Gonorrhea

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Gonorrhea (gonorrhoea in British English) is among the most common sexually transmitted diseases in the world. In the United States, gonorrhea is the second most common STD (after chlamydia).^[1] Neisseria gonorrhoeae is a species of Gram-negative, coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.^[2]

Gonorrhea can infect mucus-secreting epithelial cells in both men and women. The first place this bacterium infects is usually the columnar epithelium of the urethra and endocervix. Non-genital sites in which this bacterium thrives include the rectum, the oropharynx, and the conjunctivae of the eyes. Established routes of transmission of Neisseria gonorrhoeae include vaginal and rectal intercourse, fellatio, cunnilingus, and perinatal. The main pathogenicity of the Neisseria gonorrhea stems from the ability of the surface pili to attach to the surface of the urethra, fallopian tubes, and endocervix.^[3] In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. Additionally, development of disseminated gonococcal infection is the result of Neisserial organisms’ dissemination to the blood.^[4][5]

Common risk factors in the development of gonorrhea include sexual activity, multiple sex partners, previous history of sexually transmitted diseases, having a sexual partner with a past history of any sexually transmitted disease, and failure to use condoms during sex.^[6] In 50 to 70% of women, the initial infection with Neisseria gonorrhea may be asymptomatic. The most common complication of untreated gonorrhea is pelvic inflammatory disease (PID), which may lead to increased risks of ectopic pregnancy. If left untreated, ectopic pregnancy can be life-threatening to the mother.^[7] In men, gonorrhea usually results in urethritis, which may result in dysuria. If left untreated, gonorrhea may result in inflammation of the epididymis (epididymitis), prostate gland (prostatitis), and urethral structure. Disseminated gonococcal infection (DGI) occurs in about 0.5 to 3% of patients, commonly following asymptomatic mucosal infection in both sexes.

Empiric treatment for gonorrhea is usually initiated prior to receipt of laboratory results. Nucleic acid amplification tests (NAATs) are the test of choice in all individuals who present with urogenital symptoms.^[8] The mainstay of therapy for gonococcal infections is antimicrobial therapy. Gonorrhea treatment is complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobials; accordingly, a combination therapy with azithromycin and a cephalosporin is used to improve treatment efficacy and potentially slow the emergence and spread of antibiotic resistance.^[9] Effective measures for the primary prevention of gonorrhea infection include practicing abstinence, avoiding high-risk sexual behaviors (e.g., having unprotected sex or multiple sexual partners), and using latex condoms. Measure for the secondary prevention of gonorrhea infection include early detection, treatment of sexual partners, and treatment of other sexually transmitted infections (e.g., chlamydia).^[10][11][12]

Gonorrhea is an ancient disease with biblical references. However, the exact time of onset of gonorrhea in history cannot be accurately determined from the extant historical record.^[13] In 1879, gonorrhea was referred to as “the clap” by German bacteriologist Albert Neisser.^[14]

Based on anatomic location, gonorrhea may be classified into three subtypes: urogenital, extragenital, and disseminated gonococcal infection. Additionally, gonococcal infections may be classified into many subtypes according to the affected organ system.^[15][16][17]

Gonorrhea is a sexually transmitted disease (STD) that is caused by the bacterium Neisseria gonorrhea. It can infect mucus-secreting epithelial cells in both men and women. Established routes of transmission of the Neisseria gonorrhoeae include vaginal intercourse, rectal intercourse, fellatio, cunnilingus, and perinatal. The main pathogenicity of the Neisseria gonorrhea stems from the ability of the surface pili to attach to the surface of the urethra, fallopian tubes, and endocervix.^[3][18][19] Another virulence factor of gonorrhea is porin. There are two main porin serotypes: PorB.1A strains (resulting in a disseminated gonococcal infection) and PorB.1B strains (resulting in local genital infections).^[20][21][22]

In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the conjuctiva. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva. Additionally, development of disseminated gonococcal infection is the result of Neisserial organisms’ dissemination to the blood due to a variety of predisposing factors, such as change in PH, pregnancy, menstruation, PorB.1A strains, and complement deficiencies.^{[4][5][23][24]}

Neisseria gonorrhoeae, also known as gonococci (plural), gonococcus (singular), or gonorrhoea (in British English), is a species of Gram-negative, coffee bean-shaped diplococci bacteria that is responsible for the sexually transmitted infection gonorrhea.^[2] Gonorrhea (gonorrhoea in British English) is among the most common sexually transmitted diseases in the world. The term comes from the Ancient Greek word γονόρροια (gonórrhoia), literally “flow of seed”; in ancient times, it was incorrectly believed that the pus discharge associated with the disease contained semen.^[25]

Gonorrhea must be differentiated from other sexually transmitted pathogens, nongonococcal urethritis, vaginitis, cervicitis, urinary tract infections, prostatitis, and orchitis. Additionally, disseminated gonococcal infection must be differentiated from herpes simplex virus (HSV), nongonococcal septic arthritis, syphilis, HIV infection, rheumatic fever, reactive arthritis , and Lyme disease.^[15][16][17]

Gonorrhea is a very common infectious disease. In the United State, gonorrhea is the second most common STD (after chlamydia).^[1] In 2012, the incidence of gonorrhea was reported as 106 million cases worldwide.^[26] In 2014, a total 350,062 cases of gonorrhea were reported in United States.^[27]

Common risk factors for the development of gonorrhea include sexual activity, having multiple sex partners, previous history of sexually transmitted diseases, having a partner with a past history of any sexually transmitted disease, and failure to use a condom during sex.^[6][28][29]

The U.S. Preventive Services and Task Force (USSTF) recommends screening for gonorrhea in sexually active women age 24 years and younger and in older women who are at increased risk for infection. Current evidence is insufficient to assess the balance of benefits and harms of screening for gonorrhea in heterosexual men. However, USSTF recommends at least annual screening for gonorrhea among men who have sex with men (MSM).^[30][31][32]

In 50 to 70% of women, the initial infection with Neisseria gonorrhea may be asymptomatic. Initial infection is usually observed in the cervical region, but due to the presence of the surface pili, the infection may ascend through the uterus into the fallopian tubes and finally out into the peritoneal cavity. The exact incubation period of gonorrhea is unknown. It may result in cervicitis and urethritis, which may present with dysuria, vaginal pruritus, and vaginal mucopurulent discharge. If gonococcal infection is left untreated, it can progress to fibrosis. Fibrosis can result in fallopian tube stricture, tubo-ovarian cyst or abscess, pelvic inflammatory disease (PID), Perihepatitis (Fitz-Hugh-Curtis syndrome), and/or bartholinitis. The most common complication of untreated gonorrhea is pelvic inflammatory disease (PID), which may lead to an increased risk of ectopic pregnancy. If left untreated, ectopic pregnancy can be life-threatening for the mother.^[7][33] In men, gonorrhea usually results in urethritis, which may result in dysuria. If left untreated, gonorrhea may result in inflammation of the epididymis (epididymitis), prostate gland (prostatitis), and urethral structure (urethritis). Disseminated gonococcal infection (DGI) occurs in about 0.5 to 3% of patients, commonly following asymptomatic mucosal infection in both sexes. Disseminated gonococcal infection can lead to the infection of multiple distant sites such as the brain, heart, and joints. The most common signs and symptoms include arthritis or arthralgias, tenosynovitis, and multiple skin lesions.

Common complications of gonococcal infection in women may include salpingitis, pelvic inflammatory disease, Infertility, dyspareunia, and ectopic pregnancy. Common complications of gonococcal infection in men may include post-inflammatory urethral strictures, urethral abscess, penile lymphangitis, penile edema, urinary tract infection, and kidney failure. The prognosis of urogenital and disseminated gonococcal infection are generally good with adequate treatment.

It is critical to obtain a detailed and thorough sexual history from the patient. Specific areas of focus when obtaining a history from the patient include number and type of sexual partners, contraception use, and previous history of sexually transmitted diseases. The majority of women with gonorrhea are asymptomatic, while some have vaginal discharge, lower abdominal pain, or pain during intercourse. Common symptoms of gonococcal infection among men include urethritis, which is associated with burning with urination and discharge from the penis. Either sex may also acquire gonorrhea of the throat from performing oral sex on an infected partner, usually a male partner. Such infection is asymptomatic in 90% of cases, and produces a sore throat in the remaining 10%. The incubation period is 2 to 14 days, with most of these symptoms occurring between 4 and 6 days after infection.^{[15][34][35][36]} Rarely, gonorrhea may cause skin lesions and joint infection (pain and swelling in the joints) after traveling through the blood stream. Very rarely, it may settle in the heart, causing endocarditis, or in the spinal column, causing meningitis.^[17]

Women with gonococcal infection usually appear to be well until the development of such complications as PID. Physical examinations of women with gonococcal infection are usually remarkable for mucopurulent urethral, cervical, or vaginal discharge; friable appearance of the cervix; and cervical motion tenderness. Common physical examination finding of gonococcal infection in men include mucopurulent urethral discharge. Less commonly, penile edema and epididymal tenderness and edema (epididymitis) may also be seen as part of a complicated gonococcal infection.^[15][34][35]

Physical examination of patients with pharyngeal gonococcal infection is usually remarkable for mild pharyngeal exudates and rectal gonococcal infection is usually remarkable for mucopurulent anal discharge. Physical examination of patients with disseminated gonococcal infection (DGI) is usually remarkable for fever, pustular or vesicular rash, and musculoskeletal findings.^[15][17]

The following images are associated with gonorrhea physical examination.^[37][38]

Empiric treatment for gonorrhea is usually initiated prior to the receipt of laboratory result. A microbiologic diagnosis is important for further management in order to determine the need for further testing, partner management, and public health considerations. Any sexually active man or women presenting with signs and symptoms of urethritis, cervicitis, pelvic inflammatory disease, and epididymitis should undergo diagnostic testing for Neisseria gonorrhea. Additionally, the possibility of disseminated gonococcal infection (DGI) should be considered in all young sexually active individuals who present with arthralgias or suspected septic arthritis. Common laboratory tests for gonococcal infection may include gram stain, culture, nucleic acid amplification tests (NAAT), and non-amplified tests. Nucleic acid amplification tests are the test of choice in all individuals who present with urogenital symptoms.^[8][17] Additionally, synovial fluid analysis is usually sent for cell count, differential, gram stain, bacterial culture and NAAT in patients with suspected DGI.^[39]

Other diagnostic studies are used when NAAT or culture are not available. Other diagnostic studies for gonorrhea infection include rapid NAAT assay (modular-cartridge based platform), leukocyte esterase urine test, immunochromatographic tests, nucleic acid hybridization tests, and enzyme immunoassay (EIA).^[40][41][42]

The mainstay of therapy for gonococcal infections is antimicrobial therapy. Gonorrhea treatment is complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobials; accordingly, a combination therapy with azithromycin and a cephalosporin is used to improve treatment efficacy and potentially slow the emergence and spread of antibiotic resistance.^[43]

Gonorrhea treatment is complicated by the ability of Neisseria gonorrhoeae to develop resistance to antimicrobials. High-level resistance to expanded-spectrum cephalosporins and azithromycin is now reported, and it seems that developing another effective treatment has become unaffordable for pharmaceutical companies, though new combination antibiotic treatments are being evaluated. There are no affordable alternative therapeutic options currently available for the treatment of gonococcal disease, and it seems even newly developed antibiotics will be short-term solutions, as the bacterium may well develop resistance to them, too.^[44]

In 2006, CDC had five recommended treatment options for gonorrhea. Currently, the U.S. has only one remaining option.

Effective measures for the primary prevention of gonococcal infection include accurate risk assessment and counseling, practicing abstinence, avoiding high-risk sexual behaviors (e.g., unprotected sex or multiple sexual partners), using latex condoms, and being in a long-term and monogamous relationship with an uninfected partner.^[10][11][12]

Strategies for the secondary prevention of gonococcal infection include early detection, treatment of sexual partners, and treatment of other sexually transmitted infections (e.g., chlamydia).^[10][11][12]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Sara Mehrsefat, M.D. [2]; Priyamvada Singh, MBBS [3]

Gonorrhea is an ancient disease with biblical references. However, the exact time of onset of gonorrhea in history cannot be accurately determined from the extant historical record. The term comes from Ancient Greek γονόρροια (gonórrhoia), which literally means “flow of seed.” In ancient times, it was incorrectly believed that the pus discharge associated with the disease contained semen.^[1] In 1879, gonorrhea was referred to as “the clap” by German bacteriologist Albert Neisser.^[2]

• Gonorrhea is an ancient disease with biblical references. However, the exact time of onset of gonorrhea in history cannot be accurately determined from the extant historical record.^[3]
• In 150 AD, gonorrhea was first described and given its present day name (gon = semen + rhea = flowa/flow of semen) by Galen, a Greek physician.^[4]
• In 1161, one of the first reliable notations occur in the Acts of the (English) Parliament, which passed a law to reduce the spread of “…the perilous infirmity of burning.” The symptoms described are consistent with, but not diagnostic of, the disease we now recognize as gonorrhea.^[5]
• In 1256, a similar decree was passed by Louis IX in France with the intent of reducing the spread of similar symptoms, which were noted at the siege of Acre by Crusaders.^[6]
• In 1378, the term “the clap” was first introduced to refer to gonorrhea. The moniker likely descended from the name of the old Parisian district (Les Clapiers), where prostitutes were housed.
• In 1879, gonorrhea was referred to as “the clap” by German bacteriologist Albert Neisser.^[2]

• In 2009, the national rate of reported gonorrhea cases reached an historic low.

• Historically, treatments for gonorrhea have included thermotherapy, plant-based extracts (e.g., cubebs, copaiba), and metals (mercury and arsenic).^[3]
• Surgeons’ tools on board the recovered English warship the Mary Rose included a syringe that, according to some, was used to inject mercury via the urinary meatus into any crewman suffering from gonorrhea.^[7]
• In the 19th century, silver nitrate was one of the most widely used treatments.
• In 1897, silver nitrate was replaced by collodial silver after its invention by Arthur Eichengrün. This new type of silver was marketed by Bayer.^[8]
• In 1930s, the first reliable antibiotic (sulfonamides) proved effective against gonorrhea.^[3]
• In 1940s, gonorrhea began to show resistance to sulfanomides and penicillin became the treatment of choice.
• In the late 1960s, gonorrhea showed resistance to penicillin by producing the penicillinase enzyme.
• In the 1980s, strains of gonorrhea began developing resistance to penicillin by other mechanism rather than making penicillinase. Penicillin and tetracycline were no longer indicated in the treatment of gonorrhea.
• Since 1986, the United States Gonococcal Isolate Surveillance Project (GISP) has been monitoring antibiotic resistance to gonorrhea.
• In 2009, the first extensively drug-resistant (XDR) gonococcal strain of gonorrhea (H041) was isolated in Japan.^[9]
• In 2010, it was claimed that 27,000 per 100,000 gonorrhea samples were resistant to penicillin, tetracycline, and ciprofloxacin, or some combination of these drugs.
• In 2012, the CDC updated its treatment guidelines and recommended combination therapy with ceftriaxone and azithromycin.^[10]
• In 2015, ceftriaxone plus azithromycin is the only recommended treatment for gonorrhea.^[11]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Based on anatomic location, gonorrhea may be classified into three subtypes: urogenital, extragenital, and disseminated gonococcal infection. Additionally, gonococcal infections may be classified into many subtypes according to the affected organ system.^[1][2][3]

Based on anatomic location, gonorrhea may be classified into three subtypes: urogenital, extragenital, and disseminated gonococcal infection.^[1][2][3]

• Urogenital infection
  • Urogenital infection in women
  • Urogenital infection in men
• Extragenital infection
  • Proctitis
  • Pharyngitis
  • Conjunctivitis
• Disseminated gonococcal infection

Gonococcal infections may be classified into many subtypes according to the affected organ system.

• Abscess gonococcal
• Acute gonorrhea of genitourinary tract
• Chronic gonorrhea
• Gonococcal anal infection
• Gonococcal bursitis
• Gonococcal cystitis
• Gonococcal epididymo-orchitis
• Gonococcal female pelvic infection
• Gonococcal heart disease
• Gonococcal hepatitis
• Gonococcal infection of eye
• Gonococcal infection of the central nervous system
• Gonococcal keratosis
• Gonococcal lymphangitis of penis
• Gonococcal perihepatitis
• Gonococcal peritonitis
• Gonococcal prostatitis
• Gonococcal seminal vesiculitis
• Gonococcal spondylitis
• Gonococcal synovitis or tenosynovitis
• Gonococcal tysonitis
• Gonococcal urethritis
• Gonococcemia
• Gonorrhea of pharynx
• Gonorrhea of rectum
• Gonorrhea with local complication
• Maternal gonorrhea during pregnancy, childbirth and the puerperium
• Neonatal gonococcal infection

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Gonorrhea is a sexually transmitted disease (STD) caused by Neisseria gonorrhea. It can infect mucus-secreting epithelial cells both in men and women. Established routes of transmission of the Neisseria gonorrhoeae bacterium include vaginal intercourse, rectal intercourse, fellatio, cunnilingus, and perinatal. The main pathogenicity of the Neisseria gonorrhea stems from the ability of its surface pili to attach to the surface of the urethra, fallopian tubes, and endocervix.^[1][2][3] Anotehr virulence factor of gonorrhea is porin. The two main porin serotypes include PorB.1A strains (resulting in a disseminated gonococcal infection) and PorB.1B strains (resulting in local genital infections).^[4][5][6]

In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the conjuctiva. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva. Additionally, development of disseminated gonococcal infection is the result of Neisserial organisms’ dissemination into the blood due to a variety of predisposing factors such as change in PH, pregnancy, menstruation, PorB.1A strains, and complement deficiencies.^{[7][8][9][10]}

Gonorrhea is a sexually transmitted disease (STD) that is caused by Neisseria gonorrhea, a gram-negative intracellular diplococcus, oxidase-positive bacterium that utilizes glucose, but not sucrose, maltose, or lactose. It can infect mucus-secreting epithelial cells in both men and women.

Established routes of transmission of the Neisseria gonorrhoeae include:

• Male to female via semen (transmission rate is estimated to be 50%-70% per episode)
• Female vagina to male urethra (transmission rate is estimated to be 20% per episode)
• Rectal intercourse
• Fellatio and, less commonly, cunnilingus can result in pharyngeal gonorrhea
• Perinatal

Established virulence factors of Neisseria gonorrhoeae include:

• The main pathogenicity of the Neisseria gonorrhea stems from the surface pili by following mechanisms:^[1][2][3]
  • Mediate attachment to the surface of the urethra, fallopian tubes, and endocervix
  • Preventing phagocytosis by neutrophils
• Opa proteins (opacity-associated protein) are surface proteins that help gonococcus binds to receptors on immune cells^[11][12][13]
  • Down-regulate activated CD4+ T cells (prevent an immune response)
  • Inhibit B-cell antibody production (unable to establish immunological memory against gonorrhea)
• Porin, two main serotypes of which have been identified:^[4][5][6]
  • PorB.1A strains
    • Bind to complement inhibitory molecules, resulting in a diminished inflammatory response (disseminated gonococcal infection)
  • PorB.1B strains
    • Cause local genital infections only
• Lipooligosaccharides (LOS)^[14][15]
  • LOS binds to human asialoglycoprotein receptor (ASGP-R) expressed on sperm cells and urethral epithelial cells
• Gonococcal ribosomal protein L12^[16][17]
  • Allows attachment to and invasion of an endometrial cell line via interaction with the lutropin receptor (LHr), which lead to pelvic inflammatory disease (PID) or disseminated gonococcal infection (DGI) in women
• Release of IgA1 proteases^[18][19]
  • The exact pathogenesis is not fully understood, but it is thought that IgA protease may play a role gonococcal infection in women

In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the conjuctiva. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva.

Development of disseminated gonococcal infection is the result of Neisserial organisms’ dissemination into the blood due to a variety of predisposing factors such as:^{[7][8][9][10]}

• Host factors
  • Change in pH
    • Pregnancy
    • Menstruation
• Virulence factors of the organism itself
  • PorB.1A strains
    • Result in serum resistance
• Failures of the host’s immune defenses
  • Complement deficiencies

Host factors play an important role in mediating entry of gonococci into nonphagocytic cells by following methods:^[20][21]

1. N. gonorrhea activates phosphatidylcholine specific phospholipase C and acidic sphingomyelinase and release of diacylglycerol and ceramide
2. Accumulation of ceramide results in apoptosis
3. Apoptosis may cause disruption of epithelial integrity
4. Disturbed epithelium facilitate entry of gonococci into sub epithelial tissue

• Additionally, gonococcus can survive in neutrophils and macrophages by preventing the formation of degradative phagolysosomes^[22]
• Inflammatory cytokines may be released as a result of toxic effect of LOS
• Complement activation may result in chemotactic factors release which contributes to inflammation

Gonorrhea is associated with increased susceptibility to the transmission and acquisition of HIV infection by the following mechanisms:^[23][24][25]

• Increased HIV expression and viral production by activation of HIV infected CD4 (transmission)
• Altered HIV specific CD8 cell response (acquisition)

HIV RNA concentrations in semen are eightfold higher among those with gonococcal urethritis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Neisseria gonorrhoeae, also known as gonococci (plural), or gonococcus (singular), is a species of Gram-negative coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.^[1] N. gonorrhoeae was first described by Albert Neisser in 1879.

Neisseria are fastidious Gram-negative cocci that require nutrient supplementation to grow in laboratory cultures. To be specific, they grow on chocolate agar with carbon dioxide. These cocci are facultatively intracellular and typically appear in pairs (diplococci), in the shape of coffee beans. Of the eleven species of Neisseria that colonize humans, only two are pathogens. N. gonorrhoeae is the causative agent of gonorrhea (also called “The Clap”) and is transmitted via sexual contact.^[2]

Neisseria is usually isolated on Thayer-Martin agar (or VPN agar)—an agar plate containing antibiotics (vancomycin, colistin, nystatin, and trimethoprim) and nutrients that facilitate the growth of Neisseria species while inhibiting the growth of contaminating bacteria and fungi. Further testing to differentiate the species includes testing for oxidase (all clinically relevant Neisseria show a positive reaction) and the carbohydrates maltose, sucrose, and glucose test in which N. gonorrhoeae will oxidize (that is, utilize) only the glucose.

N. gonorrhoeae are non-motile and possess type IV pili to adhere to surfaces. The type IV pili operate mechanistically similar to a grappling hook. Pili extend and attach to a substrate that signals the pilus to retract, dragging the cell forward. N. gonorrhoeae are able to pull 100,000 times their own weight, and it has been claimed that the pili used to do so are the strongest biological motor known to date, exerting one nanonewton.^[3]

N. gonorrhoeae has surface proteins called Opa proteins, which bind to receptors on immune cells. In so doing, N. gonorrhoeae is able to prevent an immune response. The host is also unable to develop an immunological memory against N. gonorrhoeae – which means that future reinfection is possible. N. gonorrhoeae can also evade the immune system through a process called antigenic variation, in which the N. gonorrhoeae bacterium is able to alter the antigenic determinants (sites where antibodies bind) such as the Opa proteins^[4] and Type IV pili^[5] that adorn its surface. The many permutations of surface proteins make it more difficult for immune cells to recognize N. gonorrhoeae and mount a defense.^[6]

N. gonorrhoeae is naturally competent for DNA transformation as well as being capable of conjugation. These processes allow for the DNA of N. gonorrhoeae to acquire or spread new genes. Especially dangerous from the aspect of healthcare is the ability to conjugate, since this can lead to antibiotic resistance.^[7]

• 
  N. gonorrhea (Gram-negative diplococci) in conjunctivitis.^[8]

The genomes of several strains of N. gonorrhoeae have been sequenced. Most of them are about 2.1 Mb in size and encode 2,100 to 2,600 proteins (although most seem to be in the lower range).^[9] For instance, strain NCCP11945 consists of one circular chromosome (2,232,025 bp) encoding 2,662 predicted ORFs and one plasmid (4,153 bp) encoding 12 predicted ORFs. The estimated coding density over the entire genome is 87%, and the average G+C content is 52.4%, values that are similar to those of strain FA1090. The NCCP11945 genome encodes 54 tRNAs and four copies of 16S-23S-5S rRNA operons.^[10]

In 2011, researchers at Northwestern University found evidence of a human DNA fragment in a Neisseria gonorrhoeae genome, the first example of horizontal gene transfer from humans to a bacterial pathogen.^[11][12]

N. gonorrhoeae is transmitted from person to person during sexual relations. Traditionally, the bacteria was thought to move attached to spermatozoon, but this hypothesis did not explain female to male transmission of the disease. A recent study suggests that rather than “surf” on wiggling sperm, N. gonorrhoeae bacteria uses hairlike structures called pili to anchor onto proteins in the sperm and move through coital liquid.^[13]

The exudates from infected individuals contain many polymorphonuclear leukocytes (PMN) with ingested gonococci. These gonococci stimulate the PMN to release an internal oxidative burst involving reactive oxygen species in order to kill the gonococci.^[14] However, a significant fraction of the gonococci can resist killing and are able to reproduce within the PMN phagosomes.

Stohl and Seifert showed that the bacterial RecA protein, that mediates recombinational repair of DNA damage, plays an important role in gonococcal survival.^[15] The protection afforded by RecA protein may be linked to transformation, the process by which recipient gonococci take up DNA from neighboring gonococci and integrate this DNA into the recipient genome through recombination. Michod et al. have suggested that an important benefit of transformation in N. gonorrhoeae may be recombinational repair of oxidative DNA damages caused by oxidative attack by the hosts phagocytic cells.^[16]

• 
  Photomicrograph of Gram-negative Neisseria gonorrhoeae bacteria, accompanied by a number of polymorphonuclear leukocytes (PMN). From Public Health Image Library (PHIL). ^[17]
• 
  3D computer-generated image of drug-resistant Neisseria gonorrhoeae diplococcal bacteria. From Public Health Image Library (PHIL). ^[17]
• 
  Gram-stained photomicrograph revealed gram-negative diplococcal bacteria, Neisseria gonorrhoea. From Public Health Image Library (PHIL). ^[17]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Gonorrhea must be differentiated from other sexually transmitted pathogens, nongonococcal urethritis, vaginitis, cervicitis, urinary tract infections, prostatitis, and orchitis. Additionally, disseminated gonococcal infection must be differentiated from herpes simplex virus (HSV), nongonococcal septic arthritis, syphilis, HIV infection, rheumatic fever, reactive arthritis , and Lyme disease.^[1][2][3]

Gonorrhea must be differentiated from other sexually transmitted pathogens including Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, herpes simplex virus (HSV), and syphilis. Conditions that must be considered in the differential diagnosis of gonorrhea include:^[1]

• In women
  • Non gonorrheal urethritis
  • Vaginitis
  • Cervicitis
  • Urinary tract infections
  • Pregnancy
  • Endometriosis
• In men
  • Non gonorrheal urethritis
  • Prostatitis
  • Orchitis
  • Testicular torsion
  • Urinary tract infections

Disseminated gonococcal infection must be differentiated from:^[2][3][4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2], Priyamvada Singh, MBBS [3]

Gonorrhea is a very common infectious disease. In the United States, gonorrhea is the second most common STD (after chlamydia).^[1] In 2012, the incidence of gonorrhea was reported to be 106 million cases worldwide.^[2] In 2014, a total of 350,062 cases of gonorrhea were reported in the United States.^[3]

• In 2012, the incidence of gonorrhea was reported to be 106 million cases worldwide.^[2]
• Based on data for the period between 2005 and 2012, the estimated pooled prevalence for gonorrhea in women globally was 0.8% (0.6–1.0%) and 0.6% (0.4–0.9%) in men.
• In 2012, the global incidence rate for gonorrhea was estimated to be 1900 cases per 100,000 in women and 2400 per 100,000 in men.^[4]
• In 2014, a total of 350,062 cases of gonorrhea were reported in the United States or about 1000 per 100,000 people.^[3]

• In 2014, rates of reported gonorrhea cases in the United States continued to be highest among adolescents and young adults.
• In 2014, the highest rates in women were observed among those aged 20–24 years (500 cases per 100,000 females) and 15–19 years (430 cases per 100,000 females).
• In 2014, the highest rates in men were observed among those aged 20–24 years (480 cases per 100,000 males) and 25–29 years (370 cases per 100,000 males).^[5]
• In 2015, the highest rates in men and women were observed among those aged 20–24 years (547 cases per 100,000 females and 539 cases per 100,000 males).^[6]

• Globally, men are more commonly affected with gonorrhea than women. This suggests increased transmission among gay men, bisexual men, or men who have sex with men (MSM).
• Disseminated gonococcal infection (DGI) is more common in women than men.^[7]
• In 2012, the global prevalence of gonorrhea among women aged 15–49 years was estimated to range from 600 to 1,000 cases per 100,000 individuals.
• In 2012, the global prevalence of gonorrhea among men was estimated to range from 400 to 900 cases per 100,000 individuals.
• In 2014, the United States’ incidence of gonorrhea was reported to be 120 cases per 100,000 males and 100 cases per 100,000 females.^[8]
  • In 2015, the United States’ incidence of gonorrhea was reported to be 141 cases per 100,000 males and 107 cases per 100,000 females.^[6]

Rates of gonorrhea per 100,000 population in 2014 and in 2015 – Source: https://www.cdc.gov/

In 2014, the United States’ incidence of gonococcal infection among African-Americans was 400 cases per 100,000; 160 cases per 100,000 among American Indians/Alaska Natives; 100 cases per 100,000 among Native Hawaiians/Other Pacific Islanders; and 38 cases per 100,000 among Whites.

• The incidence in Blacks is 10.6 times the incidence in Whites.^[5]
• The incidence in American Indians/ Alaska Native was 4.2 times the incidence in Whites.
• The incidence in Native Hawaiians/Other Pacific Islanders was 2.7 times the incidence in Whites.

In 2015, the United States’ incidence of gonococcal infection remained highest among African-Americans was (425 cases per 100,000); 192,8 cases per 100,000 among American Indians/Alaska Natives; 123 cases per 100,000 among Native Hawaiians/Other Pacific Islanders; and 38 cases per 100,000 among Whites.^[9]

• The incidence in Blacks is 9.6 times the incidence in Whites.^[9]
• The incidence in American Indians/ Alaska Native was 4.4 times the incidence in Whites.
• The incidence in Native Hawaiians/Other Pacific Islanders was 2.8 times the incidence in Whites.

• In the United State, gonorrhea is the second most common STD (after chlamydia).^[1]
• In the United States, the CDC estimates more than 300,000 reported cases of gonorrhea per year, yet the CDC estimates that 820,000 new infections may actually occur each year.^[10]

• In 2014, a total of 350,062 gonorrhea cases were reported, and the national gonorrhea rate increased to 124 cases per 100,000 population^[3]
• In 2014, the state with the lowest prevalence of gonorrhea was Vermont, with 13 cases per 100,000 people. The state with the highest prevalence was the District of Columbia, with 291.3 cases per 100,000 people.^[8]

• In 2015, a total of 395,216 gonorrhea cases were reported, and the national gonorrhea rate increased to 110.7 cases per 100,000 population meaning that the rate of reported gonorrhea increased by 12.8% since 2014 and 19.9% since 2011.^[9]
• In 2015, the state with the lowest prevalence of gonorrhea was New Hampshire, with 18.5 cases per 100,000 people. The state with the highest prevalence was the District of Columbia, with 416.2 cases per 100,000 people.^[9]Source: Centers for disease control: https://www.cdc.gov/

Rates of reported gonorrhea cases in 2014 and 2015 inside the USA – Source: Centers for disease control: https://www.cdc.gov/

• In 2014, among the four region of the United States (South, Midwest, West, and Northeast), the South had the highest rate of reported gonorrhea cases.
• In 2015, South had the highest incidence (146 cases per 100,000) followed by the West (118 cases per 100,000) then the Midwest (115.7 per 100,000) and the Northeast (94.2 per 100,000). ^[9]

Gonorrhea Rates of reported cases by Regoin, United States, 2005-2015 – Source: Centers for disease control: https://www.cdc.gov/

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2], Priyamvada Singh, MBBS [3]

Common risk factors in the development of gonorrhea include sexual activity, multiple sex partners, previous history of sexually transmitted diseases, partner with a past history of any sexually transmitted disease, and failure to use a condom during sex.^[1][2][3]

Any sexually active person can become infected with gonorrhea. In the United States, the highest reported rates of infection are observed among sexually active teenagers, young adults, and African-Americans. Common risk factors for the development of gonococcal infection include:^[1][2][3][4]

• Having multiple sexual partners
• Having a sexual partner with a past history of any sexually transmitted disease
• Failure to use condoms during sexual intercourse
• Having a drug addiction
• Male homosexuality
  • Multiple anonymous partners
  • Abuse of substances (crystal methamphetamine)
  • History of HIV infection
• Low socioeconomic status
• Being of Black, Hispanic, or Native Americans descent
• Abuse of substances (e.g., crack, cocaine)
• Early age of onset of sexual activity
• Pelvic inflammatory disease (PID)
• History of HIV infection
• Use of an intrauterine device (IUD)

Common risk factors in the development of disseminate gonococcal infection include:^{[5][6][7][8][9]}

• Recent menstruation
• Pregnancy
• Immediate post-partum state
• Complement deficiencies (C5, C6, C7, or C8)
• Systemic lupus erythematous (SLE)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

The U.S. Preventive Services and Task Force (USSTF) recommends screening for gonorrhea in sexually active women age 24 years and younger and in older women who are at increased risk for infection. Currently available evidence is insufficient to assess the balance of benefits and harms of screening for gonorrhea in heterosexual men. USSTF recommends at least annual screenings for gonorrhea among men who have sex with men (MSM).

The U.S. Preventive Services and Task Force (USSTF) recommends screening for gonorrhea in sexually active women age 24 years and younger and in older women who are at increased risk for infection. The table below outlines the screening recommendations for gonorrhea.^[1][2][3][4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

In 50 to 70% of women, the Initial infection with Neisseria gonorrhea may be asymptomatic. Initial infection is usually observed in the cervical region, but due to the presence of the surface pili, the infection may ascend through the uterus into the fallopian tubes and finally out into the peritoneal cavity. The exact incubation period of gonorrhea is unknown. It may result in cervicitis and urethritis, which can present with dysuria, vaginal pruritus, and vaginal mucopurulent discharge. If gonococcal infection is left untreated, it can progress to fibrosis, which can result in fallopian tube stricture, tubo-ovarian cyst or abscess, pelvic inflammatory disease (PID), Perihepatitis (Fitz-Hugh-Curtis syndrome), and/or bartholinitis. The most common complication of untreated gonorrhea is pelvic inflammatory disease (PID), which may lead to increased risks of ectopic pregnancy. If left untreated, ectopic pregnancy can be life-threatening for the mother.^[1][2] In men, untreated gonorrhea may result in inflammation of the epididymis (epididymitis), prostate gland (prostatitis), and urethral structure (urethritis). Disseminated gonococcal infection (DGI) occurs in about 0.5 to 3% of patients, commonly following asymptomatic mucosal infection in both sexes. Women are more likely to develop disseminated gonococcal infection than men. Disseminated gonococcal infection can lead to the infection of multiple distant sites such as the brain, the heart, and joints. The most common signs and symptoms include arthritis or arthralgias, tenosynovitis, and multiple skin lesions.

Common complications of gonococcal infection in women may include salpingitis, pelvic inflammatory disease, infertility, dyspareunia, and ectopic pregnancy. Common complications of gonococcal infection in men may include post-inflammatory urethral strictures, urethral abscess, Penile lymphangitis, penile edema, urinary tract infection, and kidney failure. The prognosis of urogenital and disseminated gonococcal infection are generally good with adequate treatment.

• In 50 to 70% of women, the Initial infection with Neisseria gonorrhea may be asymptomatic.^[1][2]
• Initial infection is usually observed in the cervical region though, due to the presence of the surface pili, the infection may ascend through the uterus into the fallopian tubes and, finally, out into the peritoneal cavity.
• The exact incubation period of gonorrhea is unknown. It may result in cervicitis and urethritis, which can cause dysuria, vaginal pruritus, and vaginal mucopurulent discharge.
• If gonococcal infection is left untreated, it can progress to fibrosis, which can result in fallopian tube stricture, tubo-ovarian cyst or abscess, pelvic inflammatory disease (PID), Perihepatitis (Fitz-Hugh-Curtis syndrome), and bartholinitis.
• The most common complication of untreated gonorrhea is pelvic inflammatory disease (PID).
• PID caused by gonorrhea can lead to scarring of the fallopian tubes. As a result of scarring and fibrosis of fallopian tubes, the fertilized egg may not be able to pass through the narrowed and scarred fallopian tube, which may lead to increased risks of ectopic pregnancy and infertility. If left untreated, ectopic pregnancy can be life-threatening for the mother.

• In men, untreated gonorrhea may result in inflammation of the epididymis (epididymitis), prostate gland (prostatitis), and urethral structure (urethritis).

• In both sexes, disseminated gonococcal infection (DGI) can occur. Women are more likely to developed disseminated gonococcal infection than men.
• Disseminated gonococcal infection is a result of bacteremic spread of Neisseria gonorrhea from the primary site of infection (endocervix, urethra, pharynx, or rectum).
• Disseminated gonococcal infection (DGI) occurs in about 0.5 to 3% of patients, commonly following asymptomatic mucosal infection.
• Disseminated gonococcal infection can lead to the infection of multiple distant sites such as the brain, heart, and joints. The most common signs and symptoms include arthritis or arthralgias, tenosynovitis, and multiple skin lesions.
• When joints become involved, gonococcal arthritis can develop.
• Disseminated gonococcal infection usually presents as an arthritis-dermatitis syndrome. Typical symptoms include a 5–7 day history of fever, shaking, chills, multiple skin lesions, and fleeting migratory polyarthralgias and tenosynovitis in fingers, wrists, toes or ankles. This should be evaluated promptly with a culture of the synovial fluid, blood, cervix, urethra, rectum, skin lesion fluid, or pharynx.

• In the absence of adequate prophylaxis, 30% to 42% of infants born by vaginal delivery to infected mothers will develop gonococcal conjunctivitis. Gonococcal conjunctivitis tends to occur 2-7 days after birth, and tends to be more severe than ophthalmia neonatorum arising as the result of other causes. If left untreated, it may cause corneal involvement such as corneal ulceration, diffuse opacification, and corneal perforation. This may lead to blindness, sepsis, or death. The onset of chlamydial conjunctivitis is usually later than gonococcal conjunctivitis.^[3][4][5]

Complications in women may include:

• Salpingitis (scarring of the fallopian tubes), which can lead to infertility or ectopic pregnancy
• Pelvic inflammatory disease
• Infertility
• Painful intercourse (dyspareunia)

Complications in men may include:

• Post-inflammatory urethral strictures
• Abscess (collection of pus around the urethra)
• Penile lymphangitis
• Penile edema
• Urination problems
• Urinary tract infection
• Kidney failure

Complications in both men and women may include:

• Disseminated infection
• Long-term joint pain
• Endocarditis
• Meningitis

The prognosis of gonococcal infection is generally good with adequate treatment.

• Disseminated gonococcal infection is a more serious infection, but is often associated with a favorable long-term prognosis with adequate treatment.

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