What is the pathophysiology of gonorrhea?

From the Guidelines

Gonorrhea is caused by the bacterium Neisseria gonorrhoeae, which primarily infects columnar and transitional epithelial cells of mucous membranes, and its pathophysiology involves attachment, invasion, and evasion of the immune system, leading to potential complications such as pelvic inflammatory disease, epididymitis, and systemic infections. The pathophysiology of gonorrhea begins when the bacteria attach to host cells using pili and opacity-associated proteins, allowing them to colonize the genital tract, rectum, pharynx, or conjunctiva 1. After attachment, N. gonorrhoeae invades epithelial cells through endocytosis and can cross the epithelial barrier to reach subepithelial tissues. The bacteria evade the immune system through several mechanisms, including antigenic variation of surface proteins, production of IgA proteases that destroy antibodies, and resistance to complement-mediated killing.

The host inflammatory response to infection involves neutrophil recruitment, which leads to the characteristic purulent discharge. Despite this immune response, the bacteria can persist and spread, potentially causing ascending infections in women (leading to pelvic inflammatory disease) or epididymitis in men. If left untreated, gonorrhea can disseminate through the bloodstream, causing systemic complications like arthritis, dermatitis, and rarely endocarditis or meningitis. The bacteria's ability to rapidly develop antibiotic resistance through genetic mutations and horizontal gene transfer has complicated treatment, necessitating combination antibiotic therapy with ceftriaxone 250 mg intramuscularly and either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days for uncomplicated infections 1.

Some key points to consider in the pathophysiology of gonorrhea include:

• The importance of screening high-risk women for gonococcal infections to prevent complications such as pelvic inflammatory disease and infertility 1
• The potential for gonorrhea to facilitate HIV transmission 1
• The need for combination antibiotic therapy to effectively treat gonorrhea and prevent the development of antibiotic resistance 1
• The potential for gonorrhea to cause systemic complications if left untreated, including arthritis, dermatitis, and rarely endocarditis or meningitis 1

From the Research

Pathophysiology of Gonorrhea

The pathophysiology of gonorrhea is complex and involves the infection of the mucosal surfaces of the reproductive tract, pharynx, rectum, and conjunctiva by the bacterium Neisseria gonorrhoeae 2.

• Infection and Ascension: In women, asymptomatic or unnoticed infections in the lower reproductive tract can lead to serious, long-term consequences if these infections ascend into the fallopian tube, causing pelvic inflammatory disease (PID) 2.
• Host Response: The human host responds to Neisseria gonorrhoeae infection with an inflammatory response, which can produce the condition known as pelvic inflammatory disease (PID) 2.
• Damage to the Fallopian Tube: Infection can lead to tubal scarring, occlusion of the oviduct, and loss of critical ciliated cells, resulting in increased risk of ectopic pregnancy and tubal-factor infertility 2.
• Antibiotic Resistance: The emergence of antibiotic resistance in Neisseria gonorrhoeae has led to severe restriction of treatment options for gonococcal disease 3, 4.
• Iron Acquisition: Neisseria gonorrhoeae has developed mechanisms to acquire iron from the host, including the use of xenosiderophores, which are regulated by the iron-repressed regulator MpeR 5.
• Regulation of Surface Antigens: The expression, function, and regulation of surface antigens, such as FetA, are important for the pathogenesis of Neisseria gonorrhoeae and may lead to better treatment and prevention modalities in the future 5.

Gonococcal Infections in Women

Gonococcal infections in women can be asymptomatic, but they can also cause symptoms such as vaginal and pelvic discomfort, dysuria, and pelvic inflammatory disease 3.

• Pelvic Inflammatory Disease (PID): PID is a serious complication of gonococcal infection in women, which can lead to infertility, ectopic pregnancy, and chronic pelvic pain 2, 6.
• Upper Female Reproductive Tract: The upper female reproductive tract is a complex environment that is difficult to model, but the use of human three-dimensional endometrial epithelial cell models has allowed for the investigation of unique mechanisms of gonococcal pathogenesis in this tract 6.