Contents
OverviewBurden
of SufferingIn the U.S., gonorrhea was the most frequently reported sexually transmitted disease with 24% to 30% of cases occurring in adolescents. Rates per 100,000 dropped from 573 to 327 cases in males and 356 to 230 cases in females between 1981 and 1991.<2> The highest rate of 1,044 cases per 100,000 is currently in adolescent girls 15-19 years. U.S. rates are highest in black adolescents – the proportion with infection varying regionally from 3.5% to 7.3%. Although gonorrhea is a reportable disease, it is possible that some of the differences result from differential reporting or detection at private physicians’ offices versus publically funded clinics. In the former setting, treatment may be administered without laboratory confirmation of infection. This, in turn, may lead to decreased reporting.
While the overall incidence of gonorrhea has been declining, the proportion of gonorrhea organisms that are antibiotic-resistant has been increasing. The first cases of penicillinase-producing Neisseria gonorrhoeae (PPNG) in Canada and the United States were reported in 1976.<3,4> Only 0.5% of all reported gonorrhea cases in Canada in 1985 were caused by PPNG, compared to 5.5% in 1989, an 11-fold increase.<3> There were PPNG outbreaks in both Ontario and Quebec in 1988.<5> The number of reported cases of PPNG increased from 591 in 1988 to 1046 in 1989.<3> The proportions are highest in Quebec (9.9%) and Ontario (8.6%),<3> where rates are well above the hyperendemic cut-off of 3.0%.<6> Preliminary figures for Ontario and British Columbia for the first half of 1990 show that the percentage of reported cases of gonorrhea due to PPNG has doubled since 1989 in these two provinces.<3,6,7> There have been several major outbreaks of PPNG in several centers in the United States.<4,8,9>
In the U.S., the proportion increased from less than 1% in 1985 to 7% in 1989. In one survey of resistance patterns during 1991, 32% of N. gonorrheae were penicillin or tetracycline resistant.<10> However, this survey was conducted in a sentinel system for early detection of resistant bacteria and is therefore an overestimate of the national problem.
Gonococcal infection may be symptomatic, asymptomatic and/or complicated and may involve various anatomical sites. The majority of patients have anogenital and/or pharyngeal infection. Local complications may include epididymitis, lymphangitis, penile edema and urethral stricture in men, and salpingitis or pelvic inflammatory disease in women, as well as systemic complications in men or women, including disseminated gonococcal infection, endocarditis and meningitis. Over 90% of pharyngeal infections are asymptomatic. Women and unborn children carry the major physical impact of gonorrhea in the Western world. Compared with the relatively inconsequential acute gonorrhea in males, gonococcal infections in females lead much more frequently to hospitalization and surgery. Pelvic inflammatory disease (PID), a serious complication of 10-20% of gonococcal infections, can result in serious medical sequelae such as infertility, ectopic pregnancy, and chronic pelvic pain. (PID is also discussed in the Chapter 46 on preventing unintended pregnancy in adolescents). More than 80% of the total cost of gonococcal infections in the U.S. health care system in 1976 went for care necessitated by gonococcal PID.
ManeuverIn another study in Boston, culture specimens for gonorrhea were obtained from 1,441 obstetric and gynecology patients receiving routine pelvic examinations.<12> Information on sexual history and symptoms was obtained through a self-administered, 50-item questionnaire. Twenty-five (1.7%) women had positive cultures for gonorrhea. Multivariate analysis showed five factors were independently associated with gonococcal infection: partners with gonorrhea or urethral discharge (Odds Ratio = 5.7), endocervical bleeding induced by swab (OR = 4.6), age at first intercourse £16 (OR = 4.2), payment by Medicaid (OR = 2.8), and low abdominal or pelvic pain (OR = 2.6). Race was not an independent risk factor. The authors calculated that the risk of infection for a woman with one or more risk factors was 2.5%, compared to 0.2% for a woman with no risk factors.
A group in Cleveland devised a diagnostic index for estimating the probability of cervical infection with either gonorrhea or chlamydia.<13> The index, developed from examining and questioning 190 gynecologic patients, identified three independent predictors of cervical infection: age, purulent vaginal discharge, and high-risk sexual contact (a new partner in the prior 6 months, or a partner with a suspected genital infection). Points were assigned to the variables based on their multiple regression logistic coefficients, as follows: age <20 years – 2 points; age 20-29 years, 1 point; and 1 point each for purulent vaginal discharge and high-risk sexual contact. When the diagnostic index was tested on 588 women, the rate of cervical infection was directly associated with the index scores (p<0.001), with infection occurring in 28% of women with 3 or 4 points, 7% of women with 2 points, 3% of women with 1 point, and 0% of women with 0 points.
The standard diagnostic tests for gonorrhea are culture and Gram stain of clinical specimens. However, they have some limitations. The specificity of stained smears is 95-100% at all anatomical sites, and its diagnostic sensitivity for urethral specimens from males with acute symptomatic gonorrhea is high, ranging from 90-95%.<14> The Gram stain is relatively insensitive in asymptomatic males (50-70%), for female anogenital infections (45-70%), and for all pharyngeal and rectal infections.
Bacterial cultures have superior diagnostic sensitivity for female anogenital gonorrhea, male asymptomatic gonorrhea, and all pharyngeal gonococcal infections. In women, single endocervical cultures are estimated to have a sensitivity of 80-95%. Culture procedures may be limited by the inhibition of growth by antibiotics in the selective culture medium, such as the failure to detect vancomycin-susceptible strains using the usual culture medium. Also, results may be unsatisfactory if clinical specimens are inadequate or if the medium is not quality controlled, stored, inoculated, incubated and transported properly.
More recently developed diagnostic maneuvers include serological tests to detect serum antigonococcal antibodies, tests for specific endotoxins, enzymes or fatty acids, demonstration of gonococcal antigens using enzyme immunoassays or DNA hybridization techniques. Alternatives to Gram stain and culture have not been studied in an asymptomatic population. Studies in symptomatic individuals with urethral or vaginal discharge may not be generalizable to a population visiting their physician who do not have such complaints.
Serology, which was developed for population screening, is not accurate enough for detection.<3> Similarly, tests for gonococcal bacterial products are also insufficiently accurate when compared with bacterial culture.
Enzyme immunoassays for detection of gonococcal antigens in male urethral specimens have a sensitivity and specificity of 95% or more. These immunoassays also have a very high accuracy when performed on urine as compared with male urethral specimens.<4> Because obtaining urine specimens for diagnosis is substantially less uncomfortable, this diagnostic method may be of use in screening if accuracy is as high in asymptomatic men. However, the sensitivity and specificity of this test on specimens taken from the female genital tract range from 60% to 100% and 70% to 98%, respectively.<5>
Assays based on DNA hybridization techniques are limited to laboratories with molecular diagnostic capabilities. Sensitivity and specificity of this method were found to be greater than 97% and 99%, respectively.<6,8> Again, the accuracy of this method compared with culture is higher for male urethral specimens than for female cervical specimens. This methodology, however, will not shorten time for diagnosis to a clinically significant degree. Furthermore, diagnostic tests which reveal the presence or absence of N. gonorrheae do not give information about antibiotic susceptibility.
Effectiveness
of Prevention and TreatmentIf N. gonorrheae is susceptible to penicillin, oral amoxicillin remains the drug of choice for management, because it is relatively inexpensive. In areas with a high frequency of resistant N. gonorrheae, however, alternative agents are now the first line drugs. In general, these newer agents are substantially more expensive than amoxicillin. In uncontrolled trials, ceftriaxone had an average cure rate of 99.2%; the cure rate for four different quinolones ranged from 93.3% to 100%, with an average of 99.5%. Numerous clinical trials have now been conducted comparing the efficacy of a number of quinolones to intramuscular ceftriaxone. The advantage of the quinolones and cefixime, another third generation cephalosporin, is that they may be administered orally. No significant difference has been observed with single-dose oral agents compared with ceftriaxone.<9,15> Because the efficacy rate of treatment of uncomplicated gonorrhea should be at least 95%, recommendations to evaluate new treatments rigorously have been made.<16>
There has also been a general assumption, and some epidemiological evidence, that spermicidal preparations help to prevent gonococcal infections. However, large-scale well-designed studies have been lacking. A recent randomized, double-blind, placebo-controlled trial of 818 women has clearly shown benefit from the use of a vaginal gel containing Nonoxynol-9.<21> The study, which had a six-month follow-up rate of 78% (n=636, spermicide group, 317; placebo group, 319), found that the relative rate of gonococcal infection in the spermicide group was 0.75 (90% confidence limits, 0.58 and 0.96). Among women reporting at least 50% compliance, the relative rate was reduced to 0.61 (p=0.0031; 95% confidence limits, 0.42 and 0.87). (Also see Chapter 46).
Recommendations
of OthersThe U.S. Centers for Disease Control recommend that all cases should be diagnosed or confirmed by culture, to facilitate a system of antibiotic susceptibility testing. Their recommended treatment regimen for uncomplicated urogenital or rectal infection is a single intramuscular dose of Ceftriaxone 250 mg, plus Doxycycline 100 mg orally twice daily for 7 days to treat for presumptive coexisting chlamydial infection.
The Laboratory Centre for Disease Control in Canada recommends ceftriaxone as a preferred treatment plus tetracycline or doxycycline (for Chlamydia trachomatis).<23> Alternatives to ceftriaxone have been listed as spectinomycin, ciprofloxacin, cefixime or cefuroxime axetil. In areas with active monitoring for resistance and resistance levels below 3%, oral amoxicillin or ampicillin with probenecid may replace ceftriaxone. High-risk groups for screening include sexual contacts of cases, sexually active adolescents, children who have been sexually abused and their siblings, and adults with two or more of the following risk factors: age under 25, ³2 sexual partners in the previous year, a new sexual partner within the previous two months, a history of STD, non-use of contraception or use of non-barrier methods, and anal intercourse with a high-risk partner. They also strongly recommend screening for women who are pregnant, seeking an abortion, or being seen for insertion of an IUD.
Conclusions
and RecommendationsThe low prevalence rate of infection with N. gonorrheae would make mass screening of the general population an inefficient intervention (D Recommendation). However, screening should be performed in certain populations: 1) individuals under 30 years, particularly adolescents, with at least 2 sexual partners in the previous year; 2) prostitutes; 3) sexual contacts of individuals known to have a sexually transmitted disease; and 4) age £16 years at first intercourse (A Recommendation). The frequency with which such screening should take place has not been examined, but subjects are presumably at risk when they continue behaviours that place them at increased risk, such as prostitution.
Intramuscular ceftriaxone or oral quinolones, cefuroxime axetil, and cefixime should be used as initial therapy unless there is epidemiologic information indicating that the patient is unlikely to be infected with a resistant strain of N. gonorrheae. An effective agent against C. trachomatis should be initiated at the same time because of the high frequency of co-infection.
Unanswered
Questions (Research Agenda)Evidence
Link to Structured Abstract of this review
Link to Summary Table of this review
Link to Selected References list of this review
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Original Copyright
© 1994 Minister of Supply and Services Canada.
Last modified March 27, 1998.
