Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-23 (of 23 Records) |
Query Trace: Chang HY[original query] |
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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. |
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. |
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. |
Meningococcal carriage in young adults six years after meningococcal C conjugate (MCC) vaccine catch-up campaign in Salvador, Brazil.
Ferreira VM , Ferreira IE , Chang HY , Nunes Ampb , Topaz N , Pimentel ER , Moura Arss , Ribeiro GS , Feitosa CA , Reis MG , Wang X , Campos LC . Vaccine 2020 38 (14) 2995-3002 ![]() Meningococcal carriage studies are important to improve the knowledge of disease epidemiology as well as to support appropriate vaccination strategies. We conducted a cross-sectional study to determine the prevalence and genotypic characteristics of meningococci collected from young adults in Salvador, Brazil six years after a meningococcal C conjugate vaccine catch-up campaign. From August through November 2016, oropharyngeal swabs were collected from 407 students aged 1824 years attending a private college in Salvador, Brazil. Neisseria meningitidis was identified by standard microbiology methods and real time PCR. Genetic characteristics of meningococci were assessed by rt-PCR and/or whole genome sequencing. We also investigated potential factors associated with carriage. N. meningitidis was detectable in 50 students, 39 by both culture and rt-PCR, 7 by culture alone and 4 by rt-PCR alone, resulting in an overall meningococcal carriage prevalence of 12.3% (50/407). Carriage was independently associated with male sex (adjusted PR: 1.97; 95% CI: 1.12-3.46; p = 0.018) and attending bars or parties at least once per month (aPR: 3.31; 95% CI: 1.49-7.38; p = 0.003). Molecular tests identified 92% (46/50) N. meningitidis as non-groupable, of which 63% (29/46) had the capsule null genotype; 14 NG isolates contained disrupted capsule backbones and belonged to the following genogroups: 7 B, 3 Z, 3 E and 1 W. One isolate belonged to genogroup C tested only by PCR; 3 isolates contained a complete B capsule backbones, 2 of which were determined to be NG by slide agglutination serogrouping. While most meningococcal carriage isolates were non-groupable, there was a high degree of genetic diversity present in the collection, as evidenced by 25 unique STs being detected. The carriage prevalence of meningococcal serogroup C was low among young adults. Continuous vaccination is important to maintain reduced meningococcal carriage and transmission, inducing herd protection. |
A New Sequence Type of Neisseria meningitidis Serogroup C Associated With a 2016 Meningitis Outbreak in Mali.
Sanogo YO , Guindo I , Diarra S , Retchless AC , Abdou M , Coulibaly S , Maiga MF , Coumare M , Diarra B , Chen A , Chang HY , Vuong JT , Acosta AM , Sow S , Novak RT , Wang X . J Infect Dis 2019 220 S190-s197 ![]() ![]() In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouelessebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region. |
Epidemiology of Bacterial Meningitis in the Nine Years Since Meningococcal Serogroup A Conjugate Vaccine Introduction, Niger, 2010-2018.
Sidikou F , Potts CC , Zaneidou M , Mbaeyi S , Kadade G , Paye MF , Ousmane S , Issaka B , Chen A , Chang HY , Issifou D , Lingani C , Sakande S , Bienvenu B , Mahamane AE , Diallo AO , Moussa A , Seidou I , Abdou M , Sidiki A , Garba O , Haladou S , Testa J , Obama Nse R , Mainassara HB , Wang X . J Infect Dis 2019 220 S206-s215 ![]() ![]() BACKGROUND: In 2010, Niger and other meningitis belt countries introduced a meningococcal serogroup A conjugate vaccine (MACV). We describe the epidemiology of bacterial meningitis in Niger from 2010 to 2018. METHODS: Suspected and confirmed meningitis cases from January 1, 2010 to July 15, 2018 were obtained from national aggregate and laboratory surveillance. Cerebrospinal fluid specimens were analyzed by culture and/or polymerase chain reaction. Annual incidence was calculated as cases per 100 000 population. Selected isolates obtained during 2016-2017 were characterized by whole-genome sequencing. RESULTS: Of the 21 142 suspected cases of meningitis, 5590 were confirmed: Neisseria meningitidis ([Nm] 85%), Streptococcus pneumoniae ([Sp] 13%), and Haemophilus influenzae ([Hi] 2%). No NmA cases occurred after 2011. Annual incidence per 100 000 population was more dynamic for Nm (0.06-7.71) than for Sp (0.18-0.70) and Hi (0.01-0.23). The predominant Nm serogroups varied over time (NmW in 2010-2011, NmC in 2015-2018, and both NmC and NmX in 2017-2018). Meningococcal meningitis incidence was highest in the regions of Niamey, Tillabery, Dosso, Tahoua, and Maradi. The NmW isolates were clonal complex (CC)11, NmX were CC181, and NmC were CC10217. CONCLUSIONS: After MACV introduction, we observed an absence of NmA, the emergence and continuing burden of NmC, and an increase in NmX. Niger's dynamic Nm serogroup distribution highlights the need for strong surveillance programs to inform vaccine policy. |
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. |
Distribution of Neisseria meningitidis serogroup B (NmB) vaccine antigens in meningococcal disease causing isolates in the United States during 2009-2014, prior to NmB vaccine licensure.
Chang HY , Vuong J , Hu F , Liberator P , Chen A , Kretz CB , Blain A , Hao L , Retchless AC , Whaley MJ , Anderson AS , Wang X . J Infect 2019 79 (5) 426-434 ![]() OBJECTIVES: Two Neisseria meningitidis serogroup B (NmB) vaccines are licensed in the United States. To estimate their potential coverage, we examined the vaccine antigen diversity among meningococcal isolates prior to vaccine licensure. METHODS: NmB vaccine antigen genes of invasive isolates collected in the U.S. from 2009-2014 were characterized by Sanger or whole-genome sequencing. RESULTS: During 2009-2014, the predominant antigen types have remained similar to those reported in 2000-2008 for NmB and 2006-2008 for NmC, NmY, with the emergence of a few new types. FHbp of subfamily B or variant 1 (B/v1) remained prevalent among NmB whereas FHbp of subfamily A or variant 2 and 3 (A/v2-3) were more prevalent among non-NmB. FHbp peptide 1 (B24/1.1) remains the most prevalent type in NmB. Full-length NadA peptide was detected in 26% of isolates, primarily in NmB and NmW. The greatest diversity of NhbA peptides was detected among NmB, with p0005 as the most prevalent type. CONCLUSIONS: The prevalence and diversity of the NmB vaccine antigens have remained stable with common antigen types persisting over time. The data collected prior to NmB vaccine licensure provide the baseline to understand the potential impact of NmB vaccines on antigen diversity and strain coverage. |
Whole genome sequencing for investigations of meningococcal outbreaks in the United States: a retrospective analysis.
Whaley MJ , Joseph SJ , Retchless AC , Kretz CB , Blain A , Hu F , Chang HY , Mbaeyi SA , MacNeil JR , Read TD , Wang X . Sci Rep 2018 8 (1) 15803 ![]() ![]() ![]() Although rare in the U.S., outbreaks due to Neisseria meningitidis do occur. Rapid, early outbreak detection is important for timely public health response. In this study, we characterized U.S. meningococcal isolates (N = 201) from 15 epidemiologically defined outbreaks (2009-2015) along with temporally and geographically matched sporadic isolates using multilocus sequence typing, pulsed-field gel electrophoresis (PFGE), and six whole genome sequencing (WGS) based methods. Recombination-corrected maximum likelihood (ML) and Bayesian phylogenies were reconstructed to identify genetically related outbreak isolates. All WGS analysis methods showed high degree of agreement and distinguished isolates with similar or indistinguishable PFGE patterns, or the same strain genotype. Ten outbreaks were caused by a single strain; 5 were due to multiple strains. Five sporadic isolates were phylogenetically related to 2 outbreaks. Analysis of 9 outbreaks using timed phylogenies identified the possible origin and estimated the approximate time that the most recent common ancestor emerged for outbreaks analyzed. U.S. meningococcal outbreaks were caused by single- or multiple-strain introduction, with organizational outbreaks mainly caused by a clonal strain and community outbreaks by divergent strains. WGS can infer linkage of meningococcal cases when epidemiological links are uncertain. Accurate identification of outbreak-associated cases requires both WGS typing and epidemiological data. |
Seroepidemiology of Hepatitis Viruses and Hepatitis B Genotypes of Female Marriage Immigrants in Korea.
Kwon JC , Chang HY , Kwon OY , Park JH , Oh IS , Kim HJ , Lee JH , Roh HJ , Lee HW . Yonsei Med J 2018 59 (9) 1072-1078 ![]() PURPOSE: The Korean society has moved rapidly toward becoming a multicultural society. This study aimed to estimate the seroprevalence of hepatitis viruses and investigate hepatitis B virus (HBV) genotypic diversity in female marriage immigrants. MATERIALS AND METHODS: Screening program was conducted at support centers for multicultural families in 21 administrative districts in Korea between July 2011 and January 2017. A total of 963 female marriage immigrants were included in this study. Blood samples were tested for hepatitis viral markers and HBV genotype. RESULTS: Subjects' median age was 33 years (20-40 years), and they originated from nine countries including Vietnam (n=422, 43.8%), China (n=311, 32.3%), the Philippines (n=85, 8.8%), Cambodia (n=58, 6.0%), and Japan (n=39, 4.0%). About 30% (n=288) of subjects required hepatitis A vaccination. HBsAg positive rate was 5.4% (n=52). Positive HBsAg results were the highest in subjects from Southeast Asia (6.6%, n=38). Anti-HBs positive rate was 60.4% (n=582). About 34% (n=329) of subjects who were negative for anti-HBs and HBsAg required HBV vaccinations. Genotypes B and C were found in 54.6% (n=12) and 45.4% (n=10) of the 22 subjects with HBV, in whom genotypes were tested. Eight (0.8%) subjects were positive for anti-HCV. Positive anti-HCV results were the highest in subjects from Central Asia (7.9%, n=3). CONCLUSION: Testing for hepatitis viral marker (hepatitis A virus IgG and HBsAg/anti-HBs) is needed for female marriage immigrants. Especially, HBV genotype B is different from genotype C of Koreans. Therefore, interest and attention to vaccination programs for female marriage immigrants are necessary for both clinicians and public health institutes. |
BMScan: using whole genome similarity to rapidly and accurately identify bacterial meningitis causing species.
Topaz N , Boxrud D , Retchless AC , Nichols M , Chang HY , Hu F , Wang X . BMC Infect Dis 2018 18 (1) 405 ![]() ![]() BACKGROUND: Bacterial meningitis is a life-threatening infection that remains a public health concern. Bacterial meningitis is commonly caused by the following species: Neisseria meningitidis, Streptococcus pneumoniae, Listeria monocytogenes, Haemophilus influenzae and Escherichia coli. Here, we describe BMScan (Bacterial Meningitis Scan), a whole-genome analysis tool for the species identification of bacterial meningitis-causing and closely-related pathogens, an essential step for case management and disease surveillance. BMScan relies on a reference collection that contains genomes for 17 focal species to scan against to identify a given species. We established this reference collection by supplementing publically available genomes from RefSeq with genomes from the isolate collections of the Centers for Disease Control Bacterial Meningitis Laboratory and the Minnesota Department of Health Public Health Laboratory, and then filtered them down to a representative set of genomes which capture the diversity for each species. Using this reference collection, we evaluated two genomic comparison algorithms, Mash and Average Nucleotide Identity, for their ability to accurately and rapidly identify our focal species. RESULTS: We found that the results of Mash were strongly correlated with the results of ANI for species identification, while providing a significant reduction in run-time. This drastic difference in run-time enabled the rapid scanning of large reference genome collections, which, when combined with species-specific threshold values, facilitated the development of BMScan. Using a validation set of 15,503 genomes of our species of interest, BMScan accurately identified 99.97% of the species within 16 min 47 s. CONCLUSIONS: Identification of the bacterial meningitis pathogenic species is a critical step for case confirmation and further strain characterization. BMScan employs species-specific thresholds for previously-validated, genome-wide similarity statistics compiled from a curated reference genome collection to rapidly and accurately identify the species of uncharacterized bacterial meningitis pathogens and closely related pathogens. BMScan will facilitate the transition in public health laboratories from traditional phenotypic detection methods to whole genome sequencing based methods for species identification. |
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. |
Expansion of a urethritis-associated Neisseria meningitidis clade in the United States with concurrent acquisition of N. gonorrhoeae alleles.
Retchless AC , Kretz CB , Chang HY , Bazan JA , Abrams AJ , Norris Turner A , Jenkins LT , Trees DL , Tzeng YL , Stephens DS , MacNeil JR , Wang X . BMC Genomics 2018 19 (1) 176 ![]() ![]() BACKGROUND: Increased reports of Neisseria meningitidis urethritis in multiple U.S. cities during 2015 have been attributed to the emergence of a novel clade of nongroupable N. meningitidis within the ST-11 clonal complex, the "U.S. NmNG urethritis clade". Genetic recombination with N. gonorrhoeae has been proposed to enable efficient sexual transmission by this clade. To understand the evolutionary origin and diversification of the U.S. NmNG urethritis clade, whole-genome phylogenetic analysis was performed to identify its members among the N. meningitidis strain collection from the Centers for Disease Control and Prevention, including 209 urogenital and rectal N. meningitidis isolates submitted by U.S. public health departments in eleven states starting in 2015. RESULTS: The earliest representatives of the U.S. NmNG urethritis clade were identified from cases of invasive disease that occurred in 2013. Among 209 urogenital and rectal isolates submitted from January 2015 to September 2016, the clade accounted for 189/198 male urogenital isolates, 3/4 female urogenital isolates, and 1/7 rectal isolates. In total, members of the clade were isolated in thirteen states between 2013 and 2016, which evolved from a common ancestor that likely existed during 2011. The ancestor contained N. gonorrhoeae-like alleles in three regions of its genome, two of which may facilitate nitrite-dependent anaerobic growth during colonization of urogenital sites. Additional gonococcal-like alleles were acquired as the clade diversified. Notably, one isolate contained a sequence associated with azithromycin resistance in N. gonorrhoeae, but no other gonococcal antimicrobial resistance determinants were detected. CONCLUSIONS: Interspecies genetic recombination contributed to the early evolution and subsequent diversification of the U.S. NmNG urethritis clade. Ongoing acquisition of N. gonorrhoeae alleles by the U.S. NmNG urethritis clade may facilitate the expansion of its ecological niche while also increasing the frequency with which it causes urethritis. |
Impact of Florida's prescription drug monitoring program and pill mill law on high-risk patients: A comparative interrupted time series analysis
Chang HY , Murimi I , Faul M , Rutkow L , Alexander GC . Pharmacoepidemiol Drug Saf 2018 27 (4) 422-429 PURPOSE: We quantified the effects of Florida's prescription drug monitoring program and pill mill law on high-risk patients. METHODS: We used QuintilesIMS LRx Lifelink data to identify patients receiving prescription opioids in Florida (intervention state, N: 1.13 million) and Georgia (control state, N: 0.54 million). The preintervention, intervention, and postintervention periods were July 2010 to June 2011, July 2011 to September 2011, and October 2011 to September 2012. We identified 3 types of high-risk patients: (1) concomitant users: patients with concomitant use of benzodiazepines and opioids; (2) chronic users: long-term, high-dose, opioid users; and (3) opioid shoppers: patients receiving opioids from multiple sources. We compared changes in opioid prescriptions between Florida and Georgia before and after policy implementation among high-risk/low-risk patients. Our monthly measures included (1) average morphine milligram equivalent per transaction, (2) total opioid volume across all prescriptions, (3) average days supplied per transaction, and (4) total number of opioid prescriptions dispensed. RESULTS: Among opioid-receiving individuals in Florida, 6.62% were concomitant users, 1.96% were chronic users, and 0.46% were opioid shoppers. Following policy implementation, Florida's high-risk patients experienced relative reductions in morphine milligram equivalent (opioid shoppers: -1.08 mg/month, 95% confidence interval [CI] -1.62 to -0.54), total opioid volume (chronic users: -4.58 kg/month, CI -5.41 to -3.76), and number of dispensed opioid prescriptions (concomitant users: -640 prescriptions/month, CI -950 to -340). Low-risk patients generally did not experience statistically significantly relative reductions. CONCLUSIONS: Compared with Georgia, Florida's prescription drug monitoring program and pill mill law were associated with large relative reductions in prescription opioid utilization among high-risk patients. |
Meningococcal carriage among a university student population - United States, 2015.
Breakwell L , Whaley M , Khan UI , Bandy U , Alexander-Scott N , Dupont L , Vanner C , Chang HY , Vuong JT , Martin S , MacNeil JR , Wang X , Meyer SA . Vaccine 2017 36 (1) 29-35 ![]() ![]() OBJECTIVES: Several outbreaks of serogroup B meningococcal disease have occurred among university students in recent years. In the setting of high coverage of the quadrivalent meningococcal conjugate vaccine and prior to widespread use of serogroup B meningococcal vaccines among adolescents, we conducted surveys to characterize the prevalence and molecular characteristics of meningococcal carriage among university students. METHODS: Two cross-sectional oropharyngeal carriage surveys were conducted among undergraduates at a Rhode Island university. Isolates were characterized using slide agglutination, real-time polymerase chain reaction (rt-PCR), and whole genome sequencing. Adjusted prevalence ratios and 95% confidence intervals were calculated using Poisson regression to determine risk factors for carriage. RESULTS: A total of 1837 oropharyngeal specimens were obtained from 1478 unique participants. Overall carriage prevalence was 12.7-14.6% during the two survey rounds, with 1.8-2.6% for capsular genotype B, 0.9-1.0% for capsular genotypes C, W, or Y, and 9.9-10.8% for nongroupable strains by rt-PCR. Meningococcal carriage was associated with being male, smoking, party or club attendance, recent antibiotic use (inverse correlation), and recent respiratory infections. CONCLUSIONS: In this university setting, the majority of meningococcal carriage was due to nongroupable strains, followed by serogroup B. Further evaluation is needed to understand the dynamics of serogroup B carriage and disease among university students. |
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. |
Serogroup B meningococcal disease vaccine recommendations at a university, New Jersey, USA, 2016
Soeters HM , Dinitz-Sklar J , Kulkarni PA , MacNeil JR , McNamara LA , Zaremski E , Chang HY , Lujan E , Granoff D , Lasky M , Montana B . Emerg Infect Dis 2017 23 (5) 867-869 In response to a university-based serogroup B meningococcal disease outbreak, the serogroup B meningococcal vaccine Trumenba was recommended for students, a rare instance in which a specific vaccine brand was recommended. This outbreak highlights the challenges of using molecular and immunologic data to inform real-time response. |
Outbreak of serogroup C meningococcal disease primarily affecting men who have sex with men - Southern California, 2016
Nanduri S , Foo C , Ngo V , Jarashow C , Civen R , Schwartz B , Holguin J , Shearer E , Zahn M , Harriman K , Winter K , Kretz C , Chang HY , Meyer S , MacNeil J . MMWR Morb Mortal Wkly Rep 2016 65 (35) 939-940 During March 4-August 11, 2016, 25 outbreak-associated cases of meningococcal disease, including two deaths (8% case-fatality ratio), were reported in Southern California. Twenty-four of the cases were caused by serogroup C Neisseria meningitidis (NmC) and one by N. meningitidis with an undetermined serogroup (Figure). On June 24, 2016, in response to this increase in NmC cases, primarily among men who have sex with men (MSM) in Los Angeles County, the city of Long Beach, and Orange County, the California Department of Public Health (CDPH) issued a press release and health advisory, declaring an outbreak of NmC in Southern California. |
Impact of prescription drug monitoring programs and pill mill laws on high-risk opioid prescribers: A comparative interrupted time series analysis
Chang HY , Lyapustina T , Rutkow L , Daubresse M , Richey M , Faul M , Stuart EA , Alexander GC . Drug Alcohol Depend 2016 165 1-8 BACKGROUND: Prescription drug monitoring programs (PDMPs) and pill mill laws were implemented to reduce opioid-related injuries/deaths. We evaluated their effects on high-risk prescribers in Florida. METHODS: We used IMS Health's LRx Lifelink database between July 2010 and September 2012 to identify opioid-prescribing prescribers in Florida (intervention state, N: 38,465) and Georgia (control state, N: 18,566). The pre-intervention, intervention, and post-intervention periods were: July 2010-June 2011, July 2011-September 2011, and October 2011-September 2012. High-risk prescribers were those in the top 5th percentile of opioid volume during four consecutive calendar quarters. We applied comparative interrupted time series models to evaluate policy effects on clinical practices and monthly prescribing measures for low-risk/high-risk prescribers. RESULTS: We identified 1526 (4.0%) high-risk prescribers in Florida, accounting for 67% of total opioid volume and 40% of total opioid prescriptions. Relative to their lower-risk counterparts, they wrote sixteen times more monthly opioid prescriptions (79 vs. 5, p<0.01), and had more prescription-filling patients receiving opioids (47% vs. 19%, p<0.01). Following policy implementation, Florida's high-risk providers experienced large relative reductions in opioid patients and opioid prescriptions (-536 patients/month, 95% confidence intervals [CI] -829 to -243; -847 prescriptions/month, CI -1498 to -197), morphine equivalent dose (-0.88mg/month, CI -1.13 to -0.62), and total opioid volume (-3.88kg/month, CI -5.14 to -2.62). Low-risk providers did not experience statistically significantly relative reductions, nor did policy implementation affect the status of being high- vs. low- risk prescribers. CONCLUSIONS: High-risk prescribers are disproportionately responsive to state policies. However, opioids-prescribing remains highly concentrated among high-risk providers. |
Effect of a "pill mill" law on opioid prescribing and utilization: The case of Texas
Lyapustina T , Rutkow L , Chang HY , Daubresse M , Ramji AF , Faul M , Stuart EA , Alexander GC . Drug Alcohol Depend 2015 159 190-7 BACKGROUND: States have attempted to reduce prescription opioid abuse through strengthening the regulation of pain management clinics; however, the effect of such measures remains unclear. We quantified the impact of Texas's September 2010 "pill mill" law on opioid prescribing and utilization. METHODS: We used the IMS Health LRx LifeLink database to examine anonymized, patient-level pharmacy claims for a closed cohort of individuals filling prescription opioids in Texas between September 2009 and August 2011. Our primary outcomes were derived at a monthly level and included: (1) average morphine equivalent dose (MED) per transaction; (2) aggregate opioid volume; (3) number of opioid prescriptions; and (4) quantity of opioid pills dispensed. We compared observed values with the counterfactual, which we estimated from pre-intervention levels and trends. RESULTS: Texas's pill mill law was associated with declines in average MED per transaction (-0.57. mg/month, 95% confidence interval [CI] -1.09, -0.057), monthly opioid volume (-9.99. kg/month, CI -12.86, -7.11), monthly number of opioid prescriptions (-12,200 prescriptions/month, CI -15,300, -9,150) and monthly quantity of opioid pills dispensed (-714,000 pills/month, CI -877,000, -550,000). These reductions reflected decreases of 8.1-24.3% across the outcomes at one year compared with the counterfactual, and they were concentrated among prescribers and patients with the highest opioid prescribing and utilization at baseline. CONCLUSIONS: Following the implementation of Texas's 2010 pill mill law, there were clinically significant reductions in opioid dose, volume, prescriptions and pills dispensed within the state, which were limited to individuals with higher levels of baseline opioid prescribing and utilization. |
Emergency department visits by children and adolescents for antipsychotic drug adverse events
Hampton LM , Daubresse M , Chang HY , Alexander GC , Budnitz DS . JAMA Psychiatry 2015 72 (3) 292-4 The per capita number of outpatient visits in which an antipsychotic drug was supplied or prescribed increased approximately 660% among children and 380% among adolescents between the mid-1990s and the mid-2000s in the United States,1 prompting concerns about possible inappropriate prescribing. The most recent revisions to the DSM-5 were intended in part to decrease inappropriate child and adolescent antipsychotic drug use,2 and the American Psychiatric Association has warned against using antipsychotics as first-line therapy in children and adolescents for conditions other than psychotic disorders.3 To quantify acute harms from child and adolescent antipsychotic drug use, we estimated the numbers and rates of US emergency department (ED) visits and hospitalizations for adverse drug events (ADEs) from therapeutic use of antipsychotics and comparator psychotropic medications among children 10 years or younger and adolescents 11 to 18 years. |
Emergency department visits by adults for psychiatric medication adverse events
Hampton LM , Daubresse M , Chang HY , Alexander GC , Budnitz DS . JAMA Psychiatry 2014 71 (9) 1006-14 IMPORTANCE: In 2011, an estimated 26.8 million US adults used prescription medications for mental illness. OBJECTIVE: To estimate the numbers and rates of adverse drug event (ADE) emergency department (ED) visits involving psychiatric medications among US adults between January 1, 2009, and December 31, 2011. DESIGN AND SETTING: Descriptive analyses of active, nationally representative surveillance of ADE ED visits using the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance system and of drug prescribing during outpatient visits using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. PARTICIPANTS: Medical records from national probability samples of ED and outpatient visits by adults 19 years or older were reviewed and analyzed. EXPOSURES: Antidepressants, antipsychotics, lithium salts, sedatives and anxiolytics, and stimulants. MAIN OUTCOMES AND MEASURES: National estimates of ADE ED visits resulting from therapeutic psychiatric medication use and of psychiatric medication ADE ED visits per 10 000 outpatient visits at which psychiatric medications were prescribed. RESULTS: From 2009 through 2011, there were an estimated 89 094 (95% CI, 68 641-109 548) psychiatric medication ADE ED visits annually, with 19.3% (95% CI, 16.3%-22.2%) resulting in hospitalization and 49.4% (95% CI, 46.5%-52.4%) involving patients aged 19 to 44 years. Sedatives and anxiolytics, antidepressants, antipsychotics, lithium salts, and stimulants were implicated in an estimated 30 707 (95% CI, 23 406-38 008), 25 377 (95% CI, 19 051-31 704), 21 578 (95% CI, 16 599-26 557), 3620 (95% CI, 2311-4928), and 2779 (95% CI, 1764-3794) respective ADE ED visits annually. Antipsychotics and lithium salts were implicated in 11.7 (95% CI, 10.1-13.2) and 16.4 (95% CI, 13.0-19.9) ADE ED visits per 10 000 outpatient prescription visits, respectively, compared with 3.6 (95% CI, 3.2-4.1) for sedatives and anxiolytics, 2.9 (95% CI, 2.3-3.5) for stimulants, and 2.4 (95% CI, 2.1-2.7) for antidepressants. The commonly used sedative zolpidem tartrate was implicated in 11.5% (95% CI, 9.5%-13.4%) of all adult psychiatric medication ADE ED visits and in 21.0% (95% CI, 16.3%-25.7%) of visits involving adults 65 years or older, in both cases significantly more than any other psychiatric medication. CONCLUSIONS AND RELEVANCE: Psychiatric medications are implicated in many ADEs treated in US EDs. Efforts to reduce ADEs should include adults of all ages but might prioritize medications causing high numbers and rates of ED visits. |
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