1. GONORRHEA: CAUSATIVE AGENT, MODES OF TRANSMISSION, CLINICAL SYMPTOMS, COMPLICATIONS, DIAGNOSIS.
2. CHLAMYDIOSIS, TRICHOMONIASIS, GENITAL HERPES.
3. TERTIARY AND CONGENITAL SYPHILIS.
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.
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.
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.
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).
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, 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),[and fatal septic shock.Polymyositis is also a rare complication of gonococcemia. 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.
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.
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 (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.
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.)
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.
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 host’s 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.
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.
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 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 can occur when a person touches an infected site (genital organ) and contacts skin or mucosa.
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)
Multiple sex partners
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)
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.
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.
n Incubation 2-7 days
n Abrupt onset of severe dysuria
n Purulent urethral discharge
n Most urethral infections symptomatic
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, Fitz-Hugh-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.
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.
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 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.
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.
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.
The incubation period for gonorrhea is usually 2-7 days after exposure to an infected partner. In all patients who present with a possible STD, the history should include the following:
· Past history of STDs (including HIV infection and viral hepatitis)
· Treatment history for known STDs
· Known symptoms of STDs in current or past sexual partners
· Type of contraception used
· Any history of sexual assault
In women, the history should also include the date of the last menstrual period and the details of parity, including any history of ectopic pregnancies.
The most common site of gonococcal infection in women is the endocervix (80%-90%), followed by the urethra (80%), rectum (40%), and pharynx (10%-20%). If symptoms develop, they often manifest within 10 days of infection.
Major symptoms include vaginal discharge, dysuria, intermenstrual bleeding, dyspareunia (painful intercourse), and mild lower abdominal pain.
When gonococcal cervicitis is either asymptomatic or unrecognized, the patient may progress to PID, often in proximity to a menstrual period. PID may also be asymptomatic or silent and occurs in 10-20% of infected women.
Symptoms of PID 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)
Acute perihepatitis (Fitz-Hugh-Curtis syndrome) occurs primarily through direct extension of N gonorrhoeae or Chlamydia trachomatis from the fallopian tube to the liver capsule and overlying peritoneum.
Vaginal discharge from endocervicitis is the most common presenting symptom of gonorrhea and is usually described as thin, purulent, and mildly odorous. Many patients have minimal or no symptoms from gonococcal cervicitis. Dysuria or a scant urethral discharge may be due to urethritis accompanying cervicitis.
Pelvic or lower abdominal pain suggests ascending infection of the endometrium, fallopian tubes, ovaries, and peritoneum. Pain may be midline, unilateral, or bilateral. Fever, nausea, and vomiting may be present. The possibility of ectopic pregnancy should always be considered in patients with pelvic or lower abdominal pain.
Right upper quadrant pain from perihepatitis (Fitz-Hugh-Curtis syndrome) may occur following the spread of organisms upward along peritoneal planes.
Rectal infection is often asymptomatic, but rectal pain, pruritus, tenesmus, and rectal discharge may be present if the rectal mucosa is infected. Bloody diarrhea may also occur. Rectal infection may occur from anal intercourse or, in women, by local spread of the organism.
In men, urethritis is the major manifestation of gonococcal infection. Initial characteristics include burning upon urination and a serous discharge. A few days later, the discharge usually becomes more profuse, purulent, and, at times, blood-tinged.
Acute epididymitis may also be caused by N gonorrhoeae or C trachomatis, especially in men younger than 35 years. This is usually unilateral and often occurs in conjunction with a urethral exudate. The classic presentation of epididymitis is of unilateral pain and swelling localized posteriorly within the scrotum.
Urethral strictures due to gonococcal infection are now 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.
Another manifestation of gonorrhea, rectal infection, may present with pain, pruritus, discharge, or tenesmus.
Men and women may exhibit gonococcal infection of the pharynx, rectum, and eye. Gonococcal pharyngitis is most commonly acquired during orogenital contact, with fellatio predisposing to infection more so than cunnilingus. Pharyngitis is often asymptomatic; however, it may present as exudative pharyngitis with cervical lymphadenopathy.
Although rectal cultures are positive for gonorrhea in up to 40% of women with cervical gonorrhea (a similar percentage noted in infected homosexual men), symptoms of proctitis are unusual.
Eye involvement in adults occurs by autoinoculation of gonococci into the conjunctival sac from a primary site of infection, such as the genitals, and is usually unilateral. The most common form of presentation is a purulent conjunctivitis, which may rapidly progress to panophthalmitis and loss of the eye unless promptly treated.
In neonates, bilateral conjunctivitis (ophthalmia neonatorum) often follows vaginal delivery from an untreated, infected mother. However, transmission to the newborn can also occur in utero or in the postpartum period.
Symptoms of gonococcal conjunctivitis include eye pain, redness, and a purulent discharge. Neonates may also acquire pharyngeal, respiratory, or rectal infection or disseminated gonococcal infection (DGI).
The organism can cause permanent injury to the eye very quickly. Prompt recognition and treatment are essential to avoid blindness. Blindness due to neonatal gonococcal infection is a serious problem in developing countries but is now uncommon in the United States and in other countries where neonatal conjunctival prophylaxis with antimicrobial therapy is routine. Nevertheless, infants of mothers with untreated infections, poor prenatal care, and unmonitored births continue to be at risk.
Direct infection with N gonorrhoeae in neonates may also occur through the scalp at the sites of fetal monitoring electrodes.
The symptoms of DGI vary greatly from patient to patient. By the time the symptoms of DGI appear, many patients no longer have any localized symptoms of mucosal infection.
The classic presentation of DGI is an arthritis dermatitis syndrome. Joint or tendon pain is the most common presenting complaint in the early stage of infection. About 25% of patients with DGI complain of pain in a single joint, but many other patients describe migratory polyarthralgia, especially of the knees, elbows, and more distal joints. Patients may also have tenosynovitis; the early tenosynovitis most commonly affects the flexor tendon sheaths of the wrist or the Achilles tendon ("lovers' heels").
Skin rash is a presenting complaint in approximately 25% of patients, but a careful examination will reveal a rash in most patients with DGI. The rash is usually found below the neck and may also involve the palms and soles.
The dermatitis consists of lesions varying from maculopapular to pustular, often with a hemorrhagic component. Lesions usually number 5-40, are peripherally located, and may be painful before they are visible. Fever is common but rarely exceeds 39°C.
The second stage of DGI is characterized by septic arthritis, by which time the skin lesions have disappeared and blood culture results are nearly always negative. The knee is the most common site of purulent gonococcal arthritis.
Rare complications of DGI include gonococcal meningitis, pericarditis, and endocarditis. Headache, neck pain and stiffness, fever, and decreased sensorium may indicate gonococcal meningitis. This disease may be clinically indistinguishable from meningococcal meningitis on presentation, although the course of gonococcal meningitis is usually less rapid.
Gonococcal endocarditis is more common in men than in women. Patients with collagen vascular disease (especially those with systemic lupus erythematosus) may also be more prone to this complication. The aortic valve is affected most commonly. A subacute onset of fever, chills, sweats, and malaise may indicate the presence of gonococcal endocarditis. Patients with endocarditis may develop atypical chest pain, cough, and dyspnea and may also develop the arthralgias and rash typical of DGI. Gonococcal endocarditis can cause severe valvular damage and death if not recognized and treated rapidly.
N gonorrhoeae infection may be recognized by the typical signs and symptoms of the disease, but it is important to remember that, by the time disseminated or upper reproductive tract disease is present, the primary site of mucosal infection may be normal in appearance, and the patient may have no localized signs or symptoms.
With oropharyngeal infection, pharyngitis (usually mild) may be occur. With rectal infection, mucopurulent or purulent discharge may be present.
The physical examination should also always include scrutiny for signs of herpes simplex, syphilis, chancroid, lymphogranuloma venereum, and genital warts.
In neonates, look for purulent discharge from the eyes or other infected sites. The discharge from the eyes is usually bilateral in ophthalmia neonatorum, while in older patients, the condition most often is unilateral when secondary to self-inoculation.
Also examine neonates for temperature instability (fever, hypothermia), which can result from disseminated sepsis
Look for the following 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 pelvic inflammatory disease (PID)
· Upper right abdominal tenderness (with perihepatitis)
Rectal symptoms of gonorrhea include the following:
· Mucopurulent or purulent discharge with or without rectal bleeding
· Mucopurulent exudate and inflammatory in the rectal mucosa
· Rectal abscess (less common)
Ocular and periocular manifestations of gonorrhea include the following:
When evaluating a female patient with suspected gonococcal infection, also consider bacterial vaginosis, vaginitis, ectopic pregnancy, pregnancy, tubo-ovarian abscess, endometriosis, and mucopurulent cervicitis. In men, consider epididymitis, orchitis, and testicular torsion.
Other conditions that should be considered include the following:
Reactive arthritis is a human leukocyte antigen B27 (HLA-B27)–associated condition that predominantly occurs in young men and has the clinical triad of urethritis, conjunctivitis, and arthritis. However, the distribution of the arthritis is different, occurring predominantly in the joints of the axial skeleton. The clinical picture is less acute, occurring over the course of weeks rather than days and with less severe fever. This syndrome does not respond to antibiotic therapy, and it does not have the associated dermatitis that occurs in gonococcemia.
Nongonococcal septic arthritis
Nongonococcal septic arthritis can be caused by a variety of organisms, but it presents with an acute onset of joint swelling and pain. Culture of joint fluid commonly reveals organisms. This type of arthritis is a destructive form of arthritis that is usually monoarticular. It most frequently occurs in children and elderly persons. Immediate treatment with antibiotics is indicated.
Rheumatic fever is a rare illness in the modern era and can present with high fever, rash, arthritis, and endocarditis. This condition follows a streptococcal infection and requires long, emergent intravenous (IV) antibiotic therapy for endocarditis; it also responds well to anti-inflammatory medications.
Syphilis, an STD that commonly occurs in sexually active young adults, can also produce a rash, symptoms of arthritis, and genital lesions. However, genital involvement is usually in the form of an ulcer and not urethritis, and the rash can involve the palms and the soles. Laboratory tests, including rapid plasma reagin (RPR) titers, can aid in distinguishing syphilis from gonococcemia.
Other conditions to consider in a patient with arthritis and skin lesions include the following:
Systemic lupus erythematosus (SLE)
Tenosynovitis (eg, de Quervain disease, infectious)
Other seronegative arthritides - Eg, ankylosing spondylitis, Sweet syndrome, and related dermal vasculitides
Other conditions to consider in the differential diagnosis of N gonorrhoeae infection include the following:
Cutaneous manifestations of hepatitis C
Laboratory diagnosis of gonococcal infection depends on identification of N gonorrhoeae at an infected site. No available serologic test is sufficiently sensitive and specific to merit use for screening or diagnostic purposes.
1. 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.
Always obtain a pregnancy test for women of childbearing age who present with gonorrhea or any other sexually transmitted diseases (STD).
The diagnosis of DGI should be based on clinical findings and confirmed with laboratory investigations if possible
Perform a culture or nonculture detection test for N gonorrhoeae on endocervical, urethral, pharyngeal, or rectal discharge. Because organisms are intracellular, attempt to obtain specimens in a manner that will contain mucosal cells and not merely discharge (similar to a Papanicolaou smear).
Nonculture tests are less accurate in the presence of blood or during menses. Use culture instead at these times.
Culture is performed on Thayer-Martin plates that must be stored refrigerated but warmed to room temperature before obtaining a sample. The plate is then incubated in a carbon dioxide atmosphere. Poor technique drastically reduces test sensitivity.
Medicolegal cases (eg, child abuse, rape) require culture due to the possibility of false-positive results with nonculture methods. However, performing the more sensitive PCR assay-based tests to raise the likelihood of detecting an infection and then following up with culture to produce admissible evidence is appropriate.
Patients with gonococcemia may have an elevated white blood cell (WBC) count, in the range of 10,000-15,000/µL.
The erythrocyte sedimentation rate (ESR) is usually mildly elevated, with values from 20-50 in most patients. Less than 50% of patients have an ESR of higher than 50.
These tests include latex agglutination, ELISA, immunoprecipitation, and complement fixation tests. Because of their lower sensitivity and specificity, especially in populations with a low prevalence of disease, these tests are not routinely used for diagnosis, but they can be used as adjuncts to the other laboratory tests and may help in making the diagnosis.
Because of the potential severity of pericarditis and endocarditis, a cardiologic examination, including echocardiography, is recommended, even though these conditions are rare.
When DGI is suspected, blood and joint effusions should be sent for Gram stain and culture, although negative Gram stain results and sterile cultures do not rule out disseminated disease. Cerebrospinal fluid should be stained and cultured if signs or symptoms of meningitis are present.
Gram stains, cultures, and/or nucleic acid amplification tests (NAATs) of genital, rectal, conjunctival, and pharyngeal secretions should also be obtained when DGI is suspected, even if the patient has no localized symptoms at any of those sites.
The highest yield of N gonorrhoeae organisms in gonococcemia is from mucosal sites, including the pharynx, urethra, cervix, or rectum. Urethral and cervical cultures are typically the most revealing. Blood cultures yield positive culture results in 10-30% of patients and joint fluid in 20-30% of patients. Skin lesions yield organisms in only about 10% of patients. Immunofluorescence studies may improve the effectiveness in skin and joint fluid. Gram stain of material from unroofed skin lesions may show typical organisms.
Other tests that may be indicated are those for concurrent STDs. For example, the Preventive Services Task Force recommends that women at increased risk of gonorrhea also be screened for chlamydia, HIV, and syphilis.
Patients in whom gonococcal disease is suspected should be evaluated for syphilis infection, as well as for infection with C trachomatis (high rate of asymptomatic carriage), HIV (with counseling), hepatitis B virus, herpes simplex virus, and any STDs that are suggested by the history and physical examination findings. Administer hepatitis B vaccination to these individuals unless they have received the full vaccine series.
Rapid HIV test technology makes testing in the emergency department (ED) and referral more practical than enzyme-linked immunosorbent assay (ELISA). The need for additional testing depends on the situation; they are often performed as a battery of tests in suspected rape and child abuse cases.
HIV testing in cases of rape or new-onset abuse does not acutely diagnose a new infection but does establish a baseline status of the patient such that subsequent seroconversion might be linked back to the event in question.
The presence of typical gram-negative intracellular diplococci after Gram stain establishes a diagnosis of gonorrhea. If these organisms are not observed, the patient is said to have nongonococcal urethritis. Results are considered equivocal if typical morphotypes not associated with neutrophils are present or if cell-associated, but morphologically atypical, organisms are observed. A simple Gram stain is probably the method of choice for the detection of gonorrhea in symptomatic males because it is much less expensive and much more rapid than the Gen-Probe method.
In men, urethritis can be diagnosed using either of 2 methods of Gram staining. The first is via a urine sample. Preferably, examine the patient at least 2 hours after micturition or before his first morning void. The patient should provide a first-morning void, with the first 10-15mL of the urine being saved. The urine is centrifuged so that the sediment may be analyzed microscopically under high power or oil immersion. The presence of 10 or more polymorphonuclear leukocytes (PMNs) seen under high power suggests urethritis.
The second method is a Gram stain of urethral exudate. The presence of 4 or more PMNs per oil-immersion field is diagnostic for urethritis. In symptomatic males, Gram staining of urethral exudate yields a sensitivity of 90-98% and a specificity of 95-98%. However, in asymptomatic males, the sensitivity of the Gram stain is only 60%. Therefore, culture studies are recommended if an asymptomatic gonococcal infection is suggested.
In women with positive cervical culture results, the Gram stain results from the endocervix are 50-60% sensitive and 82-97% specific. In addition, the presence of more than 10 PMNs per high-power field on an endocervical smear is consistent with cervicitis. In women who lack a cervix because of hysterectomy, use urethral culture to make the diagnosis.
Gram stain is a rapid and inexpensive test available in many emergency departments (EDs). The positive predictive value is high for urethral infection, but a negative Gram stain does not rule out infection in asymptomatic men. Collect specimens from the urethra, endocervix, pharynx, rectum, conjunctiva, urine, or blood.
A Gram stain of urethral or cervical discharge may show gram-negative intracellular diplococci (diagnostic in the male) and PMNs. This is very useful if the physician has easy access to a microscope, because the diagnosis may be made without waiting for culture results.
The sensitivity and specificity of the Gram stain are lower for endocervical and rectal specimens. Gram stains from these sites are not recommended for routine use in the ED. In addition, Gram staining is not useful for the diagnosis of pharyngeal infection, because the oropharynx may be colonized by other Neisseria species that can lead to false-positive results.
Specific culture of a swab from the site of infection is a criterion standard for diagnosis at all potential sites of 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. However, empiric treatment is often necessary in patients being diagnosed through culture, because culture results are not available for 24-48 hours.
A small percentage (approximately 5%) of isolated gram-negative diplococci from genital, rectal, and pharyngeal cultures are actually Neisseria meningitidis, which can cause clinical disease that is identical to gonococcal infections of the urethra, cervix, or rectum. Hence, speciation from samples from pharyngeal and rectal sites should be standard, while samples from genital sites are recommended.
Antimicrobial susceptibility testing is generally unnecessary except in cases of resistance surveillance testing or cases of disseminated infection.
N gonorrhoeae is a fastidious organism that requires a moist carbon dioxide-rich atmosphere and must be grown on enriched media, usually chocolate agar containing lysed blood.
A single culture on most selective media yields a sensitivity of 95% or more for urethral specimens from men with symptomatic urethritis. A sensitivity rate of about 80-90% is found for endocervical infections in women. For maximized yield in cervical specimens, simultaneous inoculation on selective and nonselective media is recommended. Culture may take several days to weeks.
Although the urethra is commonly infected in women with gonorrhea, culturing urethral specimens does not materially increase the diagnostic yield except in women who lack a cervix because of hysterectomy.
Patients with possible disseminated gonococcal infection (DGI) should have culture samples taken from all possible mucosal sites (ie, pharynx, urethra, cervix, rectum) and from blood and synovial fluid. Rectal and pharyngeal specimens are inoculated onto selective medium only.
When collecting specimens in males, any discharge present at the meatus can be easily recovered for examination. If no discharge is present at the meatus, urethral material must be recovered by inserting and rotating a small swab 2-3 cm into the urethra. A calcium alginate or Rayon swab on a metal shaft is recommended.
When collecting specimens in women, the exocervix is first wiped of exudate. A swab is then placed into the external os and rotated for several seconds. However, take care to avoid contact with vaginal mucosa or secretions, as vaginal fluids are inadequate.
Chocolate agar in a carbon dioxide–enriched environment is the best medium. Blood agar, MacConkey medium, and phenylethyl alcohol with 5% sheep blood also are good media.
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. Specimens from any mucosal site should be inoculated immediately in selective media for gonorrheal organisms, such as modified Thayer-Martin, or on chocolate agar at room temperature, which should be incubated in an enriched carbon dioxide environment. The growth of typical oxidase-positive colonies that consist of gram-negative diplococci strongly suggests gonorrhea.
Samples from normally sterile sites (eg, blood, cerebrospinal fluid [CSF], synovial fluid) should be plated on nonselective and broth mediums. On the other hand, rectal and pharyngeal specimens, locations where commensal Neisseria may be present, should be inoculated onto selective medium only.
Synovial fluid aspirations in patients with septic arthritis usually yield greater than 50,000 leukocytes/µL, while synovial fluid culture is variably positive. Blood cultures, at this point, are often negative.
Gram stain and culture of vesicular or pustular skin lesions were found to have a diagnostic yield of less than 5%. Immunofluorescent techniques may be used to achieve better results.
Chest radiography may show hemidiaphragm elevation in Fitz-Hugh-Curtis syndrome. Joint plain films to evaluate septic joints are often unrevealing but may help to rule out fracture or other disease processes.
Ultrasonography may be indicated in women to investigate suspected pelvic inflammatory disease (PID) and to visualize the appendix and ovaries as other possible causes of the symptoms. Pelvic ultrasonography or computed tomography (CT) scanning may demonstrate thick, dilated fallopian tubes or abscess formation.
PID is uncommon in pregnancy when the cervical mucus plug may provide some protection to the upper tract. Ultrasonography should be used to rule out ectopic pregnancy whenever a pregnant patient has signs and symptoms of possible PID.
Abdominal imaging may give indications of peri-hepatic adhesions or abdominal loculated fluid collections or help to exclude other diagnoses.
NAATs amplify genetic sequences (DNA or ribonucleic acid [RNA]) from a few copies to millions in a short period of time. One of the key benefits of NAATs is that a wide variety of specimen types may be sampled, including swabs from the endocervix, vagina, urethra (men), and urine (men and women). Variations of this process include ligase chain reaction tests and strand displacement amplification.
These tests are very sensitive; they are also more rapid than culture, more specific than immunoassays, and do not require viable organisms. However, they are expensive, and results must be interpreted carefully because of false-positive results in certain settings.
NAATs may be of particular use when examination and mucosal swab are difficult (in children or extremely apprehensive patients) and urine specimens are more easily obtained. However, although these tests can be used on eye secretions, their performance is less well validated. In addition, NAATs are not all recommended for rectal and pharyngeal specimens at this time.
Clinicians should be familiar with specimen collection guidelines and performance parameters of the test available at their own hospitals.
NAATs of genital, rectal, conjunctival, and pharyngeal secretions should also be obtained when disseminated gonococcal infection (DGI) is suspected, even if the patient has no localized symptoms at any of those sites.
Pharyngeal gonococcal infections can occur in heterosexual men diagnosed with urethritis. Screening for pharyngeal colonization by N gonorrhoeae and C trachomatis using validated NAATs has been recommended for heterosexual men diagnosed with urethritis.
PCR and ligand chain reaction (LCR) are gene amplification techniques that markedly increase the sensitivity of specimen testing. Both techniques amplify the genetic fingerprint of specimens with very few organisms present in order to more easily detect and identify the organisms.
These methods have a high sensitivity and a high specificity (78.6% and 96.4%, respectively). They are easily performed on urethral specimens and can even be performed on first-void urine specimens. PCR and LCR are noninvasive, rapid, sensitive, and specific, and they have facilitated the diagnosis of gonococcal infection. However, they cannot report antibiotic sensitivities; therefore, these techniques do not eliminate the need for culture in these patients.
In addition, specific molecular tests may produce erroneous results. In certain circumstances, it may be advisable, in consultation with a medical microbiologist, to take a sample for culture or to perform a second molecular test aimed at a different part of the bacterial genome.
N gonorrhoeae was identified as the causative agent in a case of culture-negative dermatitis-arthritis syndrome using real-time PCR. This technology can improve the speed and sensitivity of diagnosis and consequent management of patients with this syndrome.
The immunochromatographic strip test (IST) combines antibodies from a patient’s specimen (secretions or urine) and N gonorrhoeae antigens on a nitrocellulose strip. One study showed that this technique yielded a sensitivity of 70% and specificity of 97%.
Optical immunoassay (OIA) also uses antigen-antibody reactions (monoclonal), but on a silicon wafer; a positive reaction is evidenced by a color change. A sensitivity of 60% and specificity of 90% was reported.
Both rapid tests yield results within 30 minutes and require minimal training to use. Initial test results show some promise, but additional verification of their utility in appropriate settings is still needed.
In women with symptoms and signs suggestive of pelvic inflammatory disease (PID) who are difficult to diagnose clinically, laparoscopy may be indicated to rule out (and, if need be, to treat) appendicitis, ovarian torsion, ectopic pregnancy, or other surgical emergencies.
Imaging studies such as ultrasonography are obviously a less invasive means of obtaining diagnostic information, but potentially emergent cases may require a more definitive examination, which permits rapid intervention if required.
In PID, culdocentesis, although rarely indicated, may demonstrate free purulent exudate and provide material for Gram stain and culture.
In septic arthritis cases, arthrocentesis may show purulence and/or causative organisms.
Perform lumbar puncture and joint aspiration, if indicated by clinical findings. Rarely would CSF fluid yield positive results in cases of meningitis secondary to gonorrhea.
Exudate of PMNs is typical. Gram-negative intracellular diplococci are seen microscopically (see the image below). In pelvic inflammatory disease (PID), loss of ciliated columnar epithelium from the fallopian tubes may occur. Tubes, pelvic mesentery, and ovaries may be bound together with dense fibrosis and abscess formation.
Cytologic smear of cutaneous acral pustule showing gram-negative, intracellular diplococci.
The 250-mg IM dose of ceftriaxone is now recommended over the 125-mg dose, given concern for resistance, prior lower-dose ceftriaxone dose failures, and seemingly improved efficacy in pharyngeal infections. Ceftriaxone is safe and effective in pregnant women and probably destroys incubating syphilis. Its major drawback is the necessity for IM administration.
A review of the recommendations for antimicrobial treatment of uncomplicated gonorrhea in 11 East European countries showed ceftriaxone (250-1000 mg IM once) was a first-line antimicrobial in all of them. (However, many of the second-line and alternative treatments were less than ideal, with regionally manufactured antimicrobials predominantly used.)
Data has indicated that the 400-mg oral dose of cefixime does not provide a bactericidal level that is as high or as sustained as that of the 250-mg dose of ceftriaxone. In addition, based on findings from the Gonococcal Isolate Surveillance Project (GISP), reported July 2011, from 2009-2010 a decreasing susceptibility to cefixime was found. In response, the CDC issued revised guidelines that do not include oral cephalosporins as first-line treatment.
Gonococcal pharyngeal infections may be more challenging to eradicate than infections involving urogenital and anorectal areas.
If ceftriaxone is not available, give cefixime 400 mg PO in a single dose plus azithromycin 1 g PO as a single dose or doxycycline 100 mg orally twice daily for 7 days. If a patient with gonorrhea is treated with an alternative regimen, the patient should return 1 week after treatment for a test-of-cure at the infected anatomic site. Because of the high prevalence of tetracycline resistance among GISP isolates, particularly those with elevated minimum inhibitory concentrations to cefixime, the use of azithromycin as the second antimicrobial is preferred.
Another alternative regimen for patients intolerant of cephalosporins include spectinomycin (2g IM). Spectinomycin may be costly and is currently unavailable in the United States.
Azithromycin at 2 g as a single dose is also effective; however, its use is limited by its cost, adverse gastrointestinal (GI) effects, lack of efficacy in pharyngeal infection, and growing concerns of resistance to macrolides (see Morbidity and Mortality Weekly Reports).[In addition, reports of growing macrolide resistance have been published, given that the 1-g (typically given in chlamydia treatment) exposure is sublethal for gonorrhea.
Nonetheless, because gonococcal infections are very frequently associated with urogenital chlamydial infection, most authorities now recommend either single-dose azithromycin (1 g PO) or a 7-day course of doxycycline (100 mg twice daily) as empiric treatment to include with cephalosporin therapy for gonorrhea.
Recommended therapy is with ceftriaxone at 1 g daily IV/IM. Initial IV/IM treatment should be continued for 1-2 days after symptoms improve. At that time, it is a consideration to switch to cefixime 400 mg orally twice daily to complete a total course of 7 days of antibiotics.
Oral therapy may be used initially in carefully selected, compliant patients with a definite diagnosis and only mild infection. Antibiotics for oral use in this situation include cefixime 400 mg twice daily for 7 days.
Treatment recommendations for adults are ceftriaxone 1 g IM with saline irrigation and topical antibiotic solutions.If the cornea is involved or if corneal involvement cannot be excluded due to lid swelling or chemosis, some physicians treat with a 3-day course of IV antibiotics (eg, ceftriaxone 1 g IV q12-24h).
Therapy for outpatients includes cefoxitin at 2 g IM plus probenecid at 1g orally as a single dose or ceftriaxone at 250 mg IM followed by a 14-day oral regimen of doxycycline at 100 mg twice daily. Each of the above regimens may be accompanied by metronidazole 500 mg orally twice daily for 14 days. Also, examining and treating all sexual partners of women with gonococcal pelvic inflammatory disease (PID) is crucial.
Therapy for hospitalized patients with PID consists of cefoxitin at 2 g parenterally every 6 hours or cefotetan at 2 g IV every 12 hours plus doxycycline. Alternative regimens for penicillin-allergic patients include clindamycin 900 mg IV every 8 hours with gentamicin of loading dose 2 mg/kg of body weight followed by 1.5 mg/kg of body weight every 8 hours. Again, examining and treating all sexual partners of women with gonococcal PID is crucial.
Oral regimens for mild to moderately severe symptoms have been shown not to be inferior to IV regimens. The diagnosis should be reviewed and IV antibiotics administered in patients in whom oral therapy fails after 72 hours.
Recommended therapy includes ceftriaxone 250 mg IM as a single dose with doxycycline 100 mg orally twice daily for a total of 10 days.
The summary for this regimen is as follows:
Cephalosporin-based regimens are recommended; IV therapy is recommended initially (for at least 24-48 h, until clinical improvement), before transitioning to oral therapy.
Regimens include ceftriaxone 1 g IV every 24 hours or any of the alternative regimens listed by the CDC. Cefixime 400 mg orally twice daily is the preferred oral cephalosporin, once the patient has transitioned to oral therapy.
The combination of IV and oral cephalosporin antibiotics should be administered for a total duration of 7 days.
Ceftriaxone 1-2 g IV every 12 hours is recommended. Meningococcal meningitis therapy is recommended for 10-14 days, with endocarditis therapy recommended for a minimum of 4 weeks. Infectious disease consultation may be necessary.
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16. Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections. MMWR Morb Mortal Wkly Rep. Aug 10 2012;61:590-4. [Medline]. [Full Text].
Chlamydial infection can cause disease in many organ systems, including the genitourinary tract. Chlamydiae are small gram-negative obligate intracellular microorganisms that preferentially infect squamocolumnar epithelial cells. They include the genera Chlamydia (of which the type species is Chlamydia trachomatis) and Chlamydophila (eg, Chlamydophila pneumoniae and Chlamydophila psittaci).
C trachomatis can be differentiated into 18 serovars (serologically variant strains) on the basis of monoclonal antibody–based typing assays. These serovars are associated with different medical conditions, as follows:
C trachomatis infection affects the cervix, urethra, salpinges, uterus, nasopharynx, and epididymis; it is the most commonly reported bacterial sexually transmitted disease (STD) in the United States and a leading cause of infertility in women. C trachomatis infection causes other diseases as well, including conjunctivitis, pneumonia or pneumonitis, afebrile pneumonia syndrome (in infants born vaginally to infected mothers), Fitz-Hugh-Curtis syndrome, and trachoma (the world’s leading cause of acquired blindness).
The pathophysiologic mechanisms of chlamydial infection are poorly understood at best. Chlamydia infects columnar epithelial cells, which places the adolescent female at particular risk because of the presence of the squamocolumnar junction on the ectocervix until early adulthood. The initial response of epithelial cells to infection is a neutrophilic infiltration, followed by lymphocytes, macrophages, plasma cells, and eosinophilic invasion. The release of cytokines and interferons by the infected epithelial cell initializes this inflammatory cascade.
Infection with chlamydial organisms invokes a humoral cell response, resulting in secretory immunoglobulin A (IgA) and circulatory immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies and a cellular immune response. A 40-kd major outer membrane protein (MOMP) and 10- and 60-kd chlamydial heat-shock proteins (cHSPs) have been implicated in the immunopathologic response, but further studies are needed to provide a better understanding of these cell-mediated immune responses.
Chlamydiae have a unique biphasic life cycle that is adaptable to both intracellular and extracellular environments. In the extracellular milieu, the so-called elementary body (EB) is found. EBs are metabolically inactive infectious particles; functionally, they are spore-type structures. Once inside a susceptible host cell, the EB prevents phagosome-lysozyme fusion and then undergoes reorganization to form a reticulate body (RB).
The RB synthesizes its own DNA, RNA, and proteins but requires energy in the form of adenosine triphosphate (ATP) from the host cell. After a sufficient amount of RBs have formed, some transform back into EBs, exiting the cell to infect others.
The bacterium is usually spread through sexual activity. An infected male has a 25% chance per sexual encounter of transmitting the infection to an uninfected female. Chlamydiae can be vertically spread as well. The transmission rate from infected mother to newborn is 50-60%, causing conjunctivitis (in most cases) or pneumonia (in 10-20% of cases; see Afebrile Pneumonia Syndrome).
Infection of the genital tract is the most common clinical presentation. The incubation period is 1-3 weeks. Approximately 50% of infected males and 80% of infected females are asymptomatic, but infection may cause a mucopurulent cervicitis in females and urethritis in males. Ascending infection can result in PID in women and is the most common cause of epididymitis in men younger than 35 years. Of women with PID, 5-10% develop perihepatitis (ie, Fitz-Hugh-Curtis syndrome).
Although patients with any STD are at increased risk of coinfection with another STD, coinfection of chlamydia and gonorrhea is most common. Forty percent of women and 20% of men with chlamydial infection are co-infected with gonorrhea. Patients with chlamydia also have a higher frequency of Reiter syndrome (ie, urethritis, conjunctivitis, reactive arthritis) than the general population.
LGV is rare in the United States but is responsible for 10% of cases of genital ulcer disease in tropical countries. Localized inguinal adenopathy and ulceration develop 2-12 weeks after exposure. Proctitis, rectal strictures, and lymphatic obstruction with secondary elephantiasis can occur in untreated disease.
Chlamydial transmission usually is caused by sexual contact through oral, anal, or vaginal intercourse. Neonatal infection (eg, conjunctivitis or pneumonia) may occur secondary to passage through the birth canal of an infected mother.
Specific risk factors for chlamydial infection include the following:
Multiple sexual partners or a new sexual partner
Age 15-24 years (especially age younger than 19 years)
Poor socioeconomic conditions (eg, homelessness)
Exchange of sex for drugs or money
Single marital status
Intercourse without a barrier contraceptive
History of a previous STD or current coinfection with another STD
Certain cytokine polymorphisms – These have been associated with severe disease and risk of tubal factor infertility
C trachomatis is a sexually transmitted microorganism that is responsible for a wide spectrum of diseases, including cervicitis, salpingitis, endometritis, urethritis, epididymitis, conjunctivitis, and neonatal pneumonia. In chlamydial infection, unlike gonorrhea, most men and women who are infected are asymptomatic; thus, diagnosis is delayed until a positive screening result is obtained or a symptomatic partner discovered.
· Screen for chlamydial infection in all sexually active nonpregnant young women aged 24 years or younger and for older nonpregnant women who are at increased risk
· Screen for chlamydial infection in all pregnant women aged 24 years or younger and in older pregnant women who are at increased risk
· Do not routinely screen for chlamydial infection in women aged 25 years or older, regardless of whether they are pregnant, if they are not at increased risk
Chlamydia has been isolated in approximately 40-60% of males presenting with nongonococcal urethritis. Epidemiologic studies indicate a high prevalence of asymptomatic men who act as a reservoir for chlamydial infections. A 1996 study by Quinn et al (1996) estimated that the transmission probability was 68% in both men and women.
Although genitourinary carriage of chlamydiae is often asymptomatic, certain manifestations of disease are commonly seen, including local mucosal inflammation associated with a discharge, urethritis in males, and urethritis/vaginitis/cervicitis in females.
The following may be noted in all patients with chlamydial infection:
The following may be noted in females with chlamydial infection:
The following may be noted in males with chlamydial infection:
The following may be noted in newborns with chlamydial infection:
The following may be noted in mothers diagnosed with or suspected of having a chlamydial infection during pregnancy:
Signs of chlamydial infection in women may include the following:
Signs of chlamydial infection in men may include the following:
Signs of chlamydial infection in newborns may include the following:
Signs of lymphogranuloma venereum (LGV) may include the following:
Non-Gonococcal Urethritis: Mucoid Discharge
Chlamydial infection is one of the leading causes of infertility in women. It is also a leading cause of PID. PID is a serious disease that often requires hospitalization for inpatient care, including intravenous (IV) antibiotics, testing to rule out tubo-ovarian abscess, and intensive counseling on the complications of recurrent infections.
The risk of ectopic pregnancy in women who have had PID is 7-10 times greater than that for women without a history of PID. In 15% of women who have contracted PID, chronic abdominal pain is a long-term manifestation that most likely is related to pelvic adhesions in the ovaries and fallopian tubes.
Fitz-Hugh-Curtis syndrome (perihepatitis) is a rare complication of PID that is 5 times more likely to be caused by Chlamydia than by N gonorrhoeae. It frequently presents without the typical examination findings associated with PID (ie, the pelvic examination is normal).
Women with a chlamydial infection (especially one caused by serotype G) are at increased risk for the development of cervical cancer; the risk is as much as 6.5 times greater than it is in women without infection. Chlamydial infections also increase the risk of acquiring HIV infection by increasing genital mucosal inflammation.
Pregnant women with a chlamydial infection can pass the infection on to their infants during delivery, and this may develop into chlamydial pneumonia or chlamydial conjunctivitis. Untreated neonatal conjunctivitis can result in blindness.
Reiter syndrome, a reactive arthritis secondary to an immune-mediated response, has been associated with a primary chlamydial infection. It may present as asymmetric polyarthritis, urethritis, inflammatory eye disease, mouth ulcers, circinate balanitis, and keratoderma blennorrhagica. Its etiology may not be completely clear, but 2 strong associations are observed: Reiter syndrome usually follows an infectious episode, and 80% of affected patients are positive for human leukocyte antigen (HLA)-B27.
Swollen or tender testicles (epididymitis)
In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:
Mycoplasma genitalium infection
A complete blood count (CBC) can be performed for suspected pelvic inflammatory disease (PID). The following should also be considered:
A pregnancy test is mandatory for females with suspected chlamydial infection. Obtaining a pregnancy test helps with early diagnosis and guidance of treatment. Because pregnancy is a contraindication for the use of doxycycline and ofloxacin, it is critical to obtain a pregnancy test before beginning treatment with these drugs.
Cytology is used mainly for diagnosing infant inclusion conjunctivitis and ocular trachoma through the demonstration of intracytoplasmic C trachomatis inclusions in HeLa cells (ie, continuously cultured carcinoma cell line used for tissue cultures). Cytologic diagnosis also is used to evaluate endocervical scrapings, but interpretation is difficult, and sensitivity and specificity have been low.
C trachomatis grows well in a variety of cell lines (eg, McCoy and HeLa cells) that can be maintained in tissue culture. Incubation in tissue culture is 40-72 hours, depending on the cell type and specific biovar. Intracytoplasmic inclusions can be detected either by Giemsa stains or by immunofluorescent staining with monoclonal antibodies.
Cultures are difficult to obtain; many false-negative results are returned. They are also expensive to perform, because of the expertise and laboratory resources required. In addition, they are unsuitable for large numbers of patients (eg, in the emergency department [ED]). Nevertheless, in certain clinical situations, cultures are mandatory.
Because of its high specificity (100%) and sensitivity, cell culture is the only test that should be used to establish the presence or absence of infections in cases with legal implications, such as those involving rape or sexual abuse. Cell culture is also preferred for rectal specimens because nonculture test results are difficult to interpret in the presence of stool organisms.
Because C trachomatis grows only within columnar cells, obtaining a specimen that contains cells directly from the urethra or cervix, not on pooled vaginal secretions, is important. In obtaining cells along with discharge, attempt to apply pressure to the inside of the cervix or urethra. In males, insert collection swabs 1-2 cm into the urethra after the urethra is milked to bring down secretions. Always follow the directions of the manufacturer of the kit used for collection, and follow transport instructions.
Direct fluorescent antibody (DFA) testing is a laboratory assay for C trachomatis that has a sensitivity of 50-80% and a specificity of 99% specificity. It is the method of choice for confirming other assays. However, it is labor intensive and requires skilled personnel.
Enzyme-linked immunosorbent assay (ELISA) is a laboratory assay for C trachomatis that has a sensitivity of 40-60% and a specificity of 99%. Because it is both automatable and cost-effective, it is suitable for large numbers of patients. ELISA is the most commonly used test for Chlamydia in the emergency department (ED) and in outpatient clinics.
Detection of chlamydial DNA may be accomplished by using specific probes. Newer DNA probe kits currently are available that allow detection of C trachomatis and N gonorrhoeae from voided urine specimens, obviating the need for direct sampling in uncomplicated cases. These urine tests may also be appropriate for use in the evaluation of possible sexual abuse.
Overall, such tests have a sensitivity of 80-92% and a specificity of 99%. In men, there are no differences between tests done on urine specimens and tests done on genital specimens; however, in women, the former may be less sensitive than the latter. Compared with enzyme immunoassays, these urine tests are expensive, but they are becoming more cost-effective.
The APTIMA Combo 2 Assay for ribosomal RNA (rRNA) can be used on ThinPrep liquid-based Pap smear specimens. This has the advantage of being relatively simple and inexpensive. Most studies report sensitivities greater than 70% and specificities of 97-99% in populations of men and women with a prevalence of infection of 5% or more. If a definitive diagnostic test is required, antigen detection may well be the most appropriate diagnostic test for a primary care setting in the United States.
The main disadvantage of this approach is that it is less sensitive than tissue culture. In populations with a low (< 5%) prevalence of chlamydial infection, a highly significant percentage of positive test results are false positives. Accordingly, verification of a positive test result is desirable in certain cases. Such verification can be achieved by means of culture (eg, a second nonculture test that identifies a different chlamydial antigen or nucleic acid sequence from that identified in the first test), a blocking antibody, or a competitive probe.
Polymerase chain reaction (PCR) tests and ligase chain reaction (LCR) tests have sensitivities and specificities approaching 100% but remain expensive to perform on a routine basis.Both PCR and LCR detect C trachomatis in urine or self-administered vaginal swab specimens with a sensitivity comparable to that achieved with urogenital swab specimens.
On a complement fixation test, all patients with lymphogranuloma venereum (LGV) have complement-fixing antibody titers higher than 1:16. Fifteen percent of men with urethritis and 45% of women with endocervical infection have titers of 1:16 or greater. The microimmunofluorescence test is more sensitive than the complement fixation test. Results are positive in at least 99% of women with cervicitis and in 80-90% of men with urethritis.
Antichlamydia immunoglobulin M (IgM) is uncommon in adults with genital tract infection. The prevalence of antichlamydial immunoglobulin G (IgG) is high in sexually active adults, even in those who do not have an active infection, and it likely is due to past infection. A statistically significant association exists between chlamydia-specific serum immunoglobulin A (IgA) and active disease.
The sensitivity, specificity, and predictive values of serologic studies for Chlamydia are not high enough to make any of them clinically useful in the diagnosis of active disease. Therefore, chlamydial serologies are not recommended for diagnosis of genital tract disease. The choice of the most appropriate test depends on the clinical setting, the facilities available, and the relative cost.
Imaging studies are usually not required for patients with uncomplicated genital chlamydial infections. However, computed tomography (CT) and ultrasonography are useful diagnostic adjuncts in cases of complicated (upper tract) infection. For example, CT may identify Fitz-Hugh-Curtis syndrome (perihepatitis; see the images below). Ultrasonography may be performed to look for tubo-ovarian abscess.
CT scan of adolescent with chlamydial Fitz-Hugh-Curtis syndrome demonstrating perihepatic fluid collection anterior to liver
CT scan of adolescent with chlamydial Fitz-Hugh-Curtis syndrome demonstrating free peritoneal fluid.
Obtain a chest radiograph for infants with suspected pneumonia. Chlamydial pneumonia may appear as a lobar or interstitial pneumonia in infants.
The keys to management of chlamydial infections are (1) arriving at the correct diagnosis and (2) ensuring that the patient complies with treatment.
Undiagnosed chlamydia can progress to pelvic inflammatory disease (PID), which may lead to relative or absolute infertility. This may be tragic if it occurs early in life before childbearing. Diagnostically evaluate all cases of suspected sexual abuse using chlamydial culture, not nonculture techniques.
Because of the personal nature and time-intensive diagnosis of sexually transmitted diseases (STDs), many physicians err by presuming that symptoms of an STI are caused by a urinary tract infection (UTI); therefore, patients often present with a history of multiple UTIs when, in fact, they may have had 1 or more STDs.
Adolescents are at high risk for noncompliance with treatment, especially if a patient is attempting to keep information away from parents. Single-dose, in-office treatment is increasingly being used to improve compliance and confidentiality. Partner treatment is crucial for prevention of reinfection.
Many clinicians err on the side of caution and hospitalize patients whenever PID is a concern or compliance with therapy is problematic. Consider PID an absolute indication for admission because of the potential for infertility and the poor compliance of many adolescents with prolonged treatment regimens.
Begin antibiotic therapy as soon as possible. Consider compliance, cost, and potential adverse effects. Consider treatment for possible gonorrhea coinfection. Send specimens from sites of infection to the lab for culture. Perform a pregnancy test; this can alter antibiotic treatment and patient follow-up care.
Consult obstetrics/gynecology for any patient with severe PID and any pregnant patient with chlamydial infection. Consult ophthalmology for patients with chlamydial conjunctivitis. Provide information and counseling to prevent future STDs, and consider referral for HIV testing. Encourage the patient to abstain from sexual intercourse until after treatment and testing of all partners is completed
Treatment of genitourinary chlamydial infection clearly is indicated when the infection is diagnosed or suspected. The Centers for Disease Control and Prevention (CDC) recommends azithromycin and doxycycline as first-line drugs for the treatment of chlamydial infection. Medical treatment with these agents is 95% effective. Second-line drugs (eg, erythromycin, penicillins, and sulfisoxazole) are less effective and have more adverse effects.
Lower genital infections caused by Chlamydia can be treated with single-dose, directly observed treatment. This practice is encouraged when possible to reduce noncompliance due to cost, confidentiality issues, motivational issues, and maturity issues.
Upper genital tract disease must be vigorously sought out because potential complications are serious, especially in adolescents. With the advent of newer, more sensitive DNA and antigen detection kits that use urine specimens instead of a pelvic examination, the potential to presume a chlamydial infection in uncomplicated lower tract disease is concerning.
Inadequately treated PID can lead to sepsis, infertility, and chronic pelvic pain. Many practitioners strongly advise admission for inpatient therapy and monitoring of response whenever PID is suspected because of a tendency of adolescents to minimize or ignore symptoms and eschew follow-up.
With inpatient regimens for PID, evidence of significant clinical improvement and confidence in completion of medical therapy must be present before the patient is discharged. Upper genital tract infections are often treated with a 10-day course that includes treatment of gonorrhea. Some practitioners prefer to complete the entire course of treatment on an inpatient basis, usually 10-14 days.
Chlamydial conjunctivitis and pneumonia are usually treated for a total of 14 days.
Treatment also is indicated for sexual partners of the index case if the time of the last sexual encounter was within 60 days of onset, and it should be considered for longer periods for the last sexual partner. Treatment of chlamydial infection is indicated for patients being treated for gonorrhea, as well.
In December 2010, the Centers for Disease Control and Prevention (CDC) updated treatment guidelines for gonococcal infection and associated conditions. Fluoroquinolone antibiotics remain not recommended to treat gonorrhea in the United States. The recommendation was based on analysis of new data from the CDC’s Gonococcal Isolate Surveillance Project (GISP), which showed that the percentage of fluoroquinolone-resistant gonorrhea cases in heterosexual men 6.7% in 2007, an 11-fold increase from 0.6% in 2001.
Thus, treatment of gonorrhea is limited to drugs in the cephalosporin class (eg, a single intramuscular dose of ceftriaxone 125 mg IM or a single oral dose of cefixime 400 mg). Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented. .
Follow-up culture is not recommended after azithromycin or doxycycline therapy, but it may be considered in pregnancy after erythromycin or amoxicillin therapy. Nonculture tests should be avoided in this circumstance to avoid positive results from nonviable organisms.
Patients should abstain from sexual intercourse for 7 days after single-dose therapy or until the end of a longer regimen. Patients also should refrain from sexual intercourse until all of their sex partners have been cured.
1. Hopkins MJ, Ashton LJ, Alloba F, Alawattegama A, Hart IJ. Validation of a laboratory-developed real-time PCR protocol for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine. Sex Transm Infect. Jun 2010;86(3):207-11. [Medline].
2. Keenan JD, Lakew T, Alemayehu W, Melese M, Porco TC, Yi E, et al. Clinical activity and polymerase chain reaction evidence of chlamydial infection after repeated mass antibiotic treatments for trachoma. Am J Trop Med Hyg. Mar 2010;82(3):482-7. [Medline]. [Full Text].
3. Ahrens KR, Richardson LP, Courtney ME, McCarty C, Simoni J, Katon W. Laboratory-diagnosed sexually transmitted infections in former foster youth compared with peers. Pediatrics. Jul 2010;126(1):e97-e103. [Medline].
4. Guy RJ, Kong F, Goller J, Franklin N, Bergeri I, Dimech W, et al. A new national Chlamydia Sentinel Surveillance System in Australia: evaluation of the first stage of implementation. Commun Dis Intell. Sep 2010;34(3):319-28. [Medline].
5. Goulet V, de Barbeyrac B, Raherison S, Prudhomme M, Semaille C, Warszawski J. Prevalence of Chlamydia trachomatis: results from the first national population-based survey in France. Sex Transm Infect. Aug 2010;86(4):263-70. [Medline].
Rours GI, Duijts L, Moll HA, Arends LR, de Groot R, Jaddoe VW, et al. Chlamydia trachomatis infection during pregnancy associated with preterm delivery: a population-based prospective cohort study. Eur J Epidemiol. Jun 2011;26(6):493-502. [Medline]. [Full Text].
7. Peters RPH, Nijsten N, Mutsaers J, Jansen CL, Morré SA, van Leeuwen AP. Screening of Oropharynx and Anorectum Increases Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae Infection in Female STD Clinic Visitors. Sexually Transmitted Diseases. Sept 2011;38(9):783-7.
8. Schmidt AJ, Marcus U. Self-reported history of sexually transmissible infections (STIs) and STI-related utilization of the German health care system by men who have sex with men: data from a large convenience sample. BMC Infect Dis. May 18 2011;11:132. [Medline]. [Full Text].
9. Morgan J, Colonne C, Bell A. Trends of reported chlamydia infections and related complications in New Zealand, 1998-2008. Sex Health. Sep 2011;8(3):412-8. [Medline].
10. CDC Grand Rounds: Chlamydia prevention: challenges and strategies for reducing disease burden and sequelae. MMWR Morb Mortal Wkly Rep. Apr 1 2011;60(12):370-3. [Medline].
11. [Best Evidence] [Guideline] Geisler WM. Diagnosis and management of uncomplicated Chlamydia trachomatis infections in adolescents and adults: summary of evidence reviewed for the 2010 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines. Clin Infect Dis. Dec 2011;53 Suppl 3:S92-8. [Medline].
12. [Best Evidence] [Guideline] Hammerschlag MR. Chlamydial and gonococcal infections in infants and children. Clin Infect Dis. Dec 2011;53 Suppl 3:S99-102. [Medline].
13. National Guideline Clearinghouse (NGC). Guideline synthesis: Screening, diagnosis management of chlamydial infection. National Guideline Clearinghouse (NGC) [Web site]. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); 2001 May (revised 2012 Feb). Available at http://guideline.gov/syntheses/synthesis.aspx?id=35283. Accessed May 18, 2012.
14. Taylor BD, Darville T, Ferrell RE, Kammerer CM, Ness RB, Haggerty CL. Variants in toll-like receptor 1 and 4 genes are associated with Chlamydia trachomatis among women with pelvic inflammatory disease. J Infect Dis. Feb 2012;205(4):603-9. [Medline]. [Full Text].
15. Mangin D, Murdoch D, Wells JE, Coughlan E, Bagshaw S, Corwin P, et al. Chlamydia trachomatis testing sensitivity in midstream compared with first-void urine specimens. Ann Fam Med. Jan-Feb 2012;10(1):50-3. [Medline]. [Full Text].
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. Trichomoniasis is also associated with adverse pregnancy outcomes, infertility, postoperative infections, and cervical neoplasia.
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.
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
Trichomoniasis is thought to be widely underdiagnosed due to a variety of factors, including a lack of routine testing, the low sensitivity of a commonly used diagnostic technique (wet mount microscopy),[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.
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. 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.
T vaginalis is approximately the size of a white blood cell (WBC)—about 10-20 μm long and 2-14 μm wide—though 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.
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.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.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.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.Another study showed that HIV seropositivity did not alter the rate of infection in males.
Symptoms of trichomoniasis typically occur after an incubation period of 4-28 days. 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.
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
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).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.
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.[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.
Nearly half of infected females and nearly all infected males are asymptomatic. One third of asymptomatic women become symptomatic within 6 months.
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). 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.However, it may also be asymptomatic.
T vaginalis infection is one of the top 3 causes of vaginitis.[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).
Papilliform appearance of the cervix (also known as “strawberry” cervix)
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. Some patients report pain in the urethra, testicular pain, or lower abdominal pain.
Pain or burning during urination and ejaculation
Most symptomatic infections are intermittent and self-limiting.
Vaginal discharge is found in 42% of infected women. The discharge is classically described as thin and frothy; however, this is only seen in about 10% of patients.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%.Vaginal pH is often elevated (>4.5).
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.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 clinician’s ability to accurately diagnose Tvaginalis infection on the basis of physical findings alone had a positive predictive value of only 47%. Relying on physical examination findings alone misses the diagnosis of most patients with trichomoniasis. Definitive diagnosis requires appropriate laboratory testing.
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.
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. 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.
Prompt trichomoniasis diagnosis is important for eliminating infection in the patient and sexual partners and avoiding complications (see Complications).
In women, vaginal trichomoniasis has historically been diagnosed by wet mount microscopy. Saline wet mount evaluation is performed by placing a small amount of vaginal discharge on a microscope slide and mixing with a few drops of saline solution. The slide is then examined under a microscope at low or medium power (see the video below).
Trichomonas vaginalis on a saline wet mount at 40X on the microscope. Several motile parasites transit through the field, surrounded by white blood cells and squamous epithelial cells.
The presence of flagellated pyriform protozoa, or trichomonads, indicates a positive test result. These ovoid-shaped parasites are slightly larger than polymorphonuclear leukocytes (PMNs), a type of white blood cell, and may be identified by their ameboid mobility. Trichomonads cause an inflammatory reaction; therefore, a large number of PMNs are usually present and correlate with the severity of infection.
Slides must be read immediately after collection. Kingston et al looked at samples that were positive for trichomonads on initial reading and then reevaluated them every 10 minutes. At 10 minutes, 20% of samples became negative; by 30 minutes, 35% were negative; and by 2 hours, 78% had become negative.
It is important to note that microscopy has a low sensitivity (estimated at 50-70%) in the detection of T vaginalis in vaginal secretions and is not the criterion standard technique for trichomoniasis diagnosis.Because they involve the direct visualization of the trichomonads, wet mounts are more likely to be positive in women with high organism loads.The absence of trichomonads on microscopy does not rule out a diagnosis of vaginal trichomoniasis.
Despite their limitations, wet mounts are frequently used, because they are quick, cheap, and easy to perform.
The relatively poor sensitivity of saline wet mount evaluation may be increased somewhat by using cervical vaginal lavage. In one study, sensitivity was increased to 74.4% using the cervical vaginal lavage technique versus 54.7% vaginal swab alone.
Wet mount microscopy is not an effective test for the diagnosis of trichomoniasis in men.
A short downloadable video illustrating this test is available from the Seattle STD/HIV Prevention Training Center.
Culture is the current criterion standard for trichomoniasis diagnosis. Providers should perform T vaginalis cultures when the suspicion of trichomoniasis is high but saline wet mount evaluation does not reveal the protozoan. Culture may also be useful as diagnostic screening for high-risk populations. Culture is more sensitive and specific than microscopy.In a study by Wolner-Hanssen et al, 35.6% of trichomoniasis cases were detected by culture and not by wet mount or Papanicolaou (Pap) smear.
A swab is put in broth and incubated anaerobically at 37°C. Growth is usually detected within 48 hours, and samples without growth after 7 days are considered negative for trichomoniasis.
In addition to improved diagnostic value, an advantage of culture is delayed inoculation. Swab specimens may sit for some time prior to inoculation, allowing for the reading of a wet mount prior to pouch inoculation. Another advantage of culture is that swab specimens may be obtained by the patient (self-obtained specimens), a technique useful with adolescents and in resource-poor settings. Culture has also been demonstrated to be useful in individuals with suspected resistant trichomoniasis. Physicians can determine whether trichomonads are the cause of the vaginitis and can obtain the susceptibility of the strain.
Culture is especially important for diagnosing trichomoniasis in men, in whom wet mount preparations are particularly unreliable. Urethral swab, urine, and semen cultures are used to maximize sensitivity.The CDC does not recommend oral and rectal testing, as infection rates at these sites appear to be low.
Disadvantages of the culture method include testing time and availability.
3. In Pouch TV Culture System
The InPouch TV Culture System (Biomed, White City, Ore), a combined wet mount and culture kit, is commonly used and readily available. This test kit has a sensitivity of 81-100%.It may detect as little as 1 parasite in the sample. Samples taken during menses are not adversely affected.
The clinician inoculates the upper chamber of the pouch with a cotton swab. The pouch can be kept at room temperature for up to 18 hours without significant alteration of sensitivity. In the laboratory, a viewing clamp is placed across the upper chamber and examined under a microscope at a magnification of 100. If no trichomonads are viewed, the bottom chamber is inoculated by using the medium from the upper chamber. The InPouch is incubated at 37°C and viewed at regular intervals.
Trichomonads may be viewed on Pap smear, but this test yields low sensitivity and should not be relied on for diagnosis of T vaginalis infection. The sensitivity of Pap smear for detecting trichomonads is 40-60%. Specificity approaches 95% in the hands of trained technicians. False-positive results are also common with this technique.
Vaginal pH may be determined by touching a swab containing vaginal secretions to pH indicator paper. A normal pH practically excludes the diagnosis of trichomoniasis. A pH greater than 4.5 is usually found with trichomoniasis.However, an elevation in pH is not specific for trichomoniasis. Bacterial vaginosis frequently also elevates vaginal pH.
Perform the whiff test (amine odor test) by adding several drops of 10% potassium hydroxide to a sample of vaginal discharge. A strong fishy odor is indicative of a positive test result. Such a result may suggest either trichomoniasis or bacterial vaginosis. Thus, the whiff test should not be considered an accurate means of diagnosing trichomoniasis. It is 1 of the 4 parts of the Amsel criteria used to diagnose bacterial vaginosis.
The whiff test is now combined with vaginal pH on a single card, the FemExam pH and Amines TestCard. On this card, the pH paper color change and the odor test are replaced with plus or minus signs.
Two FDA-approved tests are currently available for diagnosing trichomoniasis in women: (1) the OSOM Trichomonas Rapid Test (an antigen-based test; Genzyme Diagnostics, Cambridge, Mass) and (2) the Affirm VP III Microbial Identification Test (a DNA probe; BD Diagnostic Systems, Sparks, Md). Both tests have sensitivity greater than 83% and a specificity greater than 97% for detecting T vaginalis in vaginal secretions, according to the CDC.
The OSOM Trichomonas Rapid Test uses color immunochromatographic “dipstick” technology with murine monoclonal antibodies. Results are read within 10 minutes. Freezing and transportation of specimens do not appreciably alter the test results. In a comparison with a composite reference standard of wet mount microscopy and culture, Huppert et al found the sensitivity of the OSOM test to be 83.3% and the specificity 98.8%.A second study by Huppert et al found a sensitivity of 82% in comparison with a composite reference standard of wet mount, culture, rapid antigen testing, and polymerase chain reaction (PCR).A third study compared the OSOM test to a composite reference standard for which a positive sample was defined as one that was positive by any combination of wet mount, Aptima ATV assay, or OSOM test. The prevalence of infection in the population tested was low, at 2%. The sensitivity was 94.7%, and the specificity was 100%.
The Affirm VPIII Microbial Identification Test detects the presence of Trichomonas, Gardnerella, and Candida species by using direct hybridization technology. Its sensitivity is 90-100%, and the detection threshold is reported to be 5000 trichomonads/mL. Results from the Affirm VPIII test take about 45 minutes.
5-Nitroimidazole drugs are used for the treatment of trichomoniasis. In the United States, metronidazole and tinidazole are FDA-approved. In a Cochrane review, metronidazole and other nitroimidazoles had comparable efficacy in treating trichomoniasis. Randomized clinical trials comparing single 2-g doses have also shown metronidazole and tinidazole to be equally effective. With recommended dosages, the expected cure rate of trichomoniasis is 95%. Treating the patient’s sexual partners to prevent reinfection further improves the cure rate.
The mechanism of action is not well understood. Target organisms preferentially reduce the 5-nitro group, and active metabolites likely disrupt the helical structure of the DNA within them, preventing nucleic acid synthesis and eventually leading to cell death.
The advantages of single-dose therapy of metronidazole or tinidazole for trichomoniasis are better patient compliance, lower total dose, and, possibly, decreased subsequent candidal vaginitis.
For both metronidazole and tinidazole, patients should not consume alcohol during the course of treatment. For those on metronidazole therapy, abstinence should continue for 24 hours after the last dose. For those on tinidazole therapy, abstinence should continue for 72 hours after completion of the medication.
Despite the widespread use of nitroimidazoles in the treatment of trichomoniasis, resistance to these drugs is rare and is typically solved by increasing the dose or switching to another nitroimidazole.The CDC has reported incidents of trichomoniasis resistant to metronidazole that were susceptible to tinidazole. When standard treatment regimens fail, a regimen of 2 g of oral metronidazole or tinidazole for 5 days may be considered. Inpatient intravenous (IV) therapy may be indicated when resistance is present.
For patients in whom treatment fails and in whom reinfection is ruled out, consultation with experts from the CDC may be advisable (770-488-4115). Consultation with an infectious diseases specialist, a gynecologist, or both may be helpful.
Because trichomoniasis is an infection of multiple sites, systemic (oral) treatment is needed. Topical medications should are not recommended by the CDC, as they are unlikely to reach therapeutic levels. Topical metronidazole and other antimicrobials yield low cure rates (under 50%).
Patients allergic to this class of drug should be referred to an allergist for desensitization.
Metronidazole is the treatment of choice for trichomoniasis. Single-dose therapy with 2 g orally is as effective as prolonged therapy with 500 mg twice daily for 7 days. Single-dose therapy increases drug adherence.
Treatment failure with metronidazole increased from 0.4% to 3.5% between 1999 and 2002. Reports now describe resistance to metronidazole approaching 5-10%. If standard treatment with either single-dose or multidose therapy fails, a regimen of 2 g of oral metronidazole or tinidazole for 5 days may be considered.
Patients should not consume alcohol during the course of treatment or during the 24 hours after the completion of the medication.
Metronidazole crosses the placenta in pregnancy and is a pregnancy Class B agent. A number of clinical trials and meta-analyses have not shown it to have teratogenic effects. However, it may prevent transmission of T vaginalis to the newborn. The CDC currently recommends that infected symptomatic pregnant females be treated with 2 g metronidazole in a single dose. Infected asymptomatic pregnant women may wish to defer treatment to after 37 weeks’ gestation.
The National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network presented data suggesting that metronidazole treatment of asymptomatic carriers of T vaginalis increased the risk of preterm birth. This was a controversial conclusion in that the investigators treated T vaginalis infection with 4 doses of 2 g metronidazole, which is significantly more than what is standard practice. The women included in the study were between 16 and 23 weeks’ gestational age, suggesting a significant delay in treatment. A subsequent study by Mann et al showed no increased risk of preterm birth with the use of metronidazole for the treatment of trichomoniasis.
Tinidazole has a longer half-life (12-14 h) than metronidazole (6-7 h). Single-dose therapy consists of 2 g taken with food. Cure rates range from 86-100%. Randomized clinical trials comparing single 2-g doses have shown metronidazole and tinidazole to be equally effective. For resistant infections, some recommend using 2 g twice daily for 14 days. In a case series by Hager et al, all 3 patients who failed 3 regimens of metronidazole therapy were cured by tinidazole.
Tinidazole is a pregnancy class C agent; animal studies have demonstrated adverse effects on fetal development. Its use is not recommended in pregnant women.
In lactating women, it is recommended that breastfeeding be withheld during treatment and for 3 days after the last dose.
The CDC does not currently recommend the use of clotrimazole for treatment of trichomoniasis. Clotrimazole vaginal tablets have been used in the past. In a study by duBouchet et al, the cure rate was only 11% with this mode of therapy.
Some medical practitioners consider clotrimazole suppositories for patients with trichomoniasis who are in the first trimester of pregnancy. Clotrimazole mainly offers symptomatic treatment but may cure as many as 50% of infections. If this initial treatment fails, a single 2-g dose of metronidazole may be given during the second or third trimester of pregnancy.
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Genital herpes infect at least 45 million people ages 12 and older. Genital
Herpes infects more women than men. Most genital herpes is caused by
herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). If symptoms appear, one or more blisters will appear on or around the genitals or rectum. The blistersbreak leaving tender ulcers that take 2-4 weeks to heal. There is no cure for genital herpes.
Herpes simplex viruses are ubiquitous, host-adapted pathogens that cause a wide variety of disease states. Two types exist: herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Both are closely related but differ in epidemiology. HSV-1 is traditionally associated with orofacial disease, while HSV-2 is traditionally associated with genital disease; however, lesion location is not necessarily indicative of viral type.
Up to 80% of herpes simplex infections are asymptomatic. Symptomatic infections can be characterized by significant morbidity and recurrence. In immunocompromised hosts, infections can cause life-threatening complications.
The prevalence of HSV infection worldwide has increased over the last several decades, making it a major public health concern. Prompt recognition of herpes simplex infection and early initiation of therapy are of utmost importance in the management of the disease.
Primary genital herpes
Primary genital herpes can be caused by both HSV-1 and HSV-2 and can be asymptomatic. The clinical features and course of primary genital herpes caused by both HSV-1 and HSV-2 are indistinguishable, but recurrences are more common with HSV-2.
Primary genital herpes is characterized by severe and prolonged systemic and local symptoms. The symptoms of persons with a first episode of secondary HSV-2 infection are less severe and of shorter duration.
Preexisting antibodies to HSV-1 have an ameliorating effect on disease severity caused by HSV-2.
Prior orolabial HSV-1 infection protects against genital HSV-1 but not HSV-2.
Symptoms of primary genital herpes are more severe in women, as are complications.
Clinical features: The incubation of primary genital herpes period is 3-7 days (range, 1 d to 3 wk). Constitutional symptoms include fever, headache, malaise, and myalgia (prominent in the first 3-4 d). Local symptoms include pain, itching, dysuria, vaginal and urethral discharge, and tender lymphadenopathy.
Clinical features in women: Herpetic vesicles appear on the external genitalia, labia majora, labia minora, vaginal vestibule, and introitus. In moist areas, the vesicles rupture, leaving exquisitely tender ulcers. The vaginal mucosa is inflamed and edematous. The cervix is involved in 70%-90% of cases and is characterized by ulcerative or necrotic cervical mucosa. Cervicitis is the sole manifestation in some patients. Dysuria may be very severe and may cause urinary retention. Dysuria is associated with urethritis, and HSV can be isolated in the urine. HSV-1 infection causes urethritis more often than does HSV-2 infection.
Clinical features in men: Herpetic vesicles appear in the glans penis, the prepuce, the shaft of the penis, and sometimes on the scrotum, thighs, and buttocks. In dry areas, the lesions progress to pustules and then encrust. Herpetic urethritis occurs in 30%-40% of affected men and is characterized by severe dysuria and mucoid discharge. The perianal area and rectum may be involved in persons who engage in anal intercourse, resulting in herpetic proctitis.
In men and women, the ulcerative lesions persist from 4-15 days until encrusting and reepithelialization occur. New lesions occur during the course of the illness in 75% of patients, usually forming in 4-10 days. The median duration of viral shedding is about 12 days.
Recurrent genital herpes
The major morbidity of genital herpes is due to its frequent reactivation rate. In one study, 90% of patients reactivated within the first 12 months. In patients with HSV-2 infection, 38% had 6 recurrences in 1 year, and 20% had more than 10 recurrences in the first year.
Both subclinical and symptomatic reactivation is more common in HSV-2 infection than in HSV-1 infection. Sixty percent of patients with primary genital HSV-2 infection experience recurrences in the first year.
Patients who had severe primary genital herpes tend to have more frequent recurrences of longer duration.
Recurrent genital herpes is preceded by a prodrome of tenderness, pain, and burning at the site of eruption that may last from 2 hours to 2 days. In some patients, severe ipsilateral sacral neuralgia occurs.
In women, the vesicles are found on the labia majora, labia minora, or perineum. The lesions are often very painful. Fever and constitutional symptoms are uncommon. The lesions heal in 8-10 days, and viral shedding lasts an average 5 days. The symptoms are more severe in women than men.
In men, recurrent genital herpes presents as 1 or more patches of grouped vesicles on the shaft of the penis, prepuce, or glans. Urethritis is uncommon. Pain is mild, and lesions heal in 7-10 days. The frequency and severity of recurrences decrease with time.
Subclinical genital herpes
Most primary genital HSV infections are asymptomatic, with 70%-80% of seropositive individuals having no history of known genital herpes. However, upon education regarding the varied clinical manifestations, many patients recognize the symptoms of genital herpes.
Truly asymptomatic viral shedding may occur in 1%-2% of infected immunocompetent persons and may be as high as 6% in the first few months after acquisition of the infection.[This property is important when attempting to prevent transmission sexually or perinatally.
Herpes simplex virus (HSV) infection is best confirmed by isolation of the virus in tissue culture (the criterion standard for diagnosis). Tissue culture success is operator-dependent, but this modality can yield positive results within 48 hours of inoculation.
Characteristic cytopathic effect with ballooning of cells and cell death are observed, and death of the entire monolayer of cells may be rapid.
Immunofluorescent staining of the tissue culture cells can be used to quickly identify HSV and can distinguish between types 1 and 2.
The characteristic cytologic changes induced by HSV can be demonstrated in Tzank smears (see Procedures); however, this procedure does not distinguish between HSV-1 and HSV-2.
Rapid diagnosis (usually within an hour) is possible based on the histological appearance of the lesion.
Multinucleated giant cells and epithelial cells containing eosinophilic intranuclear inclusion bodies distinguish the lesions of herpesviruses.
Punch biopsy provides more reliable material for histological examination, particularly when lesions are infected with bacteria and fungi.
Detection of HSV DNA in clinical specimens is possible with polymerase chain reaction (PCR) techniques.
In HSV encephalitis, PCR using CSF provides a rapid, noninvasive diagnostic technique that is as sensitive as brain biopsy.
PCR has been used to detect HSV-2 as the cause of recurrent meningitis (Mollaret) and has shown a strong association between HSV-1 and Bell's palsy.
PCR can be used to detect asymptomatic viral shedding.
Direct fluorescent antigen (DFA): Cells scraped from ulcer bases can be stained with a direct fluorescent antibody, used to distinguish HSV-1 from HSV-2. Additionally, tissue culture cells can also be stained (see above). This procedure can usually be performed within 2-3 hours.
Antibody testing can demonstrate a primary seroconversion, particularly with HSV-1 in childhood.
o Because of sero–cross-reactivity, HSV-1 and HSV-2 are not generally distinguishable unless a glycoprotein G antibody assay is available. Testing for HSV-specific immunoglobulin M (IgM) antibodies is not available.
o Antibody titer increases generally do not occur during recurrences of HSV infection. Therefore, the test is generally not used for the diagnosis of mucocutaneous HSV relapse.
o Antibody testing has been the mainstay of large-scale epidemiologic studies.
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Tertiary and congenital syphilis
Syphilis is an infectious venereal disease caused by the spirochete Treponema pallidum. Syphilis is transmissible by sexual contact with infectious lesions, from mother to fetus in utero, via blood product transfusion, and occasionally through breaks in the skin that come into contact with infectious lesions. If untreated, it progresses through 4 stages: primary, secondary, latent, and tertiary.
Syphilis has a myriad of presentations and can mimic many other infections and immune-mediated processes in advanced stages. Hence, it has earned the nickname “the great impostor.” The complex and variable manifestations of the disease prompted Sir William Osler to remark, “The physician who knows syphilis knows medicine.”
Many famous personages throughout history are thought to have suffered from syphilis, including Bram Stoker, Henry VIII, and Vincent Van Gogh. Since the discovery of penicillin in the mid-20th century, the spread of this once very common disease has been largely controlled, but efforts to eradicate the disease entirely have been unsuccessful.
Three genera of spirochetes cause human infection:
The particular spirochete responsible for syphilis is Treponema pallidum.
T pallidum is a fragile spiral bacterium 6-15 micrometers long by 0.25 micrometers in diameter. Its small size makes it invisible on light microscopy; therefore, it must be identified by its distinctive undulating movements on darkfield microscopy. It can survive only briefly outside of the body; thus, transmission almost always requires direct contact with the infectious lesion.
S yphilis is usually classified into 4 stages: primary, secondary, latent, and tertiary. It can be either acquired or congenital. That is, it can be transmitted either by intimate contact with infectious lesions (most common) or via blood transfusion (if blood has been collected during early syphilis), and it can also be transmitted transplacentally from an infected mother to her fetus.
Congenital syphilis, discussed briefly here, is a veritable potpourri of antiquated medical terminology. The treponemes readily cross the placental barrier and infect the fetus, causing a high rate of spontaneous abortion and stillbirth. Within the first 2 years of life, symptoms are similar to severe adult secondary syphilis with widespread condylomata lata and rash. “Snuffles” describes the mucopurulent rhinitis caused by involvement of the nasal mucosae.
Later manifestations of congenital syphilis include bone and teeth deformities, such as “saddle nose” (due to destruction of the nasal septum), “saber shins” (due to inflammation and bowing of the tibia), “Clutton’s joints” (due to inflammation of the knee joints), “Hutchinson’s teeth” (in which the upper incisors are widely spaced and notched), and “mulberry molars” (in which the molars have too many cusps).
Tabes dorsalis and general paresis may develop as in adults, with 8th cranial nerve deafness and optic nerve atrophy as well as a variety of other ophthalmologic involvement leading to blindness being additional features.
Syphilis in pregnancy can lead to spontaneous abortion, stillbirth, premature delivery, or perinatal death. Any woman who delivers a stillborn infant after 20 weeks' gestation should be tested for syphilis. Infected infants may experience significant morbidity during infancy, childhood, and adolescence.
Routine prenatal screening for syphilis remains the most important factor in identifying infants at risk of developing congenital syphilis. Screening is legally required at the beginning of prenatal care in all states in the United States.
Screen women at high risk for syphilis more frequently because they may have repeat infections during pregnancy or may become reinfected late in pregnancy. A study in Nigeria has demonstrated the usefulness of syphilis screening during pregnancy. These researchers recommended that syphilis screening should be continued as part of routine antenatal testing.
Early manifestations of congenital infection vary and involve multiple organ systems. About 60% of infants born with congenital syphilis are asymptomatic at birth. Symptoms develop within the first 2 months of life. In symptomatic infants, the most common physical finding, reported in almost 100% of cases, is hepatomegaly; biochemical evidence of liver dysfunction is usually observed.
The other common findings are skeletal abnormalities, rash, and generalized lymphadenopathy. Radiographic abnormalities, periostitis or osteitis, involve multiple bones and are seen in the vast majority of symptomatic infants, but they also can be found in on fifth of infants with no symptoms or relevant findings on physical examination. Sometimes, the lesion is painful and an infant will favor an extremity (pseudopalsy). The rash is maculopapular and may involve palms and soles. In contrast to acquired syphilis, a vesicular rash and bullae may develop. These lesions are also highly contagious.
Mucosal involvement may present as rhinitis ("snuffles"). Nasal secretions are highly contagious.
Hematological abnormalities include anemia and thrombocytopenia. Some have leukocytosis. Abnormal CSF examination is seen in a half of symptomatic infants but also can be found in 10% of those who are asymptomatic.
Scarring from the early systemic disease causes late manifestations of congenital syphilis. Manifestations include neurosyphilis and involvement of the teeth, bones, eyes, and the eighth cranial nerve, as follows:
Tertiary syphilis manifestations are divided into the following subgroups: benign, cardiovascular, and late.
In benign tertiary syphilis, gummatous lesions are found in skin and bones but rarely in other organs. Gummas are considered benign because they rarely involve vital body structures. (See the photographs below.)
These photographs show close-up images of gummas observed in tertiary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Cardiovascular tertiary syphilis can cause aortitis, aortic aneurysm, coronary stenosis, aortic insufficiency, and myocarditis.
Late neurosyphilis may present with focal neurological findings suggestive of a stroke.
Late Syphilis - Serpiginous Gummata of Forearm
Late Syphilis - Ulcerating Gumma
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