Bacteriology

NEISSERIA GONORRHOEAE

Written by MicroDok

Neisseria gonorrhoeae is a Gram-negative, oxidase-positive, non-motile, non-sporulating, non-capsulate, diplococcus found asymptomatically in humans. N. gonorrhoeae is found in the family Neisseriaceae and genus Neisseria which contains two important human pathogens viz: N. gonorrhoeae and N. meningitidis (which causes meningococcal meningitis, an inflammation of the meninges of the brain and spinal cord).  N. gonorrhoeae, a bacterium known to occur in pairs (i.e. diplococcus) can also be called gonococcus. Gonorrhea is usually symptomatic in men and asymptomatic in women. The genitourinary tract, conjunctiva of the eye, pharynx, throat, and the rectum are usually the parts of the body that are affected in N. gonorrhoeae infection. In men, the urethra, epididymis, bladder and prostrate are usually affected by the organism but N. gonorrhoeae colonizes the urethra more than these other parts causing urethritis and dysuria (difficulty in urination).

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Illustration of Gram stain of N. gonorrhoeae. N. gonorrhoeae appears as a diplococcus; and the organism can either be intracellularly or extracellularly located in cells such as neutrophils

But in women, N. gonorrhoeae infects the cervix, rectum, urethra and vulva. In women, infertility or ectopic pregnancy (i.e. development of the embryo in the fallopian tube instead of the uterus) can result following N. gonorrhoeae colonization of the pelvis (where it causes pelvic inflammatory disease, PID). Sexual intercourse especially with an infected individual is the primary route via which this pathogen can be acquired and transmitted. The endocervix and urethra are mostly affected in females, but in males the urethra is the most affected organ. Gonorrhea infection in women can also facilitate the easy contraction of HIV due to the inflammation of the genital region which allows the virus to gain entry during sexual intercourse. Ophthalmic neonatorum (blindness in neonates) can also occur in newborn infants whose mother’s vagina is infected with N. gonorrhoeae. The infant’s eye primarily become infected with gonococcus during delivery, and if left untreated the child can go blind.  

PATHOGENESIS OF NEISSERIA GONORRHOEAE INFECTION

Upon invasion, N. gonorrhoeae attaches to the mucosal surfaces of the urethra in males and cervix in female using its pili, fimbriae and other adherence molecules (known as adhesins). This initial attachment sparks up a local inflammatory reaction at the site of invasion, and attachment and penetration of the microbe into the host cell is largely made possible by the action of the pili and adhesins. The most common symptom of gonorrhea in adult male’s aside urethritis and dysuria may include frequent painful urination, and the discharge of scanty, clear or cloudy and purulent fluid. Purulent vaginal discharges are the major symptom of the disease in adult females who are usually covert with the infection. N. gonorrhoeae specifically attaches to the columnar epithelial cells of the urogenital tract with its surface protein, opacity associated protein (Opa) and other adhesins that allows it to do so.

Adhesion of gonococcus to the mucosal surfaces of the genitourinary tract prevents it from being washed away by the flushing action of the urine in males and the natural vaginal discharges in females. Infection with gonococcus is predominantly through a direct and intimate person-to-person sexual contact, and painful urination (in males) and unusual purulent vaginal discharge (in females) are the most important syndromes that follow infectivity. Gonococcus infection is usually limited to its site of entry where it cause local injury and inflammation, and can rarely spread to the blood stream or other vital tissues of the body. Several disseminated bacterial infections including pelvic inflammatory disease (PID), gonorrheal bacteremia, gonorrheal arthritis, and gonorrheal endocarditis can ensue following the spread and dissemination of gonococcus in the body. These later infection are generally referred to as disseminated gonococcal infections (DGIs). Anal intercourse (especially in homosexual males) can also result to a variety of symptomatic rectal infections in persons engaging in such activity.

LABORATORY DIAGNOSIS OF NEISSERIA GONORRHOEAE INFECTION

Centrifuged urine, urethral exudates, and cervical exudates are the main specimens collected in suspected cases of N. gonorrhoeae infection. Rectal swab can also be obtained from patients suspected to have engaged in anal sex, and who may have presented clinical syndromes of rectal infections. Gram smear of genitourinary samples which demonstrates the kidney-bean shape of the microbe (i.e. Gram-negative diplococci within a neutrophil) is predominantly the most important laboratory diagnostic decisive factor for gonorrhea especially in adult males. Gram smear is rarely used to diagnose the disease in infected females due to morphological similarity of other bacteria from the female vagina with gonococcus. Gram smears of urethral exudates on swab sticks should be rolled onto clean glass slide immediately after collection, fixed (using methanol) and stained without any prior immersion in normal saline. Throat swabs can also be obtained from patients engaging in oral sex for culture.

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Illustration of the growth of N. gonorrhoeae  on New York City medium agar, which is a selective medium for isolating the organism from clinically important samples

Gonococcus is a very sensitive organism, thus care must be taken in handling specimen, selecting culture media and in analyzing culture results in order to differentiate the pathogen from normal microflora of the body. N. gonorrhoeae produces small, raised, translucent or grey colonies after one or two days of culture or overnight incubation in the presence of CO2 at 35oC. N. gonorrhoeae is a fastidious, aerobic or facultative microbe, and thus requires additional nutrient (e.g. blood and animal protein) for growth in selective or enriched culture media such as the Modified New York City medium. It occurs intracellularly and extracellularly in its host cell, but it is typically seen as diplococcus in pus (polymorphonuclear) cells under the microscope. N. gonorrhoeae grows well on chocolate agar and on other enriched medium including Martin-Lewis medium and Thayer Martin medium (each of which contain antibiotics that inhibit bacteria and fungi) that enhances its growth. Serological investigations including the use of PCR for DNA amplification and DNA probe has also been developed for the laboratory diagnosis of gonococcus infection.

TREATMENT OF NEISSERIA GONORRHOEAE INFECTION

In the past, gonorrhea was successfully treated with penicillin G (which is administered intramuscularly), but the development of resistance mechanisms including β-lactamase enzymes and alteration of N. gonorrhoeae penicillin-binding-proteins (PBPs) due to the widespread use of penicillin has made this antibiotic to be ineffective for treating gonorrhea. Currently, the center for disease control and prevention (CDC) recommends the use of fluoroquinolones (e.g. levofloxacin, ofloxacin and ciprofloxacin) and third-generation cephalosporins (e.g. cefixime, ceftriaxone) which can either be administered orally or intramuscularly for the treatment of gonorrhea. Antibiotics such as azithromycin, erythromycin, or doxycycline are also included in the treatment options for gonococcus infected patients due to the possibility of co-infection with other STIs including syphilis and Chlamydia trachomatis infection. Gonorrhea infection is incomplete if sex partners are left out. Due to the asymptomatic nature of the infection in females, it is critical to refer and treat sex partners of infected individuals in order to avoid the recurrence of the disease in the treated patient.

PREVENTION AND CONTROL OF NEISSERIA GONORRHOEAE INFECTION

Awareness and education of the general public, coupled with proper treatment of infected patients especially those that are covert are very paramount to the control and prevention of N. gonorrhoeae infection. Avoiding multiple sexual partners and remaining faithful to one’s partner are critical in preventing the spread and transmission of the disease. Use of protection (e.g. condoms) during sexual intercourse can also confer some level of protection.

REFERENCES

Prescott L.M., Harley J.P and Klein D.A (2005). Microbiology. 6th ed. McGraw Hill Publishers, USA.

Madigan M.T., Martinko J.M., Dunlap P.V and Clark D.P (2009). Brock Biology of Microorganisms, 12th edition. Pearson Benjamin Cummings Inc, USA.

Balows A, Hausler W, Herrmann K.L, Isenberg H.D and Shadomy H.J (1991). Manual of clinical microbiology. 5th ed. American Society of Microbiology Press, USA.

Barrett   J.T (1998).  Microbiology and Immunology Concepts.  Philadelphia,   PA:  Lippincott-Raven Publishers. USA.

Basic laboratory procedures in clinical bacteriology. World Health Organization (WHO), 1991. Available from WHO publications, 1211 Geneva, 27-Switzerland.

Murray P.R, Baron E.J, Jorgensen J.H., Pfaller M.A and Yolken R.H (2003). Manual of Clinical Microbiology. 8th edition. Volume 1. American Society of Microbiology (ASM) Press, Washington, D.C, U.S.A.

Murray P.R, Baron E.J, Jorgensen J.H., Pfaller M.A and Yolken R.H (2003). Manual of Clinical Microbiology. 8th edition. Volume 2. American Society of Microbiology (ASM) Press, Washington, D.C, U.S.A.

Murray P.R., Rosenthal K.S., Kobayashi G.S., Pfaller M. A. (2002). Medical Microbiology. 4th edition. Mosby Publishers, Chile.

 

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