Gonorrhea is a venereal or sexually transmitted disease that involves the urogenital tract of both male and female. It is caused by a bactentim Neisseria gonorrhoeae. The meaning of the term Gonorrhea is ‘flow of sperm' and was first coined by Galen as early as 130 AD to describe the manifestations of gonorrhea urethritis. Gulielmus de Saliceto was the first person who described it as a disease having a venereal origin in 13th century. Arderne, in 1376, was probably the first to describe clinical features of the contagious urethritis that are comparable to those considered now characteristic for gonorrhea. In 1879, Neisser demonstrated the presence of diplococci inside neutrophils of purulent discharges from various patients of gonorrhea. The name of the genus, Neisseria, was given in his honor. It was Bumm, however, who succeeded in 1885 in cultivating the Gonococci in pure culture and proving the pathogenicity by inoculating human volunteers with the culture.
CELLULAR MORPHOLOGY
N. gonorrhoeae, or gonococcus, is a spherical bacterium that typically appears in pairs with the opposing sides flattened. It divides in two planes at right angles to each other. The diameter of the cell is 0.6 to 1.0µm. It is nonmotile, nonsporing, and noncapsulated. It is a Gram-negative bacterium.
CULTURAL CHARACTERISTICS
PHYSICAL REQUIREMENTS
The gonococci are aerobes or facultative anaerobes. They grow best at 37°C range being 22 to 40°C. Their growth is greatly enhanced in the presence of 5 to 10 percent CO2. A slightly alkaline pH is highiy favorable.
NUTRITIONAL REQUIREMENTS
The gonococci are fastidious bacteria and require enrich media for optimal growth. Several media are available for the isolation of gonococci from the clinical materials. These include Thayer-Martin medium modified Thayer-Martin medium, and Martin-Lewis medium. These media consist of supplemented GC basal medium plus heated hemoglobin and various antibiotics. A clear medium, New York City medium, is also used for primary isolation of gonococci. These bacteria grow very poorly on the blood agar but grow well on chocolate agar.
COLONIAL MORPHOLOGY
Gonococci produce small, round, smooth, entire, transparent, and colorless colonies. Colonies of primary isolates are small and transparent and are recognized as T1 and T2. The gonococci in such colonies possess pili and are virulent. Colonies of older cultures are large with lobate margin. They are designated as T3 and T4. Such gonococci are apiliated and avirulent.
BIOCHEMICAL CHARACTERISTICS
N. gonorrhoeae shows very little biochemical activities. It ferments only glucose with out gas. It produces catalase and cytochrome oxidase. Since only a few other bacteria produce cytochrome oxidase so abundantly, this characteristic has been used for the identification of gonococci (as well as other neisseriae). It possesses autolytic enzyme systems, and therefore it is bile soluble.
SENSITIVITY TO PHYSICAL AND CHEMICAL AGENTS
The gonococci are extremely sensitive to physical and chemical agents. Exposure to sunlight, desiccation, and heat kills this organism within a few minutes. Common disinfectants, such as phenol, alcohol, detergents, and metal salts, are very effective gonococcicidals.
ANTIGENIC STRUCTURE
N. gonorrhoeae possesses two types of antigens: pili and outer membrane protein (0MP) Il. This organism shows lot of diversity in the production of antigenic components, particularly 0MP II. The gonococci are thus classified into various serotypes on the basis of variations in the epitopes of 0MP ll. These types are termed serovars. One point should be made clear that a single serovar produces more than one antigenic types of antigen. It has been documented that under different conditions, either a cell produces or fails to produce pili. This property is called phase variation. Despite variations in the antigenic structure of the pili, a single gonococcus produces only one antigenic type of pili at a time.
PATHOGENESIS
Gonorrhea is the most frequent venereal disease all over the world. Human are the only natural host for gonococci. These bacteria grow best in warm mucus secreting epithelia. The portal of entry can be the urogenital tract, eyes, oropharynx, anorectum, or the skin. Transmission of gonococci occurs in adults almost exclusively by sexual contact, either homosexual or heterosexual. The sources of Infection are the exudates and purulent discharge from urethra or cervix. Among children transmission may result from sexual abuse or through contact with contaminated fomites. Newborns may acquire the gonococci during passage through the infected birth canal. Autoinoculation of the organism to the conjunctiva is possible.
The infection commonly becomes manifest 2 days to 7 days after exposure. It usually begins in the anterior urethra, accessory urethral glands, Bartholin's or Skene’s glands, and the cervix. The organism attaches to the mucosal epithelium with the help of its pili and multiplies. If untreated, the organisms spread from their initial sites upwards into the genital tract. ln male, they spread to the prostate and epididymis; in female, they commonly move to the fallopian tubes. Pharyngitis may follow oraI-genital contact. The organisms penetrate through intercellular spaces of the columnar epithelium, reach the subepithelial tissues by the third day of the infection, and elicit an inflammatory response characterized by dense infiltration by polymorphonuclear leucocytes. The spread of infection occurs usually through local lymphatic channels.
The gonococci can also invade the blood stream (disseminated gonococcal infection) causing serious sequelae such as bacteremic involvement of joint spaces, heart valves, meninges, and other body organs and tissues.
CLINICAL MANIFESTATIONS
Persons with gonorrhea may be asymptomatic and thus may unwittingly spread the disease to their sexual partners. Men are more likely to be symptomatic than women. The initial symptoms in man and women are same. The burning sensations during urination and discharge from urethra and/or vagina are initial signs of acute gonorrhea. ln addition female patients often present with fever and abdominal pain.
GONORRHEA IN MALE
ln men, the initial symptoms include urethral pain and a creamy-yellow, some times bloody, discharge due to acute urethritis. The infection may spread directly from the anterior urethra to the posterior urethra and Cowper’s glands in 10 to 14 days with increasing dysuria, polyuria, and occasionally general symptoms, such as headache and fever. The common complication is strictural of the urethra. Gonococci reach the bladder neck and incite inflammation, which causes urination urgency and pain. Increased intravesicular and abdominal pressure forces infected secretions through the prostatic duct into the prostate and through the ejaculatory ducts into the seminal vesicle. This leads to inflammation in prostate (prostatitis) and seminal vesicle (seminal vesiculitis). Extension of the infection to the epididymis causes painful inflammation and swelling of the whole epididymis (epididymitis). Bilateral involvement of the epididymis may lead to permanent obstruction of the lumina resulting in lasting sterility. The testis usually escapes the infection. Gonococci may persist, usually in the prostate.
GONORRHEA IN FEMALE
In women, the disease begins with same symptoms as in men, that is, dysuria, urgency, and frequency. However, the urethritis is frequently of short duration and often is mild or completely asymptomatic. Involvement of the paraurethral Skene’s glands (skenitis) as well as Bartholin’s glands (bartholinitis) is common. Because the stratified squamous epithelium is resistant to the gonococcal infection, the vagina of an adult female is not involved in infection. However, the infection is well established in cervix causing cervicitis. This condition gives rise to a mucopurulent discharge that varies from scant to profuse. ln many female patients, rectum is also involved (proctitis) that is manifested by anal discharge, burning rectal pain, blood and pus in the stools, and pain on defecation. There is an unusual vaginal bleeding, including bleeding after intercourse. Symptoms may occur or increase during or immediately after menses, since the gonococci are intracellular diplococci that thrive in menstrual blood but cannot survive long outside the human body. There may be infection of the uterus (uteritis) and development of acute or chronic infection in the fallopian tubes (salpingitis). It is manifested by acute onset of the fever, backache, lower abdominal pain, and profuse menstrual flow. The exudate in the fallopian tubes becomes purulent and is sometimes pushed into the peritoneal cavity causing pelvic peritonitis. The major consequence of chronic gonorrhea in females is the development of pelvic inflammatory disease resulting from the infection of the fallopian tubes. Acute pelvic inflammatory disease tends to recur, and pelvic pain and fever are present intermittently. Sterility is common.
EXTRAGENITAL GONOCOCCAL INFECTIONS
The gonococcal infection sometimes spreads from the urogenital tract to many other organs of the body both in man and woman. This condition is called extragenital or systemic gonorrhea. The main cause of systemic gonorrhea is bacteremia, which is a rather rare event. Entry of gonococci in the circulation is believed to be the penile and prostatic veins in males and venous plexuses around genital organs in females. Lymphatic invasion by gonococci can also occur. The most
common manifestations of the systemic gonorrhea are given in the following.
Arthritis-dermatitis syndrome
This type of systemic gonorrhea is characterized by fever, chills, malaise, polyarthritis, and development of unique skin lesions. The anhritis is most common in the joints of the knees, ankles, and wrists. Majority of the patients develop red popular lesions to pustular, hemorrhagic, or necrotic lesions mostly on the extremities.
Gonococcal endocarditis
It is a rare extragenital condition. ln most patients, previously normal valves are attacked. A double daily temperature elevation is common in patients with gonococcal endocarditis, and jaundice occurs in a higher proportion of patients.
Gonococcal bacteremia
It can produce a syndrome with recurrent episodes of fever, skin lesions, arthralgia or arthritis, mild to severe constitutional symptoms, and intermittently positive blood cultures.
Ophthalmia neonatorum
lt is the most common manifestation of gonococcal disease in infants. It is developed from the infection of the eyes as the baby passes through the birth canal of an infected mother. It is a destructive inflammation of the eye and before the use of antimicrobial agents frequently caused blindness.
Gonococcal conjunctivitis
A person may acquire this infection usually through the transfer of gonococci in the genital discharges by contaminated fingers. The conjunctivitis is characterized by intensely red and swollen conjunctiva with profuse purulent discharge.
LABORATORY DIAGNOSIS
CLINICAL SPECIMENS
The diagnosis of gonorrhea depends on the isolation and identification of gonococci in the clinical material obtained from a suspected case. The most important clinical material is the urethral or cervical discharge. A specimen should be collected from the appropriate site (urethra, endocervix, anal canal, and oropharynx). Normally, only urethral specimens are obtained from heterosexual women; urethral, rectal, and pharyngeal specimens from homosexual men. All specimens should be obtained before administration of antibiotic therapy.
MICROSCOPIC EXAMINATION
A thin smear of the specimen is prepared on a clean glass slide, it is then Gram stained and observed under microscope. A presumptive diagnosis of gonorrhea may be made if intracellular and extracellular Gram-negative diplococci are observed in leukocytes from exudates. Gonococci are generally present in large numbers in urethral discharges from symptomatic men. In contrast, gonococci generally occur in low numbers in cervical specimens and in early and late infection in symptomatic and asymptomatic men.
CULTURAL CHARACTERS
The specimens should be inoculated on selective media, i.e., Thayer-Martin medium, modified Thayer-Martin medium, and Martin-Lewis medium. Immediately after inoculation, the media plates should be incubated at 35-37 °C in a chamber with ca. 70% relative humidity and ca. 5% CO2. A CO2-enriched atmosphere may be provided by either a CO2 incubator, candle-extinction jar, or a sealed container with a CO2-generating tablet. Plates should be examined after 24 hours of incubation.
Suspicious colonies are Gram-stained and tested for oxidase production using a 1% aqueous solution of tetramethyl-
IDENTIFICATION OF ISOLATES
The isolated gonococci are identified on the basis at biochemical properties. Two types of biochemical tests are currently available for identifying gonococci.These are carbohydrate fermentation and tests that detect the presence of various enzymes. N. gonorrhoeae ferments glucose without gas. Rapid enzyme tests are recommended for confirmation of strains isolated on selective media. N. gonorrhoeae produces only prolyl aminopeptidase but no gamma-glutamyl aminopeptidase and beta-galactosidase.
SEROLOGICAL IDENTIFICATION
THERAPY
Isolated gonococci can be identified on the basis of their serological properties. The most common techniques now available include fluorescent antibody staining technique, ELlSA test, and coagglutination test. In all these techniques, absorbed polyvalent antibodies are used for the identification of gonococcal isolates.
The standard therapy of gonorrhea has been with the use of injectable penicillin and oral probenecid, a drug that delays the renal excretion of penicillin. Patients allergic to the penicillin were treated with oral tetracycline for 7 days instead. The current treatment recommendation to combat tetracycline and penicillin-resistant strains of gonococci is ceftriaxone in a single injection. Spectinomycin, ciprofloxacin, and amoxycillin are also recommended for the treatment.
CONTROL AND PREVENTION
There is no effective vaccine available for the prevention of gonorrhea. A number of vaccines containing pill protein, protein ll, and lipopolysaccharide have been used in the preparation of the vaccines but with very little success. Use of the condom provides a high degree of protection for the uninfected partner. Prophylactic use of oral penicillin has become useless after the emergence of penicillin- resistant varieties. Sexual partners of patients with gonorrhea should be identified and treated as quickly as possible to prevent further spread of disease.
The installation of 1% silver nitrate (Credé method) or an antimicrobial drug into the eyes of the newborn has largely eradicated gonococcal ophthalmia neonatorum.
The evolution of multiple drug-resistant strains has made control of gonorrhea difficult. These strains are responsible for majority of the cases of this disease all over the world.
