Risk of Invasive Meningococcal Disease in Men Who Have Sex with Men: Lessons Learned from an Outbreak in Germany, 2012—2013 - Fig 2

IMD cases due to the outbreak finetype C:P1.5–1,10–8:F3-6 according to fHbp and aniA alleles in (A) men and (B) women aged 20–49 years, Germany, 2002–2014 (N = 68).aniA(6A) is associated with expression of a nitrite reductase that facilitates survival of meningococci in microanaerobic environments (see text).</p

Additional file 1: of Influenza and pertussis vaccination during pregnancy – attitudes, practices and barriers in gynaecological practices in Germany

Table S1. Results of logistic regression analysis of variables potentially associated with vaccinating pregnant women against influenza. Table S2. Additional perceived barriers for vaccinating against influenza during pregnancy provided in participants’ additional comments. Table S3. Results of logistic regression analysis of variables potentially associated with vaccinating pregnant women against pertussis. Table S4. Additional perceived barriers for vaccinating against pertussis during pregnancy provided in participants’ additional comments. Table S5. Measures to attain high pertussis vaccination coverage in pregnant women (and high vaccination coverage in general) provided in participants’ additional comments. (DOCX 37 kb

Description of IMD cases in men who have sex with men (MSM) and their isolates Germany, 2012–2014.

<p>Description of IMD cases in men who have sex with men (MSM) and their isolates Germany, 2012–2014.</p

Additional file 2: of Influenza and pertussis vaccination during pregnancy – attitudes, practices and barriers in gynaecological practices in Germany

Translated questionnaire (originally used in German) used for this survey. (PDF 138 kb

IMD cases detected as spatiotemporally linked based on a common finetype using SaTScan (see methods) or as epidemiologically linked according to sex and in relation to all cases.

<p>IMD cases detected as spatiotemporally linked based on a common finetype using SaTScan (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160126#sec006" target="_blank">methods</a>) or as epidemiologically linked according to sex and in relation to all cases.</p

Cases of IMD in men who have sex with men (MSM) and non-MSM in relation to the number of MSM in the German population, 01.01.2012–30.09.2014.

<p>Cases of IMD in men who have sex with men (MSM) and non-MSM in relation to the number of MSM in the German population, 01.01.2012–30.09.2014.</p

Additional file 1 of Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review

Additional file 1: Figure S1. Systematic review on safety and effectiveness of pertussis vaccination in pregnancy; flowchart selection of included studies. Table S1. Systematic review on safety and effectiveness of pertussis vaccination in pregnancy; excluded studies. Table S2. Systematic review on safety and effectiveness of pertussis vaccination in pregnancy; results of the risk of bias (ROB) assessment. Table S3. Systematic review on safety and effectiveness of pertussis vaccination in pregnancy; GRADE Evidence profile

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men - Fig 3

<p><b>Impact of fHbp expression of invasive MSM isolates and urethritis isolates on meningococcal pathogenesis</b> (A) Western blotting analysis to detect fHbp. Meningococci from IMD cases in MSM expressing functional fHbp and isolates harboring the <i>fhbp</i> allele 669 (with a pre-mature stop codon) were tested. Meningococcal strain MC58 was used as a positive control (+). (B) Survival of meningococci in transgenic mice expressing human factor H (hfH). Bacterial counts recovered from blood after intraperitoneal challenge with 5x10⁷ colony forming units of meningococcal isolates from urethritis (red) and MSM cases (black). A representative experiment with data representing individual mice is shown. Mice infected with isolates from MSM showed significantly higher bacterial counts 2, 6 and 24 hours after infection compared to those infected with urethritis isolates (p values derived from a Student´s <i>t</i> test are displayed). (C) Flow cytometry analysis of C3b surface deposition on (1) meningococci from IMD cases in MSM expressing fHbp and (2) on meningococci isolated from urethritis cases not expressing fHbp due to an early stop codon. The X axis represents logarithmic scale binding of C3b expressed as the geometric mean of fluorescence. The number of events is displayed on the Y axis. Different coloured lines were used to indicate the isolates for better clarity.</p

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men

<div><p>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.</p></div

Whole genome sequence based phylogenetic tree.

<p>The neighbor-joining tree was calculated from 1,056 concatenated and multiple aligned core genome genes shared by all studied isolates. Numbers at the branches indicate the percentage of bootstrap support (1,000 replications). Labels in blue represent IMD isolates in MSM; in red urethritis and proctitis isolates; in green adolescent IMD isolates; and in black FAM18 cc11 and MC58 outgroup [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154047#pone.0154047.ref042" target="_blank">42</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154047#pone.0154047.ref043" target="_blank">43</a>]. A distance scale-bar is shown at the bottom left.</p