Urethritis caused by Neisseria meningitidis serogroup C

Abstract

Neisseria meningitidis and Neisseria gonorrhoeae infections in humans have traditionally been distinguished by their clinical manifestations and site of isolation. N. meningitidis usually causes meningococcemia and/or meningitis, while N. gonorrhoeae usually infects the anogenital mucous membranes. Nevertheless, the ecological niches of these two species occasionally overlap, and it has been observed that N. meningitidis can colonize the anogenital tract in men and women, causing urethritis, proctitis and cervicitis; N. gonorrhoeae has been observed in the oropharyngeal mucous membranes, causing meningitis and pharyngitis [1Knapp JS Rice RJ Neisseria and Branhamella.in: Murray PR. Baron EJ Pfaller MA Tenover FC Yolken RH Manual of clinical microbiology. American Society for Microbiology, Washington1995: 324-340Google Scholar]. Between 1974 and 1993, the majority of cases of N. meningitidis urethritis were caused by strains belonging to serogroups A [2Carpenter CM. Charles R Isolation of meningococcus from the genitourinary tract of seven patients.Am J Public Health. 1942; 32: 640-643Crossref Google Scholar, 3Hagman M Forslin L Moi H Danielsson D Neisseria meningitidis in specimens from urogenital sites. Is increased awareness necessary.Sex Transm Dis. 1991; 18: 228-232Crossref PubMed Scopus (39) Google Scholar, 4Wilson APR Watia JW Acute urethritis due to Neisseria meningitidis group A acquired by orogenital contact: case report.Genitourin Med. 1989; 65: 122-123PubMed Google Scholar] and B [3Hagman M Forslin L Moi H Danielsson D Neisseria meningitidis in specimens from urogenital sites. Is increased awareness necessary.Sex Transm Dis. 1991; 18: 228-232Crossref PubMed Scopus (39) Google Scholar,5Conde-Glez CJ Calderón E Urogenital infection due to meningococcus in men and women.Sex Transm Dis. 1991; 18: 72-75Crossref PubMed Scopus (20) Google Scholar,6Beck A Fluker JL Platt DJ Neisseria meningitidis in urogenital infection.Br J Vener Dis. 1974; 50: 367-369PubMed Google Scholar]; isolated cases caused by strains belonging to serogroups C [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar], 29E [8William DC Felman YM Corsaro MC Neisseria meningitidis. Probable pathogen in two related cases of urethritis, epididymins, and acute pelvic inflammatory disease.JAMA. 1979; 242: 1653-1654Crossref PubMed Scopus (15) Google Scholar], X [9Shanmugaratnam K Pattman RS Acute urethritis due to Neisseria meningitidis.Genitourin Med. 1989; 65: 401-403PubMed Google Scholar] and Y [3Hagman M Forslin L Moi H Danielsson D Neisseria meningitidis in specimens from urogenital sites. Is increased awareness necessary.Sex Transm Dis. 1991; 18: 228-232Crossref PubMed Scopus (39) Google Scholar, 6Beck A Fluker JL Platt DJ Neisseria meningitidis in urogenital infection.Br J Vener Dis. 1974; 50: 367-369PubMed Google Scholar] and non-groupables [9Shanmugaratnam K Pattman RS Acute urethritis due to Neisseria meningitidis.Genitourin Med. 1989; 65: 401-403PubMed Google Scholar] have also been published. This either is related to the greater ability of these serogroups to colonize the urethra, or else reflects the predominant serogroups in the community. Epidemiologic studies show that in Spain a considerable increase in infections caused by N. meningitidis serogroup C has occurred since 1990, the serotype 2b:P1.2,5 being the most frequent [10Vàzquez JA De la Fuente L Berrón S Infeccion meningo-cócica. Informe del laboratorio de referencia de meningococos (1995).Bol Epidemiol Semanal. 1996; 4: 37-40Google Scholar]. In our population this increase has been happening since 1994. In this report we present a case of acute urethritis caused by N. meningitidis C:2b:P1.2. In October 1996, a 42-year-old heterosexual male presented at the clinic at his health center, with purulent urethral exudate and pain during micturition during the previous 8 days. The patient reported two episodes of urethritis of unknown etiology several years previously. He had no regular partner and stated having had sexual intercourse with a prostitute, without fellatio or use of a condom, 20 days before presenting symptoms. His doctor referred him to the microbiology laboratory for examination of urethral exudate. The patient received treatment with 1 g cefonicid every 24 h for 2 days, after which he was asymptomatic. At the time of obtaining the sample, the patient presented little exudate. On direct microscopic examination, 5–7 leukocytes/ X400 field were observed. No Gram-negative diplococci or other microorganisms were seen on the Gram stain. The exudate was streaked on Martin–Lewis agar (Biomedics, Madrid, Spain), vaginalis agar (made with Columbia agar (Becton Dickinson, Cockeysville, USA), protease peptone no. 3 (Difco, Detroit, USA) and human blood), chocolate agar (Oxoid, Madrid, Spain) and Mycoplasma-Lyo (bioMérieux, Marcy-L'Étoile, France). Direct immuno-fluorescence was performed for the detection of Chlamydia trachomatis antigen (Syva Company, San José, USA). The plates were incubated at 37°C for 48 h in 5% CO2. After 24 h, oxidase-positive colonies grew on Martin–Lewis agar and chocolate agar which on Gram stain had the appearance of Gram-negative diplococci. Identification was performed by the Api NH battery of biochemical tests (bioMerieux, Marcy-L'Étoile, France), with positive results for glucose oxidation and γ-glutamyl transpeptidase (GGT). The strain was not β-lactamase-producing. It was presumed to be N. gonorrhoeae because of the kind of infection and the sugar oxidation. The microorganism was sent to the Carlos III Institute (Majadahonda, Madrid, Spain) for biotyping. No other microorganism was isolated from the urethra. The patient underwent further tests for the serologic determination of syphilis, HIV, and hepatitis viruses B and C; the results were negative in all cases. One month later, a follow-up of the urethral exudate was performed; no leukocytes were observed on direct microscopic examination, and the culture was negative. In the reference center, Carlos III Institute, biochemical identification with Api NH was positive for glucose oxidation and GGT production, and doubtful for maltose oxidation. Sugar oxidation was confirmed in trypticase cysteine medium, with positive results for glucose and maltose oxidation. Biotyping revealed the strain to be N. meningitidis. Monoclonal antibody typing identified it as N. meningitidis C:2b:P1.2. No crossover agglutinations with gonococci were found. No clinical or laboratory data are available on the women with whom che patient had sexual intercourse. N. meningitidis can be isolated from the nasopharynx in 5–15% of individuals [1Knapp JS Rice RJ Neisseria and Branhamella.in: Murray PR. Baron EJ Pfaller MA Tenover FC Yolken RH Manual of clinical microbiology. American Society for Microbiology, Washington1995: 324-340Google Scholar], with a greater proportion being observed in confined populations or certain groups. Janda et al [11Janda WM Bohnhoff M Morello JA Lerner SA Prevalence and site-pathogen studies of Neisseria meningitis and Neisseria gonorrhoeae in homosexuál men.JAMA. 1980; 244: 2060-2064Crossref PubMed Scopus (66) Google Scholar] found a prevalence of 42.5% meningococcal carriers in the nasopharynx in homosexual men attending a sexually transmitted diseases (STD) clinic. In the general population, the proportion of N. meningitidis isolated from the urethra ranges from 0.05% [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar] to 0.07% [12Maini M French P Prince M Bingham JS Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population.Int J STD AIDS. 1992; 3: 423-425PubMed Google Scholar], while Conde-Glez and Calderón [5Conde-Glez CJ Calderón E Urogenital infection due to meningococcus in men and women.Sex Transm Dis. 1991; 18: 72-75Crossref PubMed Scopus (20) Google Scholar] found a rate of 0.4% in high-risk populations. In homosexual men, the proportion of meningococci isolated from the urethra ranges from 0.03% [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar] to 0.7% [11Janda WM Bohnhoff M Morello JA Lerner SA Prevalence and site-pathogen studies of Neisseria meningitis and Neisseria gonorrhoeae in homosexuál men.JAMA. 1980; 244: 2060-2064Crossref PubMed Scopus (66) Google Scholar]. Maini et al [12Maini M French P Prince M Bingham JS Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population.Int J STD AIDS. 1992; 3: 423-425PubMed Google Scholar] did not isolate any meningococci from 8992 urethral samples from heterosexual males, while McKenna et al [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar] isolated this microorganism at a rate of 0.03%. Meningococci may colonize the rectum of homosexual men (1.1% [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar] to 2.1% [13Judson FN Ehret JM Anogenital infection with Neisseria meningitidis in homosexual men.J Infect Dis. 1978; 137: 458-463Crossref PubMed Scopus (40) Google Scholar]) and of 0.2% of women [13Judson FN Ehret JM Anogenital infection with Neisseria meningitidis in homosexual men.J Infect Dis. 1978; 137: 458-463Crossref PubMed Scopus (40) Google Scholar], and while Maini et al [12Maini M French P Prince M Bingham JS Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population.Int J STD AIDS. 1992; 3: 423-425PubMed Google Scholar] did not isolate any meningococci from 15 975 samples of cervical exudate, other authors report a rate of 0.03% [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar]. These studies show that the presence of N. meningitidis in the anogenital tract ranges widely, depending on the population studied. Despite the prevalence of N. meningitidis in the urethra, its capacity for producing urethritis is relatively low. The first case published was in 1942 by Carpenter and Charles [2Carpenter CM. Charles R Isolation of meningococcus from the genitourinary tract of seven patients.Am J Public Health. 1942; 32: 640-643Crossref Google Scholar], but the majority of the cases described accumulated between the years 1974 and 1993 [3Hagman M Forslin L Moi H Danielsson D Neisseria meningitidis in specimens from urogenital sites. Is increased awareness necessary.Sex Transm Dis. 1991; 18: 228-232Crossref PubMed Scopus (39) Google Scholar, 4Wilson APR Watia JW Acute urethritis due to Neisseria meningitidis group A acquired by orogenital contact: case report.Genitourin Med. 1989; 65: 122-123PubMed Google Scholar, 5Conde-Glez CJ Calderón E Urogenital infection due to meningococcus in men and women.Sex Transm Dis. 1991; 18: 72-75Crossref PubMed Scopus (20) Google Scholar, 6Beck A Fluker JL Platt DJ Neisseria meningitidis in urogenital infection.Br J Vener Dis. 1974; 50: 367-369PubMed Google Scholar, 7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar, 8William DC Felman YM Corsaro MC Neisseria meningitidis. Probable pathogen in two related cases of urethritis, epididymins, and acute pelvic inflammatory disease.JAMA. 1979; 242: 1653-1654Crossref PubMed Scopus (15) Google Scholar, 9Shanmugaratnam K Pattman RS Acute urethritis due to Neisseria meningitidis.Genitourin Med. 1989; 65: 401-403PubMed Google Scholar, 10Vàzquez JA De la Fuente L Berrón S Infeccion meningo-cócica. Informe del laboratorio de referencia de meningococos (1995).Bol Epidemiol Semanal. 1996; 4: 37-40Google Scholar, 11Janda WM Bohnhoff M Morello JA Lerner SA Prevalence and site-pathogen studies of Neisseria meningitis and Neisseria gonorrhoeae in homosexuál men.JAMA. 1980; 244: 2060-2064Crossref PubMed Scopus (66) Google Scholar, 12Maini M French P Prince M Bingham JS Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population.Int J STD AIDS. 1992; 3: 423-425PubMed Google Scholar, 13Judson FN Ehret JM Anogenital infection with Neisseria meningitidis in homosexual men.J Infect Dis. 1978; 137: 458-463Crossref PubMed Scopus (40) Google Scholar, 14Miller MA Millikin P Griffin PS Sexton RA Yousuf M Neisseria meningitidis urethritis. A case report.JAMA. 1979; 242: 1656-1657Crossref PubMed Scopus (18) Google Scholar, 15Phillips EA Shultz TR Tapsall JW Chambers IW Maltosenegative Neisseria meningitidis isolated from a case of male urethritis.J Clin Microbiol. 1989; 27: 2851-2852PubMed Google Scholar]. From this date on, we have not found any cases reported in the databases consulted: Medline and Embase. Although McKenna et al [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar] did not find any variation between the prevalence and incidence of non-gonococcal Neisseria in anogenital samples in the period pre- and post-AIDS, our not finding any case of urethritis caused by meningococci from 1993 on may be related to the public awareness of HIV infection, as has been observed with other STDs such as gonococcal urethritis, which has been decreasing in our population since 1990 [16Nebreda T Merino FJ Campos A Vázquez M Variacion de la incidencia y sensibilidad antibiótica de Neisseria gonorrhoeae en un periodo de 7 años.Enferm Infecc Microbiol Clin. 1996; 14: 441-443PubMed Google Scholar]. This may be more obvious among homosexuals, who had a greater incidence of urethritis caused by meningococci [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar,11Janda WM Bohnhoff M Morello JA Lerner SA Prevalence and site-pathogen studies of Neisseria meningitis and Neisseria gonorrhoeae in homosexuál men.JAMA. 1980; 244: 2060-2064Crossref PubMed Scopus (66) Google Scholar,12Maini M French P Prince M Bingham JS Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population.Int J STD AIDS. 1992; 3: 423-425PubMed Google Scholar] as these comprise the population group which has taken greatest measures regarding the prevention of HIV infection. Urethritis caused by N. meningitidis may be either symptomatic, generally as exudate without dysuria [8William DC Felman YM Corsaro MC Neisseria meningitidis. Probable pathogen in two related cases of urethritis, epididymins, and acute pelvic inflammatory disease.JAMA. 1979; 242: 1653-1654Crossref PubMed Scopus (15) Google Scholar, 14Miller MA Millikin P Griffin PS Sexton RA Yousuf M Neisseria meningitidis urethritis. A case report.JAMA. 1979; 242: 1656-1657Crossref PubMed Scopus (18) Google Scholar], or indistinguishable from gonococcal urethritis [4Wilson APR Watia JW Acute urethritis due to Neisseria meningitidis group A acquired by orogenital contact: case report.Genitourin Med. 1989; 65: 122-123PubMed Google Scholar, 5Conde-Glez CJ Calderón E Urogenital infection due to meningococcus in men and women.Sex Transm Dis. 1991; 18: 72-75Crossref PubMed Scopus (20) Google Scholar, 6Beck A Fluker JL Platt DJ Neisseria meningitidis in urogenital infection.Br J Vener Dis. 1974; 50: 367-369PubMed Google Scholar,9Shanmugaratnam K Pattman RS Acute urethritis due to Neisseria meningitidis.Genitourin Med. 1989; 65: 401-403PubMed Google Scholar], or asymptomatic [12Maini M French P Prince M Bingham JS Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population.Int J STD AIDS. 1992; 3: 423-425PubMed Google Scholar]. Probably the most common route of transmission of meningococcal urethritis among heterosexuals was orogenital [4Wilson APR Watia JW Acute urethritis due to Neisseria meningitidis group A acquired by orogenital contact: case report.Genitourin Med. 1989; 65: 122-123PubMed Google Scholar, 9Shanmugaratnam K Pattman RS Acute urethritis due to Neisseria meningitidis.Genitourin Med. 1989; 65: 401-403PubMed Google Scholar], while among homosexuals transmission was both orogenital and anogenital [7McKenna JG Fallon RJ Moyes A Young H Anogenital nongonococcal Neissenae: prevalence and clinical significance.Int J STD AIDS. 1993; 4: 8-12PubMed Google Scholar, 12Maini M French P Prince M Bingham JS Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population.Int J STD AIDS. 1992; 3: 423-425PubMed Google Scholar]. In the case described here, the route of transmission of the infection could not be determined, although it is clear from the medical history either that the meningococcus was colonizing the woman's cervix or that this was not a case of STD. The majority of cases of meningococcal urethritis described are caused by serogroup B; this may be due to it being more pathogenic in the genitoanal area, or else to it being the predominant serogroup in the population [1Knapp JS Rice RJ Neisseria and Branhamella.in: Murray PR. Baron EJ Pfaller MA Tenover FC Yolken RH Manual of clinical microbiology. American Society for Microbiology, Washington1995: 324-340Google Scholar, 10Vàzquez JA De la Fuente L Berrón S Infeccion meningo-cócica. Informe del laboratorio de referencia de meningococos (1995).Bol Epidemiol Semanal. 1996; 4: 37-40Google Scholar]. Cases of maltose-negative N. meningitidis have occasionally been published [16Nebreda T Merino FJ Campos A Vázquez M Variacion de la incidencia y sensibilidad antibiótica de Neisseria gonorrhoeae en un periodo de 7 años.Enferm Infecc Microbiol Clin. 1996; 14: 441-443PubMed Google Scholar]. This appears to be related to the inactivation of a permease [17Kingsbury DT Relationship between sulfadiazine resistance and the failure to ferment maltose in Neisseria meningitidis.J Bacteriol. 1967; 94: 557-561PubMed Google Scholar]. Our strain, while it did not ferment maltose in a rapid test, was positive when a more sensitive test was used. The clinical picture, site of isolation and identification may all contribute to initial confusion over urethritis due to N. meningitidis, and this indicates the need for typing of genital tract isolates. We thank J. A. Vázquez of Carlos III Laboratory in Majadahonda (Madrid) for doing the identification and the biotyping, as well as Bristol Myers Squibb for help with the translation of the manuscript.