Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-9 (of 9 Records) |
Query Trace: McNamara Lucy A[original query] |
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Using Neisseria meningitidis genomic diversity to inform outbreak strain identification.
Retchless AC , Chen A , Chang HY , Blain AE , McNamara LA , Mustapha MM , Harrison LH , Wang X . PLoS Pathog 2021 17 (5) e1009586 Meningococcal disease is a life-threatening illness caused by the human-restricted bacterium Neisseria meningitidis. Outbreaks in the USA involve at least two cases in an organization or community caused by the same serogroup within three months. Genome comparisons, including phylogenetic analysis and quantification of genome distances can provide confirmatory evidence of pathogen transmission during an outbreak. Interpreting genome distances depends on understanding their distribution both among isolates from outbreaks and among those not from outbreaks. Here, we identify outbreak strains based on phylogenetic relationships among 141 N. meningitidis isolates collected from 28 outbreaks in the USA during 2010-2017 and 1516 non-outbreak isolates collected through contemporaneous meningococcal surveillance. We show that genome distance thresholds based on the maximum SNPs and allele distances among isolates in the phylogenetically defined outbreak strains are sufficient to separate most pairs of non-outbreak isolates into separate strains. Non-outbreak isolate pairs that could not be distinguished from each other based on genetic distances were concentrated in the clonal complexes CC11, CC103, and CC32. Within each of these clonal complexes, phylodynamic analysis identified a group of isolates with extremely low diversity, collected over several years and multiple states. Clusters of isolates with low genetic diversity could indicate increased pathogen transmission, potentially resulting in local outbreaks or nationwide clonal expansions. |
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. |
Acquisition of ciprofloxacin resistance among an expanding clade of β-lactamase positive, serogroup Y Neisseria meningitidis in the United States.
Potts CC , Retchless AC , McNamara LA , Marasini D , Reese N , Swint S , Hu F , Sharma S , Blain AE , Lonsway D , Karlsson M , Hariri S , Fox LM , Wang X . Clin Infect Dis 2021 73 (7) 1185-1193 BACKGROUND: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 β-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA), have been recently reported in the USA. METHODS: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011-February 2020 to identify IMD cases caused by strains with blaROB-1 or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. RESULTS: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1-containing US isolates with wild-type gyrA were identified from 2013-2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from six other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to six CCs and contained 10 unique gyrA alleles; seven were similar or identical to alleles from N. lactamica or N. gonorrhoeae. CONCLUSIONS: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the USA. The emerging dual-resistance is due to acquisition of ciprofloxacin resistance by β-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread. |
Detection of Ciprofloxacin-Resistant, β-Lactamase-Producing Neisseria meningitidis Serogroup Y Isolates - United States, 2019-2020.
McNamara LA , Potts C , Blain AE , Retchless AC , Reese N , Swint S , Lonsway D , Karlsson M , Lunquest K , Sweitzer JJ , Wang X , Hariri S , Fox LM . MMWR Morb Mortal Wkly Rep 2020 69 (24) 735-739 Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis. Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts. Historically, N. meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin. This report describes detection of penicillin-resistant and ciprofloxacin-resistant N. meningitidis serogroup Y (NmY) isolates in the United States. NmY isolates containing a blaROB-1 beta-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020. Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA). Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013. Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin. Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations. |
Coronavirus Disease 2019 in Children - United States, February 12-April 2, 2020.
CDC COVID-19 Response Team , Bialek Stephanie , Gierke Ryan , Hughes Michelle , McNamara Lucy A , Pilishvili Tamara , Skoff Tami . MMWR Morb Mortal Wkly Rep 2020 69 (14) 422-426 As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States (1,2). In the United States, 22% of the population is made up of infants, children, and adolescents aged <18 years (children) (3). Data from China suggest that pediatric COVID-19 cases might be less severe than cases in adults and that children might experience different symptoms than do adults (4,5); however, disease characteristics among pediatric patients in the United States have not been described. Data from 149,760 laboratory-confirmed COVID-19 cases in the United States occurring during February 12-April 2, 2020 were analyzed. Among 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children aged <18 years. Data were available for a small proportion of patients on many important variables, including symptoms (9.4%), underlying conditions (13%), and hospitalization status (33%). Among those with available information, 73% of pediatric patients had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18-64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18-64 years (10%) or those with known hospitalization status (33%). Three deaths were reported among the pediatric cases included in this analysis. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults (4). Whereas most COVID-19 cases in children are not severe, serious COVID-19 illness resulting in hospitalization still occurs in this age group. Social distancing and everyday preventive behaviors remain important for all age groups as patients with less serious illness and those without symptoms likely play an important role in disease transmission (6,7). |
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. |
Distinct evolutionary patterns of Neisseria meningitidis serogroup B disease outbreaks at two universities in the USA.
Hao L , Holden MTG , Wang X , Andrew L , Wellnitz S , Hu F , Whaley M , Sammons S , Knipe K , Frace M , McNamara LA , Liberator P , Anderson AS . Microb Genom 2018 4 (4) Neisseria meningitidis serogroup B (MnB) was responsible for two independent meningococcal disease outbreaks at universities in the USA during 2013. The first at University A in New Jersey included nine confirmed cases reported between March 2013 and March 2014. The second outbreak occurred at University B in California, with four confirmed cases during November 2013. The public health response to these outbreaks included the approval and deployment of a serogroup B meningococcal vaccine that was not yet licensed in the USA. This study investigated the use of whole-genome sequencing(WGS) to examine the genetic profile of the disease-causing outbreak isolates at each university. Comparative WGS revealed differences in evolutionary patterns between the two disease outbreaks. The University A outbreak isolates were very closely related, with differences primarily attributed to single nucleotide polymorphisms/insertion-deletion (SNP/indel) events. In contrast, the University B outbreak isolates segregated into two phylogenetic clades, differing in large part due to recombination events covering extensive regions (>30 kb) of the genome including virulence factors. This high-resolution comparison of two meningococcal disease outbreaks further demonstrates the genetic complexity of meningococcal bacteria as related to evolution and disease virulence. |
Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt-Liberia, 2017: an epidemiological and laboratory investigation.
Bozio CH , Vuong J , Dokubo EK , Fallah MP , McNamara LA , Potts CC , Doedeh J , Gbanya M , Retchless AC , Patel JC , Clark TA , Kohar H , Nagbe T , Clement P , Katawera V , Mahmoud N , Djingarey HM , Perrocheau A , Naidoo D , Stone M , George RN , Williams D , Gasasira A , Nyenswah T , Wang X , Fox LM . Lancet Infect Dis 2018 18 (12) 1360-1367 BACKGROUND: On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. METHODS: We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. FINDINGS: 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. INTERPRETATION: This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt. FUNDING: US Global Health Security. |
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. |
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