Gonorrhea is an infection of the mucous membrane of the urethra and genital tract caused by Neisseria gonorrhoeae. Involvement of the pharynx and rectal mucosa is common. Infection is almost always Uv result of sexual contact. After invasion of mucosal sites, gonococci may spread and cause infections such as arthritis, tenosynovitis, perihepatitis, endocarditis, and meningitis.
Etiology of Gonorrhea.
N. gonorrhoeae is a gram-negative coccus that was first described bv Neisser in 1879 in exudates from patients with gonorrhea. In stained smears of exudates the organisms appear asdiplococci with flattened or slightly concave adjacent sides and resemble a pair of kidney beans. A considerable portion of the organisms in exudates are within polymorphonuclear leukocytes.
Gonococci grown in laboratory media assume an oval or spherical form, and single cocci and clumps of cocci may be found in addition to diplococci. N. gonorrhoeae can be distinguished from other Neisseria by its ability to ferment glucose but not maltose or sucrose.
Primary isolation of the gonococcus is difficult. The organism is fastidious in its growth requirements, and is susceptible to toxic substances that are present in many media. Blood, serum, ascitic fluid, or other agents must be added for enrichment, as growth will usually not occur on plain agar. Blood is commonly used, and the medium is heated (chocolate agar) to reduce the deleterious effect exerted by certain amino acids toxic to the gonococcus.
Commercial media are available that satisfy the various growth requirements of N. gonorrhoeae. Most strains require an atmosphere of 2 to 10 per cent carbon dioxide. Colonies of N. gonorrhoeae are round, gray-white, and translucent. Overgrowth with other bacteria occasionally occurs in cultures of exudate from the urethra, vagina, and cervix and is frequent in cultures from the pharynx and rectum if nonselective media are used.
All Neisseria produce an oxidase that can be used for tentative identification of colonies of N. gonorrhoeae (colonies turn purple on exposure to 1 per cent para-aminodimethylaniline monohydrochloride). With cultures from the genital tract, the combination of colonies of typical morphology composed of gram-negative diplo-cocci and a positive oxidase test is strong presumptive evidence of the presence of N. gonorrhoeae. However, other Neisseria and members of the tribe Mimeae resemble N. gonorrhoeae both in colonial morphology and microscopic appearance and give a positive oxidase reaction (Mima polymorphavar. oxidans is the only Mimeae that is oxidase positive). Therefore cultures that are presumptively positive for N. gonorrhoeae should be confirmed by fermentation reactions or by fluorescent antibody techniques.
Thayer-Martin selective medium, containing vancomycin, sodium colistimethate, and nystatin, permits growth of AT. meningitidis and N. gonorrhoeae but inhibits growth of many other bacteria frequently found in specimens from urethra, cervix, vagina, rectum, and pharynx. Growth of other Neisseria and of Mima poly-morpha var. oxidans is inhibited.
Incidence and Prevalence of Gonorrhea.
There has been an increase in the reported incidence of gonococcal infections in recent years. However, the true incidence and prevalence of gonorrhea are unknown because of problems in diagnosis, antimicrobial therapy by nonmedical persons, incomplete reporting by physicians, and the presence of many undetected asymptomatic female carriers. It has been estimated that over 2 million new cases of gonorrhea occur annually in the United States. The magnitude of the problem ofasymptomaticgonorrhea in females may be demonstrated by the fact that there is about a 5 per cent prevalence of asymptomatic gonorrhea in pregnant women.
Gonorrhea is a disease of the sexually active, and most cases occur in patients 15 to 24 years of age. Gonorrhea rates are higher among military personnel, migrant groups (such as itinerant laborers and seafarers), homosexuals, and prostitutes. In surveys 10 to 33 per cent of prostitutes have gonorrhea.
Diagnosis of Gonorrhea.
In the male the combination of urethritis and the presence of intracellular gram-negative diplo-cocci in smears of exudate from the urethra is strong presumptive evidence of gonorrhea. Confirmation is obtained by culture or, if available, fluorescent antibody studies. Anorectal cultures should be obtained in homosexual males.
For routine screening, cervical cultures will detect the vast majority of females with asymptomatic gonorrhea. Gonorrhea should be suspected in any female contact of an infected male. Similarly the asymptomatic carrier state should be suspected in asymptomatic male contacts of symptomatic females or asymptomatic females detected by routine cultures. In the female with suspected gonorrhea, cultures of exudate from the cervix and anorectal area should be obtained in addition to urethral cultures.
Pharyngeal cultures for N. gonorrhoeae should be obtained from homosexual males and females practicing fellatio. In all patients with suspected disseminated gonococcal infections, cultures of the pharynx and anorectal area should be obtained in addition to genital tract cultures.
Gonococci die within hours if allowed to dry. Therefore exudates should be inoculated as soon as possible on Thayer-Martin medium or on a suitable transport medium for N. gonorrhoeae. Transgrow, a commercially available antibiotic-containing medium, is packaged in a bottle with an increased carbon dioxide tension, and is preferred for transporting specimens containing gonococci or meningococci to central laboratories.
With use of fluorescent antibody it is frequently possible to make a definite identification of N. gonorrhoeae in exudate within one hour of obtaining a specimen.
Genital tract infection with the chlamydiae of inclusion conjunctivitis may occur in both sexes, and in the male can present as urethritis. Strictly speaking, it is the genital infection that is primary, with the conjunctivitis representing a secondary involvement. This disease is a common finding in venereal disease clinics where its incidence may approach that of gonococcal urethritis in the male. Since the discharge in the chlamydial infection is not grossly purulent, it is seldom confused with acute gonorrhea, but it can resemble gonococcal urethritis at the time of onset of post-treatment relapse.
Treatment and Prognosis of Gonorrhea
Penicillin is the drug of choice for all gonococcal infections. Prior to 1954 a single injection of 300,000 units of penicillin cured almost all cases of gonorrhea. In recent years gonococcal strains of increased resistance to penicillin (requiring up to 2.0 fig per milliliter for inhibition) have constituted as much as 50 per cent or more of all isolates. Concomitantly there has been a striking increase in the incidence of failure of therapy with 600,000 to 2,400,000 units of penicillin. It must be stressed that penicillin remains the drug of choice for gonorrhea but that much larger doses are required than in previous years. If the trend in increasing resistance to penicillin continues, the point will soon be reached at which the doses of penicillin required will preclude the use of parenteral penicillin for routine therapy of uncomplicated gonorrhea.
N. gonorrhoeae organisms have also been becoming more resistant to tetracycline. Although the level of resistance to tetracycline is not yet of clinical importance in the United States, more resistant strains are being isolated in certain areas of the Far East. The same strains of N. gonorrhoeae that are relatively resistant to penicillin also tend to have increased resistance to tetracycline and ampicillin but not to spectinomycin.
Urethritis should subside within two to three days after therapy. A watery urethral discharge may persist in males for weeks despite elimination of gonococci and usually requires no treatment (postgonococcal urethritis or nongonococcal urethritis). Several studies have demonstrated that postgonococcal urethritis can usually be prevented by use of tetracycline for t herapy of gonorrhea and that postgonococcal urethritis will usually respond to tetracycline treatment.
Relapse of gonorrhea occurs most commonly during the first week after treatment. Therefore to evaluate cure, a culture should be obtained one week after therapy and, if possible, at two more weekly intervals. In homosexual males and in females, anorectal cultures should be obtained as well as cervical cultures to evaluate cure of genital tract gonorrhea. If relapse occurs (and relapse is often difficult to differentiate from reinfection), the patient may be retreated with one of the alternative regimens, preferably spectinomycin.
Causes of failure of therapy, other than infection with gonococci relatively resistant to penicillin, are failure to distinguish between relapse and reinfection; failure to identify nongonococcal urethritis, e.g., Reiter’s syndrome or infection with chlamydiae; and possibly the presence of penicillinase-producing bacteria at the site of infection.