatory disease
(PID) and approximately 50%-80% after 3 attacks. (However, infertility may be more common after
chlamydial PID than after gonococcal PID, presumably because the more acute inflammatory signs
associated with gonorrhea prompt women to seek diagnosis and treatment sooner.)
Failure to diagnose PID can result in acute morbidity, including tuboovarian abscess, endometritis, FitzHugh-Curtis syndrome (perihepatitis), and other chronic sequelae. Perihepatitis secondary to gonorrhea
presents as right upper quadrant pain and nausea.
The incidence of ectopic pregnancy is increased from 7-fold to 10-fold in women with previous
salpingitis, with resultant increased fetal and maternal mortality rates.

Gonococcal infections in women may also manifest as gonococcal urethritis or infection of periurethral
(Skene) or Bartholin glands.
Pelvic inflammatory disease
PID is generally the most feared complication of gonococcal infection, because it is one of the leading
causes of female infertility and often leads to hospitalization. This can be devastating to any woman,
especially an adolescent who potentially has many years of childbearing ahead of her. In a 2011 study,
female adolescents with PID were more likely than older women to have a rapid recurrence of PID or to
become pregnant despite reporting more consistent condom use. [27]
Tubo-ovarian abscess and, rarely, tubal perforation with peritonitis and death, can occur, especially if the
tubo-ovarian abscess was recurrent. Females with recurrent PID have high rates of ectopic pregnancy and
infertility.
Epididymitis and orchitis
Epididymitis and orchitis occur infrequently in males who go untreated. These conditions usually respond
well to the same antibiotics used for uncomplicated urethritis, but the drugs are administered for a longer
course.
Arthritis
Gonorrhea is the most common cause of arthritis in the adolescent. However, arthritis (septic or reactive)
is a rare complication of this disease.
Because it mimics septic arthritis, excluding the possibility of gonococcal infection in any adolescent with
acute onset of pyogenic arthritis is important. Adequate diagnosis may require culturing extraarticular
sites for N gonorrhoeae.
Additional complications
Complications of gonococcal infections also include the following [28] :
Corneal scarring after ocular gonococcal infections
Destruction of cardiac valves in gonococcal endocarditis
Death from congestive heart failure related to endocarditis
Central nervous system (CNS) complications of gonococcal meningitis
It has been suggested that a person with a gonococcal infection may be at a 3- to 5-fold increased risk of
acquiring HIV infection, if exposed to the virus.
DGI is an acute illness that causes fever, asymmetrical polyarthralgias, and skin pustules overlying small
joints in patients with gonorrhea. Disseminated infection may also lead to meningitis or endocarditis.
In newborns, vertical transmission can cause conjunctivitis, known as ophthalmia neonatorum, and
permanent damage and blindness, if untreated.
Oral sex with an infected partner can result in pharyngitis, and, similarly, anal infection can arise from
anal sex or local spread from a vaginal source.
Patient Education
Discuss safe sexual practices with all individuals in whom gonorrhea is suspected. Proper education to
prevent gonorrhea may be more effective than simplistic instructions to avoid sex, especially in the
teenaged population. Teenagers involved with abstinence-only campaigns have unchanged STD rates and
disproportionately acquire anal and oral infections, rather than vaginal infections (the perception being
that if an activity is not vaginal sex, it is not sex). Stress that oral or anal sex can also transmit disease.
Patients should know the method of disease transmission and the adverse impact of recurrent infections
on future fertility, they should be counseled about the risks of complications following gonococcal
infection and the risk of other STDs, and they should always be instructed to refer any sex partners for
prompt evaluation and treatment.
In addition, these individuals should be aware that they should avoid sexual contact until medication is
finished and until their partners are fully evaluated and treated. Thereafter, they should avoid unprotected
contact.
The discussion of responsible sexual behavior should not be limited or withheld because of personal
religious or moral views, because these may not be shared by the patient, and teenagers are notorious for
sexual experimentation; evidence suggests that offering only limited discussion does the teenage

population a huge disservice. This advice is especially pertinent in states where sexual education is almost
nonexistent in the school system because of abstinence-only teaching, which is misleading and factually
inaccurate.
In one study in Peru, a bundle of interventions that included extensive public health efforts, including
training of local medical personnel, specific and presumptive treatment, outreach to female sex workers,
and supply of barrier contraception, may have been effective at reducing the prevalence of several STDs,
although the effect did not reach statistical significance overall.
The effects were more greatly pronounced (and significant) among female sex workers and young adult
women. The study was hampered by several methodologic limitations, such as comparing different cities
as controls, which made drawing conclusions from the data difficult. [29]
Abstinence education
Although the most effective STD prevention is abstinence from sex, this is oftentimes an unrealistic
expectation, especially in the teenaged population. In fact, 88% of teenagers who pledged abstinence in
middle and high school still engaged in premarital sex. Moreover, they tend to have riskier, unprotected
sex because of their lack of education. Those who pledge before having sex have been found to have a
33% higher prevalence rate of STDs than have those who had sex and then retrospectively pledged, with
nonpledgers falling in between. This is despite a lower number of partners and an older age at first
intercourse in pledgers.
Moreover, pledgers are less likely to be aware of their STD status and are less likely to seek testing, even
if their STD rates are similar overall (again, highlighting a lack of appropriate sexual education).
Of course, abstinence should be explained to be the best option, but a more practical expectation is
abstinence from sex with someone known or suspected of having an STD until treatment is obtained and
completed. In light of the difficulty of knowing a potential partner's sexual history (or honesty), strongly
recommend the use of condoms as a reasonable alternative to abstinence. [13]
Risks of unprotected sex
Patients should also be counseled about the additional risks of unprotected sex, including the acquisition
of more serious or lifelong infections such as herpes, hepatitis B, and HIV, and, of course, about the risks
of pregnancy. The emotional aspect of sexual relationships may also need to be addressed, especially in
teenage girls. Teenagers are vulnerable in that they are sexually mature but not yet emotionally mature.
For patient education information, see the Sexual Health Center, as well as Sexually Transmitted
Diseases, Gonorrhea, and Chlamydia.
Patient education materials are also available at The Centers for Disease Control and Prevention (CDC)
Website (Sexually Transmitted Diseases Gonorrhea) and from many local public health departments.