### Microbiology Gram-negative diplococci. *N*. *cinerea*, *N*. *gonorrhoeae*, *N*. *lactamica*, *N*. *meningitidis* (serogroups A, B, C, W135 in US. X in Africa. E in Australia), *N*. *subflava*, *N*. *sicca*. On gram stain *[[Neisseria]]* are side to side footballs, *Streptococci* tend to be end to end footballs. Culture and nucleic acid amplification (NAAT) are the way to make the diagnosis. Some *gonorrhoeae* lack the prolyliminopeptidase and as a result, may not have a positive antigen test. [^1] ### Epidemiologic Risks ***N*. *gonorrhoeae*** Sex with an infected partner. If you blame acquisition on a toilet seat, all I can say is that's a hell of a place to have sex. Neonates can acquire it at birth. Getting ready for a date? Listerine (which does NOT contain [[Listeria]]) can kill oral GC. [^2] Men who have sex with men have markedly more transmission; perhaps they should use Listerine? [^3] Newly single men (not women) asking for ED (erectile dysfunction, not emergency department) meds are at risk and the rates go up with eviction. [^4] And use of ED meds in general. [^5] There was a cluster of oropharyngeal *gonorrhoeae* in the absence of urogenital *gonorrhoeae* transmitted by tongue kissing. [^6] ***N*. *meningitidis*** Can be part of normal flora, especially in the winter and during times of crowding. Carriage rates depends on age: > "Carriage prevalence increased through childhood from 4·5% in infants to a peak of 23·7% in 19-year-olds and subsequently decreased in adulthood to 7·8% in 50-year-olds. The odds of testing positive for carriage decreased if swabs were not plated immediately after being taken, compared with if swabs were plated immediately." [^7] You may live or die by the nature of your snot: > "mutation in SPLUNC1 affecting mucosal attachment, biofilm formation, and invasion of mucosal epithelial cells is a new genetic cause of meningococcal disease. [^8] MSM have increased rates of *N*. *meningitidis*. and [[HIV]] positive MSM even more. [^9] Females may be more likely to die from the disease. [^10] Terminal complement deficiency [^11] is a risk, as is the use of Eculizumab a terminal complement inhibitor used to treat paroxysmal nocturnal hemoglobinuria (PNH) and atypical [[Hemolytic Uremic Syndrome]] (aHUS), including an increased risk for Disseminated Gonococcal Infections. [^12] ***N*. *lactamica*, *N*. *sicca*, *N*. *subflava*, *N*. *cinerea*** All are part of normal human flora. 7% of patients under age 40 with bacteremia from *[[Streptococcus]]* *pneumoniae*, *[[Streptococcus]]* *pyogenes* group A, *[[Neisseria]]* *meningitidis*., *[[Neisseria]]* *gonorrhoeae*, or *[[Haemophilus]]* *influenzae* will die and 25% will be readmitted in the subsequent two years. They have immunologic issues: low immunoglobulins or a complement deficiency. [^13] So anyone with *[[Neisseria]]* in the blood should get their complement checked, but AFTER they have improved. During active disease complement is wonky and can't be properly evaluated. ### Syndromes ***N*. *gonorrhoeae*** [[Urethritis]], [[Cervicitis]], disseminated disease with a migratory [[tenosynovitis]] followed by oligoarticular [[arthritis]] (with and without a purpuric rash), PID, occasionally [[Pharyngitis]] (not uncommon in men who have sex with men but 95% are asymptomatic [^14]), and [[Proctitis]] . When testing one orifice, remember to test them all. [^16] In men who have sex with men, GC can often be found in the pharynx and routine therapy for urethral diseases may not eradicate it. [^17] ***N*. *meningitidis*** [[Meningitis]] and [[Sepsis and Bacteremia]] with and without purpura. About 8% will develop [[arthritis]] (clinically, making you wonder if GC) that will respond to antibiotics and a tap without taking to the OR, although the fact that many needed steroids to get better suggests better debridement may have been in order. [^18] [[HIV]] patients have 10 x the incidence of disease. [^19] W is different: > "Compared with other serogroups, IMD-W patients were diagnosed more often with septicemia (46%) or [[pneumonia]] (12%) and less often with *meningitidis* (17%, P < .001). IMD-W cases presented more often with respiratory symptoms (45%, P < .001); 16% of IMD-W patients presented with [[diarrhea]] without IMD-specific symptoms (P = .061)." [^20] This is a rare, chronic, form of the disease. [^21] And [[Neisseria]] *meningitidis* sequence type 11 is a cause [[Urethritis]] in MSM with oral-genital transmission [^22] [^23] and [[Proctitis]] . [^24] Patients with bactermia from *[[Neisseria]]* can present with acute abdominal pain that leads to surgery. [^15] I have seen such a presentation myself. This presentation tends to be hyper-virulent strains, type W, and with a high mortality rate. ***N*. lactamica, *N*. sicca, *N*. subflava, *N*. cinerea** Will be isolated in sputum, blood and other body fluids on occasion, the significance depends on the patient and the body fluid. I see the occasional [[endocarditis]] with these [[Neisseria]]. ### Treatment ***N*. *gonorrhoeae*** *N*. *gonorrhoeae* is well on its way to becoming the first completely resistant common pathogen. [^25] Resistance is climbing in Asia Pacific. [^27] MSM seems a particular risk for resistance. I bet it beats *S*. *aureus* to the punch. Here is a nice review of *[[Neisseria]]* antibiotic evolution. [^26] *N*. *gonorrhoeae*: follow the CDC STD Guidelines. Look 'em up. Given resistance rates, YOU CANNOT USE quinolones for GC and rely on it. [^28] GC can become resistant to [[Azithromycin]] in as little as 12 days after exposure. And [[Azithromycin]] resistance is increasing as well, [^29] like in England. [^30] Antibiotic resistance by STD always seems to be reported in areas where people like to go for a vacation, like Hawaii. Must be intense evolutionary pressure. There is now a strain resistant to all antibiotics except the carbapenems. [^31] Whenever you treat GC, you treat *[[Chlamydia]]* and vice versa. For resistant GC, there is Zoliflodacin in the pipeline. [^32] And, no, it is not "metal as f--k" as Ars Technica would have you believe. [^33] I have added "metal as f--k" to the list of 'strong,' 'big gun' and 'powerful': adjectives that mark the speaker as someone who is Jon Snow. [^34] 90% will be symptom-free a week after therapy. If they have [[Chlamydia]], it may take a bit longer. [^35] ***N*. *meningitidis*** Penicillin (although resistance is starting to creep up in some parts of the world) OR a third-generation cephalosporin or, if no [[Meningitis]], quinolones. While we usually treat for 10 days, 5 may be sufficient. > "Dexamethasone use is safe and can prevent some [[arthritis]] episodes, and prophylactic phenytoin might be useful in a selected population. A rapid response and antibiotic therapy may help improve prognosis." [^36] Do not forget steroids if there is [[Meningitis]]. BEWARE: there has been quinolone resistance in the US as of 2008 and it may not be the right drug in your area. Type Y can have penicillin and [[ciprofloxacin]] resistance. [^37] Prophylaxis: if they were sharing air with the index case for greater than 4 hours or exchanging body fluids (saliva) or a roommate in a crowded situation (prison or dorms) up to 10 days from the onset of the index case disease. Use [[rifampin]] 600 mg po q 12 x 2 d OR [[ciprofloxacin]] 500 mg po x 1 OR [[ceftriaxone]] 250 mg im x 1 (in pregnancy). Here is my 'take'/opinion on Meningococcal post-exposure prophylaxis: There is apparently some misunderstanding about the necessity of post-exposure prophylaxis for health care providers exposed to real or potential cases of Meningococcal [[Meningitis]] or bacteremia. Exposure to colonized patients is not a risk and can be present in 2%--10% of children and > "In Europe, as much as 35% of young adults are carriers at a given time." Family members exposed to an index case of invasive disease are transiently at increased risk for disease with an attack rate of .3 to 1%. This is likely partly due to genetic/hereditary variations in the immune system that predispose the patient and their family to invasive disease. It is likely as much the patient as the organism that leads to infection. For family members, greater than 4 hours of exposure or contact with respiratory secretions antibiotic prophylaxis is recommended. And no physician has EVER spent 4 hours in a room with a patient. In contrast, despite studies, there is no benefit to be found in treating colonized people or their contacts outside of invasive disease as nicely summed up by UpToDate: > "There are no recommendations for eradicating nasopharyngeal carriage in the community outside of an outbreak or a patient with invasive meningococcal disease. There are three problems with attempting to eliminate nasopharyngeal carriage in the community: Spontaneous loss and acquisition of carriage are common. This was illustrated in a study in military recruits in which 34 percent experienced one or more changes in carrier status over time. Recurrent colonization may occur after prophylaxis. In a community-wide prophylaxis program in a semi-closed kibbutz population in Israel, the colonization rate of group B *[[Neisseria]]* *meningitidis* dropped from 4.6 percent at baseline to 0 percent at three weeks; it then rose to 0.5 percent at six months and 3.9 percent (similar to the baseline level) at one year. Antimicrobial prophylaxis has no proven clinical efficacy outside of an outbreak. The meta-analysis cited above-included trials in healthy carriers. Clinical efficacy of eradication could not be assessed, since there were no cases of disease following antibiotics or placebo." How about health care providers? There are, at best, a half-dozen cases of secondary spread to HCWs ever reported and they all had one factor in common: exposure to respiratory secretions without proper PPE: > "Transmission of *N*. *meningitidis*. to health-care personnel has occurred after unprotected exposure to infected patients during endotracheal intubation, airway suctioning, and oxygen administration (6--8), but more than one occupationally acquired infection from the same index patient has not been reported. Findings from this investigation indicate that breaches in infection control...likely contributed to secondary cases of meningococcal disease (1)." And the first step when the issue of [[Meningitis]] is raised should be to put on a mask. Unless exposed to direct secretions, no antibiotic prophylaxis is warranted, only driving cost, toxicity, and resistance without benefit. > "To be on the safe side, any person directly exposed to the case's nasopharyngeal secretions (e.g., through kissing or mouth-to-mouth resuscitation) is also advised to take prophylaxis. On the other hand, health care workers who haven't had contact with secretions are not at risk and do not benefit from prophylaxis." Here is my suggested algorithm 1) [[Meningitis]] is suspected. Droplet Isolation i.e., surgical masks. Viola. Everyone is safe. 2) LP shows [[Meningitis]] by cell count, protein, and glucose. Wait. No hurry for prophylactic antibiotics, *[[Neisseria]]* *meningitidis* * is not like [[Lice]], jumping off the patient on to you. 3) Gram stain is negative or has gram-negative rods or gram-positive cocci. *[[Neisseria]]* *meningitidis* is gram-negative diplococci. Wait. It isn't *[[Neisseria]]* *meningitidis* ; prophylactic antibiotics will not be needed. 4) Gram stain has gram-negative diplococci. Wait. No hurry. 5) Cultures grow *N*. *meningitidis* Prophylaxis for those who were directly exposed to respiratory secretions: mouth-to-mouth, suctioning, intubation or other respiratory procedures without PPE. Other health care providers do not need prophylaxis and to do so would be, and I have to be careful of the adjective I use in an official communication, let's say ill-advised. However, everyone who has even the remotest contact with a meningococcal disease freaks out and wants prophylaxis. In a recent case, I had an anesthesiologist place a line in a patient with meningococcal disease, actually followed all isolation procedures, and still thought they have an exposure that warranted the use of [[ciprofloxacin]], What are you gonna do? It is a battle that is probably not worth fighting; I figure the [[ciprofloxacin]] is more of an anxiolytic. **Prevention** There is a [[Vaccine]] that covers A, C, and W-135. It's an OK [[Vaccine]]; my children got it when they went off to college; it does not cover serotype B, for which a separate [[Vaccine]] became available in 2015. There are two types of meningococcal [[Vaccine]] available in the United States: Meningococcal conjugate [[Vaccine]] (Menactra® and Menveo®) and Serogroup B meningococcal [[Vaccine]] (Bexsero® and Trumenba®). The CDC recommendations Meningococcal Conjugate [[Vaccine]] Recommendations Adults should get a meningococcal conjugate [[Vaccine]] (Menactra® or Menveo®) if they: - Have a rare type of disorder (complement component deficiency) - Taking Eculizumab - Have a damaged spleen or their spleen has been removed - Have [[HIV]] - Are a microbiologist who is routinely exposed to [[Neisseria]] *meningitidis*. - Are traveling to or residing in countries in which the disease is common - Are part of a population identified to be at increased risk because of a serogroup A, C, W, or Y meningococcal disease outbreak - Are not up to date with this [[Vaccine]] and are a first-year college student living in a residence hall. They are a military recruit. Talk to your doctor to find out if, and when, you will need booster shots. Serogroup B Meningococcal [[Vaccine]] Recommendations Adults should get a serogroup B meningococcal [[Vaccine]] (Bexsero® or Trumenba®) if they: - Have a rare type of disorder (complement component deficiency) - Taking Eculizumab - Have a damaged spleen or their spleen has been removed - Are a microbiologist who is routinely exposed to [[Neisseria]] *meningitidis*. As of 2007, serotype X (yes X, it infects the Mac OS) is on the rise in Africa. [^38] For those at high risk, the [[Vaccine]] should be given every 5 years: persistent complement component deficiencies (such as C3, properdin, Factor D, and late complement component deficiencies), anatomic or functional [[asplenia]], and prolonged exposure (e.g., microbiologists routinely working with [[Neisseria]] *meningitidis*., or travelers to or residents of countries where meningococcal disease is hyperendemic or epidemic). ***N*. *lactamica*, *N*. *sicca*, *N*. *subflava*, *N*. *cinerea*** Penicillin OR a third-generation cephalosporin OR quinolones. ### Notes The meningococcal B [[Vaccine]] may partially protect against GC [^39] and it elicits cross-reacting antibodies. [^40] Recurrent, and probably any, *[[Neisseria]]* bacteremia except *gonorrhoeae*, should raise suspicion of a terminal complement deficiency. So anyone with non-gonococcal [[Neisseria]] in their blood should get a CH50. Just do not get it during active illness, as complement levels are wonky during disease. W-135 may have a worse disease. [^41] What flabbers my gaster is something that should be as brain dead simple as the treatment of GC per the guidelines can't be done correctly by around 20% of providers. [^42] While ERs and private clinics were worst, even STD clinics got it wrong 10% of the time. How hard is it to look it up? Very, evidently. As macrolide use goes up in the winter for [[Cystitis]]'s, there is a parallel increase in GC macrolide resistance. [^43] Blue light kills GC, [^44] although delivery to infected tissues can't be pleasant. And it makes me wonder just what was going on at K-Mart. [^45] ### Puswhisperers [Rash Decisions](http://www.pusware.com/PW1/RashDecisions.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop99.mp3) [A New Personal Record](http:\\www.pusware.com/PW1/ANewPersonalRecord.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop128.mp3) [A Surprise](http:\\www.pusware.com/PW1/ASurprise.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop133.mp3) [Prophylaxis?](http://www.pusware.com/PW1/Prophylaxis.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop94.mp3) [Purpura](http://www.pusware.com/PW2/Purpura.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop267.mp3) [Curbside](http://www.pusware.com/PW2/Curbside.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop572.mp3) [You Can Wait. Really. You Can.](http://www.pusware.com/PW6/Wait.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop799.mp3) [How did THAT get THERE?](http://www.pusware.com/PW7/HowDidThatGetThere.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop860.mp3) [Like Birding. But Interesting.](http://www.pusware.com/PW7/Birding.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop886.mp3) [Brave New World](http://www.pusware.com/PW8/BraveNewWorld.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1029.mp3) [Sine qua non part deux](http://www.pusware.com/PW1/Sine2.html) ### Rationalizations [^1]: Unemo M, Palmer HM, Blackmore T, Herrera G, Fredlund H, Limnios A, Nguyen N, Tapsall J. Global transmission of prolyliminopeptidase-negative [[Neisseria]] gonorrhoeae strains: implications for changes in diagnostic strategies. Sex Transm Infect. 2007 Feb;83(1):47-51. doi: 10.1136/sti.2006.021733. Epub 2006 Aug 10. PMID: 16901915; PMCID: PMC2598591. [^2]: Chow EP, Howden BP, Walker S, et al Antiseptic mouthwash against pharyngeal _Neisseria gonorrhoeae_: a randomised controlled trial and an in vitro study Sexually Transmitted Infections 2017;93:88-93. [^3]: Fairley CK, Hocking JS, Zhang L, Chow EP. Frequent Transmission of Gonorrhea in Men Who Have Sex with Men. Emerg Infect Dis. 2017 Jan;23(1):102-104. doi: 10.3201/eid2301.161205. PMID: 27983487; PMCID: PMC5176237. [^4]: Niccolai LM, Blankenship KM, Keene DE. Eviction From Renter-occupied Households and Rates of Sexually Transmitted Infections: A County-level Ecological Analysis. Sex Transm Dis. 2019 Jan;46(1):63-68. doi: 10.1097/OLQ.0000000000000904. PMID: 30148755; PMCID: PMC6289707. [^5]: Jena AB, Goldman DP, Kamdar A, Lakdawalla DN, Lu Y. [[Sexually Transmitted Diseases]] among users of erectile dysfunction drugs: analysis of claims data. Ann Intern Med. 2010 Jul 6;153(1):1-7. doi: 10.7326/0003-4819-153-1-201007060-00003. PMID: 20621899; PMCID: PMC3673772. [^6]: Cornelisse VJ, Bradshaw CS, Chow E, et al. Oropharyngeal Gonorrhea in Absence of Urogenital Gonorrhea in Sexual Network of Male and Female Participants, Australia, 2018. _Emerging Infectious Diseases_. 2019;25(7):1373-1376. doi:10.3201/eid2507.181561. [^7]: Christensen H, May M, Bowen L, Hickman M, Trotter CL. Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis. 2010 Dec;10(12):853-61. doi: 10.1016/S1473-3099(10)70251-6. Epub 2010 Nov 11. Erratum in: Lancet Infect Dis. 2011 Aug;11(8):584. PMID: 21075057. [^8]: Bayarchimeg Mashbat, Evangelos Bellos, Stephanie Hodeib, Fadil Bidmos, Ryan S Thwaites, Yaxuan Lu, Victoria J Wright, Jethro A Herberg, Daniela S Klobassa, William G Walton, Werner Zenz, Trevor T Hansel, Simon Nadel, Paul R Langford, Luregn J Schlapbach, Ming-Shi Li, Matthew R Redinbo, Y Peter Di, Michael Levin, Vanessa Sancho-Shimizu, for the European Union Childhood Life-Threatening Infectious Disease Study (EUCLIDS) Consortium, A Rare Mutation in _SPLUNC1_ Affects Bacterial Adherence and Invasion in Meningococcal Disease, _Clinical Infectious Diseases_, Volume 70, Issue 10, 15 May 2020, Pages 2045–2053, [https://doi.org/10.1093/cid/ciz600](https://doi.org/10.1093/cid/ciz600) [^9]: Folaranmi TA, Kretz CB, Kamiya H, MacNeil JR, Whaley MJ, Blain A, Antwi M, Dorsinville M, Pacilli M, Smith S, Civen R, Ngo V, Winter K, Harriman K, Wang X, Bowen VB, Patel M, Martin S, Misegades L, Meyer SA. Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the United States, 2012-2015. Clin Infect Dis. 2017 Sep 1;65(5):756-763. doi: 10.1093/cid/cix438. PMID: 28505234; PMCID: PMC5737672. [^10]: Bloch D, Murray K, Peterson E, Ngai S, Rubinstein I, Halse TA, Ezeoke I, Miller L, Arakaki L, Ramautar A, Antwi M, Del Rosso P, Dorsinville M, Clark S, Halbrook M, Kennedy J, Braunstein S, Weiss D. Sex Difference in Meningococcal Disease Mortality, New York City, 2008-2016. Clin Infect Dis. 2018 Aug 16;67(5):760-769. doi: 10.1093/cid/ciy183. PMID: 29509877. [^11]: Ram S, Lewis LA, Rice PA. Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev. 2010 Oct;23(4):740-80. doi: 10.1128/CMR.00048-09. PMID: 20930072; PMCID: PMC2952982. [^12]: Crew PE, Abara WE, McCulley L, Waldron PE, Kirkcaldy RD, Weston EJ, Bernstein KT, Jones SC, Bersoff-Matcha SJ. Disseminated Gonococcal Infections in Patients Receiving Eculizumab: A Case Series. Clin Infect Dis. 2019 Aug 1;69(4):596-600. doi: 10.1093/cid/ciy958. PMID: 30418536; PMCID: PMC6744347. [^13]: Jackson N, Sutton T, Bedford L, Ugrinovic S, Kumararatne D, Gkrania-Klotsas E. A First Unexplained Invasive Encapsulated Bacterial Infection in Young Adults Associated With High Mortality and Readmission Rates. Clin Infect Dis. 2020 Jan 16;70(3):528-530. doi: 10.1093/cid/ciz470. PMID: 31157862. [^14]: Morris SR, Klausner JD, Buchbinder SP, Wheeler SL, Koblin B, Coates T, Chesney M, Colfax GN. Prevalence and incidence of pharyngeal gonorrhea in a longitudinal sample of men who have sex with men: the EXPLORE study. Clin Infect Dis. 2006 Nov 15;43(10):1284-9. doi: 10.1086/508460. Epub 2006 Oct 10. PMID: 17051493. [^15]: Guiddir T, Gros M, Hong E, Terrade A, Denizon M, Deghmane AE, Taha MK. Unusual Initial Abdominal Presentations of Invasive Meningococcal Disease. Clin Infect Dis. 2018 Sep 28;67(8):1220-1227. doi: 10.1093/cid/ciy257. PMID: 29608658. [^16]: Tao G, Hoover KW, Nye MB, Peters PJ, Gift TL, Body BA. Infrequent Testing of Women for Rectal [[Chlamydia]] and Gonorrhea in the United States. Clin Infect Dis. 2018 Feb 1;66(4):570-575. doi: 10.1093/cid/cix857. PMID: 29028971. [^17]: Ota KV, Fisman DN, Tamari IE, Smieja M, Ng LK, Jones KE, Diprima A, Richardson SE. Incidence and treatment outcomes of pharyngeal [[Neisseria]] gonorrhoeae and [[Chlamydia]] trachomatis infections in men who have sex with men: a 13-year retrospective cohort study. Clin Infect Dis. 2009 May 1;48(9):1237-43. doi: 10.1086/597586. PMID: 19323630. [^18]: Cabellos C, Nolla JM, Verdaguer R, Pelegrin I, Ribera A, Ariza J, Viladrich PF. [[Arthritis]] related to systemic meningococcal disease: 34 years' experience. Eur J Clin Microbiol Infect Dis. 2012 Oct;31(10):2661-6. doi: 10.1007/s10096-012-1610-1. Epub 2012 Apr 3. PMID: 22476361. [^19]: Christine M. Harris, Henry M. Wu, Jianmin Li, H. Irene Hall, Adria Lee, Elizabeth Zell, Lee H. Harrison, Susan Petit, Monica M. Farley, Ruth Lynfield, Lisa Miller, Megin Nichols, Arthur Reingold, William Schaffner, Ann Thomas, Jessica R. MacNeil, Thomas A. Clark, Amanda C. Cohn, Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000–2008, _Open Forum Infectious Diseases_, Volume 3, Issue 4, Fall 2016, ofw226, [https://doi.org/10.1093/ofid/ofw226](https://doi.org/10.1093/ofid/ofw226) [^20]: Anna D Loenenbach, Arie van der Ende, Hester E de Melker, Elisabeth A M Sanders, Mirjam J Knol, The Clinical Picture and Severity of Invasive Meningococcal Disease Serogroup W Compared With Other Serogroups in the Netherlands, 2015–2018, _Clinical Infectious Diseases_, Volume 70, Issue 10, 15 May 2020, Pages 2036–2044, [https://doi.org/10.1093/cid/ciz578](https://doi.org/10.1093/cid/ciz578) [^21]: Lefèvre B, Poinsignon Y, Piau C, Javaugue FC, Talarmin JP, Lefebvre M, Varache N, Drouin H, Tattevin P; pour le Groupe d’Epidémiologie et Recherche en Infectiologie Clinique du Centre et de l’Ouest (GERICCO). Chronic meningococcemia: a report of 26 cases and literature review. Infection. 2019 Apr;47(2):285-288. doi: 10.1007/s15010-0Jannic A, Mammeri H, Larcher L, et al. Orogenital Transmission of [[Neisseria]] meningitidis Causing Acute [[Urethritis]] in Men Who Have Sex with Men. _Emerging Infectious Diseases_. 2019;25(1):175-176. doi:10.3201/eid2501.171102. 18-1238-x. Epub 2018 Oct 19. PMID: 30341638. [^22]: Jannic A, Mammeri H, Larcher L, et al. Orogenital Transmission of [[Neisseria]] meningitidis Causing Acute [[Urethritis]] in Men Who Have Sex with Men. _Emerging Infectious Diseases_. 2019;25(1):175-176. doi:10.3201/eid2501.171102. [^23]: Toh E, Gangaiah D, Batteiger BE, Williams JA, Arno JN, Tai A, Batteiger TA, Nelson DE. [[Neisseria]] meningitidis ST11 Complex Isolates Associated with Nongonococcal [[Urethritis]], Indiana, USA, 2015-2016. Emerg Infect Dis. 2017 Feb;23(2):336-339. doi: 10.3201/eid2302.161434. PMID: 28098538; PMCID: PMC5324800. 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