Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
Records 1-18 (of 18 Records) |
Query Trace: Schmink S[original query] |
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Direct Real-Time PCR for the Detection and Serotyping of Haemophilus influenzae without DNA Extraction.
Marasini D , Whaley MJ , Jenkins LT , Hu F , Jiang W , Topaz N , Chen A , Schmink S , DolanThomas J , Harcourt BH , Marjuki H , Wang X . J Clin Microbiol 2022 60 (4) e0211121 To monitor the burden and changes in Haemophilus influenzae (Hi) disease, direct real-time PCR (drt-PCR) assays have been developed for Hi detection in monoplex form and its six serotypes in triplex form, directly from cerebrospinal fluid (CSF) specimens. These assays target the phoB gene for the species detection (Hi-phoB) and serotype-specific genes in region II of the capsule biosynthesis locus (Hi-abf and Hi-cde), identified through comparative analysis of Hi and non-Hi whole-genome sequences. The lower limit of detection (LLD) is 293 CFU/mL for the Hi-phoB assay and ranged from 11 to 130 CFU/mL for the triplex serotyping assays. Using culture as a reference method, the sensitivity and specificity of Hi-phoB, Hi-abf, and Hi-cde were 100%. Triplex serotyping assays also showed 100% agreement for each serotype compared to their corresponding monoplex serotyping assay. These highly sensitive and specific drt-PCR assays do not require DNA extraction and thereby reduce the time, cost, and handling required to process CSF specimens. Furthermore, triplex drt-PCR assays combine the detection of three serotypes in a single reaction, further improving testing efficiency, which is critical for laboratories that process high volumes of Hi specimens for surveillance and diagnostic purposes. |
Genomic Insights on Variation Underlying Capsule Expression in Meningococcal Carriage Isolates From University Students, United States, 2015-2016.
Whaley MJ , Vuong JT , Topaz N , Chang HY , Thomas JD , Jenkins LT , Hu F , Schmink S , Steward-Clark E , Mathis M , Rodriguez-Rivera LD , Retchless AC , Joseph SJ , Chen A , Acosta AM , McNamara L , Soeters HM , Mbaeyi S , Marjuki H , Wang X . Front Microbiol 2022 13 815044 In January and February 2015, Neisseria meningitidis serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates (N = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS). Functional capsule polysaccharide synthesis (cps) loci belonging to one of seven capsule genogroups (B, C, E, W, X, Y, and Z) were identified in 122 isolates (8.1%). Approximately half [732 (48.4%)] of isolates could not be genogrouped because of the lack of any serogroup-specific genes. The remaining 660 isolates (43.5%) contained serogroup-specific genes for genogroup B, C, E, W, X, Y, or Z, but had mutations in the cps loci. Identified mutations included frameshift or point mutations resulting in premature stop codons, missing or fragmented genes, or disruptions due to insertion elements. Despite these mutations, 49/660 isolates expressed capsule as observed with slide agglutination, whereas 45/122 isolates with functional cps loci did not express capsule. Neither the variable capsule expression nor the genetic variation in the cps locus was limited to a certain clonal complex, except for capsule null isolates (predominantly clonal complex 198). Most of the meningococcal carriage isolates collected from student populations at three US universities were non-groupable as a result of either being capsule null or containing mutations within the capsule locus. Several mutations inhibiting expression of the genes involved with the synthesis and transport of the capsule may be reversible, allowing the bacteria to switch between an encapsulated and non-encapsulated state. These findings are particularly important as carriage is an important component of the transmission cycle of the pathogen, and understanding the impact of genetic variations on the synthesis of capsule, a meningococcal vaccine target and an important virulence factor, may ultimately inform strategies for control and prevention of disease caused by this pathogen. |
Genetic Diversity of Meningococcal Serogroup B Vaccine Antigens among Carriage Isolates Collected from Students at Three Universities in the United States, 2015-2016.
Marjuki H , Chang HY , Topaz N , Whaley MJ , Vuong J , Chen A , Jenkins LT , Hu F , Schmink S , Retchless AC , Thomas JD , Acosta AM , McNamara LA , Soeters HM , Mbaeyi S , Wang X . mBio 2021 12 (3) Carriage evaluations were conducted during 2015 to 2016 at two U.S. universities in conjunction with the response to disease outbreaks caused by Neisseria meningitidis serogroup B and at a university where outbreak and response activities had not occurred. All eligible students at the two universities received the serogroup B meningococcal factor H binding protein vaccine (MenB-FHbp); 5.2% of students (181/3,509) at one university received MenB-4C. A total of 1,514 meningococcal carriage isolates were obtained from 8,905 oropharyngeal swabs from 7,001 unique participants. Whole-genome sequencing data were analyzed to understand MenB-FHbp's impact on carriage and antigen genetic diversity and distribution. Of 1,422 isolates from carriers with known vaccination status (726 [51.0%] from MenB-FHbp-vaccinated, 42 [3.0%] from MenB-4C-vaccinated, and 654 [46.0%] from unvaccinated participants), 1,406 (98.9%) had intact fHbp alleles (716 from MenB-FHbp-vaccinated participants). Of 726 isolates from MenB-FHbp-vaccinated participants, 250 (34.4%) harbored FHbp peptides that may be covered by MenB-FHbp. Genogroup B was detected in 122/1,422 (8.6%) and 112/1,422 (7.9%) isolates from MenB-FHbp-vaccinated and unvaccinated participants, respectively. FHbp subfamily and peptide distributions between MenB-FHbp-vaccinated and unvaccinated participants were not statistically different. Eighteen of 161 MenB-FHbp-vaccinated repeat carriers (11.2%) acquired a new strain containing one or more new vaccine antigen peptides during multiple rounds of sample collection, which was not statistically different (P = 0.3176) from the unvaccinated repeat carriers (1/30; 3.3%). Our findings suggest that lack of MenB vaccine impact on carriage was not due to missing the intact fHbp gene; MenB-FHbp did not affect antigen genetic diversity and distribution during the study period.IMPORTANCE The impact of serogroup B meningococcal (MenB) vaccines on carriage is not completely understood. Using whole-genome sequencing data, we assessed the diversity and distribution of MenB vaccine antigens (particularly FHbp) among 1,514 meningococcal carriage isolates recovered from vaccinated and unvaccinated students at three U.S. universities, two of which underwent MenB-FHbp mass vaccination campaigns following meningococcal disease outbreaks. The majority of carriage isolates recovered from participants harbored intact fHbp genes, about half of which were recovered from MenB-FHbp-vaccinated participants. The distribution of vaccine antigen peptides was similar among carriage isolates recovered from vaccinated and unvaccinated participants, and almost all strains recovered from repeat carriers retained the same vaccine antigen profile, suggesting insignificant vaccine selective pressure on the carriage population in these universities. |
Molecular insights into meningococcal carriage isolates from Burkina Faso 7 years after introduction of a serogroup A meningococcal conjugate vaccine.
Topaz N , Kristiansen PA , Schmink S , Congo-Ouédraogo M , Kambiré D , Mbaeyi S , Paye M , Sanou M , Sangaré L , Ouédraogo R , Wang X . Microb Genom 2020 6 (12) In 2010, Burkina Faso completed the first nationwide mass-vaccination campaign of a meningococcal A conjugate vaccine, drastically reducing the incidence of disease caused by serogroup A meningococci. Since then, other strains, such as those belonging to serogroups W, X and C, have continued to cause outbreaks within the region. A carriage study was conducted in 2016 and 2017 in the country to characterize the meningococcal strains circulating among healthy individuals following the mass-vaccination campaign. Four cross-sectional carriage evaluation rounds were conducted in two districts of Burkina Faso, Kaya and Ouahigouya. Oropharyngeal swabs were collected for the detection of Neisseria meningitidis by culture. Confirmed N. meningitidis isolates underwent whole-genome sequencing for molecular characterization. Among 13 758 participants, 1035 (7.5 %) N. meningitidis isolates were recovered. Most isolates (934/1035; 90.2 %) were non-groupable and primarily belonged to clonal complex (CC) 192 (822/934; 88 %). Groupable isolates (101/1035; 9.8 %) primarily belonged to CCs associated with recent outbreaks in the region, such as CC11 (serogroup W) and CC10217 (serogroup C); carried serogroup A isolates were not detected. Phylogenetic analysis revealed several CC11 strains circulating within the country, several of which were closely related to invasive isolates. Three sequence types (STs) were identified among eleven CC10217 carriage isolates, two of which have caused recent outbreaks in the region (ST-10217 and ST-12446). Our results show the importance of carriage studies to track the outbreak-associated strains circulating within the population in order to inform future vaccination strategies and molecular surveillance programmes. |
Meningococcal carriage 7 years after introduction of a serogroup A meningococcal conjugate vaccine in Burkina Faso: results from four cross-sectional carriage surveys.
Mbaeyi S , Sampo E , Dinanibe K , Yameogo I , Congo-Ouedraogo M , Tamboura M , Sawadogo G , Ouattara K , Sanou M , Kiemtore T , Dioma G , Sanon B , Somlare H , Kyetega A , Ba AK , Ake F , Tarbangdo F , Aboua FA , Donnou Y , Kamate I , Patel JC , Schmink S , Spiller MW , Topaz N , Novak R , Wang X , Bicaba B , Sangare L , Ouedraogo-Traore R , Kristiansen PA . Lancet Infect Dis 2020 20 (12) 1418-1425 BACKGROUND: In the first 2 years after a nationwide mass vaccination campaign of 1-29-year-olds with a meningococcal serogroup A conjugate vaccine (MenAfriVac) in Burkina Faso, carriage and disease due to serogroup A Neisseria meningitidis were nearly eliminated. We aimed to assess the long-term effect of MenAfriVac vaccination on meningococcal carriage and herd immunity. METHODS: We did four cross-sectional studies of meningococcal carriage in people aged 9 months to 36 years in two districts of Burkina Faso between May 2, 2016, and Nov 6, 2017. Demographic information and oropharyngeal swabs were collected. Meningococcal isolates were characterised using whole-genome sequencing. FINDINGS: Of 14 295 eligible people, 13 758 consented and had specimens collected and laboratory results available, 1035 of whom were meningococcal carriers. Accounting for the complex survey design, prevalence of meningococcal carriage was 7.60% (95% CI 5.67-9.52), including 6.98% (4.86-9.11) non-groupable, 0.48% (0.01-0.95) serogroup W, 0.10% (0.01-0.18) serogroup C, 0.03% (0.00-0.80) serogroup E, and 0% serogroup A. Prevalence ranged from 5.44% (95% CI 4.18-6.69) to 9.14% (6.01-12.27) by district, from 4.67% (2.71-6.64) to 11.17% (6.75-15.59) by round, and from 3.39% (0.00-8.30) to 10.43% (8.08-12.79) by age group. By clonal complex, 822 (88%) of 934 non-groupable isolates were CC192, all 83 (100%) serogroup W isolates were CC11, and nine (69%) of 13 serogroup C isolates were CC10217. INTERPRETATION: Our results show the continued effect of MenAfriVac on serogroup A meningococcal carriage, for at least 7 years, among vaccinated and unvaccinated cohorts. Carriage prevalence of epidemic-prone serogroup C CC10217 and serogroup W CC11 was low. Continued monitoring of N meningitidis carriage will be crucial to further assess the effect of MenAfriVac and inform the vaccination strategy for future multivalent meningococcal vaccines. FUNDING: Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance. |
Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities.
Joseph SJ , Topaz N , Chang HY , Whaley MJ , Vuong JT , Chen A , Hu F , Schmink SE , Jenkins LT , Rodriguez-Rivera LD , Thomas JD , Acosta AM , McNamara L , Soeters HM , Mbaeyi S , Wang X . mSphere 2020 5 (2) In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to Neisseria meningitidis serogroup B (NmB) disease outbreaks. A simultaneous carriage evaluation was also conducted at a university near one of the outbreaks, where no NmB cases were reported and no mass vaccination occurred. A total of ten cross-sectional carriage evaluation rounds were conducted, resulting in 1,514 meningococcal carriage isolates collected from 7,001 unique participants; 1,587 individuals were swabbed at multiple time points (repeat participants). All isolates underwent whole-genome sequencing. The most frequently observed clonal complexes (CC) were CC198 (27.3%), followed by CC1157 (17.4%), CC41/44 (9.8%), CC35 (7.4%), and CC32 (5.6%). Phylogenetic analysis identified carriage isolates that were highly similar to the NmB outbreak strains; comparative genomics between these outbreak and carriage isolates revealed genetic changes in virulence genes. Among repeat participants, 348 individuals carried meningococcal bacteria during at least one carriage evaluation round; 50.3% retained N. meningitidis carriage of a strain with the same sequence type (ST) and CC across rounds, 44.3% only carried N. meningitidis in one round, and 5.4% acquired a new N. meningitidis strain between rounds. Recombination, point mutations, deletions, and simple sequence repeats were the most frequent genetic mechanisms found in isolates collected from hosts carrying a strain of the same ST and CC across rounds. Our findings provide insight on the dynamics of meningococcal carriage among a population that is at higher risk for invasive meningococcal disease than the general population.IMPORTANCE U.S. university students are at a higher risk of invasive meningococcal disease than the general population. The responsible pathogen, Neisseria meningitidis, can be carried asymptomatically in the oropharynx; the dynamics of meningococcal carriage and the genetic features that distinguish carriage versus disease states are not completely understood. Through our analyses, we aimed to provide data to address these topics. We whole-genome sequenced 1,514 meningococcal carriage isolates from individuals at three U.S. universities, two of which underwent mass vaccination campaigns following recent meningococcal outbreaks. We describe the within-host genetic changes among individuals carrying a strain with the same molecular type over time, the primary strains being carried in this population, and the genetic differences between closely related outbreak and carriage strains. Our results provide detailed information on the dynamics of meningococcal carriage and the genetic differences in carriage and outbreak strains, which can inform future efforts to reduce the incidence of invasive meningococcal disease. |
Genomic characterization of Haemophilus influenzae: a focus on the capsule locus.
Potts CC , Topaz N , Rodriguez-Rivera LD , Hu F , Chang HY , Whaley MJ , Schmink S , Retchless AC , Chen A , Ramos E , Doho GH , Wang X . BMC Genomics 2019 20 (1) 733 BACKGROUND: Haemophilus influenzae (Hi) can cause invasive diseases such as meningitis, pneumonia, or sepsis. Typeable Hi includes six serotypes (a through f), each expressing a unique capsular polysaccharide. The capsule, encoded by the genes within the capsule locus, is a major virulence factor of typeable Hi. Non-typeable (NTHi) does not express capsule and is associated with invasive and non-invasive diseases. METHODS: A total of 395 typeable and 293 NTHi isolates were characterized by whole genome sequencing (WGS). Phylogenetic analysis and multilocus sequence typing were used to characterize the overall genetic diversity. Pair-wise comparisons were used to evaluate the capsule loci. A WGS serotyping method was developed to predict the Hi serotype. WGS serotyping results were compared to slide agglutination (SAST) or real-time PCR (rt-PCR) serotyping. RESULTS: Isolates of each Hi serotype clustered into one or two subclades, with each subclade being associated with a distinct sequence type (ST). NTHi isolates were genetically diverse, with seven subclades and 125 STs being detected. Regions I and III of the capsule locus were conserved among the six serotypes (>/=82% nucleotide identity). In contrast, genes in Region II were less conserved, with only six gene pairs from all serotypes showing >/=56% nucleotide identity. The WGS serotyping method was 99.9% concordant with SAST and 100% concordant with rt-PCR in determining the Hi serotype. CONCLUSIONS: Genomic analysis revealed a higher degree of genetic diversity among NTHi compared to typeable Hi. The WGS serotyping method accurately predicted the Hi capsule type and can serve as an alternative method for Hi serotyping. |
Population structure of invasive Neisseria meningitidis in the United States, 2011-15.
Potts CC , Joseph SJ , Chang HY , Chen A , Vuong J , Hu F , Jenkins LT , Schmink S , Blain A , MacNeil JR , Harrison LH , Wang X . J Infect 2018 77 (5) 427-434 OBJECTIVES: Meningococcal conjugate vaccines (MenACWY) were licensed in the United States in 2005. We assessed the population structure of invasive Neisseria meningitidis (Nm) ten years after recommended use of MenACWY among adolescents. METHODS: Meningococcal isolates obtained through Active Bacterial Core surveillance (ABCs) from 2000-05, 2006-10, and 2011-15 underwent whole genome or Sanger sequencing. Genome phylogenies were completed using maximum likelihood methods; and distribution of multilocus sequence typing (MLST) sequence type (ST) and clonal complex (CC), and PorA and FetA types were assessed. RESULTS: Prevalent serogroups (B, C, Y and W), CCs, and PorA and FetA types were detected in all three time periods, but dynamic changes were observed. The proportion of serogroup W CC11 isolates increased in 2011-15 and were most related to South American strains. Changes in CC distribution were also observed in serogroup C and serogroup Y. Phylogenetic analysis showed that U.S. serogroup W CC11s are closely related to a subset of U.S. serogroup C isolates; combined global analysis demonstrated that some CCs, including CC11, exhibit regional clustering. CONCLUSIONS: Overall, the Nm population structure has remained stable after MenACWY introduction. Dynamic changes in genotypes, unlikely related to vaccination, also occurred, highlighting the need for continued whole genome-based surveillance. |
Effect of breastfeeding and additional household children on cytomegalovirus seroprevalence among U.S. children 1 to 5 years of age
Schmink S , Kruszon-Moran D , Dollard SC , Lanzieri TM . Clin Vaccine Immunol 2017 24 (11) Congenital cytomegalovirus (CMV) infection may occur as a consequence of primary or nonprimary maternal infection during pregnancy (1). Postnatal CMV infection may develop in up to 40% of infants who are fed breast milk for ≥1 month by a CMV-seropositive mother (1). Further spread of CMV may result from child-to-child transmission in the household or day care center (2). | In the 2011–2012 National Health and Nutrition Examination Survey (NHANES), overall CMV IgG seroprevalence among U.S. children 1 to 5 years of age was 21%, with a significant increase among those who were 5 years old (31%) compared to those who were 1 year old (12%) (3). CMV seroprevalence was significantly higher among non-Hispanic black (25%) and Hispanic (31%) children than among non-Hispanic white children (11%) and among children living below versus at or above the poverty line (31% versus 15%) (3). Here, we describe additional results for the history of breastfeeding and number of household children ≤5 years old. | NHANES, a nationally representative cross-sectional survey of the civilian noninstitutionalized U.S. population (4), included CMV antibody testing for 699 (62%) of the 1,135 children who were 1 to 5 years old examined in 2011 to 2012. To assess independent predictors of CMV IgG seroprevalence, we repeated the analysis as described in the previous report (3) and performed additional logistic-regression modeling on 636 children with complete data (out of the 682 children in the survey born in the 50 U.S. states and the District of Columbia). We performed all analyses using SUDAAN version 9.0 (Research Triangle Institute, Research Triangle Park, NC); results for which the P value was <0.05 were considered statistically significant. |
Meningococcal Carriage Following a University Serogroup B Meningococcal Disease Outbreak and Vaccination Campaign with MenB-4C and MenB-FHbp - Oregon, 2015-2016.
McNamara LA , Thomas JD , MacNeil J , Chang HY , Day M , Fisher E , Martin S , Poissant T , Schmink SE , Steward-Clark E , Jenkins LT , Wang X , Acosta A . J Infect Dis 2017 216 (9) 1130-1140 Background: Limited data exist on the impact of the serogroup B meningococcal (MenB) vaccines MenB-FHbp and MenB-4C on meningococcal carriage and herd protection. We therefore assessed meningococcal carriage following a MenB vaccination campaign in response to a university serogroup B meningococcal disease outbreak in 2015. Methods: A convenience sample of students recommended for vaccination provided oropharyngeal swabs and completed questionnaires during four carriage surveys over 11 months. Isolates were tested by real-time PCR, slide agglutination, and whole genome sequencing. Vaccination history was verified via university records and the state immunization registry. Results: A total of 4,225 oropharyngeal swabs were analyzed from 3,802 unique participants. Total meningococcal and genotypically serogroup B carriage prevalence among sampled students were stable at 11-17% and 1.2%-2.4% during each round, respectively; no participants carried the outbreak strain. Neither 1-3 doses of MenB-FHbp nor 1-2 doses of MenB-4C was associated with decreased total or serogroup B carriage prevalence. Conclusions: While few participants completed the full MenB vaccination series, limiting analytic power, these data suggest that MenB-FHbp and MenB-4C do not have a large, rapid impact on meningococcal carriage and are unlikely to provide herd protection in the context of an outbreak response. |
Changes in the Population Structure of Invasive Neisseria meningitidis in the United States After Quadrivalent Meningococcal Conjugate Vaccine Licensure.
Wang X , Shutt KA , Vuong JT , Cohn A , MacNeil J , Schmink S , Plikaytis B , Messonnier NE , Harrison LH , Clark TA , Mayer LW . J Infect Dis 2015 211 (12) 1887-94 BACKGROUND: Meningococcal conjugate vaccines (MenACWY) against serogroups A, C, W and Y are recommended for routine use in adolescents aged 11-18 years. Impact of these vaccines on meningococcal population structure in the US remained to be evaluated. METHODS: Meningococcal isolates from 2006-10 (post-MenACWY) collected through Active Bacterial Core surveillance (ABCs) were characterized; serogroup distribution and molecular features of these isolates were compared to previously published data on ABCs isolates from 2000-05 (pre-MenACWY). p values were generated using chi-squared statistics and exact methods. RESULTS: There was a significant change (p<0.05) in serogroup distribution among all age groups between the two periods. A small proportion of isolates has shown evidence of capsular switching in both periods. Between the two periods, significant changes were observed in the distribution of PorA, FetA, and strain genotypes among vaccine and non-vaccine serogroups. CONCLUSIONS: The population structure of U.S. meningococcal isolates is dynamic; some changes occurred over time but the basic structure remained. Vaccine-induced serogroup replacement was not observed, although a small proportion of isolates had undergone capsule switching possibly driven by non-vaccine mediated selection. Changes in the distribution of molecular features are likely due to horizontal gene transfer and changes in serogroup distribution. |
Meningococcal carriage among Georgia and Maryland high school students
Harrison LH , Shutt KA , Arnold KE , Stern EJ , Pondo T , Kiehlbauch JA , Myers RA , Hollick RA , Schmink S , Vello M , Stephens DS , Messonnier NE , Mayer L , Clark TA . J Infect Dis 2014 211 (11) 1761-8 BACKGROUND: Meningococcal disease incidence in the U.S. is at an all-time low. In a previous study of Georgia high school students, meningococcal carriage prevalence was 7%. The purpose of this study was to measure the impact of a meningococcal conjugate vaccine on serogroup Y meningococcal carriage and to define the dynamics of carriage in high school students. METHODS: This was a prospective cohort study at 8 high schools, 4 each in Maryland and Georgia during a school year. In each state, 2 high schools were randomized for participating students to receive MCV4-DT at the beginning of the study and 2 at the end. Oropharyngeal swab cultures for meningococcal carriage were performed three times during the school year. RESULTS: Among 3,311 students, prevalence of meningococcal carriage was 3.21%- 4.01%. Phenotypically non-groupable strains accounted for 88% of carriage isolates. There were only 5 observed acquisitions of serogroup Y strains during the study; therefore, the impact of MCV4-DT on meningococcal carriage could not be determined. CONCLUSIONS: Meningococcal carriage rates in U.S. high school students were lower than expected and the vast majority of strains did not express capsule. These findings may help explain the historically low incidence of meningococcal disease in the U.S. |
Prolonged university outbreak of meningococcal disease associated with a serogroup B strain rarely seen in the US
Mandal S , Wu HM , Macneil JR , Machesky K , Garcia J , Plikaytis BD , Quinn K , King L , Schmink SE , Wang X , Mayer LW , Clark TA , Gaskell JR , Messonnier NE , Diorio M , Cohn AC . Clin Infect Dis 2013 57 (3) 344-8 BACKGROUND: College students living in residential halls are at increased risk of meningococcal disease. Unlike for serogroups prevented by quadrivalent meningococcal vaccines, public health response to outbreaks of serogroup B meningococcal disease is limited by lack of a US licensed vaccine. METHODS: In March 2010 we investigated a prolonged outbreak of serogroup B disease associated with a university. In addition to case ascertainment, molecular typing of isolates was performed to characterize the outbreak. We conducted a matched case-control study to examine risk factors for serogroup B disease. Five controls per case, matched by college year, were randomly selected. Participants completed a risk factor questionnaire. Data were analyzed using conditional logistic regression. RESULTS: Between January 2008 and November 2010, we identified 13 meningococcal disease cases (seven confirmed, four probable, and two suspected) among university students (ten) or university-linked persons (three). One student died. Ten cases were determined to be serogroup B. Isolates from six confirmed cases had an indistinguishable pulse-field gel electrophoresis pattern and belonged to sequence type ST-269, clonal complex 269. Factors significantly associated with disease were Greek Society membership (matched odds ratio [mOR] 15.0; p=0.03), >1 kissing partner (mOR 13.7; p=0.03) and attending bars (mOR 8.1; p=0.04). CONCLUSIONS: The outbreak was associated with a novel serogroup B strain (CC269) and risk factors indicative of increased social mixing. Control measures were appropriate but limited by lack of vaccine. Understanding serogroup B transmission in college and other settings will help inform use of serogroup B vaccines currently under consideration for licensure. |
sodC-based real-time PCR for detection of Neisseria meningitidis.
Dolan Thomas J , Hatcher CP , Satterfield DA , Theodore MJ , Bach MC , Linscott KB , Zhao X , Wang X , Mair R , Schmink S , Arnold KE , Stephens DS , Harrison LH , Hollick RA , Andrade AL , Lamaro-Cardoso J , de Lemos AP , Gritzfeld J , Gordon S , Soysal A , Bakir M , Sharma D , Jain S , Satola SW , Messonnier NE , Mayer LW . PLoS One 2011 6 (5) e19361 Real-time PCR (rt-PCR) is a widely used molecular method for detection of Neisseria meningitidis (Nm). Several rt-PCR assays for Nm target the capsule transport gene, ctrA. However, over 16% of meningococcal carriage isolates lack ctrA, rendering this target gene ineffective at identification of this sub-population of meningococcal isolates. The Cu-Zn superoxide dismutase gene, sodC, is found in Nm but not in other Neisseria species. To better identify Nm, regardless of capsule genotype or expression status, a sodC-based TaqMan rt-PCR assay was developed and validated. Standard curves revealed an average lower limit of detection of 73 genomes per reaction at cycle threshold (C(t)) value of 35, with 100% average reaction efficiency and an average R(2) of 0.9925. 99.7% (624/626) of Nm isolates tested were sodC-positive, with a range of average C(t) values from 13.0 to 29.5. The mean sodC C(t) value of these Nm isolates was 17.6+/-2.2 (+/-SD). Of the 626 Nm tested, 178 were nongroupable (NG) ctrA-negative Nm isolates, and 98.9% (176/178) of these were detected by sodC rt-PCR. The assay was 100% specific, with all 244 non-Nm isolates testing negative. Of 157 clinical specimens tested, sodC detected 25/157 Nm or 4 additional specimens compared to ctrA and 24 more than culture. Among 582 carriage specimens, sodC detected Nm in 1 more than ctrA and in 4 more than culture. This sodC rt-PCR assay is a highly sensitive and specific method for detection of Nm, especially in carriage studies where many meningococcal isolates lack capsule genes. |
Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States.
Wang X , Cohn A , Comanducci M , Andrew L , Zhao X , Macneil JR , Schmink S , Muzzi A , Bambini S , Rappuoli R , Pizza M , Murphy E , Hoiseth SK , Jansen KU , Anderson AS , Harrison LH , Clark TA , Messonnier NE , Mayer LW . Vaccine 2011 29 4739-44 Neisseria meningitidis (Nm) serogroups B, C and Y are the major causes of meningococcal diseases in the United States. NmB accounts for approximately 1/3 of the disease but no licensed vaccine is yet available. Two candidate vaccines are being developed specifically to target NmB, but may also provide protection against other serogroups. To assess the potential impact of these vaccines on NmB and other serogroups causing disease in the US, we determined the prevalence, genetic diversity and epidemiological characteristics of three candidate antigen genes in Nm isolates collected through Active Bacterial Core surveillance (ABCs), a population-based active surveillance program. fHbp was detected in all NmB, NmY and NmW135 isolates. Eleven NmC isolates contain fHbp with a single base-pair deletion creating a frame shift in the C-terminal region. Among NmB, 59% were fHbp subfamily/variant B/v1 and 41% A/v2-3. Among NmC and NmY, 39% and 3% were B/v1, respectively. nadA was detected in 39% of NmB, 61% of NmC and 4% of NmY. Among isolates tested, nhbA was present in all NmB and 96% of non-B. For the subset of strains sequenced for NadA and NhbA, pairwise identity was greater than 93% and 78%, respectively. The proportion of FHbp subfamily/variant was different between ABCs site and year, but no linear temporal trend was observed. Although assessment of the vaccine coverage also requires understanding of the antigen expression and the ability to induce bactericidal activity, our finding that all isolates contain one or more antigen genes suggests these vaccines may protect against multiple Nm serogroups. |
Early estimate of the effectiveness of quadrivalent meningococcal conjugate vaccine
MacNeil JR , Cohn AC , Zell ER , Schmink S , Miller E , Clark T , Messonnier NE . Pediatr Infect Dis J 2011 30 (6) 451-5 BACKGROUND: In January 2005, a quadrivalent meningococcal conjugate vaccine (MenACWYD) was licensed for use in the United States. The Advisory Committee on Immunization Practices recommends MenACWYD for all adolescents aged 11 to 18 years and others at increased risk for meningococcal disease. METHODS: Reports of breakthrough meningococcal disease after vaccination with MenACWYD were collected. A simulation approach was used to estimate the expected number of cases in vaccinated persons. RESULTS: Between 2005 and 2008, 14 breakthrough cases, including 3 deaths occurred. At a vaccine effectiveness (VE) of 90%, 7 breakthrough cases would be expected (range, 1-17); at VE of 85%, 11 cases (range, 2-30); at VE of 80%, 15 cases (range, 5-28); and at VE of 75%, 18 cases (range, 7-32) would be expected. The probability of the ≥14 observed cases occurring was 2.9% at VE of 90%, 29.3% at VE of 85%, 66.1% at VE of 80%, and 83.0% at VE of 75%. CONCLUSIONS: This report provides an early estimate of MenACWYD effectiveness within 3 to 4 years after vaccination, and suggests that MenACWYD effectiveness is 80% to 85%, similar to the VE reported for meningococcal polysaccharide vaccine. |
Population structure and capsular switching of invasive neisseria meningitidis isolates in the pre-meningococcal conjugate vaccine era-United States, 2000-2005
Harrison LH , Shutt KA , Schmink SE , Marsh JW , Harcourt BH , Wang X , Whitney AM , Stephens DS , Cohn AA , Messonnier NE , Mayer LW . J Infect Dis 2010 201 (8) 1208-24 BACKGROUND: A quadrivalent meningococcal conjugate vaccine (MCV4) was licensed in the United States in 2005; no serogroup B vaccine is available. Neisseria meningitidis changes its capsular phenotype through capsular switching, which has implications for vaccines that do not protect against all serogroups. METHODS: Meningococcal isolates from 10 Active Bacterial Core surveillance sites from 2000 through 2005 were analyzed to identify changes occurring after MCV4 licensure. Isolates were characterized by multilocus sequence typing (MLST) and outer membrane protein gene sequencing. Isolates expressing capsular polysaccharide different from that associated with the MLST lineage were considered to demonstrate capsular switching. RESULTS: Among 1160 isolates, the most common genetic lineages were the sequence type (ST)-23, ST-32, ST-11, and ST-41/44 clonal complexes. Of serogroup B and Y isolates, 8 (1.5%) and 3 (0.9%), respectively, demonstrated capsular switching, compared with 36 (12.9%) for serogroup C ([Formula: see text]); most serogroup C switches were from virulent serogroup B and/or serogroup Y lineages. CONCLUSIONS: A limited number of genetic lineages caused the majority of invasive meningococcal infections. A substantial proportion of isolates had evidence of capsular switching. The high prevalence of capsular switching requires surveillance to detect changes in the meningococcal population structure that may affect the effectiveness of meningococcal vaccines. |
Meningococcus genome informatics platform: a system for analyzing multilocus sequence typing data
Katz LS , Bolen CR , Harcourt BH , Schmink S , Wang X , Kislyuk A , Taylor RT , Mayer LW , Jordan IK . Nucleic Acids Res 2009 37 W606-11 The Meningococcus Genome Informatics Platform (MGIP) is a suite of computational tools for the analysis of multilocus sequence typing (MLST) data, at http://mgip.biology.gatech.edu. MLST is used to generate allelic profiles to characterize strains of Neisseria meningitidis, a major cause of bacterial meningitis worldwide. Neisseria meningitidis strains are characterized with MLST as specific sequence types (ST) and clonal complexes (CC) based on the DNA sequences at defined loci. These data are vital to molecular epidemiology studies of N. meningitidis, including outbreak investigations and population biology. MGIP analyzes DNA sequence trace files, returns individual allele calls and characterizes the STs and CCs. MGIP represents a substantial advance over existing software in several respects: (i) ease of use-MGIP is user friendly, intuitive and thoroughly documented; (ii) flexibility--because MGIP is a website, it is compatible with any computer with an internet connection, can be used from any geographic location, and there is no installation; (iii) speed--MGIP takes just over one minute to process a set of 96 trace files; and (iv) expandability--MGIP has the potential to expand to more loci than those used in MLST and even to other bacterial species. |
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