GONORRHEA 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. Definition Gonorrhea is a sexually transmitted disease (STD). Gonorrhea is caused by Neisseria gonorrhoeae, a bacterium that can grow and multiply easily in the warm, moist areas of the reproductive tract, including the cervix (opening to the womb), uterus (womb), and fallopian tubes (egg canals) in women, and in the urethra (urine canal) in women and men. The bacterium can also grow in the mouth, throat, eyes, and anus. Morphology of Neisseria gonorrhoeae Neisseria gonorrhoeae is a Gram-negative coccus, 0.6 to 1.0 m in diameter, usually seen in pairs with adjacent flattened sides. The organism is frequently found intracellularly in polymorphonuclear leukocytes (neutrophils) of the gonorrhea pustular exudates (Figure 1). Fimbriae, which play a major role in adherence, extend several micrometers from the cell surface (Figure 2).

Fig 1. Gram stain of male urethral exudates showing N. gonorrhoeae inside a PMN (LM x500)

Fig 2. N. gonorrhoeae

Bacteriology Neisseria gonorrhoeae possesses a typical Gram-negative outer membrane composed of proteins, phospholipids, and lipopolysaccharide (LPS). However, neisserial LPS is distinguished from enteric LPS by its highly-branched basal oligosaccharide structure and the absence of repeating O-antigen subunits. For these reasons, neisserial LPS is referred to as lipooligosaccharide (LOS). The bacterium characteristically releases outer membrane fragments called "blebs" during growth. These blebs contain LOS and probably have a role in pathogenesis if they are disseminated during the course of an infection. N. gonorrhoeae is a relatively fragile organism, susceptible to temperature changes, drying, UV light, and other environmental conditions. Strains of N. gonorrhoeae are variable in their cultural requirements so that media containing hemoglobin, NAD, yeast extract and other supplements are needed for isolation and growth of the organism. Cultures are grown at 35-36 degrees in an atmosphere of 3-10% added CO2. Pathology a) Organism is equipped with fimbria, which enable it to attach to inner surface tissue or urethra. Incubation period is 2 to 8 days. b) Organism spreads intercellularly to deeper urethral tissues. Endotoxin in the bacterial cell wall causes inflammation of these tissues. Large amounts of pus (yellow) are exuded into the urethra and out of urethral opening. c) Accumulation of pus in urethra makes urination painful. Endotoxin also causes inflammatory pain. Symptoms usually milder in women. d) The untreated infection in women may spread to fallopian tubes and other abdominal tissues to cause PID (pelvic inflammatory disease). Sterility may result from PID involvement in females and vas deferens involvement in males. e) During birth from an infected mother, the child's eyes may become infected, causing blindness (opthalmia neonatorum). This is prevented by adding 1% AgNO3 or penicillin to eyes of newborns.

F ig 3. Pathogenesis gonorrhea Habitat and Portal of Entry Genitourinary tract and the eyes of infected persons Mode of Transmission Gonorrhea is spread through contact with the penis, vagina, mouth, or anus. Ejaculation does not have to occur for gonorrhea to be transmitted or acquired. Gonorrhea can also be spread from mother to baby during delivery (through passage of fetus in the infected genital tract). How does Gonorrhea affect a pregnant woman and her baby? If a pregnant woman has gonorrhea, she may give the infection to her baby as the baby passes through the birth canal during delivery. This can cause blindness, joint infection, or a life-threatening blood infection in the baby. Treatment of gonorrhea as soon as it is detected in pregnant women will reduce the risk of these complications. Pregnant women should consult a health care provider for appropriate examination, testing, and treatment, as necessary. People who have had gonorrhea and received treatment may get infected again if they have sexual contact with a person infected with gonorrhea. Host Defenses Infection stimulates inflammation and a local immune (IgA) response. Inflammation focuses the host defenses but also becomes the pathology of the disease. It is not known whether the secretory immune response is protective. Serum antibodies also appear, and IgG and complement may be components of the inflammatory exudates. But whether the immune defenses provide much protection against reinfection has not been clearly shown. In any case, immunity is expected to be strain specific so that reinfection may occur. Not everyone exposed to N. gonorrhoeae acquires the disease. This may be due to variations in the size or virulence of the inoculum, 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. The variability in the susceptibility of gonococcal strains to the bactericidal and bacteriostatic properties of urine is thought to be one of the reasons some males apparently do not develop a gonorrhea infection when exposed. Most uninfected individuals have serum antibodies that react with gonococcal antigens. These antibodies probably result from colonization or infection by various Gram-negative bacteria that possess cross-reactive antigens. Such "natural

antibodies" may be important in individual natural resistance or susceptibility to infection, but this has not been clearly demonstrated. Infection with N. gonorrhoeae stimulates both mucosal and systemic antibodies to a variety of gonococcal antigens. Mucosal antibodies are primarily IgA and IgG. In genital secretions, antibodies have been identified that react with Por, Opa, Rmp and LOS. Vaccine trials have suggested that specific antifimbrial antibodies inhibit the fimbrialmediated attachment of the homologous gonococcal strain. In general, the IgA response is brief and declines rapidly after treatment; IgG levels decline more slowly. Anti Por antibodies apparently are bactericidal for the gonococcus. IgG that reacts with Rmp blocks the bactericidal activity of antibodies directed against Por and LOS. Genital infection with N. gonorrhoeae stimulates a serum antibody response against the LOS of the infecting strain. Disseminated gonococcal infection results in much higher levels of anti-LOS antibody than do genital infections. Strains that cause uncomplicated genital infections usually are killed by normal human serum and are termed serum sensitive. This bactericidal activity is mediated by IgM and IgG antibodies that recognize sites on the LOS. Strains that cause disseminated infections are not killed by most normal human serum and are referred to as serum resistant. Resistance is mediated, in part, by IgA that blocks the IgG-mediated bactericidal activity of the serum. Serum from convalescent patients with disseminating infections contains bactericidal IgG to the LOS of the infecting strain. Individuals with inherited complement deficiencies have a markedly increased risk of acquiring systemic neisserial infections and are subject to recurring episodes of systemic gonococcal and meningococcal infections, indicating that the complement system is important in host defense. Gonococci activate complement by both the classic and alternative pathways. Complement activation by gonococci leads to the formation of the C5b-9 complex (membrane attack complex) on the outer membrane. In normal human serum, similar numbers of C5b9 complexes are deposited on serum-sensitive and serumresistant organisms, but the membrane attack complex is not functional on serum-resistant organisms. Signs and Symptoms Although many men with gonorrhea may have no symptoms at all, some men have some signs or symptoms that appear two to five days after infection; symptoms can take as long as 30 days to appear. Symptoms and signs include a burning sensation when urinating, or a white, yellow, or green discharge from the penis. Sometimes men with gonorrhea get painful or swollen testicles. Males Urethritis (pain during and frequency of urination) Urethral Discharge In women, the symptoms of gonorrhea are often mild, but most women who are infected have no symptoms. Even when a woman has symptoms, they can be so non-specific as to be mistaken for a bladder or vaginal infection. The initial symptoms and signs in women include a painful or burning sensation when urinating, increased vaginal discharge, or vaginal bleeding between periods. Women with gonorrhea are at risk of developing serious complications from the infection, regardless of the presence or severity of symptoms.

Females Urinary Tract Infection Bartholins Glands may become inflamed and painful Increased Vaginal Discharge (slight yellowish/ thick greenish yellow) Symptoms of Extreme Inflammation Symptoms of rectal infection in both men and women may include discharge, anal itching, soreness, bleeding, or painful bowel movements. Rectal infection also may cause no symptoms. Infections in the throat may cause a sore throat but usually causes no symptoms. Assessment and Diagnostic Findings 1. Assess for fever; urethral, vaginal and rectal discharge; and for signs of arthritis. 2. Specimen Culture Urine for gonococcal bacillus Vaginal on all children with vulvovaginitis Urethral or urethral discharge Where to obtain specimens? In males: Urethra, anal canal, and pharynx In females: Endocervix, anal canal and pharynx Diagnosis: a) Presence of Gram negative diplococci in exuded pus. b) Transfer pus specimen to plates of Thayer-Martin agar (selective for N. gonorrhoeae) Observe for growth of N. gonorrhoeae. c) Gonozyme test - ELISA test for Ag in urethral samplings (does not detect Ag very well in rectal or pharyngeal forms of the disease). Complications Untreated gonorrhea can cause serious and permanent health problems in both women and men. In women, gonorrhea is a common cause of pelvic inflammatory disease (PID). Women with PID do not necessarily have symptoms. When symptoms are present, they can be very severe and can include abdominal pain and fever. PID can lead to internal abscesses (pus-filled pockets that are hard to cure) and long-lasting, chronic pelvic pain. PID can damage the fallopian tubes enough to cause infertility or increase the risk of ectopic pregnancy. Ectopic pregnancy is a life-threatening condition in which a fertilized egg grows outside the uterus, usually in a fallopian tube. In men, gonorrhea can cause epididymitis, a painful condition of the testicles that can lead to infertility if left untreated. Gonorrhea can spread to the blood or joints. This condition can be life threatening. In addition, people with gonorrhea can more

easily contract HIV, the virus that causes AIDS. HIV-infected people with gonorrhea are more likely to transmit HIV to someone else. Medical Management The recommended treatment for uncomplicated infections is a thirdgeneration cephalosporin or a fluoroquinolone plus an antibiotic (e.g., doxycycline or erythromycin) effective against possible coinfection with Chlamydia trachomatis. 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. 1. Administration of ceftriaxone (Rocephine) (or cefixime [Suprax] ciprofloxacin [Cipro]), or ofloxacin [Floxin]) along with doxicycline 2. Note: If the patient is pregnant, give amoxicillin. 3. Serologic Testing for syphilis and HIV Nursing Management 1. Obtain patients history 2. Encourage treatment and follow up care 3. Identify patients sexual contacts Prevention and Control There is no effective vaccine to prevent gonorrhea. Candidate vaccines consisting of PilE protein or Por 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. The surest way to avoid transmission of sexually transmitted diseases is to abstain from sexual intercourse, or to be in a long-term mutually monogamous relationship with a partner who has been tested and is known to be uninfected. Latex condoms, when used consistently and correctly, can reduce the risk of transmission of gonorrhea. The evolution of antimicrobial resistance in N. gonorrhoeae may ultimately affect the control of gonorrhea. Strains with multiple chromosomal resistance to penicillin, tetracycline, erythromycin, and cefoxitin have been identified in the United States and most other parts of the world. Sporadic high-level resistance to spectinomycin and fluoroquinolones has been reported. Penicillinase producing strains of N. gonorrhoeae were first described in 1976. Five related lactamase plasmids of different sizes have been identified. Their prevalence penicillin-resistant strains has increased dramatically in the United States since 1984. Plasmid-mediated resistance of N. gonorrhoeae to tetracycline was first described in 1986 and has now been reported in most parts of the world. This resistance is due to the presence of the streptococcal tetM determinant on a gonococcal conjugative plasmid. Any genital symptoms such as discharge or burning during urination or unusual sore or rash should be a signal to stop having sex and to see a doctor immediately. If a person has been diagnosed and treated for gonorrhea, he or she should notify all recent sex partners so they can see a

health care provider and be treated. This will reduce the risk that the sex partners will develop serious complications from gonorrhea and will also reduce the persons risk of becoming re-infected. The person and all of his or her sex partners must avoid sex until they have completed their treatment for gonorrhea. Also: Rapid treatment Facilities for early diagnosis and treatment Health and sex education Suppression of commercialized prostitution Credes prophylaxis for newborn

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