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Abstract
Introduction Outbreaks of invasive Neisseria meningitidis subtype C in networks of gay, bisexual and other men who have sex with men (MSM) have been reported. We aimed to explore any factors seen in MSM with invasive N.meningitidis subtype C.
Method We searched three bibliographical databases for manuscripts written in English exploring at least one factor seen in MSM with invasive N. meningitidis subtype C published up to May 2024. Following an initial search, removal of duplicates and abstract review, two authors independently reviewed full-text manuscripts and performed a risk of bias assessment using the Joanna Briggs Institute toolkit. Narrative data were synthesised to generate themes.
Results 16 manuscripts were included in this review from the USA (n=10), Germany (n=2), France (n=2), Canada (n=1) and Italy (n=1) and consisted of nine case series, four cross-sectional studies, two case reports and one case–control study published between 2003 and 2024 involving 236 MSM with invasive N. meningitidis subtype C, of which at least 64 died. We have highlighted some demographic (African-American or Hispanic identity in the USA, living with HIV), behavioural (kissing, sharing drinks, visiting sex-on-premises venues, visiting gay-oriented venues, using websites/mobile phone apps to meet sexual partners, recreational drug use, multiple and non-regular sexual partners) and infection (previous Chlamydia trachomatis, Treponema pallidum, Neisseria gonorrhoeae, Mpox) factors in MSM with invasive N. meningitidis subtype C.
Conclusion These data serve as an important resource to inform and target future public health strategies and outbreak control measures for the prevention of invasive N. meningitidis subtype C in MSM.
PROSPERO registration number CRD42024543551.
- MEN
- NEISSERIA MENINGITIDIS
- MENINGITIS
- Homosexuality, Male
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Neisseria meningitidis is present in anogenital and oropharyngeal sites in men who have sex with men (MSM) suggesting some sexual transmission.
Outbreaks of invasive N. meningitidis subtype C in gay, bisexual and other MSM) have been reported.
WHAT THIS STUDY ADDS
This review has highlighted some demographic (African-American or Hispanic identity in the USA, living with HIV), behavioural (kissing, sharing drinks, visiting sex-on-premises venues, visiting gay-oriented venues, using websites/mobile phone apps to meet sexual partners, recreational drug use, multiple and non-regular sexual partners) and infection (previous Chlamydia trachomatis, Treponema pallidum, Neisseria gonorrhoeae, Mpox) factors in MSM with invasive N. meningitidis subtype C.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
This review provides some important insights into targeting MSM at risk of invasive N. meningiditis subtype C to prevent outbreaks and guide research.
Introduction
Invasive meningococcal disease is caused by the bacteria Neisseria meningitidis, a group of Gram-negative encapsulated diplococci that cause a broad clinical spectrum of diseases from a mild febrile illness to septicaemia, meningitis, multiorgan failure and death.1 N. meningitidis are classified into 13 serogroups, 4 of which (B, C, W, Y) are most commonly associated with invasive N. meningitidis in Europe.2 Approximately 10% of the general population has nasopharyngeal colonisation with N. meningitidis, but rates vary with age, peaking in adolescents and young adults when colonisation can be as high as 37%.3 Transmission is believed to occur mainly through prolonged direct contact with upper respiratory secretions from colonised or infected individuals.3 4 In a small percentage of exposed individuals, N. meningitidis invades the nasopharyngeal mucous membrane and after a few days enters the bloodstream and causes invasive disease.3 4 High carriage rates of oropharyngeal (43%), rectal (2%) and urethral (1%), and symptomatic anogenital N. meningitidis have been seen in gay bisexual and other men who have sex with men (MSM), suggesting sexual transmissibility.4–6 Recently, significant increases in sexually transmitted infections (STI) seen in MSM have corresponded with outbreaks of novel pathogens in some sexual networks of MSM including enteric infections (Shigella spp), viral hepatitis (hepatitis C), systemic viruses (Mpox virus) and invasive N. meningitidis subtype C.7–10 Although rare, meningococcal disease poses a major public health risk; epidemiological surveys suggest that MSM are significantly more at risk of acquisition of MenC and morbidity and mortality from MenC than non-MSM.11 Overall, the incidence of invasive N. meningitidis is declining due to the introduction of MenACWY conjugated vaccines in national childhood vaccination programmes.12 A MenACWY vaccination programme for MSM in response to an outbreak in Victoria, Australia, in 2017 coincided temporally with a dramatic reduction in the incidence of invasive N. meningitidis among MSM.13 14 The MenACWY vaccine has been used in combination with HIV pre-exposure prophylaxis (PrEP) delivery in MSM; however, the uptake was poor.15 4CMenB vaccines designed for the prevention of N. meningitidis subtype B also reduce the sexual transmission of Neisseria gonorrhoeae, and MSM are being targeted for vaccination.14 16 The transmission of N. meningitidis subtype C between MSM is poorly understood. To design effective public health interventions, including outbreak control strategies and targeted delivery of vaccines, it is important to understand the factors associated with invasive N. meningitidis subtype C in MSM. We aimed to review the literature to explore any factors seen in MSM with invasive N. meningitidis subtype C.
Methods
Search strategy and selection
A systematic review of the literature was conducted in May 2024 to explore any factors seen in MSM with invasive N. meningitidis subtype C using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.17 Relevant manuscripts were identified by searching three bibliographical databases (MEDLINE, EMBASE and Scopus) using the following search terms (Meningitis C OR Neisseria meningitidis C OR Meningococcal C OR meningococcal disease) AND (MSM OR MSM or men who have sex with men OR queer OR homosexual OR gay OR gays OR bisexual). Manuscripts meeting the following criteria were included in the review; written in English, containing primary data, participants at least 16 years of age, participants identified as MSM and with a diagnosis of invasive meningococcal disease subtype C. We defined invasive meningococcal disease as anyone with N. meningitidis subtype C and meningitis and/or sepsis. We only included manuscripts where at least one socio-demographic or behavioural risk factor was explored. There was no restriction on the date of article publication. All study types containing primary data were included. We excluded manuscripts involving exclusively non-MSM populations, conference abstracts, reviews or opinion pieces and other grey literature. Where manuscripts included mixed populations of MSM and non-MSM participants, data were only extracted and analysed for MSM.
Study selection and risk of bias
Following the initial database search, a list of relevant citations was generated. A stepwise process was used to select manuscripts; initially, the primary author (LR) reviewed the initial citations and abstracts. Three authors (LR, SS and DR) then independently reviewed the remaining full-text manuscripts to determine the final set of manuscripts according to the inclusion criteria. Hand-searching from the reference lists of the final manuscripts was done to seek more eligible manuscripts. Discrepancies between independent authors were resolved by discussion between LR, SS and DR. The risk of bias was assessed for each manuscript independently by two researchers (LR, DR) using the Joanna Briggs Institute (JBI) critical appraisal checklists.18 The risk of bias was assessed for each manuscript including a review of any methods used to account for confounding factors, analysis and overall risk of bias. Inclusion in the review was not contingent on quality of reporting or risk of bias. Each manuscript was graded as having a low, medium or high risk of bias.
Data extraction and synthesis
Data were extracted from the manuscripts, including article title, publication year, sample size, study design, population and the factors associated with transmission into a pre-determined table. Narrative data was synthesised from the factors explored in each manuscript and tabulated, and themes were generated. The review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42024543551).
Results
Figure 1 presents the PRISMA flowchart for the manuscript selection process. Sixteen manuscripts were included in the final review from the USA (n=10), Germany (n=2), France (n=2), Canada (n=1) and Italy (n=1) and consisted of four cross-sectional studies, nine case series, two case reports and one case–control study published between 2003 and 202410 11 19–32 (table 1). The 16 manuscripts represented 14 outbreaks of N. meningitidis subtype C as two manuscripts from New York and two from the United States Centres for Disease Control and prevention were reporting from the same two outbreaks.10 11 22 26 Overall, there were 236 MSM diagnosed with invasive N. meningitidis subtype C and at least 64 died during their illness. We assessed the risk of bias as being high in 10 manuscripts and medium in six manuscripts (online supplemental table 1)
Supplemental material
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of manuscript review process.
Manuscripts and factors seen in MSM with invasive Neisseria meningitidis subtype C
Demographic factors
Where reported, MSM identifying as African American (n=63) was associated with invasive N. meningitidis subtype C in manuscripts from the USA (n=193)10 22 25 26 29 (table 2). Where reported, identifying as Hispanic (n=43) was observed in MSM-invasive N. meningitidis subtype C in manuscripts from the USA (n=193). Living with HIV was associated in MSM with invasive N. meningitidis subtype C .10 11 22 24–27 29 31 32 One manuscript suggested that mortality (42% vs 20%) may be related to living with HIV in MSM with invasive N. meningitidis subtype C.22 Living in a household of >1 other person was observed in MSM with invasive N. meningitidis subtype C in one manuscript.25
Factors seen in MSM with Neisseria meningitidis subtype C
Behavioural factors
MSM-diagnosed invasive N. meningitidis subtype C reported kissing, sharing drinks, visiting ‘gay’-oriented venues and sex-on-premises venues prior to diagnosis.19–21 23 28 30 Using websites and mobile phone applications to meet sexual partners, using recreational drugs (including crystal methamphetamine and cocaine) and having (multiple) non-regular (including anonymous) sexual partners were reported by MSM who were subsequently diagnosed with invasive N. meningitidis subtype C.20–22 25 28 30
Infection factors
MSM diagnosed with invasive N. meningitidis subtype C reported previous bacterial STIs, namely, Chlamydia trachomatis, Treponema pallidum, N. gonorrhoeae and a recent Mpox infection (during the 2022 Mpox outbreak).25 32
Discussion
This is the first systematic review to explore the factors seen in MSM with N. meningitidis subtype C. We have highlighted some demographic (identify as being African-American and Hispanic in the USA, living with HIV), behavioural (kissing, sharing drinks, visiting sex-on-premises venues, visiting gay-oriented venues, using websites/mobile phone apps to meet sexual partners, recreational drug use, including crystal methamphetamine, reporting multiple and non-regular sexual partners) and infection (previous C. trachomatis, T. pallidum, N. gonorrhoeae, Mpox) factors reported by MSM who subsequently develop invasive N. meningitidis subtype C.
MSM who identify as African American or Hispanic, particularly those living with HIV, experience significant health inequalities in the USA, including the transmission of sexually transmitted infections and HIV, poor access to healthcare and premature death.33–37 Vaccine uptake and other health interventions in minoritised communities globally remain poor and therefore these populations remain highly vulnerable.38 Co-designed and co-delivered public health interventions with communities have been shown to improve access to public health interventions, including access to healthcare for MSM.39 MSM living with HIV may be at increased risk of death from some non-opportunistic infectious diseases such as N. meningitidis, and during outbreaks of invasive N. meningitidis in MSM, targeted vaccine programmes have been shown to be effective.40 MSM living with HIV may be part of unique social or sexual networks affected N. meningitidis subtype C. Before the era of HIV PrEP (and other effective HIV prevention strategies), sexual networks and the epidemiology of STIs in MSM living with HIV and HIV-negative MSM were discrete and this may have also included social networks. It will be interesting to see how the epidemiology of N. meningitidis subtype C in MSM evolves in the era of PrEP, as we would speculate that living with HIV will be a less important predictor.
Social behaviours that include very close contact have previously been associated with invasive N. meningitidis outbreaks; for example, during the Islamic religious festival of Haj, there have been several outbreaks of N. meningitidis subtypes A and W; and multi-subtype outbreaks have been reported in students living in dormitories.41–46 This review suggests that close contact including sexual contact between MSM could contribute to outbreaks of invasive N. meningitidis subtype C including sharing drinks, kissing and sexual behaviours.20–22 25 28 30 Similar to other novel sexually transmissible pathogens in MSM, the intersectionality of attending gay venues including sex on premises venues, using dating websites and mobile phone applications to meet sexual partners and recreational drug use (including crystal methamphetamine and cocaine) are observed in MSM with N. meningitidis subtype C.19 20 22 23 25 28 30 47 48 It is therefore not surprising that other concomitant STIs are seen in the networks of MSM affected by N. meningitidis subtype C including N. gonorrhoeae, C. trachomatis, T. pallidum and Mpox.9 25
There are several important limitations to this analysis including significant reporting bias, being from a relatively small number of medium and high risk of bias manuscripts including only reporting invasive N. meningitidis subtype C from high-income settings. The high death rate among MSM in this analysis limits the accuracy of some reporting which relies on pre-morbidly collected data from retrospectively designed studies. It is likely that some MSM with invasive N. meningitidis subtype C are not included in this review due to a lack of adequate surveillance mechanisms including inaccurate sexual behaviour data collection. Acute outbreaks of N. meningitidis subtype C reported by statutory bodies are not always published in the scientific literature or do not report sexual orientation or behaviours, or factors and were therefore would not be included in this analysis. Synthesising data from 16 highly heterogeneous manuscripts with different reporting strategies and data selection and reporting can miss important findings, making the overall interpretation of the results challenging.
There have been some significant outbreaks of invasive N. meningitidis subtype C among social and sexual networks of MSM described in North America, Europe and Australia over the past 21 years, including relatively high fatality. MenACWY conjugated vaccines are available and can prevent invasive N. meningitidis subtype C in MSM.13 Combining the access of HIV-PrEP, 4CMenB and MenACWY vaccines, Mpox and HPV vaccines for MSM and other groups at risk of N. gonorrhoeae and N. meningitidis in sexual health clinics could optimise public health prevention strategies.4 14 15 49 50
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
Ethics approval
This research was conducted in accordance with the World Medical Association declaration of Helsinki. This is a systematic review, so no patient consent was required. The review was registered on PROSPERO.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Handling editor Stefano Rusconi
Contributors DR came up with the study concept and designed the study protocol, LR conducted the data search, LR, SS DR independently reviewed the manuscripts for eligibility, LR and DR independently conducted the risk of bias assessment, LR and DR conducted the data synthesis and LR, SS, CC, CF, DW and DR all contributed to the final manuscript. DR is acting as the guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.