Bacteriology at UW-Madison

The Microbial World

Lectures in Microbiology by Kenneth Todar PhD    University of Wisconsin-Madison    Department of Bacteriology

Gonorrhea


© 2009 Kenneth Todar PhD

Neisseria gonorrhoeae, the Gonococcus, and Gonorrhea

Gonorrhea
is a prevalent sexually transmitted disease (std) caused by the bacterium Neisseria gonorrhoeae.  Infections are acquired by sexual contact and usually affect the mucous membranes of the urethra in males and the endocervix and urethra in females, although the infection may disseminate to a variety of tissues.

Although many species of Neisseria are normally found in the upper respiratory tract of humans,  Neisseria gonorrhoeae is never part of the normal flora. The bacterium is only found after sexual contact with an infected person (or direct contact, in the case of infections in the newborn). In the vocabulary of the public health and medical microbiology N. gonorrhoeae is often referred to as the "gonococcus".



Figure 1. Left: Neisseria gonorrhoeae Gram stain of pure culture;
Right: Neisseria gonorrhoeae Gram stain of a pustular exudate.

Neisseria gonorrhoeae is a relatively small Gram-negative coccus, usually seen in pairs with adjacent flattened sides (Figure 1 Left and Fig 2 below). The organism is frequently observed inside of phagocytic cells (neutrophils) that have become  part of the gonorrhea pustular exudate (Figure 1 Right).



Figure 2. Neisseria gonorrhoeae

N. gonorrhoeae is a relatively fragile organism, susceptible to temperature changes, drying, uv light, and other environmental conditions. It is also a nutritionally "fastidious" bacterium so it requires blood or hemoglobin and several amino acids and vitamins in order to grow.  In the laboratory, cultures must be grown at 35-36 degrees in an atmosphere of 3-10% added CO2.

A Bit of History

The disease gonorrhea is a specific type of urethritis that practically always involves mucous membranes of the urethra, resulting in a copious discharge of pus, more apparent in the male than in the female. The first usage of the term "gonorrhea", by Galen in the Second Century, implied a "flow of seed".

For centuries thereafter, gonorrhea and syphilis were confused, resulting from the fact that the two diseases were often present together in infected individuals. Paracelsus (1530) thought that gonorrhea was an early symptom of syphilis. The confusion was further heightened by the classic blunder of English physician John Hunter, in 1767. Hunter intentionally inoculated himself with pus from a patient with symptoms of gonorrhea and wound up giving himself syphilis!

The causative agent of gonorrhea, Neisseria gonorrhoeae, was first described by A. Neisser in 1879, in the pustular exudate of a case of gonorrhea. The organism was grown in pure culture in 1885, and its etiological relationship to human disease was later established using human volunteers in order to fulfill the experimental requirements of Koch's postulates.

Infections caused by N. gonorrhoeae

Infections caused by N. gonorrhoeae are generally limited to mucous surfaces that are lined with columnar epithelium cells. The areas most frequently involved are the urethra, cervix, rectum, pharynx, and conjunctiva of the eye. Squamous epithelium, which lines the adult vagina, is not susceptible to infection by the N. gonorrhoeae. However, the prepubescent vaginal epithelium may be infected, and gonorrhea occasionally presents in young girls as vulvovaginitis.

Ocular infections by N. gonorrhoeae can have serious consequences of corneal scarring or perforation. Ocular infections (ophthalmia neonatorum) occur most commonly in newborns who are exposed to infected secretions in the birth canal. Part of the intent in adding silver nitrate or an antibiotic to the eyes of the newborn is to prevent ocular infection by N. gonorrhoeae.

Gonorrhea

Uncomplicated gonorrhea in the adult male is an inflammatory pyogenic (pus -forming) infection of the mucous membranes of the anterior urethra. The most common symptom is a discharge that may range from a scanty, clear or cloudy fluid to one that is copious and purulent. Dysuria (difficulty in urination) is often present. Inflammation of the urethral tissues results in the characteristic redness, swelling, heat, and pain in the region. There is intense burning and pain upon urination.

Endocervical infection is the most common form of uncomplicated gonorrhea in women. Such infections are usually characterized by vaginal discharge and sometimes by dysuria. About 50% of women with cervical infections are asymptomatic. Asymptomatic infections occur in males, as well. Males with asymptomatic urethritis are an important reservoir for transmission of the disease Asymptomatic males and females are a major problem as unrecognized carriers of the disease, which occurs in the U.S. at an estimated rate of over one million cases per year.

In the male, the organism may invade the prostate resulting in prostatitis, or extend to the testicles resulting in orchitis. In the female, cervical involvement may extend through the uterus to the fallopian tubes resulting in salpingitis, or to the ovaries resulting in ovaritis. As many as 15% of women with uncomplicated cervical infections may develop pelvic inflammatory disease (PID). The involvement of testicles, fallopian tubes or ovaries may result in sterility. Occasionally, disseminated infections occur. leading to arthritis, endocarditis and meningitis.

Rectal infections (proctitis) with N. gonorrhoeae occur in about one-third of women with cervical infection. They most often result from autoinoculation with cervical discharge and are rarely symptomatic. Rectal infections in homosexual men usually result from anal intercourse and are more often symptomatic. Partners must be treated as well to avoid reinfection.

Resistance and Immunity to Gonorrhea

The pathology and symptoms of gonorrhea result from activation of the inflammatory response. Inflammation is the only way to check the growth of the bacterium without antibiotic intervention. Inflammation focuses the host defenses but also becomes the pathology of the disease.

Although it has been shown that antiibodies are produced in response to infection by N. gonorrhoeae, (meaning that the immune system has also been activated) immunity against reinfection has not been clearly shown. In any case, immunity would only be specific for the infecting strain of bacterium so reinfections may occur.

Not everyone exposed to N. gonorrhoeae acquires the disease. This may be due to variations in the number of infectious organisms, to natural resistance, or to specific immunity.  A 50% infective dose (ID50) of about 1,000 bacteria has been determined based on experimental urethral inoculation of male volunteers.  No data is available for females.

Nonspecific factors have been implicated in natural resistance to gonococcal infection. In women, changes in the genital pH and hormones may increase resistance to infection at certain times of the menstrual cycle. Urine contains bactericidal and bacteriostatic components against N. gonorrhoeae. Factors in urine that may be important are pH, osmolarity, and the concentration of urea.

Treatment

The recommended treatment for uncomplicated infections is a third-generation cephalosporin or a fluoroquinolone plus an antibiotic effective against possible coinfection with Chlamydia trachomatis (e.g., doxycycline or erythromycin) . Sex partners should be referred and treated. The current CDC Treatment Guidelines recommend treatment of all gonococcal infections with antibiotic regimens effective against resistant strains. The recommended antimicrobial agents are ceftriaxone, cefixime, ciprofloxacin, or oflaxacin.

Control

There is no effective vaccine to prevent gonorrhea. Various types of acellular (component) vaccines have been tried but are of little benefit. The development of an effective vaccine has been hampered by the lack of a suitable animal model and the fact that an effective immune response has never been demonstrated. Condoms are effective in preventing the transmission of gonorrhea.

Drug Resistance

The evolution of antimicrobial resistance in N. gonorrhoeae began in 1976. before then any patient presenting with urethritis was administered penicillin and it usually worked.  Today, strains with multiple drug resistance to penicillin, tetracycline, erythromycin, and cefalosporins have been identified in the United States and in most other parts of the world. Sporadic high-level resistance to spectinomycin and fluoroquinolones has been reported.

Penicillin resistance in N. gonorrhoeae was first described in 1976. The prevalence of penicillin-resistant strains has increased dramatically in the United States since 1984.

Tetracycline resistance of N. gonorrhoeae was first noted in 1986 and has now been reported in most parts of the world.

Tailpiece

The only natural host for N. gonorrhoeae is  humans. Gonorrhea has all but disappeared in Scandinavia and several other European countries. In the United States, gonorrhea remains the most frequently reported infectious disease, even though between 1977 and 1993, the number of reported cases decreased 56 percent, from 1 million to 440,000 cases per year. The CDC estimates that there are two unreported cases for every reported case of gonorrhea. Gonorrhea is transmitted almost exclusively by sexual contact. The highest rates occur in women between the ages of 15 and 19 years and in men 20 and 24 years of age. Persons who have multiple sex partners are at highest risk. Rates of gonorrhea are higher in males and in minority and inner-city populations.

Gonorrhea is usually contracted from a sex partner who is either asymptomatic or has only minimal symptoms. It is estimated that the efficiency of transmission after one exposure is about 35 percent from an infected woman to an uninfected man and 50 to 60 percent from an infected man to an uninfected woman. More than 90 percent of men with urethral gonorrhea will develop symptoms within 5 days; fewer than 50 percent of women with genital gonorrhea will do so. Women with asymptomatic infections are at higher risk of developing pelvic inflammatory disease and disseminated gonococcal infection.


Written and Edited by Kenneth Todar. All rights reserved.

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