Adolescent Health Care: A Practical Guide

Chapter 61

Gonorrhea

Margaret J. Blythe

Gonorrhea is one of the most important sexually transmitted diseases (STDs) in adolescents because of its high incidence and potential for serious complications.

Etiology

Gonorrhea is an STD caused by Neisseria gonorrhoeae, which has the following characteristics:

  1. The organisms are small, gram-negative cocci, kidney shaped and arranged in pairs (diplococci) with long axes in parallel.
  2. The organisms are typically intracellular and usually located within or associated with polymorphonuclear (PMN) leukocytes.
  3. The organisms grow optimally at 36°C to 37°C, with a moist environment enriched with 10% carbon dioxide in media containing blood or serum to ensure growth. N. gonorrhoeaeis an oxidase-positive diplococcus, which can be differentiated from other Neisseria species by its use or nonuse of different carbohydrates.
  4. As a human pathogen, the organism cannot live outside its host, and is easily killed by drying, soap and water, and other antiseptic agents.
  5. Gonococci are killed by PMN cells, but when phagocytosed by macrophages, survive and replicate. Surrounded by macrophages' intracellular organelles, and granules, the cocci multiply within them and as such are not recognized by host's PMN cells.
  6. Gonococci have the ability to turn off or vary the expression of cell surface components; this antigenic variation of surface proteins is thought to be a means of escape from host-specific antibody detection.
  7. Cell envelope of the gonococci is composed of three parts—outer membrane, a peptidoglycan layer, and cytoplasmic membrane.
  8. Pili are hair-like appendages which attach to the cell membrane. Pili from different strains are diverse with the ability of the same bacteria to “antigenically” vary the composition of its pili. There are pilated and nonpilated strains of gonococci.
  9. Three proteins associated with the cell membrane and surface of the gonococci characterize the bacteria with regard to its virulence and association with clinical presentation and disease. These are protein I (PI), protein II (PII) (opacity-associated protein [Opa]), and protein III (PIII).
  10. Types of organisms: There are >70 different strains of Neisseria. N. gonorrhoeaespecies have been differentiated by several characteristics:
  11. Presence or absence of pili
  12. Opaque or transparent colonies
  13. Auxotyping
  14. Serotyping
  15. Molecular methods: Molecular methods were first used to characterize the plasmids associated with antibiotic resistance. Nucleic acid amplification techniques (NAATs) such as polymerase chain reaction (PCR) are now available to analyze entire gonococcus chromosome. The method is currently being used to determine the Opa-typing of different gonococci to study sexual networks.

Epidemiology

Incidence

  1. Gonorrhea is the second most frequently reportable disease in the United States after Chlamydia trachomatisinfections. Approximately 339,583 cases were reported in 2005, with reported cases thought to represent less than 50% of all cases. Rates of gonorrhea declined by 73.8% between 1975 and 1998 to 122.4 per 100,000, but then increased by 7.8% in 1998. Since 1998, the rates have continued to decline with the most recent rate from 2005 reported at 115.6 cases per 100,000, only a slight increase from the 113.5 per 100,000 reported in 2004, which was the lowest rate ever reported by the Centers for Disease Control and Prevention (CDC) (Table 61.1) (Weinstock, 2004; Centers for Disease Control and Prevention, 2004).
  2. The incidence remains high in some groups as defined by age, race/ethnicity, geography, or sexual risk behavior (Centers for Disease Control and Prevention, 2004).
  3. Age: Adolescents (ages 15–19 years) and young adults (ages 20–24 years) continue to be at highest risk in 2004 for acquiring this disease with the peak incidence occurring in men aged 20 to 24 years (430.6 per 100,000), and in female adolescents aged 15 to 19 years (610.9 per 100,000). Approximately 60% of all reported cases

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occur in men and women between ages 15 and 24 years and 80% between ages 15 and 29 years.

TABLE 61.1
Cases and Incidence of Gonorrhea in the United States, 1975–2004

 

1975

1985

1998

2000

2001

2002

2003

2004

2005

Adapted from Centers for Disease Control and Prevention Division of STD Prevention. Department of Health and Human Services, with permission. Centers for Disease Control and Prevention. STD Surveillance 2004. National Profile
(http://www.cdc.gov/STD/stats/tables/tablel.htm).

Cases

999,937

911,419

356,492

363,136

361,705

351,852

335,104

330,132

339,593

Incidence per 100,000

467.7

383.0

129.2

128.7

126.8

122.0

115.2

113.5

115.6

  1. Ethnicity: Rates vary dramatically among adolescents from different racial/ethnic backgrounds and practice settings. Incidence in African-Americans, Hispanics, and Native Americans, is disproportionately high compared with whites and Asians. The gonorrhea rate among African-Americans declined from 2003 to 2005, falling 4.5% (from 655.8 to 626.4); however, African-Americans remained the group most heavily affected by gonorrhea. Reported rates of gonorrhea in African-Americans were 18 times greater than those of whites in 2005, down from 20 times in 2003. Rates increased 27.2% among American-Indians/Alaska Natives from 2003 to 2005 (from 103.5 to 131.7). Rates increased 7.3% in these two years among Latinos to 74.8 per 100,000, and 8% among whites to 35.2 per 100,000. Rates increased between 2003 and 2005 for Asians/Pacific Islanders from 22.8 to 25.9 (Centers for disease Control and Prevention, 2004 and http://www.cdc.gov/std/stats/trends2005.htm# trendsgonorrhe)
  2. Geography: The highest reported rates of gonorrhea are in the Southeastern region of United States. In 2005, rates among parts of the United States varied-South, 143.9 per 100,000; Midwest, 142.5 per 100,000; Northeast, 74.7; West 71.8 per 100,000. However, in contrast to declines in the other areas of the country, gonorrhea rates in the West have increased steadily in recent years (35.4% between 2001 and 2005).
  3. Gender: The male-to-female ratio of reported gonorrhea infection approaches 1:1. In 2004, the N. gonorrhoeaerate for women was 116.5 per 100,000 compared with men, 110 per 100,000.
  4. Risk factors: Risk factors for acquiring gonorrhea include:
  • Multiple or new sex partners
  • Inconsistent, incorrect or no condom use
  • Belonging to a minority group
  • Living in an urban area where prevalence of gonorrhea is high
  • Being adolescent (especially female)
  • Having a lower socioeconomic status
  • Using drugs including alcohol
  • Exchanging sex for drugs or money
  • Men who have sex with men (MSM)
  1. Approximately the same number of cases of gonorrhea is reported in the age-groups of 15 to 19 years and 20 to 24 years, when combining cases in males and females. However, almost twice as many individuals are sexually active in the 20- to 24-year-old age-group as in the 15- to 19-year-old age-group. When corrected for this difference, the incidence in sexually active 15- to 19-year-olds is twice that of 20- to 24-year-olds.
  2. The reasons for the high incidence in 15- to 19-year-old adolescents include psychosocial and biological factors.
  3. Psychosocial factors
  • Increased number of sexual partners, increased frequency of sexual intercourse, and decreased age at first intercourse.
  • Low rates of consistent and appropriate use of condoms and other barrier methods (Crosby et al., 2005; Paz-Bailey et al., 2005).
  • Lack of accessible clinical services providing confidential services for adolescents.
  • Lack of screening by health care providers in health care settings (Chacko et al., 2004).
  1. Biological factors
  • More columnar epithelial cells exposed on the ectocervix of teens referred to as cervical ectopy. N. gonorrhoeaepreferentially infects these cells.
  • High percentage of infections, asymptomatic particularly in females.

Prevalence

  1. The prevalence rates vary and depend on rates of “routine screening” for gonorrhea. Public health clinics and therefore the populations that attend such clinics as minorities are more likely screened and reported (Centers for Disease Control and Prevention, 2004).
  2. National sample: The overall prevalenceof gonococcal infection in a nationally representative sample of 14,322 young adults aged 18 to 26 years was 0.43% with little variation between males (0.44%) and females (0.42%) and among the different ages studied. Substantial variation occurred by race/ethnicity with the lowest prevalence noted for white men and women (0.07%) and highest for black men and women (2.36%) (Miller et al., 2004).
  3. STD clinics: Males, range 8% to 25%.

For 32,595 men with 45,390 visits to STD clinics at each of three cities, range of gonorrhea positive cultures varied from 8.1% in Seattle, to 20.8% in Indianapolis, and 24% in New Orleans (Kohl et al., 2004). In 2004, as in prior years, a higher proportion of male gonorrhea cases (42.7%) were reported from STD clinics than female cases (17.9%).

  1. Family planning clinics in the United States serving 15- to 24-year-old females: In 2004, median rate was 0.88% (range 0.1%–4.2%). One study of family planning clinics in Missouri indicated an overall prevalence for gonorrhea of 0.7% for 31,762 women aged 15

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to 24 years and 4% for chlamydia. The gonorrhea rate was 4% for blacks and 0.4% for whites; the chlamydia rate was 9% for black women and for white, 4%. Independent predictors of gonorrhea in both races were presence of symptoms, recent sexual contact with a partner who had STD symptoms, and Chlamydia infection (Einwalter et al., 2005).

  1. Job Corps: In 2004, the female median rate was 2.4%, (range 0.0%–6.4%) and in males the median rate was 3.7% (range 1.0%–5.7%) from different states.
  2. University and college student health centers: <1% to 2% positive for gonorrhea.
  3. Juvenile detention facilities: In 2004, in males the median gonorrhea prevalence rate was 0.8% (range 0%–18.2%) compared to 4.5% in females (range 0%–16.6%). In another study, the prevalence of gonorrhea was 5.1% in 33,619 adolescent females and 1.3% in 98,296 adolescent males. This compared to chlamydia rates of 15.6% in the adolescent females and 5.9% in the males. Of females with gonorrhea, 54% were coinfected with Chlamydia, and 51% of males with gonorrhea were coinfected with Chlamydia(Kahn et al., 2005). At a study at three juvenile facilities, approximately 93% of adolescent males testing positive for gonorrhea were asymptomatic. This compared to 97% of those testing positive for chlamydial infections (Mertz et al., 2002).
  4. Adolescent clinics: Approximately 3% to 9% of teens are positive for gonorrhea. Similar rates were found for teens attending adolescent clinics when comparing cervical cultures (9.4%) with urine specimens using NAATs (9.1%) (Xu et al., 1998; Jones et al., 2000).
  5. Urban emergency departments (EDs): One percent to 7% (Aledort et al., 2005).
  6. Correlation with drug use: Thirty-two percent of female adolescents with gonorrhea in San Francisco had received money or drugs in exchange for sex (Schwarcz et al., 1992).

Host

Humans are the only natural host for N. gonorrhoeae.

Transmission

Transmission is virtually exclusively through oral, vaginal, or anal sexual contact. The exception is gonococcal ophthalmia, which usually occurs in newborns but has been reported in physicians, laboratory technicians, and the general adult population presumably when direct contact of the organism with the eye through hand transmission has occurred.

Pathophysiology

  1. gonorrhoeaecauses disease by direct invasion and spread on mucosal and glandular structures lined by columnar or cuboidal, noncornified epithelium.

Virulence

The virulence of the infection may be related to certain characteristics of the organism.

  1. Pili: Pili increase adhesion of gonococci to tissues, are associated with small colonies and increased virulence. Pili also decrease the ability of neutrophils to ingest and kill the organism. Nonpilated organisms have advantages once past mucosal entry.
  2. Colony morphology: Cells with protein II or Opa have “opaque” colony morphology, whereas strains without Opa are “transparent.” Opaque colonies have increased adherence to host cells and are more often found in specimens from males with gonococcal urethritis and in cervical isolates obtained from females. Transparent colonies appear to represent the invasive form of N. gonorrhoeae. The other proteins in the outer membrane are protein I and protein III.
  3. Auxotype: This is determined by the nutritional or specific growth requirements of the organism including amino acids, nucleic acid bases such as purines and pyrimidines, as well as vitamins.
  4. Other virulence factors
  5. Lipo-oligosacchride (LOS): As the major protein in the outer membrane of gram-negative bacteria, LOS with potent endotoxic activity serves as the target protein for much of the bactericidal antibody produced.
  6. Other possible molecular mechanisms: Immunoglobulin A1(IgA1) protease and iron-regulated proteins.

Clinical Manifestations

Clinical manifestations of N. gonorrhoeae are similar to those caused by C. trachomatis, and both C. trachomatis and N. gonorrhoeae occur frequently together in the same individual. Susceptible sites are usually mucosal columnar epithelial areas. The spectrum of gonococcal infections includes the following:

  1. Asymptomatic infections:
  2. Urethral/cervical infections may persist for months if untreated.
  3. In women, asymptomatic rates range from 25% to 90% of the infections.
  4. Estimates suggest that less than 10% of infections in males are asymptomatic, but studies of adolescent males in juvenile detention facilities report high rates of asymptomatic males (Pack et al., 2000).
  5. More than half of men with rectal infections are asymptomatic.
  6. Because symptomatic individuals seek treatment and most asymptomatic individuals do not, asymptomatic individuals remain untreated, infected, and spread infection.
  7. Asymptomatic infections can involve the following:
  • Urethra: male and female
  • Endocervix
  • Rectum
  • Pharynx
  1. Symptomatic uncomplicated infections may result in the following:
  2. Urethritis
  3. Cervicitis
  4. Proctitis
  5. Pharyngitis
  6. Bartholinitis
  7. Conjunctivitis

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  1. Local complications include the following:
  2. Pelvic inflammatory disease
  3. Epididymitis
  4. Bartholin gland abscess
  5. Penile edema
  6. Periurethral abscess: Abscess of bulbourethral glands (Cowper glands) or sebaceous glands of the prepuce or foreskin (Tyson glands)
  7. Prostatitis
  8. Perihepatitis: Complication of salpingitis (Fitz-Hugh-Curtis Syndrome)
  9. Seminal vesiculitis
  10. Systemic complications might include the following:
  11. Disseminated gonococcal infection (DGI)
  12. Arthritis-dermatitis syndromes
  13. Gonococcal meningitis
  14. Gonococcal endocarditis

Genitourinary Infections

The most common clinical manifestation of gonorrhea is a genitourinary infection.

Males

  1. Urethritis
  2. Incubation period: Ranges from 1 to 14 days with most men symptomatic 2 to 5 days after exposure
  3. Symptoms: Dysuria, meatal pruritus
  4. Clinical findings: Profuse purulent urethral discharge (25% scanty, minimally purulent discharge)
  5. Infection can spread and cause epididymitis, prostatitis, seminal vesiculitis, and infection of Cowper and Tyson glands.
  6. Epididymitis: Ten percent to 30% of untreatedmen develop this complication, which is manifested by the following:
  • Urethral discharge and dysuria
  • Scrotal pain and tenderness, usually unilateral
  • Scrotal swelling and erythema
  • Pain in the inguinal area and flank pain in severe cases
  • Pain, tenderness, or swelling of the lower pole of the epididymis, which can spread to the head of the epididymis
  • Swelling and pain of spermatic cord
  1. Prostatitis: Prostatitis is a rare complication of gonorrhea. Signs and symptoms include the following:
  • May be asymptomatic
  • Chills, fever, malaise, myalgia
  • Rectal pain and discomfort
  • Lower back pain
  • Lower abdominal pain, suprapubic discomfort
  • Dysuria, urinary frequency, and occasionally acute urinary retention
  1. Risk of infection: Risk of infection is approximately 20% to 50% for a male after a single exposure through vaginal intercourse with an infected female (McMillian, 2002).

Females

Signs and symptoms are less specific in females than in males. Often the teen may complain of vaginal discharge, dysuria, or frequency. The incubation period is more variable than in males, but symptoms usually appear within 10 days of exposure. Common local problems include the following:

  1. Endocervicitis
  2. Increased vaginal discharge, often purulent
  3. Dyspareunia
  4. Erythema, edema, and friability of cervix resulting in spotting
  5. Risk of infection: Estimated at 60% to 90% for a female after single exposure to an infected male
  6. Urethritis
  7. Dysuria
  8. Urinary frequency
  9. Exudate from urethra or periurethral glands (Skene gland)
  10. Suprapubic pain
  11. Bartholinitis: Purulent exudate from Bartholin gland
  12. Bartholin gland abscess: Labial pain and swelling. The most common complication in females apart from pelvic inflammatory disease (PID) is abscess of the Bartholin gland.
  13. Spread of infection can extend into the following areas:
  14. Endometritis: Recent data suggests that one in four women infected with C. trachomatisor N. gonorrhoeae and 15% of women with bacterial vaginosis have histological endometritis, in the absence of signs or symptoms of acute PID (Wiesenfeld et al., 2002).
  15. Fallopian tubes: PID (see Chapter 63) occurs in as many as 10% to 20% of females with acute urogenital gonorrhea. Strains causing PID have different auxotypes, different patterns of antibiotic resistance, and are often “transparent” colonies. Patients with gonococcal-associated PID compared to chlamydial-associated PID or nongonococcal, nonchlamydial–associated PID may be more ill and febrile at clinical presentation with the onset on symptoms within 7 days of the menstrual cycle (Wiesenfeld et al., 2005).
  16. Upper abdomen: Perihepatitis (Fitz-Hugh-Curtis syndrome): Presents as right-upper-quadrant pain.
  17. Ovary: Tuboovarian abscess.

Extragenital Sites

  1. Pharyngitis
  2. Pharyngeal involvement is usually asymptomatic in >90% of infected individuals.
  3. Pharyngitis may be manifested by a sore throat 3 to 7 days after exposure and occasionally with fever and cervical adenopathy.
  4. Positive pharyngeal cultures may be found in 3% to 7% of heterosexual males, 10% to 20% of heterosexual females, and 10% to 25% of homosexual males with genital gonorrhea, with the pharynx as the sole site of infection estimated in <5% of individuals. Fellatio is a more effective mode of transmission than cunnilingus. Pharyngeal infection may be a significant cause of urethral gonorrhea in MSM.
  5. Spontaneous elimination of the organism can occur in 12 weeks.
  6. Significance of infection: Infected individuals may be at risk for dissemination of gonorrhea.
  7. Rectal gonorrhea
  8. Prevalence rates: Rectal cultures may be positive in 35% to 50% of females with genital infection. Most anorectal infections in females are asymptomatic and are thought related to infected perineal secretions. In one study, anorectal gonococcal infections in MSM were associated with distinct auxotype/serovar classes (Geisler et al., 2002).
  9. Rectal gonorrhea can produce the following symptoms of distal proctitis:
  • Mucopurulent anal discharge
  • Rectal bleeding

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  • Anorectal pain or pruritus ani
  • Tenesmus
  • Constipation
  1. Proctoscopic examination may show a normal appearance or patchy, generalized erythema of rectal mucosa or purulent exudate, erythema, edema, friability, or other inflammatory changes of the rectal mucosa.
  2. The differential diagnosis for infections involving the first 5 to 10 cm of the rectum causing proctitis is chlamydia, herpes, (cytomegalovirus [CMV] infection, and syphilis. Inflammation extending more than 15 cm and causing proctocolitis is usually caused by Shigella, Campylobacter, Entamoeba histolytica,or Salmonella. Other diagnoses to consider are ulcerative colitis and Crohn disease.
  3. Conjunctivitis is usually severe with high risk of sequelae

Disseminated Disease

Less than 1% of individuals with gonorrhea develop disseminated disease (DGI) characterized by fever, rash, arthritis, or arthralgia. Certain strains of N. gonorrhoeae are more likely to disseminate. These strains tend to cause asymptomatic urogenital infection or pharyngeal infections and are more resistant to complement-mediated bacterial activity in serum. DGI is more common in females with a 4:1 ratio of female:male. Recurrent bacteremia has been described in individuals with deficiency of 6th, 7th, and/or 8th components of complement (Young and McMillan, 2002). Other risk factors for dissemination include immune-altering disease states such as lupus erythematosus.

Arthritis-Dermatitis Syndrome

  1. Purulent arthritis: Purulent arthritis is the most common systemic complication of N. gonorrhoeaeand usually occurs within 1 month of exposure. Approximately 25% to 50% of patients complain of pain in a single joint. The knee is the most common site of purulent gonococcal arthritis but may involve the wrist, metacarpophalangeal joints, and ankle. Monoarticular septic arthritis may present without preceding dermatitis or tenosynovitis.
  2. Migratory polyarthralgias/arthritis: Others have migratory polyarthralgia or asymmetrical polyarticular arthritis involving the knees, wrists, small joints of hands, ankles, and elbows with not enough fluid to aspirate. Knees are the most frequently involved joints, but all joints including the hip and shoulder have been affected. Sacroiliac, temporomandibular, and sternoclavicular joints are rarely involved.
  3. Tenosynovitis: Tenosynovitis may affect the hands and fingers but less likely the lower extremities, involving the extensor and flexor tendons and sheaths of the hands and feet.
  4. Fever, chills, and leukocytosis are common but 40% are afebrile.
  5. Approximately 90% will have a skin rash:
  6. Variable presentations:
  • Hemorrhagic lesionspresenting as purpura and necrotic centers
  • Vesiculopapular lesionson an erythematous base
  1. All lesions begin as erythematous papuleswith hemorrhagic lesions most often on palms and soles while others progress from papules, to vesicles, to pustules.
  2. Frequently painful, asymmetrical lesions over extremities near the joints, palms, soles of feet and occasionally on trunk and rarely on face.
  3. Diagnosis:
  4. Positive blood cultures in 20% to 30% of patients, but cultures should be done in the first few days of the illness.
  5. Joint cultures are rarely positive with polyarticular presentation. For monoarticular presentation, the affected joint's synovial fluid will appear turbid, with predominance of PMN cells and low glucose. Positive cultures result in less than 50% of cases and are associated with negative blood cultures. PCR has been used on joint fluid to make the diagnosis.
  6. Gram stain results and cultures are usually negative from skin, but immunofluorescent stains if available on biopsy specimens of skin identify gonorrhea in more than half the specimens in studies.
  7. Elevated peripheral white counts occur in the majority and elevation of sedimentation rate in most. Elevated liver enzymes occur in 50% of cases.
  8. Gonococci have been found on the mucosal surfaces of cervix and pharynx 80% of the time despite negative blood, skin, and joint fluid cultures.
  9. Differential diagnosis of gonococcal arthritis
  10. Infections: Meningococcemia, bacteremias, endocarditis, infectious arthritis, and infectious tenosynovitis
  11. Seronegative arthritides: Reiter syndrome, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, rheumatic fever, Lyme disease, bacterial endocarditis
  12. Lupus erythematosus
  13. Allergic reaction to drugs

Sexually Acquired Reactive Arthritis (Reiter Syndrome)

See Chapter 62 on Chlamydia infections. Table 61.2 compares gonococcal arthritis and acute Reiter syndrome.

Other Sites of Dissemination

  1. Perihepatitis: Most often a complication of salpingitis, found rarely in men. Presentation usually involves pain in right upper quadrant and occasionally right shoulder suggesting irritation of right side of diaphragm.
  2. Mild hepatitis: Found in up to 50% of patients, but not usually clinically suspected and usually follows bacteremia of DGI.
  3. Gonococcal meningitis: Rare complication that can be clinically indistinguishable from other meningococcal infections.
  4. Rare cardiac manifestations: Myopericarditis, heart block, endocarditis.
  5. Other: Osteomyelitis, pneumonia.

Diagnosis

Gonococcal Urethritis: Males

  1. Gram-negative intracellular diplococci on smear of urethral exudates:
  2. If positive, sufficient for diagnosis of gonorrhea.
  3. Sensitivity and specificity of Gram stains for infected male urethra is 90% to 95% and 95% to 100%

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respectively if symptomatic and 50% to 70% and 95% to 100% if asymptomatic.

TABLE 61.2
Comparison of Acute Gonococcal Arthritis and Acute Reiter Syndrome

Characteristic

Acute Gonococcal Arthritis (%)

Acute Reiter Syndrome (%)

Back pain

0

20

Urethritis

28

76

Migratory arthralgias

83

10

Chills

33

0

Temperature >39.4°C

27

39

Skin lesions

Isolated papules and pustules on extremities and trunk

Circinate balanitis; keratoderma of shaft of penis. Asymptomatic oral macular lesions on palate, buccal mucosa.

Sacroiliac involvement

3

30

Wrist involvement

67

30

Heel involvement

7

67

Antigen HLA-B27

Usually negative

>90 positive

  1. If Gram stain result is negative or not done or urethral exudate not present, culture a specimen from anterior urethra:
  2. Use a sterile calcium alginate urethral swab inoculating a modified Thayer-Martin medium culture plate (chocolate [blood] agar), which has antibiotics added to suppress other organisms that “normally” colonize the sites.
  3. Cultures obtained from other sites normally colonized by other organisms (i.e., rectum, pharynx, or endocervix) should be cultured on selective medium (Thayer-Martin) as well.
  4. Cultures obtained from sterile areas (i.e., blood, spinal fluid, or synovial fluid) can be plated onto nonselective, chocolate agar.
  5. Organisms have to be inoculated directly on medium, transported in warm 36°C to 37°C environment with 5% to 10% carbon dioxide.
  6. Growth of oxidase-positive, gram-negative diplococci on selective media is sufficient evidence for a diagnosis.
  7. Carbohydrate tests to discriminate types of Neisseria show that N. gonorrhoeaemetabolize only glucose and not other sugars such as lactose, maltose, sucrose, and/or fructose as do other Neisseria species. Culture sensitivity is 92.7% in symptomatic males and 46.2% in asymptomatic men but 100% specific (Martin et al., 2000).
  8. NAATs are used to diagnose male urethral infections (Table 61.3).
  9. In symptomatic patients: Sensitivities of NAATs are 96.5% to 100%, specificities, 95% to 98.8% (Martin et al., 2000; Wheeler et al., 2005; Chernesky et al., 2005).
  10. In asymptomatic patients:}?> Sensitivities of NAATs are 73.1% to 98.1%, specificities, 97.5% to 99% (Martin et al., 2000; Wheeler et al., 2005; Chernesky et al., 2005).
  11. An alternative to urethral swab would be urine testing with NAATs:
  12. All methods—PCR, transcriptional mediated amplification (TMA), and strand displacement amplification (SDA)—have been FDA approved for chlamydia and gonorrhea screening on both male and female urine except PCR for gonorrhea on female urine.
  13. Although urethral culture for gonorrhea is less expensive than NAATs, many males prefer urine testing.
  14. In symptomaticmale patients: Sensitivities of NAATs using urine are 98.2% to 99.9%, specificities 98.2% to 99.9% (Martin et al., 2000; Chernesky et al., 2005; Cook et al., 2005).
  15. In asymptomaticmale patients: Sensitivities of NAATs using urine are 42.3% to 98.2%, specificities 98% to 99.9% (Martin et al., 2000; Chernesky et al., 2005; Cook et al., 2005).
  16. Urethral gonorrhea culture in asymptomaticmales also has a relatively poor sensitivity (46.2%).
  17. Although testing with urine (42.3%) did not perform as well as urethral swab (73.1%) for PCR in asymptomaticmales, it may be easier to get cooperation collecting a urine sample rather than a urethral specimen.
  18. The homosexual male adolescent should also have cultures obtained from the rectum and pharynx to assess those sites, because NAAT methods are not approved for those sites.
  19. In asymptomaticmales, the urinary leukocyte esterase dipstick test (LET) on first-catch urine, in certain situations, can be a valuable screening technique.
  20. In low-prevalence settings (<5%), LET has poor positive predictive value but has a high negative predictive value.
  21. As a cost-saving measure, LET may be used to screen with any positive test sent for a specific diagnosis by NAAT.

Gonococcal Endocervicitis: Females

  1. Cultures should be obtained from the endocervical canal and inoculated on Thayer-Martin medium to diagnose gonorrhea:
  2. Do not use a lubricant during the pelvic examination, because this may be toxic to the organism.
  3. Place a swab in the cervical os for 20 to 30 seconds and rotate. For screening purposes, only endocervical cultures are recommended. A single culture is 80% to 95% sensitive in detecting gonorrhea.
  4. If anorectal sex has occurred, a separate swab can be used in the anal canal. Approximately 5% of females

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have positive culture from this site only. The swab can be inserted approximately 2 cm, avoiding fecal mass, and moved side to side for 20 to 30 seconds.

TABLE 61.3
Comparison of Nucleic Acid Amplification Tests (NAATS) for Neisseria gonorrhoeae

 

PCR

SDA

TMA

Culture

PCR, polymerase chain reaction: COBAS Amplicor (Roche); TMA, transcriptional mediated amplification: Aptima Combo (Gen Probe); Aptima Ct and Aptima N. gonorrhoeae (Gen Probe); SDA, strand displacement amplification: Probe Tec (Becton Dickinson).
a Asymptomatic, 73.1%.
b Asymptomatic, 46.2%.
c Asymptomatic, 42.3%.
d All sites for all tests FDA approved except for female urine N. gonorrhoeae PCR; only TMA FDA approved for vaginal swabs (Martin et al., 2000; Wheeler et al., 2005; Chernesky et al., 2005; Crotchfelt et al., 1997; Cook et al., 2005; Cosentino et al., 2003; Schachter et al., 2003).

 

Test

COBAS Amplicor

Probe Tec

Aptima

 

Company

Roche

Becton Dickinson

Gen Probe

 

Gender/site

       

Male/urethra

       

 Sensitivity

97.3%–99.0%a

98.5%–100%

73.1%–98.1%

80%–95%b

 Specificity

98.8%–99.9%

91.9%–100%

95.9%–97.5%

100%

Male/urine

     

Not available

 Sensitivity

94.1%–100%c

97.9%

95.2%

 

 Specificity

99.2%–99.9%

92.5%–100%

98.2%

 

Female/cervix

       

 Sensitivity

92.4%–100%

95.6%–99.6%

83.7%–96.1%

76.6%–84.8%

 Specificity

99.5%

99.3%–99.6%

98.1%–99.6%

100.0%

Female/urined

     

Not available

 Sensitivity

64.8%–94.4%

98.5%–100%

86.5%–97.4%

 

 Specificity

95.9%–99.5%

99.3%–99.6%

99.1%–99.5%

 

Vaginal swab

   

FDA approved

Not available

         
  1. Gram stain smears from the endocervix are not recommended. Such smears are only 50% to 70% sensitive in uncomplicated endocervical infection.
  2. Newer diagnostic methods (e.g., NAATs)
  3. PCR, TMA, and SDA tests can be used on endocervical specimensfor both chlamydia and gonorrhea (Martin et al., 2000; Crotchfelt et al., 1997; Gaydos et al., 2003; Van der Pol et al., 2001) (Table 61.3).
  4. PCR, TMA, and SDA tests are approved for first-void urine specimensin females for chlamydia, and TMA and SDA are approved for gonorrhea but not PCR (Martin et al., 2000;Crotchfelt et al., 1997; Gaydos et al., 2003; Van der Pol et al., 2001) (Table 61.3).
  5. PCR* and SDA tests on vaginal swabsshow similar or superior results to cervical specimens. SDA was recently FDA approved for vaginal samples (Wiesenfeld et al., 1996; Black et al., 2002; Cosentino et al., 2003; Schachter et al., 2003).

Note: *Cross-reacts with other nonpathogenic Neisseria species found in the vagina.

  1. Summary and limitations of NAATs testing for chlamydia and gonorrhea:
  • For each of the three commercially available nucleic acid tests for C. trachomatis, the sensitivity and specificity of urine and endocervical samples for women as well as urine and urethral samples for men were nearly identical.
  • Sensitivity and specificity of the PCR urine to detect N. gonorrhoeaein women were significantly lower than cervical samples, but did not appear different for SDA and TMA (Cook et al., 2005).
  • Results of sensitivity and specificity testing for gonorrhea in symptomatic men comparing urine and urethral samples were similar.
  • Specificities were high (from 98%–100%). However, if specificity is closer to 98% then screening in low-prevalence populations could result in almost one third of positives to be falsely positive (Cook et al., 2005).
  • Inhibitors of enzyme amplification can prevent assays from providing a positive result leading to decreased sensitivity. For PCR and TMA, rates of inhibition vary from 5% to 20% whereas SDA did not seem to be affected (Cook et al., 2005).

Anorectal Gonorrhea

Positive cultures from the rectum are required for diagnosis of anorectal gonorrhea. The nucleic acid assays have not been adequately studied for this site. Gram stains are not suitable as anal swabs are only 40% to 60% sensitive and 95% to 100% specific.

Gonococcal Pharyngitis

  1. Diagnosis requires a positive culture from the pharynx. As with anal infection, nucleic acid detection techniques

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are not considered appropriate and Gram stains are not appropriate.

  1. Several studies have indicated that routine pharyngeal screening in adolescents is not cost-effective (Brown et al., 1989; Roochvarg and Lovchik, 1991).

Systemic Infection

  1. Positive cultures from the urethra, endocervix, pharynx, rectum, and conjunctiva, or positive NAATs from urethra and/or endocervix/vagina.
  2. Positive cultures from skin lesions, synovial fluid, or blood.

Therapy

Treatment of gonorrhea should take into account that strains of N. gonorrhoeae resistant to traditional treatment are rising, that chlamydial infections often coexist with gonorrhea, and that serious complications can arise from both gonococcal and chlamydial infections.

Resistance

The incidence of isolates of N. gonorrhoeae resistant to antibiotics has increased dramatically since the early 1980s. The 2004 report on surveillance of antibiotics used to treat N. gonorrhoeae is available (Centers for Disease Control and Prevention, 2004) and included the following information:

  1. Plasmid mediated
  2. Penicillin: Penicillinase-producing N. gonorrhoeae(PPNG)
  3. Tetracycline: Tetracycline-resistant N. gonorrhoeae(TRNG)
  4. Penicillin and tetracycline: Plasmid-mediated penicillin and tetracycline-resistant N. gonorrhoeae(PPNG/TRNG)
  5. Chromosomally mediated resistant N. gonorrhoeae
  6. Penicillin (chromosomally mediated penicillin-resistant N. gonorrhoeae): PenR
  7. Tetracycline (chromosomally mediated tetracycline-resistant N. gonorrhoeae): TetR
  8. Penicillin and tetracycline (chromosomally mediated penicillin- and tetracycline-resistant N. gonorrhoeae): CMRNG
  9. Ciprofloxacin (intermediate resistance and resistance)
  10. Spectinomycin
  11. Ceftriaxone (decreased susceptibility)
  12. Cefixime (decreased susceptibility)
  13. Azithromycin (susceptibility)

In 1986, the Gonococcal Isolate Surveillance Project (GISP) was established to monitor trends in antimicrobial susceptibilities of strains of N. gonorrhoeae in the United States. In 1976, PPNG was recognized in the United States and TRNG since 1985. In 1983, a mechanism of resistance involving multiple chromosomal mutations was identified that caused alterations in the cell membrane to antibiotics and changes in antibiotic-binding proteins. Data from the GISP showed that in 2004, 15.9% of isolates were resistant to either penicillin or tetracycline or both. A shift in type of resistance has evolved over the last decade from plasmid to chromosomal with the most recent data showing 0.6% PPNG, 3.4% TRNG, 0.5% PPNG-TRNG, 1.1% PenR, 6.1% TetR, and 4.3% CMRNG.

In 2004, all isolates were susceptible to spectinomycin, ceftriaxone, and cefixime. In 2003, 4.1% of the isolates demonstrated resistance to ciprofloxacin and in 2004, 6.8%. This is in comparison to 0.4% in 2000. Most of the “resistant” samples were from California. In 2004, Honolulu, Hawaii, continues to experience a high percentage of gonorrhea samples resistant to ciprofloxacin (22.8%) up from 13.3% in 2003. Other West-coast cities have experienced high rates of resistance. Resistance to ciprofloxacin increased from 7.2% in 2002 to 15% in 2003 and 23.8% in 2004 in MSM; whereas it increased from 0.9% in 2002 to 1.5% in 2003 and 2.9% in 2004 in heterosexuals.

Therefore the recommendation as of April 13th, 2007 in the CDC update to the 2006 STD Guidelines is to no longer use fluoroquinolones for the treatment of gonococcal infections and associated conditions such as pelvic inflammatory disease.

In 2004, 57 samples (0.9%) demonstrated decreased susceptibility to azithromycin compared to 26 (0.4%) in 2003.

Coinfection

  1. Household sample 18- to 26-year-olds: 0.3% of the population had both gonorrhea and chlamydia. For those with gonorrhea, 70% had chlamydia. For those with chlamydia, 7.9% had gonorrhea (Miller et al., 2004).
  2. In an STD population, the prevalence of chlamydia in those with diagnosed or contact of gonorrhea was 20% for men and 42% for women. Among patients with gonorrhea, the chlamydia prevalence was higher among men younger than 25 years than older (27% versus 13%) and also among women younger than 25 years than older (54% versus 20%) (Lyss et al., 2003).
  3. Of females in juvenile detention facilities with gonorrhea, 54% were coinfected with Chlamydia, and 51% of males with gonorrhea were coinfected with Chlamydia(Kahn et al., 2005).
  4. Another study of family planning attendees indicated approximately 40% of those with gonorrhea were also infected with Chlamydia(Einwalter et al., 2005).

Treatment Recommendations

Guidelines from Centers for Disease Control and Prevention, 2006.

  1. Uncomplicated urethral, endocervical, or rectal infections in adolescents and adults:
  2. Recommended regimens
  • Cefixime 400 mg PO in a single dose OR
  • Ceftriaxone 125 mg IM at one time

PLUS

A regimen effective against possible coinfection with C. trachomatis such as azithromycin (1 g PO in a single dose) OR doxycycline (100 mg PO b.i.d. for 7 days)

  • –Each of these regimens appears to cure >97% of anal and genital infections.
  • –Cefixime has the advantage of a one-time oral dose, but availability is uncertain. The serum levels are not as high as with ceftriaxone or

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as sustained and therefore not recommended for oral infections. Its effectiveness against incubating syphilis is not known.

  • –125 mg of ceftriaxone appears to be as effective as 250 mg, and no ceftriaxone-resistant strains of N. gonorrhoeaehave been reported.
  1. Alternative regimens
  • Spectinomycin (2 g IM in a single dose): Disadvantages include the expense, injectable use only, and ineffectiveness against syphilis.
  • Injectable cephalosporins are ceftizoxime (500 mg IM in a single dose), cefotaxime (500 mg IM in a single dose), cefotetan (1 g IM in a single dose), and cefoxitin (2 g IM with 1 g of probenecid in a single dose). None offers any significant advantage compared with ceftriaxone.
  • Oral cephalosporins other than cefixime (400 mg): These include cefuroxime axetil (1 g PO in a single dose) and cefpodoxime (1 g PO in a single dose). These appear to have less antigonococcal activity than cefixime (400 mg).

These regimens should be followed with a therapy that treats chlamydia. Although, azithromycin (2 g as a single dose) is effective for uncomplicated gonococcal infection, the expense and gastrointestinal side effects make it difficult to use. The 1-g dose is not considered effective.

  1. Treatment of sex partners
  2. All adolescents exposed to gonorrhea should be examined, cultured, and treated presumptively, as should sex partner(s) of patients diagnosed with gonorrhea.
  3. Treatment should be given for both chlamydia and gonorrhea, if chlamydia was not ruled out.
  4. Teens should be instructed to avoid sexual intercourse until they and their partners are cured.
  5. No sexual intercourse for 7 days after one-dose treatment and no longer having symptoms OR
  6. No sexual intercourse until 7 days of therapy completed and no longer having symptoms. Expedited partner therapy (EPT): EPT refers to the practice of treating sex partners of persons with STDs without an intervening medical evaluation or professional prevention counseling. One study of 2,751 patients demonstrated reduced levels of recurrent gonorrhea with EPT compared to standard management (3% versus 11%; RR  =  0.32 [0.13–0.77]) (Golden et al., 2005). In another study in an STD clinical setting, many partners of identified patients with infection had infections different from or in addition to those infections identified in the index patient (Khan et al., 2005). A recent CDC communication addressed the legal concerns and safety/benefits of EPT (Centers for Disease Control and Prevention, 2005).
  7. Follow-up

Routine follow-up cultures are not needed for persons treated for uncomplicated gonorrhea. Adolescents should be told to return for an examination if symptoms or signs persist after therapy. Most treatment failures are due to reinfection.

  1. Pharyngeal gonococcal infection

Gonococcal infection of the pharynx may be more difficult to eradicate than urogenital and anorectal sites. Few regimens have consistent cure rates >90%.

Recommended regimens include the following:

Ceftriaxone 125 mg IM in a single dose

PLUS treatment for chlamydia

Azithromycin 1 g PO in a single dose

OR

Doxycycline 100 mg PO b.i.d. for 7 days

Cefixime or any other oral cephalosporin or spectinomycin IM is not considered effective enough for pharyngeal infection. Only ceftriaxone should be used to treat MSM and heterosexuals with history of recent foreign travel or partners' travel.

  1. Treatment of gonorrhea in pregnant adolescents

Pregnant adolescents should be screened for gonorrhea, chlamydia, and syphilis at the first prenatal care visit, with tests repeated in the third trimester. Tetracyclines (i.e. doxycline) should be avoided during pregnancy. N. gonorrhoeae infection should be treated with one of the recommended cephalosporin regimens. Spectinomycin (2 g IM) can be used as an alternative, but may be difficult to obtain.

Recommended regimens to cover potential Chlamydia coinfection include:

o    Azithromycin 1 g orally, single dose

o    OR

o    Amoxicillin 500 mg orally three times daily for 7 days

Alternative Regimens

o    Erythromycin base 500 mg orally four times a day for 7 days

o    OR

o    Erythromycin base 250 mg orally four times a day for 14 days

o    OR

o    Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days

o    OR

o    Erythromycin ethylsuccinate 400 mg orally four times a day for 14 days

Note: Erythromycin estolate is contraindicated during pregnancy because of drugrelated hepatotoxicity

  1. Human immunodeficiency virus (HIV) infection

Teens infected with HIV and N. gonorrhoeae should receive the same treatment as those not infected with HIV.

  1. Acute salpingitis

See Chapters 60 and 63 for discussion and treatment of PID.

  1. Acute epididymitis

 .    Ceftriaxone 250 mg IM once

PLUS

Doxycycline 100 mg b.i.d. for 10 days

  1. Disseminated gonococcal infection

Hospitalization for intravenous treatment is recommended for initial therapy.

Recommended regimen

 .    Ceftriaxone 1 g IM or IV every 24 hours

Alternative regimens

  1. Cefotaxime 1 g IV every 8 hours

OR

  1. Ceftizoxime 1 g IV every 8 hours

OR

  1. Spectinomycin 2 g IM every 12 hours

All of the preceding regimens should be continued for 24 to 48 hours after improvement begins, at which time therapy may be switched to the following regimen to complete at least 1 week of antimicrobial therapy.

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  1. Cefixime† 400 mg orally twice daily

OR

  1. Cefixime suspension 500 mg twice daily orally (25 cc twice daily)

OR

  1. Cefpodoxime 400 mg orally twice daily

The tablet formulation of cefixime is currently not available in the United States

  1. Meningitis and endocarditis

These serious complications require high-dose intravenous therapy with an antibiotic effective against the causative strain. The recommended initial regimen is 1 to 2 g of ceftriaxone IV every 12 hours. Although optimal duration is not known, most authorities treat gonococcal meningitis for 10 to 14 days and endocarditis for at least 4 weeks.

  1. Gonococcal ophthalmia

For adolescents and children weighing >20 kg, the treatment includes ceftriaxone (1 g IM once), and eye irrigation with buffered ophthalmic solution should be performed once to help clear the discharge followed by careful eye examination, including slit-lamp examination. For neonates and infants, 25 to 50 mg/kg IV or IM in a single dose not to exceed 125 mg. Simultaneous infection with C. trachomatis should be considered and appropriate treatment given if the individual does not respond to antibiotics.

  1. Doses in adolescents

Adolescents weighing >45 kg should be treated with the adult doses, as already outlined. Adolescents who weigh <45 kg should be treated as follows:

 .    For uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, and proctitis

  • Ceftriaxone (125 mg IM once)

OR

  • Spectinomycin (40 mg/kg of body weight IM [maximum 2 g] once)

PLUS

  • Doxycycline (100 mg b.i.d. for 7 days) in addition to the previously described regimen (if 8 years or older and >45 kg)

OR

  • Azithromycin (20 mg/kg [maximum 1 g] once)
  1. For bacteremia or arthritis
  • Ceftriaxone (50 mg/kg as a single dose [maximum 1 g] IV/IM for 7 days)
  1. For meningitis
  • Ceftriaxone (50 mg/kg as a single daily dose [maximum 2 g] IV/IM for 10 to 14 days)

Adolescents with documented gonorrhea but no history of sexual activity should be carefully evaluated for sexual abuse.

Prevention

Male Latex Condoms

Used consistently and correctly, male latex condoms are effective in preventing the sexual transmission of HIV infection and can reduce the risk for other STDs (i.e., gonorrhea, chlamydia, and trichomonas). Generally, studies evaluating the effectiveness of male condoms to protect from gonorrhea infection have been supportive, including a “dose response protection” (Holmes et al., 2004; Sanchez et al., 2003; Crosby et al., 2003; Ahmed et al., 2001; Warner et al., 2004,2005). Condom failure usually results from not only inconsistent but incorrect use (e.g., condom breakage) (Crosby et al., 2005; Paz-Bailey et al., 2005).

Public Health Issues

  1. High prevalence rates of gonorrhea in adolescents, particularly among minority youth, as compared with other age-groups
  2. Poor screening rates for infection by clinicians in health care settings (Chacko et al., 2004)
  3. High prevalence in certain groups—urban populations; young men who have sex with men; teens and young adults; street involved and substance-abusing youth; and youth in detention centers
  4. High coinfection rates with other STDs, particularly C. trachomatisinfections
  5. Rapid emergence of multiple types of antibiotic resistance to gonorrhea
  6. Large number of asymptomatic gonococcal infections in both females and males

Web Sites

For Teenagers and Parents

http://www.cdc.gov/std/Gonorrhea/STDFact-gonorrhea.htm CDC fact sheet on gonorrhea (Accessed 09/04/05).

http://www.niaid.nih.gov/factsheets/stdgon.htm. National Institutes of Health (NIH) fact sheet on gonorrhea. (Accessed 09/04/05).

http://www.plannedparenthood.org/. Planned parenthood website with STD information (Accessed 05/02/07).

http://kidshealth.org/teen/infections/stds/std gonorrhea. html Teen health site information sheet on gonorrhea. (Accessed 09/04/05)

http://www.iwannaknow.org/. American Social Health Web Site for Teen Sexual Health (Accessed 09/04/05).

http://www.youngwomenshealth.org/gonorrhea.html. The Center for Young Women's Health. Children's Hospital of Boston (Accessed 09/04/05).

For Health Professionals

http://www.cdc.gov/std/stats/gonorrhea.htm Centers for Disease Control and Prevention. STD Surveillance 2004. National Profile (Accessed 12/02/05).

http://www2a.cdc.gov/stdtraining/self-study/gonorrhea.asp Web-based training course designed to guide clinicians in the diagnosis, treatment, and prevention of gonorrhea, based on STD curriculum developed by the National Network of STD/HIV Prevention Training Centers (Accessed 12/05/05).

http://www.ahrq.gov/clinic/uspstf/uspsgono.htm. U.S. Preventive Services Task Force report on Screening for Gonorrhea (Accessed 12/02/05).

http://www2a.cdc.gov/stdclinic/PowerPoint/Gonorrhea.ppt. CDC PowerPoint slides on gonorrhea and other STDs (Accessed 12/02/05).

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http://www.cdc.gov/std/stats/CDC Power Point slides on gonorrhea (Accessed 11/28/05). Centers for Disease Control and Prevention found at Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. MMWR 2006;55(RR-11): 42. http://www.cdc.gov/std/treatment (Accessed 04/21/07) Updated recommended treatment regimens for gonococcal infections and associated conditions-United States, April 2007 MMWR 2007; 56 (14): 332. http://www.cdc.gov/std/treatment/2006/updated-regimens.htm

References and Additional Readings

Ahmed S, Lutalo T, Wawer M, et al. HIV prevalence associated with condom use: a population study in rakai, uganda. AIDS 2001;15:2171.

Aledort JE, Hook EW III, Weinstein MC, et al. The cost effectiveness of gonorrhea screening in urban emergency departments. Sex Transm Dis 2005;32:425.

Black CM, Marroazzo J, Johnson RE, et al. Head-to head multicenter comparison of DNA probe and nucleic acid amplification tests for Chlamydia trachomatis infections in women performed with an improved reference standard. J Clin Microbiol 2002;40:3757.

Brown RT, Lossick JG, Mosure DJ, et al. Pharyngeal gonorrhea screening in adolescents: is it necessary. Pediatrics 1989;84:623.

Centers for Disease Control and Prevention found at Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. MMWR 2006;55(RR-11):42–49. http://www.cdc.gov/std/treatment (Accessed 04/12/07).

Centers for Disease Control and Prevention. Trends in reportable sexually transmitted diseases in the United States, 2003. National Data on Chlamydia, Gonorrhea and Syphilis. http://www.cdc.gov/std/stats/2003SurveillanceSummary. pdf (Accessed 12/02/05).

Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2003 supplement: Gonococcal Isolate Surveillance Project (GISP) annual report—2003. Atlanta, GA: U.S. Department of Health and Human Services; November 2004. http://www.cdc.gov/std/gisp2003/GISP2003.pdf (Accessed 12/02/05)

Center for Disease Control and Prevention. STD Surveillance 2004. Trends in reportable sexually transmitted diseases in the United States. http://www.cdc.gov/std/stats/) (Accessed 12/18/05).

Centers for Disease Control and Prevention. Expedited partner treatment. 2005.

Centers for Disease Control and Prevention. STD Surveillance 2004. National Profile. http://www.cdc.gov/std/stats/gonorrhea.htm (Accessed 12/02/05)

Chacko MR, Wiemann CM, Smith PB. Chlamydia and gonorrhea screening in asymptomatic young women. J Pediatr Adolesc Gynecol 2004;17:169.

Chernesky MA, Martin DH, Hook EW, et al. Ability of new APTIMA CT and APTIMA GC assays to detect Chlamydia trachomatis and neisseria gonorrhoeae in male urine and urethral swabs. J Clin Microbiol 2005;43:127.

Cook RL, Hutchinson SL, Ostergaard L, et al. Systematic review: non-invasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med 2005;142:914.

Cosentino La, Landers DV, Hillier SL. Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by strand displacement amplification and relevance of the amplification control for use with vaginal swab specimens. J Clin Microbiol 2003;41:3592.

Crosby RA, DiClemente RJ, Wingood GM, et al. Value of consistent condom use: a study of sexually transmitted disease prevention among African American adolescent females.Am J Public Health 2003;93:901.

Crosby RA, DiClemente RJ, Wingood GM, et al. Condom failure among adolescents: implications for STD prevention. J Adolesc Health 2005;36:534.

Crotchfelt KA, Pare B, Gaydos C, et al. Detection of Chlamydia trachomatis by the Gen Probe Amplified Chlamydia trachomatis Assay (AMP CT) in urine specimens from men and women and endocervical specimens. J Clin Microbiol 1997; 36:391.

Einwalter LA, Ritchie JM, Ault KA, et al. Gonorrhea and Chlamydia infection among women visiting family planning clinics: racial variation in prevalence and predictors. Perspect Sex Reprod Health 2005;37:135.

Emans SJ, Laufer MR, Goldstein DP, eds. Pediatric and adolescent gynecology, 5th ed. Philadelphia: Lippincott–Raven Publishers; 2004.

Gaydos CA, Quinn TC, Willis D, et al. Performance of the APTIMA Combo2 assay for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in female urine and endocervical swab specimens. J Clin Microbiol 2003;41:304.

Geisler WM, Whittington WL, Suchland RJ, et al. Epidemiology of anorectal Chlamydial and gonococcal infections among men having sex with men in seattle: utilizing serovar and auxotype strain typing. Sex Transm Dis 2002;29:189.

Golden MR, Whittington WL, Handsfield HH, et al. Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or Chlamydial infection. N Engl J Med 2005; 352:676.

Holmes KK, Levine R, Weaver M. Effectiveness of condoms in preventing sexually transmitted infections. Bull WHO 2004;82:454.

Joffe A, Blythe M. Handbook of adolescent medicine. State Art Rev Adolesc Med 2003;14:345.

Jones CA, Knaup RC, Hayes M, et al. Urine screening for gonococcal and Chlamydial infections at community-based organizations in a high-morbidity area. Sex Transm Dis 2000; 27:146.

Kahn RH, Mosure DJ, Blank S, et al. Jail STD Prevalence Monitoring Project. Chlamydia trachomatis and Neisseria gonorrhoeae prevalence and coinfection in adolescents entering selected US juvenile detention centers, 1997–2002. Sex Transm Dis 2005; 32:255.

Khan A, Fortenberry JD, Temkit MH, et al. Gender differences in sexual behaviors in response to genitourinary symptoms. Sex Transm Dis 2005;32:260.

Kohl KS, Sternberg MR, Markowitz LE, et al. Screening of males for Chlamydia trachomatis and Neisseria gonorrhoeae infections at STD clinics in three US cities—Indianapolis, New Orleans, Seattle. Int J STD AIDS 2004;15:822.

Lyss SB, Kamb ML, Peterman TA, et al. Project Respect Study Group. Chlamydia trachomatis among patients infected with and treated for Neisseria gonorrhoeae in sexually transmitted disease clinics in the united states. Ann Intern Med 2003; 139:178.

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Martin DH, Cammarata C, Van Der Pol B, et al. Multicenter evaluation of Amplicor and automated Cobas Amplicor CT/NG tests for Neisseria gonorrhoeaeJ Clin Microbiol 2000; 38:3544.

McMillan A. Sexually acquired reactive arthritis. In: McMillan A, Young H, Ogilvie MM, et al., eds. Clinical practice in sexually transmissible infections. Edinburgh: WB Saunders; 2002:379.

Mertz KJ, Voigt RA, Hutchins K, et al. Jail STD Prevalence Monitoring Group. Findings from STD screening of adolescents and adults entering corrections facilities: implications for STD control strategies. Sex Transm Dis 2002;29:834.

Miller WC, Ford CA, Morris M, et al. Prevalence of Chlamydial and gonococcal infections among young adults in the united states. JAMA 2004;291:2229.

Pack RP, DiClemente RJ, Hook EW III, et al. High prevalence of asymptomatic STDs in incarcerated minority male youth: a case for screening. Sex Transm Dis 2000; 27:175.

Paz-Bailey G, Koumans EH, Sternberg M, et al. The effect of correct and consistent condom use on Chlamydial and gonoccoccal infection among urban adolescents. Arch Pediatr Adolesc Med 2005;159:536.

Peter NG, Clark LR, Jaeger JR. Fitz-Hugh-Curtis syndrome: a diagnosis to consider in women with right upper quadrant pain. Cleve Clin J Med 2004;71:233.

Rice PA. Gonococcal arthritis (disseminated gonococcal infection). Infect Dis Clin North Am 2005;19:853.

Roochvarg LB, Lovchik JC. Screening for pharyngeal gonorrhea in adolescents. A reexamination. J Adolesc Health 1991; 12:269.

Sanchez J, Campos PE, Courtois B, et al. Prevention of sexually transmitted diseases (STDs) in female sex workers: prospective evaluation of condom promotion and strengthened STD services. Sex Transm Dis 2003;30:273.

Schachter J, McCormack WM, Chernesky MA, et al. Vaginal swabs are appropriate specimens for diagnosis of genital tract infection with Chlamydia trachomatisJ Clin Microbiol2003;41:3784.

Schwarcz SK, Bolan GA, Fullilove M, et al. Crack cocaine and the exchange of sex for money or drugs. Risk factors for gonorrhea among black adolescents in San Francisco. Sex Transm Dis 1992;19:7–13.

Spigarelli MG, Biro FM. Sexually transmitted disease testing: evaluation of diagnostic tests and methods. Adolesc Med Clin 2004;15:287.

Van Der Pol B, Ferrero DV, Buck-Barrington L, et al. Multicenter evaluation of BDProbeTec ET system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens, female endocervical swabs, and male urethral swabs. J Clin Microbiol 2001;39:1008.

Vickerman P, Peeling RW, Watts C, et al. Detection of gonococcal infection : pros and cons of a rapid test. Mol Diagn 2005;9:175.

Warner L, Newman DR, Austin HD, et al. Project Respect Study Group. Condom effectiveness for reducing transmission of gonorrhea and Chlamydia: the importance of assessing partner infection status. Am J Epidemiol 2004;159: 242.

Warner L, Macaluso M, Sustin HD, et al. Application for the case cross-over design to reduce unmeasured confounding in studies of condom effectiveness. Am J Epidemiol 2005; 162:765.

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