Neisseria gonorrhoeae: Infectious substances pathogen safety data sheet

For more information on Neisseria gonorrhoeae, see the following:

Section I: Infectious agent

Name

Neisseria gonorrhoeae

Agent type

Bacteria

Taxonomy

Family

Neisseriaceae

Genus

Neisseria

Species

gonorrhoeae

Synonym or cross reference

Gonococci, GonorrheaFootnote 1.

Characteristics

Brief description

Neisseria gonorrhoeae was discovered in 1879 and is a member of the genus Neisseria within the family NeisseriaceaeFootnote 2 Footnote 3. It is a Gram-negative bacterium, 0.6 to 1.0 µm in diameter, which appears kidney bean shaped under the microscope, typically in diplococcal arrangement with adjacent flattened sidesFootnote 1 Footnote 4. N. gonorrhoeae is oxidase positive, non-spore-forming, non-motile and an obligate aerobeFootnote 1 Footnote 5. It has fastidious growth requirements, requiring CO2 supplementation and enriched media, such as chocolate agar, with various antibiotics to grow in cultureFootnote 4. The circular gonococcal genome is approximately 2219 kb in size, with a G+C content of 50%Footnote 4. The bacterium possesses more than one copy of the genome and is therefore polyploid. Most gonococci possess a 24.5 mega-Dalton conjugative plasmid that can facilitate the transfer of other, usually non-transferable, plasmids without mobilization of chromosomal genesFootnote 4. There are at least 70 different strains of N. gonorrhoeae, characterized by the absence or presence of pili, opacity of colonies, auxotyping (nutritional requirements), serotyping and genotypingFootnote 5.

Properties

The outer membrane of N. gonorrhoeae harbours the gonococcal endotoxin lipooligosaccharide (LOS) and numerous fimbriae, such as N-methylphenylalanine pili, which exhibit great affinity for most human cellsFootnote 4. Protein IA (Por A), protein IB (Por B), protein III (Rmp), and the gonococcal capsule are important in avoiding phagocytic activity. LOS facilitates release of enzymes such as proteases and phospholipases, which also contribute to pathogenesis. N. gonorrhoeae also produces β-lactamaseFootnote 1 Footnote 5 and exhibits antigenic variation through genetic recombination of its pili and surface proteins to evade host immune selectionFootnote 6. Recently, human genomic elements were found in the N. gonorrhoeae genome, demonstrating horizontal gene transfer from human hosts to a bacterial pathogenFootnote 7.

Section II: Hazard identification

Pathogenicity and toxicity

N. gonorrhoeae is associated with a wide range of clinical presentations in humansFootnote 1 Footnote 2.

N. gonorrhoeae is most often implicated in urogenital tract infectionsFootnote 8. Coinfection with Chlamydia trachomatis is common. In females, the most common manifestation is cervicitis, which usually occurs 5 to 10 days after exposure, and is characterized by increased vaginal discharge, dysuria, abdominal pain, and menstrual abnormalitiesFootnote 1 Footnote 2 Footnote 5 Footnote 8. However, in most females with cervical gonococcal infection, up to 70%, are asymptomaticFootnote 9. N. gonorrhoeae can be isolated from up to 90% of females with cervical gonorrhea, although urethral infection can occur without concomitant cervical involvementFootnote 10. As with gonococcal cervicitis, urethritis is typically asymptomatic in femalesFootnote 8, but symptoms may include dysuria, urethral pruritis, and mucoid, mucopurulent, or purulent dischargeFootnote 11. Untreated cervical gonorrhea is associated with 10-20% of cases of pelvic inflammatory disease (PID), and 15% of women with PID develop infertility from tubal scarringFootnote 8. Signs and symptoms of PID associated with N. gonorrhoeae typically occur during menses, and include fever, abdominal pain, adnexal or cervical motion tenderness, and leukocytosisFootnote 5. If undiagnosed and untreated, PID can lead to additional complications with the female reproductive tract, including tubo-ovarian abscess, Fitz-Hugh-Curtis syndrome (perihepatitis), chronic abdominal pain, and an increased risk for ectopic pregnancy.

Perihepatitis is an inflammation of the hepatic capsule, with symptoms including colicky, right upper quadrant abdominal pain, and vomiting. Symptomatic bartholinitis may occur in up to 7% of females with genital gonococcal infection, while asymptomatic involvement of Bartholin's glands may occur in up to 28% of casesFootnote 12. Urogenital gonococcal infections have also been associated with chorioamnionitis (infection of the placenta and amniotic fluid), premature rupture of membranes, preterm birth, low birth weight, and spontaneous abortions in pregnant womenFootnote 13 Footnote 14 Footnote 15. N. gonorrhoeae is also implicated in menometrorrhagia (excessive and prolonged uterine bleeding at irregular and/or frequent intervals), as well as endometritis during the postpartum periodFootnote 5. In males, symptomatic urogenital gonococcal infection mainly causes urethritis, characterized by purulent urethral/penile discharge and dysuriaFootnote 1 Footnote 2 Footnote 5. Rarely, the local infection can spread to other areas and cause epididymitis, prostatitis, and penile lymphangitis. Patients with epididymitis present with scrotal edema and scrotal, inguinal, and flank painFootnote 5.

N. gonorrhoeae can infect the anorectum (proctitis) and pharynx (pharyngitis), although infections at these sites are typically asymptomaticFootnote 8. Patients with pharyngitis present with sore throat, fever, and cervical lymphadenopathy, and those with proctitis present with anal pruritus, anal discharge, rectal bleeding, anorectal pain, tenesmus, and constipationFootnote 5 Footnote 8.

Adult gonococcal conjunctivitis ranges from mild infections to aggressive infections characterized by conjunctival injection, purulent discharge, and periorbital edema, which, if untreated, can progress to corneal ulceration, perforation, and blindnessFootnote 16.

Disseminated gonococcal infection (DGI) is rare, affecting 0.4-3% of patients with gonorrheaFootnote 8. A range of clinical findings are associated with DGI, including migratory polyarthralgia, tenosynovitis, dermatitis, fever, purulent arthritis, and genitourinary symptomsFootnote 17. Skin lesions are present in 75% of patients with DGI, including painless or painful petechiae, macules, papules, pustules, vesicles, and bullaeFootnote 8. These signs and symptoms can be divided into two groups, namely tenosynovitis, dermatitis, and polyarthralgia without purulent arthritis (also called gonococcal arthritis-dermatitis syndrome)Footnote 18, or purulent arthritis with or without associated symptomsFootnote 19. In rare cases, further complications such as meningitis, septic shock, or endocarditis may occurFootnote 4 Footnote 8.

Gonococcal infections can occur in neonates from exposure to infected cervical secretions during delivery, and include ophthalmia neonatorum (neonatal conjunctivitis), scalp abscesses, meningitis, arthritis, bacteremia, pharyngitis, rhinitis, vaginitis, urethritis, and, rarely, pneumoniaFootnote 5 Footnote 8. Gonococcal ophthalmia neonatorum is typically characterized by conjunctival erythema with mucopurulent eye dischargeFootnote 8.

Epidemiology

In 2020, the estimated global incidence of N. gonorrhoeae was 82.4 million cases, as reported by the World Health Organization (WHO)Footnote 20. The WHO African region had the highest incidence rate, followed by the South-East Asia region. In 2020, gonorrhea was the second most common notifiable STI in the United States with 677,769 reported cases, a 45% increase since 2016Footnote 21. Incidence rates in the United States were highest among males and females aged 20-24 years, as well as in Black/African American males and femalesFootnote 22.

In Canada, 30,874 cases of gonorrhea were reported in 2018, corresponding to a rate of 95.8 cases per 100,000 peopleFootnote 23. Since 2009, males comprised most reported gonorrhea cases in Canada. In 2018, the national male-to-female gonorrhea ratio was 1.9:1, with reported rates of 125 cases per 100,000 males compared to 66.6 cases per 100,000 femalesFootnote 22.

The largest recorded N. gonorrhoeae outbreak to date occurred over an 8-month period in 1987-1988 in North Omo, Ethiopia, with over 9,000 reported cases of severe pustular conjunctivitisFootnote 24. Both sexes and all age groups were affected, particularly children under 5 years of age; only a small minority were neonates. Surveillance data was suggestive of person-to-person transmission, but there was no concurrent genital gonorrhea outbreak. In the setting of intense crowding and relative lack of water, peak transmission coincided with two periods following rains, suggesting that flies were important in transmissionFootnote 24.

In Canada, an outbreak was declared in a northern region of Alberta, with 81 cases reported in 8 neighbouring communities between January 1999 and March 2001Footnote 25. Cases were predominantly Aboriginal (96.3%) and involved individuals aged less than 30 years (77.6%), and at least 39% of cases reported multiple sex partners. Attendance at a public bar in one community was associated with infection. In New Brunswick, 96 cases were reported in 2018, compared to an annual average of 54 cases over the previous five years, leading the province to declare an outbreak in April 2019Footnote 26. In another outbreak between January and July 2021, 74 cases were reported in the provinceFootnote 27.

Outbreaks have been reported in several other countries, including the United StatesFootnote 28, SpainFootnote 29, the NetherlandsFootnote 30, IsraelFootnote 31, ArgentinaFootnote 32, JapanFootnote 33, and AustraliaFootnote 34.

In adults, risk factors for gonorrhea include age younger than 25 years, history of previous gonococcal infection or other sexually transmitted infections (STIs), inconsistent condom use, men who have sex with men (MSM), and practices associated with risky sexual behaviours, including new or multiple sexual partners, prostitution, and substance abuseFootnote 8 Footnote 35. The risk of complications during pregnancy in the setting of gonococcal infection has been reported as approximately 2 to 5 times greater than uninfected controlsFootnote 13 Footnote 14 Footnote 15. In children, predisposing factors for gonococcal infection include mothers with a history of STIs or substance abuse, mothers without prenatal care, not receiving ophthalmic prophylaxis at birth, and sexual abuseFootnote 8.

Host range

Natural host(s)

N. gonorrhoeae is an obligate human pathogen with no other known natural hostFootnote 36.

Other host(s)

Experimental infection with N. gonorrhoeae has been induced in mouse, rat, rabbit, guinea pig, hamster, and chick modelsFootnote 37 Footnote 38.

Infectious dose

A cross-sectional study in Namibia identified an infectious dose (ID50) of 103 organisms in human urethral or vaginal swab samplesFootnote 39. Although injection is not considered to be a primary mode of transmission, N. gonorrhoeae strains FA1090 and MS11mkC have an experimentally determined ID50 of 1.8 x 103 and 1.0 x 105 colony-forming units (cfu), respectively, by urethral inoculation in human malesFootnote 40. Chicken embryos artificially exposed by injection died when inoculated with less than 100 gonococci via the yolk sac but were less susceptible to infection via the chorioallantoic membrane, where an inoculum of 1.0 x 105 to 1.0 x 106 cfu was lethal by 42 hoursFootnote 41.

Incubation period

2-14 days in male urethritis and over 10 days in female cervicitisFootnote 42. However, most females with cervical gonococcal infection are asymptomaticFootnote 9. Thus, the incubation period of gonorrhea is less well characterized in females than males. Average incubation period of 6 days for gonococcal ophthalmia neonatorumFootnote 8.

Communicability

Preferred route of transmission is sexual contact with an infected partner; ejaculation is not required for transmission or acquisitionFootnote 5. Transmission efficiency (a measure of transmission through one sexual exposure) is estimated to be 50-60% in male-to-female transmission and 20% in female-to-male transmissionFootnote 43. Transmission from untreated infected mother to newborn may occur during vaginal delivery in 30-50% of casesFootnote 43 Footnote 44. Transmission via human-to-human non-sexual contact, fomites, or vectors (flies) has been reported in pediatric and outbreak settingsFootnote 45 Footnote 46 Footnote 47.

Section III: Dissemination

Reservoir

HumansFootnote 1.

Zoonosis

None.

Vectors

The Australian bushfly (Musca vetustissima) has been reported as a possible vector of N. gonorrhoeae conjunctivitisFootnote 46 Footnote 48, although it is unknown whether transmission occurs through a bite or if it acts as a mechanical vector.

Section IV: Stability and viability

Drug susceptibility/resistance

Susceptible to third generation cephalosporins (ceftriaxone, cefixime, cefotaxime and ceftizoxime), macrolides (azithromycin), tetracyclines (tetracycline and doxycycline), and aminoglycosides (spectinomycin, gentamicin)Footnote 35.

Between 2006 and 2011, surveillance of N. gonorrhoeae strains in the United States and other countries showed an increase in cefixime minimum inhibitory concentrations (MICs) (≥ 0.25 mcg/mL), demonstrating a possible decline in cefixime efficacyFootnote 35. During 2007, emergence of fluroquinolone-resistant N. gonorrhoeae strains in the United States prompted the Centers for Disease Control and Prevention (CDC) to cease recommending fluoroquinolones for treatment of gonorrheaFootnote 35. Treatment failures with cefixime or other oral cephalosporins have been reported in Canada, Asia, Europe, and South Africa. Decreasing susceptibility of gonorrhea to ceftriaxone has increased in recent years, with cases of ceftriaxone treatment failure for pharyngeal infections reported in Australia, Japan, and EuropeFootnote 35. Since 2013, the proportion of Gonococcal Isolate Surveillance Projects (GISP) isolates with reduced susceptibility to azithromycin (MIC ≥ 2.0 µg/mL) has increased almost tenfold, with a rate of 5.1% in 2019Footnote 35. Strains of N. gonorrhoeae circulating in the United States are not adequately susceptible to penicillin, tetracycline, and older macrolides (e.g., erythromycin), and are therefore not recommendedFootnote 48.

Multidrug-resistant strains have been reported worldwide, including in the United Kingdom, Australia, France, Japan, Slovenia, Sweden, Denmark, and AustriaFootnote 49. An extensively drug-resistant (XDR) strain has been reported and is being monitored, and there are currently no other effective treatments for XDR gonorrheaFootnote 50.

Susceptibility to disinfectants

N. gonorrhoeae is sensitive to most disinfectants used against vegetative bacteria including 0.1% sodium hypochlorite, 70% ethanol, phenolics, 2% glutaraldehyde, formaldehyde, and peracetic acidFootnote 51 Footnote 52. Laboratory tests have demonstrated that the use of 5%, 1%, and 0.1% povidone-iodine for 1 minute is effective at destroying N. gonorrhoeaeFootnote 53. When exposed to 12.5 µg/mL chlorhexidine (CHG) for 30 minutes at pH 5 and in the absence of blood, N. gonorrhoeae was killedFootnote 54. In presence of 10% blood, N. gonorrhoeae was killed by 250 µg/mL CHG at pH 4-6, and 125 µg/mL CHG at pH 7-8Footnote 54.

Physical inactivation

N. gonorrhoeae is sensitive to desiccationFootnote 29. It can also be inactivated by heat treatment at 65°C for 30 minutesFootnote 55, and by antimicrobial blue light (aBL), with complete eradication of bacterial CFU suspensions noted at aBL exposures between 45 J/cm2 (for strain ATCC 700825) and 108 J/cm2 (for strain 199) at 405 nm under aerobic conditionsFootnote 56Footnote 57. Most vegetative bacteria can be inactivated by moist heat (121°C for 15 to 30 minutes) and dry heat (160-170°C for 1-2 hours)Footnote 58.

Survival outside host

At room temperature, N. gonorrhoeae can survive for 17 hours in purulent secretion on a glass slide and 24 hours on a towelFootnote 47. N. gonorrhoeae has been recovered from pus on linen kept moist with sterile saline after 5 hours, and from dry linen within 2 hoursFootnote 47. N. gonorrhoeae has survived for brief periods on a toilet seatFootnote 1, with reports of up to 2 hoursFootnote 59, and on toilet paper for 3 hoursFootnote 32.

Section V: First aid/medical

Surveillance

Monitor for symptoms. The clinical syndromes associated with N. gonorrhoeae are typically diagnosed by history and physical examination, but a microbiologic diagnosis is required due to the lack of sensitivity and specificity of the clinical diagnosisFootnote 35. Bacterial culture, nucleic acid amplification testing (NAAT), and point-of care NAAT are available for detecting genitourinary infection with N. gonorrhoeaeFootnote 35. Culture is available for genital, rectal, oropharyngeal, and conjunctival infection in both men and women with and without symptomsFootnote 35. While NAATs are associated with better sensitivity and allow for the widest variety of specimen types, including endocervical and vaginal swabs and urine for women, urethral swabs and urine for men, and rectal swabs and pharyngeal swabs for both, certain NAATs have been demonstrated to detect commensal Neisseria species and may have comparable low specificity when testing oropharyngeal specimens for N. gonorrhoeaeFootnote 35. Because of its high specificity (> 99%) and sensitivity (> 95%), Gram staining (microscopy) of urethral discharge or secretions can be used for diagnosis in symptomatic men but has low specificity in females and is considered unreliable for extragenital infectionsFootnote 35. Cultures for N. gonorrhoeae are processed on Thayer-Martin agar at 35 to 37°C in a CO2-enriched environment, and aid in assessing antibiotic susceptibilities, which is of particular importance when antibiotic-resistant infection is suspectedFootnote 4 Footnote 60. Other less commonly used diagnostic testing methods include methylene blue or gentian violet staining of urethral secretionsFootnote 35.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

Due to rising rates of resistance to other agents (sulfonamides, penicillins, tetracyclines, and fluroquinolones), third generation cephalosporins are generally considered first-line -uhy monotherapy to treat uncomplicated infectionFootnote 35. Of these, is favoured for uncomplicated infection of the cervix, urethra, rectum, and pharynx, as well as for gonococcal conjunctivitisFootnote 61. If ceftriaxone is not available, alternative regimens for treatment of urogenital or anorectal gonococcal infection include oral cefixime or a different injectable cephalosporin, such as ceftizoxime, cefoxitin, or cefotaximeFootnote 35 Footnote 62. Gentamicin and azithromycin combination therapy is indicated in patients with severe allergies that preclude cephalosporin useFootnote 35. Ceftriaxone is also the recommended regimen for disseminated gonococcal infection, including treatment of arthritis and arthritis-dermatitis syndrome, gonococcal meningitis, and endocarditisFootnote 35.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine is currently available; however, a number of candidate vaccine antigens are being considered for development and the effectiveness of vaccines against other Neisseria species are being investigatedFootnote 60 Footnote 62 Footnote 63 Footnote 64.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

Recommended prophylaxis for gonococcal ophthalmia neonatorum is 0.5% erythromycin ophthalmic ointment in each eye in a single application as soon as possible after birthFootnote 60. If unavailable, alternative regimen is intravenous or intramuscular ceftriaxone. Ceftriaxone is currently recommended for post-exposure prophylaxis after sexual assaultFootnote 65.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI: Laboratory hazards

Laboratory-acquired infections

Globally, there has been six reported cases of laboratory-acquired infection, 5 of which involved gonococcal conjunctivitis and one case involving gonococcal cutaneous abscessFootnote 66. In Canada, a laboratory technician developed gonococcal conjunctivitis after he was struck on the right eye by the strap of his sterile mask while examining mice injected intracerebrally with N. gonorrhoeae strain 188 T1. An incident was reported in England in 1998, where a laboratory scientist developed gonococcal conjunctivitis, likely through contaminated finger-to-eye contactFootnote 67. An American microbiologist contracted gonococcal conjunctivitis resulting from a spray while opening a liquid nitrogen-frozen vial of pure cultureFootnote 68. An American microbiology graduate student was hospitalized 6 days after exposure in a research laboratory, with hand-to-nose/mouth as presumed route of exposure (1983). A case of cutaneous abscess following a needlestick injury was reported in a Croatian laboratory in 2015Footnote 68.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Conjunctival, endocervical, urethral, oropharyngeal and vaginal exudates, synovial fluid, urine, skin lesions, endometrium, fallopian tubes, rectum, faeces, blood, and cerebrospinal fluidFootnote 2 Footnote 50.

Primary hazards

Accidental parenteral inoculation and direct contact of mucous membranes/skin with infectious material are known primary hazards associated with exposure to N. gonorrhoeaeFootnote 50 Footnote 67 Footnote 68.

Special hazards

None.

Section VII: Exposure controls/personal protection

Risk group classification

N. gonorrhoeae is a Risk Group 2 Human Pathogen and Risk Group 1 Animal PathogenFootnote 69.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS are required for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the CBS are to be followed. The personal protective equipment could include the use of a labcoat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, PM rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

Use of needles and syringes to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

For diagnostic laboratories handling primary specimens that may contain N. gonorrhoeae, the following resources may be consulted:

Section VIII: Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with the disinfectant before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials should be completely decontaminated before removal from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 2 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX: Regulatory and other information

Canadian regulatory context

Controlled activities with N. gonorrhoeae require a Human Pathogens and Toxins licence issued by the Public Health Agency of Canada.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

Updated

March 2023

Prepared by

Centre for Biosecurity, Public Health Agency of Canada

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright© Public Health Agency of Canada, 2023, Canada

References

Footnote 1

Ryan, K. J., and C. G. Ray. 2004. Neisseria, p. 327-341. K. J. Ryan and C. G. Ray (eds.), Sherris Medical Microbiology: An Introduction to Infectious Diseases, 4th ed., McGraw-Hill, United States.

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Footnote 2

Janda, W. M., and C. A. Gaydos. 2007. Neisseria, p. 601-620. P. R. Murray, E. J. Baron, J. H. Jorgensen, M. L. Landry, and M. A. Pfaller (eds.), Manual of Clinical Microbiology, 9th ed., ASM Press, United States.

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Footnote 3

Tonjum, T., and J. Van Putten. 2017. Neisseria, p. 1553-1564. J. Cohen, W. G. Powderly, and S. M. Opal (eds.), Infectious Diseases, 4th ed., Elsevier, United States.

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Footnote 4

Goire, N., D. J. Speers, M. M. Lahra, and D. M. Whiley. 2015. Neisseria gonorrhoeae: The pathogen, diagnosis, and antimicrobial resistance. Human Emerging and Re-Emerging Infections. 1:683-697.

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Footnote 5

Holder, N. A. 2008. Gonococcal infections. Pediatr. Rev. 29:228-234.

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Footnote 6

Cahoon, L. A., and H. S. Seifert. 2011. Focusing homologous recombination: Pilin antigenic variation in the pathogenic Neisseria. Mol. Microbiol. 81:1136-1143.

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Footnote 7

Anderson, M. T., and H. S. Seifert. 2011. Opportunity and means: Horizontal gene transfer from the human host to a bacterial pathogen. Mbio. 2.

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Footnote 8

Mayor, M. T., M. A. Roett, and K. A. Uduhiri. 2012. Diagnosis and management of gonococcal infections. Am. Fam. Phys. 86:931-938.

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Footnote 9

McCormack, W., K. Johnson, R. Stumacher, A. Donner, and R. Rychwalski. 1977. Clinical spectrum of gonococcal infection in women. Lancet. 309:1182-1185.

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Footnote 10

Barlow, D., and I. Phillips. 1978. Gonorrhoea in women. Diagnostic, Clinical, and Laboratory Aspects. Lancet. 311:761-764.

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Footnote 11

WHO. 2022. Diseases Characterized by Urethritis and Cervicitis. 2023.

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Footnote 12

Rees, E. 1967. Gonococcal bartholinitis. Br. J. Vener. Dis. 43:150-156.

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Footnote 13

Liu, B., C. L. Roberts, M. Clarke, L. Jorm, J. Hunt, and J. Ward. 2013. Chlamydia and gonorrhoea infections and the risk of adverse obstetric outcomes: A retrospective cohort study. Sex. Transm. Infect. 89:672-678.

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Footnote 14

Donders, G. G. G., J. Desmyter, D. H. De Wet, and F. A. Van Assche. 1993. The association of gonorrhoea and syphilis with premature birth and low birthweight. Genitourin. Med. 69:98-101.

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Footnote 15

Gao, R., B. Liu, W. Yang, Y. Wu, B. Wang, M. K. Santillan, K. Ryckman, D. A. Santillan, and W. Bao. 2021. Association of Maternal Sexually Transmitted Infections with Risk of Preterm Birth in the United States. JAMA Netw. Open.

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Footnote 16

Lee Wan, W., G. C. Farkas, W. N. May, and J. B. Robin. 1986. The clinical characteristics and course of adult gonococcal conjunctivitis. Am. J. Ophthalmol. 102:575-583.

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Footnote 17

O'Brien, J. P., D. L. Goldenberg, and P. A. Rice. 1983. Disseminated gonococcal infection: A prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. Medicine. 62:395-406.

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Footnote 18

Bleich, A. T., J. S. Sheffield, G. D. Wendel Jr., A. Sigman, and F. G. Cunningham. 2012. Disseminated gonococcal infection in women. Obstet. Gynecol. 119:597-602.

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Footnote 19

Rice, P. A. 2005. Gonococcal arthritis (disseminated gonococcal infection). Infect. Dis. Clin. North Am. 19:853-861.

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Footnote 20

WHO. 2021. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021. 2023.

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Footnote 21

CDC. 2022. National Overview of STDs, 2020. 2023.

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Footnote 22

CDC. 2022. Table 9. Gonorrhea – Reported Cases and Rates of Reported Cases by Age Group and Sex, United States, 2016-2020. 2023.

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Footnote 23

Public Health Agency of Canada. 2021. Report on sexually transmitted infections in Canada, 2018.

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Footnote 24

Mikru, F. S., T. Molla, M. Ersumo, T. H. Henriksen, P. Klungseyr, P. J. Hudson, and T. T. Kindan. 1991. Community-wide outbreak of Neisseria gonorrhoeae conjunctivitis in Konso district, North Omo administrative region. Ethiop. Med. J. 29:27-35.

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Footnote 25

De, P., A. E. Singh, T. Wong, and W. Yacoub. 2003. Outbreak of Neisseria gonorrhoeae in northern Alberta, Canada. Sex. Transm. Dis. 30:497-501.

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Footnote 26

Government of New Brunswick. 2019. Gonorrhea on the rise in New Brunswick. 2023.

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Footnote 27

Government of New Brunswick. 2021. Gonorrhea cases continue to rise in New Brunswick. 2023.

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Footnote 28

CDC. 1993. Gang-related outbreak of penicillinase-producing Neisseria gonorrhoeae and other sexually transmitted diseases--Colorado Springs, Colorado, 1989-1991. MMWR Morb. Mortal. Wkly. Rep. 42:25-28.

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Footnote 29

Salmeron, P., A. Moreno-Mingorance, J. Trejo, R. Amado, B. Vinado, T. Cornejo-Sanchez, M. Alberny, M. J. Barbera, M. Arando, T. Pumarola, Y. Hoyos-Mallecot, J. Serra-Pladevall, and J. J. Gonzalez-Lopez. 2021. Emergence and dissemination of three mild outbreaks of Neisseria gonorrhoeae with high-level resistance to azithromycin in Barcelona, 2016-18. J. Antimicrob. Chemother. 76:930-935.

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Footnote 30

Van Der Veer, B. M. J. W., P. F. G. Wolffs, C. J. P. A. Hoebe, J. N. A. P. Wijers, G. A. F. S. Van Liere, M. I. L. S. Werner, A. Verhaegh, N. H. T. M. Dukers-Muijrers, and L. B. Van Alphen. 2021. Culture-Independent Genotyping Revealed 3 Strain Clusters in a Potential Neisseria gonorrhoeae Outbreak in Young Heterosexuals (<25 Years), the Netherlands, October 2017 to March 2019. Sex. Transm. Dis. 48:536-541.

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Footnote 31

Schlaeffer, F., O. T. Dolberg, N. Peled, N. Hendler, and A. Porath. 1991. An outbreak of penicillin-resistant Neisseria gonorrhoea in Southern Israel. Isr. J. Med. Sci. 27:311-315.

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Footnote 32

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Mak, D. B., D. W. Smith, G. B. Harnett, and A. J. Plant. 2001. A large outbreak of conjunctivitis caused by a single genotype of Neisseria gonorrhoeae distinct from those causing genital tract infections. Epidemiol. Infect. 126:373-378.

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