Regional Laboratory
AllianceRegional Laboratory
Alliance|
|
|
|
|
|
|
| |
|
|
|
|
|
|
|
|
Incidence, Transmission and Complications
The incidence of gonorrhea in the USA peaked in 1978 with greater than one million cases (468 cases per 100,000 population) reported to the CDC, and since then has declined (202 cases per 100,000 population in 1992). Sexually active men and women aged 20-24 have the highest attack rate of the disease. More cases are reported in men since males with urogenital gonococcal infection usually have urethral discharge and discomfort, making them more likely to seek medical attention than women, who often have asymptomatic infection or minimal symptoms. Co-infection with Chlamydia trachomatis is not uncommon (3.5% in men, 17.6% in women). Gonococcal infection is not confined to sexually active adults: Neisseria gonorrhoeae is the most common sexual pathogen seen in sexually abused children. Ascending genital infections in women can lead to acute salpingitis, one of the most common causes of female infertility. Acute epididymitis in men, neonatal conjunctivitis, and acute perihepatitis (Fitz-Hugh and Curtis syndrome) are other serious complications of infection. Gonorrhea in pregnant women is associated with increased risk for spontaneous abortion, premature labor, early rupture or membranes, and perinatal infant mortality.
Excluding perinatal transmission, the most important factor for acquiring gonorrhea is sexual intercourse with an infected partner. The risk of transmission of gonorrhea from an infected woman to the urethra of her male partner is approximately 20% per episode of vaginal intercourse, rising to 60-80% after four or more exposures. The risk of male-to-female transmission is about 50% per contact, and greater than 90% after three exposures. Transmission by rectal intercourse and by orogenital sexual activity also occurs. Woman using anovulatory contraceptives may be at increased risk for gonorrhea.
Diagnosis of Gonorrhea
Appropriate specimens for diagnosis of suspected gonorrhea vary with different populations. In heterosexual men, a urethral specimen may be tested. In homosexual men, urethral, rectal and pharyngeal specimens should be obtained. In women, urethral and rectal specimens are appropriate, but specimens may also be obtained from Bartholin’s and Skenes glands when clinically indicated. Blood culture should be performed on patients with suspected disseminated infection, and synovial fluid culture is indicated when septic arthritis is present. Cultures of skin lesions are discouraged because they are usually negative.
Culture is the reference method for diagnosis of gonorrhea, and must be performed in cases of suspected sexual assault or abuse. If culture is indicated, a swab with a plastic or wire shaft (not wood) with a tip made of rayon, dacron or calcium alginate should be used. In women with suspected urogenital infection, a swab from the endocervical canal is optimal. The cervical os should be wiped free of secretions and discharge. The swab should then be inserted 1-2 cm into the endocervical canal and rotated firmly against the wall for 10-30 seconds. The swab is then withdrawn without touching the vaginal walls. The swab should be quickly placed in transport media and sent immediately to the lab. Alternatively, a Thayer-Martin plate can be immediately inoculated by the clinician at the bedside. Delays in sending the specimen to the lab or inoculating the Thayer-Martin plate adversely affect the viability of the gonococcal organisms, and decrease the sensitivity of culture. In men with suspected urogenital infection, urethral exudate may be cultured. If no exudate is present, a urethral swab obtained two hours after the patient has voided may be used. The urethral swab is smaller than an endocervical swab, and must be inserted 2-4 cm into the urethra, rotated in one direction for 5 seconds, withdrawn, and placed in transport media or immediately inoculated onto a Thayer-Martin plate. Confirmation of a culture isolate as N. gonorrhoeae can be accomplished by biochemical means or with commercial kits that utilize DNA probes or monoclonal antibodies.
Although culture is the reference method for diagnosis of gonorrhea, several other reliable methods that are less expensive and time-consuming are replacing culture in many clinical situations. (In one recent national survey, culture for N. gonorrhoeae was the most frequently discontinued test in sexually transmitted disease clinics). In males with symptomatic urethritis, the Gram stain performed on urethral discharge is considered diagnostic if gram-negative kidney-shaped diplococci are found extracellularly and intracellularly within neutrophils, and few or no other bacteria are present. Properly performed, the sensitivity and specificity of the Gram stain are >95%. In women, Gram stain is highly specific if the cervix is wiped clean prior to obtaining the endocervical swab, but sensitivity is only about 50%. Gram stain alone is not recommended for diagnosis of gonococcal cervicitis because organisms that appear similar to N. gonorrhoeae are part of the normal flora of the female genital tract.
Several kits are available which detect gonococcal organisms in endocervical or urethral swabs. One such kit is the Gen-Probe PACE 2 Neisseria gonorrhoeae assay. This kit provide an endocervical swab, a urethrral swab and transport media for the specimen. The kit utilizes a DNA probe that is labeled with acridinium ester and allows direct detection of N. gonorrhoeae in urogenital specimens. A confirmatory probe competition assay has recently become available. The sensitivity is 86-99% with a specificity of 97-100%. Advantages of the Gen-Probe assay are 1) more rapid results than culture, 2) the need to collect only one specimen for detection of N. gonorrhoeae and C. trachomatis if probes are used for diagnosis of both infections. The disadvantages are increased cost, and the lack of an isolate for susceptibility testing. This kit is not approved for testing pharyngeal, rectal, synovial or conjunctival specimens; these specimens require culture for diagnosis.
A second kit (Gonozyme) uses an enzyme immunoassay to detect N. gonorrhoeae directly in urethral and endocervical swab specimens. This kit can also be used on voided urine for detection of N. gonorrhoeae in males with suspected gonococcal urethritis. Sensitivity of the test using urine specimens compared to urethral or endocervical swab specimens was 83.6% in men, but only 62.5% in women, with specificities of 89.2% and 81.8% respectively. Urine specimens from female patients are not recommended for use with this kit.
DNA amplification methods for direct detection of N. gonorrhoeae are now available. The COBAS AMPLICOR is a fully automated RNA and DNA amplification and detection system for routine diagnostic PCR. Amplified products are captured and detected using an avidin-horseradish peroxidase conjugate. In addition to N. gonorrhoeae, this technique can be used to diagnose C. trachomatis, M. tuberculosis and Hepatitis C virus. Also, a ligase chain reaction test has been developed. These tests show good sensitivity and specificity.
Treatment of Gonorrhea
In times past, the drug of choice for treatment of gonorrhea was penicillin, but this is no longer the case since many strains have plasmid- or chromosomally-mediated resistance to penicillin. Penicillinase-producing strains have been noted since 1976. Susceptibility testing of isolates of N. gonorrhoeae in many institutions now involves testing only for presence of beta lactamase, and this may be deleted in the future if resistance increases to the point where beta lactam antibiotics are no longer useful. Resistance to tetracycline, erythromycin and cefoxitin have also emerged. Resistance to tetracycline was first reported in 1986. Recommended agents now include ceftriaxone, cefixime, ciprofloxacin or oflaxacin (see table below). Ceftriaxone is safe in pregnant women, and the recommended dose is 250 mg IM.
Initial Single-Dose Treatment - choose one of the following:
Ceftriaxone 125 mg IM*
OR
Cefixime 400 mg orally
OR
Ciprofloxacin 500 mg orally
OR
Ofloxacin 400 mg orally
PLUS
Azithromycin 1.0 g orally in a single dose
OR
Doxycycline 100 mg orally twice daily for 7 days
From: Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, p.1921, modified from Centers for Disease Control and Prevention
*125 mg IM is effective, but 250 mg IM is the smallest commercially available unit dose
Decreased susceptibility to ciprofloxacin has been noted in some strains since 1991. Chromosomally-mediated antibiotic resistance is especially common in homosexually active men, probably because the hostile environment of the rectum selects for genes that reduce the permeability of the outer membrane of the organism to toxic substances, including antibiotics.
Retesting to document cure of uncomplicated cases of gonorrhea is not recommended if one of the recommended treatment regimens is used, unless therapeutic compliance is questionable or symptoms persist. In patients who continue to have a high risk for sexually transmitted diseases, rescreening for gonorrhea and other infections is recommended 1-2 months after treatment. Reinfection, rather than persistent infection, is more likely in high risk groups.
Treatment of complicated cases of gonorrhea (pelvic inflammatory disease, acute epididymitis, disseminated gonococcal infection) and gonorrhea in children require different treatment regimens, and consultation with an Infectious Disease specialist may be indicated.
References:
“COBAS AMPLICOR: Fully Automated RNA and DNA Amplification and Detection System for Routine Diagnostic PCR.” N. DiDomenico, et al. Clinical Chemistry. 1996, Dec; 42(12): 1915-23.
“Diagnosis of Urogenital Gonorrhoea: Evaluation of an Enzyme Immunoassay and Use of Urine as a Non-invasive Specimen.” K.C. Wong, et al. British Journal of Biomedical Science. 1994, Dec; 51(4): 312-5.
“The Emergence of Neisseria gonorrhoeae with Decreased Susceptibility to Ciprofloxacin in Cleveland, Ohio: Epidemiology and Risk Factors.” S.M. Gordon, et al. Annals of Internal Medicine. 1996, Sept. 15; 125(6): 465-70.
“Laboratory Diagnosis of Sexually Transmitted Diseases in Facilities within the United States. Results of a national Survey.” C.M. Beck-Sague, et al. Sexually Transmitted Diseases. 1996, July-Aug.; 23(4): 342-9.
Mandell, Douglas and Benett’s Principles and Practice of Infectious Diseases. Edited by Gerald L Mandell, M.D., John E. Bennet, M.D. and Raphael Dolin, M.D. Churchill Livingstone, Fourth Edition. New York, 1995: pp. 1,909- 23 and 2,493-6.
Medical Microbiology. Edited by Samuel Baron, M.D. Fourth Edition. Churchill Livinstone Inc., 1991: pp. 224-5.
“Sexually Transmitted Diseases in Children and Evidence of Sexual Abuse.” A.C. Argent, et al. Child Abuse and Negligence. 1995, October;19(10): 1303-10.
“Update on Laboratory Diagnosis of Sexually Transmitted Diseases.” Gail L. Woods, M.D. Clinics in Laboratory Medicine. 1995 Sept. 15(3): 665-84.