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Socially-induced Biological Health Hazard – New Fatal Meningococcal strain strikes blow to Queer Nations: Europe

2016/05/14

MENINGITIS, MENINGOCOCCAL – EUROPE: FATAL, MEN WHO HAVE SEX WITH MEN, NEW SEXUALLY TRANSMITTED STRAIN
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Published Date: 2016-05-13 17:35:55
Subject: PRO/EDR> Meningitis, meningococcal – Europe: fatal, MSM, new sexually transmitted strain
Archive Number: 20160513.4220814

Date: Wed 11 May 2016
Source: PLOS One [edited]

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men
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Taha M-K, Claus H, Lappann M, Veyrier FJ, Otto A, Becher D, et al.

Abstract
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Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract.

Discussion
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Our results demonstrate the power of combining laboratory infection surveillance, genomics and proteomics technologies and transgenic animal models to unravel the molecular basis of meningococcal evolution that lead to short-term changes in the epidemiology of meningococcal disease. Our data also suggest that genomic plasticity of meningococci permits a rapid generation of variants with increased fitness for alternative/novel niches. The AniA+, fHbp- phenotype seems to be associated with urethral and rectal colonization, leading to the clinical manifestation of urethritis/proctitis as well as the capacity for direct sexual transmission. These findings further highlight the link between metabolic processes and virulence.

Our finding that cc11/ET-15 meningococci adapted to a gonococcus-like lifestyle suggests that the variant may be widely distributed in the MSM community. This should be further investigated by meningococci C carriage studies in MSM. As suggested by our results, reversion to a hypervirulent phenotype (AniA+, fHbp+) is possible through the reacquisition of functional fHbp that enhances bacterial survival in the blood. The spontaneous reversion to fHbp+ state may occur but at low frequency (less than 5 x 10^-4). Alternatively, transformation and recombination during mixed carriage and/or mixed urethral infection may be responsible for this reversion [15].

The impact of the acquired capacity for sexual transmission on meningococcal evolution remains to be followed. If persistent wide-spread transmission in the MSM community is confirmed, time-limited vaccination strategy specifically targeting MSM implemented thus far mainly in areas affected by the outbreaks should be reconsidered [11, 41], since more widespread vaccination of MSM could limit international spread in the MSM community.

[The full article, including Figures, Methods, Results, and References, is available at the source URL.]


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ProMED-mail
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[_Neisseria meningitidis_, the cause of invasive meningococcal disease (meningitis and sepsis), is usually transmitted from person to person via droplets of respiratory secretions, mostly from asymptomatic nasopharyngeal carriers of the microorganism. It is estimated that between 10 to 25 percent of the population carry _N. meningitidis_ in the nasopharynx at any given time, and the carriage rate may be much higher in epidemic situations. Close and prolonged contact (such as kissing, sneezing, and coughing on someone), living in close quarters or dormitories (military recruits, students), sharing eating or drinking utensils, etc., facilitates the spread of the disease. The average incubation period for meningococcal meningitis is 4 days, ranging between 2 and 10 days (http://www.who.int/mediacentre/factsheets/fs141/en/). Invasive meningococcal disease (IMD) carries a high case fatality rate if untreated. Even with early and appropriate treatment, patients can die within 24-48 hours.

Outbreaks of IMD have occurred in the past several years among men who have sex with men (MSM) in Germany, Belgium and France caused by a _Neisseria meningitidis_ serogroup C strain with a certain genotype (http://www.ecdc.europa.eu/en/publications/Publications/rapid-risk-assessment-invasive-meningococcal-disease-among-MSM.pdf). Similar outbreaks among MSM caused by _N. meningitidis_ serogroup C have occurred in Canada and the US (see prior ProMED-mail posts below).

Molecular epidemiology has revealed that most cases of IMD are caused by only a few hypervirulent clonal lineages, whereas the genetic diversity is higher in meningococci recovered from healthy carriers (Claus H, Weinand H, Frosch M, Vogel U. Identification of the hypervirulent lineages of _Neisseria meningitidis_, the ST-8 and ST-11 complexes, by using monoclonal antibodies specific to NmeDI. J Clin Microbiol. 2003; 41(8): 3873-6; available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC179822/).

Severely immunosuppressed patients with HIV infection and a low CD4 cell count of less than or equal to 200/mm3 are likely to be at greater risk of developing bacterial meningitis (Domingo P, Suarez-Lozano I, Torres F, et al. Bacterial meningitis in HIV-1-infected patients in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2009; 51(5): 582-7; available at http://www.researchgate.net/publication/26279285) and less virulent strains have been reported to cause IMD in immunocompromised HIV-infected patients (Ferreira de Andrade C, Cotrim da Cunha D, Cavalcanti V, de Filippis I. Fatal meningococcal meningitis in a HIV-infected patient caused by serogroup C _Neisseria meningitidis_ belonging to the non-hypervirulent clonal complex ST-60 (cc60). Braz J Infect Dis. 2011; 15(2): 178-80; available at http://dx.doi.org/10.1590/S1413-86702011000200017). However, MSM who have developed meningococcal meningitis have been mostly HIV-negative, according to the above report.

Mass vaccination campaigns using meningococcal C vaccine have been used to control outbreaks of IMD in MSM (CDC. Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1997; 46(RR-5): 13-21; available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00046237.htm).

A meningococcal genotype (serogroup C, PorA type P1.5-1,10-8, FetA type F3-6 and cc11) was identified in isolates from MSM with IMD in Germany and France (http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20523 and http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21016). Meningococci with the identical genotype were also isolated in Germany and France from cases with urethritis/proctitis. In the present study, genome sequencing analysis showed that isolates from MSM with IMD clustered with urethritis and proctitis isolates collected in the 2 countries, distinct from other cc11/ET-15 isolates. The meningococcal isolates from both MSM with IMD and urethritis were able to grow anaerobically in the presence of nitrite, as do gonococci, unlike non-MSM/urethrtis meningococcal isolates. Anaerobic growth, usually rare in meningococci but found in gonococcus, is thought to allow gonococci to survive under anaerobic and acidic pH in the urethra or rectum, leading to the clinical manifestation of urethritis/proctitis as well as the capacity for direct sexual transmission. However, strains that were isolated from MSM with IMD were found to have genes that facilitated survival in the blood, unlike strains that remained in the urethra or rectum, causing urethritis and proctitis. These studies suggest that in the outbreak of IMD in MSM, meningococci were transmitted sexually and that reverted to a phenotype with enhanced bacterial survival in the blood, which facilitated meningococcemia and systemic dissemination. – Mod.ML

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/promed/p/100.]

See Also

2015
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Meningitis, meningococcal – USA (03): (MN,IL) fatal, MSM, vaccine 20150718.3520169
Meningitis, meningococcal – USA (02): (IL) fatal, MSM, vaccine, RFI 20150711.3502722
Meningitis, meningococcal – France: (Paris) serogroup C, MSM, vaccination 20150124.3116307

2014
—-
Meningitis, meningococcal – USA (04): (CA) fatal, MSM, vaccination, RFI 20140404.2379584

2013
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Meningitis, meningococcal – Germany: (BE) fatal, MSM, vaccination 20130725.1844122
Meningitis, meningococcal – USA (02): (New York City) fatal, MSM, vaccination 20130520.1725339
Meningitis, meningococcal – USA: (New York City) fatal, MSM, alert 20130308.1576590

2012
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Meningitis, meningococcal – USA (02): (NY) fatal, MSM 20120929.1315676
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Source:
A ProMED-mail post
ProMED-mail is a program of the International Society for Infectious Diseases


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