From the *Department of Genitourinary Medicine, Sunderland Royal Hospital, UK; †Health Waikato Laboratory, and ‡Sexual Health Clinic, Waikato Hospital, Hamilton, New Zealand
Correspondence: Dr. Jane Morgan, Sexual Health Clinic, Waikato Hospital, Private Bag 3200, Hamilton, New Zealand. E-mail: email@example.com.
Received for publication June 24, 2007, and accepted December 16, 2007.
REPORTS OF ANOGENITAL DISEASE caused by Neisseria meningitidis are uncommon, and occasional anogenital isolates found in otherwise healthy individuals are generally held to be incidental findings that do not require treatment. Such isolates are infrequent in our clinic setting but an unexpected increase of 4 genital N. meningitidis isolates was noted during February and March 2007. We discuss the recent cases and review their significance.
A 20-year-old woman presented with intermenstrual and postcoital bleeding. She reported unprotected vaginal and oral sex with a regular male partner of 1 year. She had completed vaccination for group B meningococcus and hepatitis B. Examination was unremarkable with no cervicitis noted. Pharyngeal, vaginal, cervical, and urethral swabs were taken, with N. meningitidis isolated from all sites. Tests for other sexually transmitted infections (STIs), including HIV, were negative. The isolate was susceptible to ciprofloxacin, which she was given. At follow-up, her symptoms had resolved and repeat swabs were negative. The cervical isolate was serogroup B, serotype 15P1.7,16. Her 23-year-old partner attended subsequently with N. meningococcus serogroup B15P1.7,16 isolated from his pharyngeal swab. Apart from known chronic hepatitis B infection, all his other tests for STIs, including HIV, were negative. Although asymptomatic, both were keen he was treated in view of her symptoms and he received ciprofloxacin. His repeat pharyngeal swab 4 days later was negative.
An asymptomatic 21-year-old woman presented, requesting a termination of pregnancy. Culture of a routine preoperative cervical swab exhibited heavy growth of N. meningitidis. The isolate was not sent for serogrouping. Tests for other STIs, including HIV, were negative. She did not provide any partner details. Although asymptomatic, she was treated with ceftriaxone before her procedure because of concerns about invasive disease developing postinstrumentation.1
An asymptomatic 23-year-old heterosexual humans presented because his regular partner was diagnosed elsewhere with Chlamydia trachomatis. He reported unprotected vaginal and oral sex with another partner in the preceding 3 months. Examination was unremarkable. He was treated presumptively for chlamydia and gonorrhoea with azithromycin and ceftriaxone on the basis of his history and the finding of gram-negative intracellular diplococci on his urethral Gram stain. Tests for HIV, Hepatitis B, and syphilis were negative. His chlamydia test (Roche PCR) was positive and urethral culture isolated N. meningitidis, which was susceptible to ciprofloxacin and ceftriaxone. This isolate was not serogroupable, but was serosubtype P1.6. He did not attend for follow-up.
An asymptomatic 28-year-old heterosexual humans presented for a sexual health screen. He reported 4 sexual partners in the preceding 3 months, with inconsistent condom use, and recent vaginal, but not oral, sex. Examination revealed genital warts. Tests for other STIs, including HIV, were negative. Culture of his urethral swab exhibited heavy growth of N. meningitidis, serogroup Y14.p1.5 to 2,10 to 4, with reduced susceptibility to ciprofloxacin (E-test MIC 0.125 μg/mL) but susceptible to ceftriaxone (MIC 0.064 μg/mL). The findings were discussed with the patient and he was not treated. Three months later, he remained asymptomatic and declined follow-up testing.
N. meningitidis is a commensal bacterium that occasionally causes invasive disease. At any time, approximately 10% of the healthy population carry N. meningitidis in the nasopharynx, with peak carriage rates of 24% to 37% occurring among those aged 15 to 24 years.2 Isolation of N. meningitidis from the genitourinary tract was first reported in the late 1930s3 and is generally believed to be an incidental finding. However, there have been reports supporting a pathogenic role in cases of urethritis, cervicitis, salpingitis, pelvic inflammatory disease, vulvovaginitis, proctitis, peritonitis, and preterm birth.1,3–11 It seems unusual for disseminated disease to develop although a case of meningococcal meningitis after removal of a cervical polyp in a woman with genital N. meningitidis has been reported.1 Vertical transmission resulting in purulent conjunctivitis12 and fatal meningitis in a neonate have also been reported.13
N. meningitidis may be transferred from nasopharyngeal to genital tract mucosa by oral sex, with studies using pulsed field gel electrophoresis to demonstrate phenotypically and genotypically identical isolates at both sites, suggesting cross-colonisation of sexual partners.10,14 Changes in sexual practice, with increasing orogenital contact, may account for increasing genital isolation of respiratory pathogens and increases in the proportion of genital Herpes simplex virus type 1 isolates over recent years.15,16 Small studies support increasing urogenital N. meningitidis isolates, with one finding 8.7% (8/92) of all Neisseria isolates in 19815 and another reporting 3 isolates as being 20% of their pathogenic urogenital Neisseria isolates over 8-months in 1989–1990.4
However, a larger study by McKenna et al.17 reports less than 1% of all isolates as being N. meningitidis, with prevalence among those screened of only 0.11%; there were 99 meningococcal isolates in 88,670 patients screened for anogenital gonorrhoea between 1978 and 1990. During the same period, there were approximately 9000 anogenital gonococcal infections. Nongonococcal isolates were more prevalent among men who have sex with men, and prevalence and incidence remained unchanged in all patient groups during the study. In our population, from 18,308 anogenital gonococcal samples between January 2002 and 2007, 1.2% (5/399) of anogenital Neisseria isolates were N. meningitidis. However, between February and March, a 15.4-fold increase occurred (5 meningococcal isolates from 27 Neisseria isolates of 754 anogenital samples).
Our setting is a publicly funded urban clinic for a regional population of 340,000, with approximately 9000 consultations annually. Average age is 27.5 years (48% below 25 years), 57% are female and 20% Maori, reflecting local population ethnicity proportions. The majority self-report as heterosexual. All attendees are offered testing for STIs, with specimen collection adjusted for sexual history.
The meningococci were isolated on the same media used for isolation of Neisseria gonorrhoeae. Samples for gonococcal detection are directly inoculated in clinic onto New York City and Thayer Martin plates, from an unchanged supplier, with isolates of Gram-negative, oxidase-positive cocci undergoing identification to a species level, using a combination of rapid carbohydrate utilization with API NH (BioMérieux) and enzyme detection with Bacticard Neisseria (Remel, Lenexa, KS). Susceptibility testing is performed using the Etest (AB Biodisk, Solna, Sweden) on Müller-Hinton agar subcultures. The Institute of Environmental Science and Research (ESR), a Crown reference laboratory, undertakes serogrouping and serotyping using PCR for serogroup, whole-cell ELISA method for serotype and DNA sequence analysis for subtype.18
Nasopharyngeal meningococcal carriage is not fully understood but colonization of the nasopharynx seems to produce an antibody response within a few weeks and may act as an immunizing event.2 It is possible that high nasopharyngeal prevalence may have contributed to the low number of genital isolates in our attendees during recent years but, as gonococcal pharyngeal swabs are not routinely undertaken among our heterosexual patients, we do not have a measure of nasopharyngeal meningococcal carriage within our clinic population. Another possibility is that the coexistence of N. meningitidis and N. gonorrhoeae within the same genital site, whether it be urethra, cervix or rectum, appears rare. It has been suggested that meningococci produce a locally acting antibacterial substance, bacteriocin, which inhibits the growth of N. Gonorrhoeae,19 although genital gonococcal infections remain relatively uncommon among our patients.20 It may simply be that gonococci preferentially infect anogenital mucosa whereas meningococci seem to preferentially infect nasopharyngeal mucosa.3
Is the New Zealand context of a protracted group B meningococcal epidemic and a meningococcal vaccination program relevant? From mid-1991, N. meningitidis strain B: 4:P1.7b.4 caused an epidemic of invasive meningococcal disease in New Zealand. In the 1980s, the incidence of serogroup B meningococcal disease was 1.5/100,000 population, reaching 17.4/100,000 by 2001.18 The Ministry of Health introduced MeNZB vaccine in 2004–2005 for all aged 6 months to 19 years to target the epidemic strain.21 By the end of December 2005, 75.6% of those eligible had been fully vaccinated. Only 1 of our cases was vaccinated with the remainder not eligible on age. Although nasopharyngeal meningococcal carriage is surveyed periodically, e.g., among New Zealand army recruits, it is not yet known if immunization against group B meningococci alters carriage rates in any way (personal communication, D Martin, ESR). The number and proportion of cases of meningococcal disease caused by the epidemic strain have decreased significantly since 2005 and so far there has been no significant change in the rate of meningococcal disease because of alternative group B or other strains.18
Apart from one partner who was an asymptomatic carrier, our recent cases do not seem to be linked and our recent increase in isolates may be merely an incidental finding.
The optimum management of anogenital N. meningitidis isolation remains unclear and seems based on empirical evidence. Although some advocate that genital N. meningitidis be considered a pathogen and treated, whether symptomatic or not, if found in the urethra or cervix,5 most suggest that it is an insignificant finding and that asymptomatic anogenital carriage does not require treatment. However, it seems prudent to treat those with anogenital symptoms as in our first case, or with a higher risk of developing disease, such as our second case. Finally, these cases reemphasize the importance of accurate species identification of genital isolates to ensure distinction from anogenital gonococcal infection.
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