Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 39 Records) |
Query Trace: Wan C[original query] |
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Performance of CHROMagar ESBL media for the surveillance of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) from rectal swabs in Botswana
Mannathoko N , Lautenbach E , Mosepele M , Otukile D , Sewawa K , Glaser L , Cressman L , Cowden L , Alby K , Jaskowiak-Barr A , Gross R , Mokomane M , Paganotti GM , Styczynski A , Smith RM , Snitkin E , Wan T , Bilker WB , Richard-Greenblatt M . J Med Microbiol 2023 72 (11) Introduction. Lack of laboratory capacity hampers consistent national antimicrobial resistance (AMR) surveillance. Chromogenic media may provide a practical screening tool for detection of individuals colonized by extended-spectrum beta-lactamase (ESBL)-producing organisms.Hypothesis. CHROMagar ESBL media represent an adequate screening method for the detection of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), isolated from rectal swabs.Aim. To evaluate the performance of CHROMagar ESBL media to accurately identify ESCrE isolates from rectal swab samples attained from hospitalized and community participants.Methodology. All participants provided informed consent prior to enrolment. Rectal swabs from 2469 hospital and community participants were inoculated onto CHROMagar ESBL. The performance of CHROMagar ESBL to differentiate Escherichia coli and Klebsiella spp., Enterobacter spp. and Citrobacter spp. (KEC spp.) as well as select for extended-spectrum cephalosporin resistance were compared to matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-TOF-MS) and VITEK-2 automated susceptibility testing.Results. CHROMagar ESBL had a positive and negative agreement of 91.2 % (95 % CI, 88.4-93.3) and 86.8 % (95 % CI, 82.0-90.7) for E. coli and 88.1 % (95 % CI 83.2-92.1) and 87.6 % (95 % CI 84.7-90.2) for KEC spp. differentiation, respectively, when compared to species ID by MALDI-TOF-MS. When evaluated for phenotypic susceptibilities (VITEK-2), 88.1 % (714/810) of the isolates recovered on the selective agar exhibited resistance to third-generation cephalosporins.Conclusion. The performance characteristics of CHROMagar ESBL media suggest that they may be a viable screening tool for the identification of ESCrE from hospitalized and community participants and could be used to inform infection prevention and control practices in Botswana and potentially other low-and middle-income countries (LMICs). Further studies are required to analyse the costs and the impact on time-to-result of the media in comparison with available laboratory methods for ESCrE surveillance in the country. |
Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season (preprint)
Levine MZ , Martin ET , Petrie JG , Lauring AS , Holiday C , Jefferson S , Fitzsimmons WJ , Johnson E , Ferdinands JM , Monto AS . bioRxiv 2018 439471 Background The 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.Methods Serum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.Results MN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P>0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.Conclusion Although individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.We thank Maryna Eichelberger, Hongquan Wan, Jin Gao, and Laura Couzens (Food and Drug Administration) for technical support and providing reassortant influenza viruses for use in the enzyme-linked lectin assays. St Jude Children’s Research Hospital provided plasmids that were used to generate these reassortant influenza viruses. We thank Mrs F Liaini Gross, Lauren Horner and Makeda Kay from Influenza Division, Centers for Disease Control and Prevention for technical support for virus propagation and specimen management. |
Expression-based diagnosis, treatment selection, and drug development for breast cancer
Ye Q , Wang J , Ducatman B , Raese RA , Rogers JL , Wan YW , Dong C , Padden L , Pugacheva EN , Qian Y , Guo NL . Int J Mol Sci 2023 24 (13) There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer. |
Transmission of SARS-CoV-2 in free-ranging white-tailed deer in the United States
Feng A , Bevins S , Chandler J , DeLiberto TJ , Ghai R , Lantz K , Lenoch J , Retchless A , Shriner S , Tang CY , Tong SS , Torchetti M , Uehara A , Wan XF . Nat Commun 2023 14 (1) 4078 SARS-CoV-2 is a zoonotic virus with documented bi-directional transmission between people and animals. Transmission of SARS-CoV-2 from humans to free-ranging white-tailed deer (Odocoileus virginianus) poses a unique public health risk due to the potential for reservoir establishment where variants may persist and evolve. We collected 8,830 respiratory samples from free-ranging white-tailed deer across Washington, D.C. and 26 states in the United States between November 2021 and April 2022. We obtained 391 sequences and identified 34 Pango lineages including the Alpha, Gamma, Delta, and Omicron variants. Evolutionary analyses showed these white-tailed deer viruses originated from at least 109 independent spillovers from humans, which resulted in 39 cases of subsequent local deer-to-deer transmission and three cases of potential spillover from white-tailed deer back to humans. Viruses repeatedly adapted to white-tailed deer with recurring amino acid substitutions across spike and other proteins. Overall, our findings suggest that multiple SARS-CoV-2 lineages were introduced, became enzootic, and co-circulated in white-tailed deer. |
SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.
Nilles EJ , Paulino CT , de St Aubin M , Restrepo AC , Mayfield H , Dumas D , Finch E , Garnier S , Etienne MC , Iselin L , Duke W , Jarolim P , Oasan T , Yu J , Wan H , Peña F , Iihoshi N , Abdalla G , Lopez B , Cruz L , Henríquez B , Espinosa-Bode A , Puello YC , Durski K , Baldwin M , Baez AA , Merchant RC , Barouch DH , Skewes-Ramm R , Gutiérrez EZ , Kucharski A , Lau CL . Lancet Reg Health Am 2022 16 100390 BACKGROUND: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. METHODS: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. FINDINGS: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. INTERPRETATION: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. FUNDING: This study was funded by the US CDC. |
MicroRNA, mRNA, and proteomics biomarkers and therapeutic targets for improving lung cancer treatment outcomes
Ye Qing , Raese Rebecca , Luo Dajie , Cao Shu , Wan Ying-Wooi , Qian Yong , Guo Nancy Lan . Cancers (Basel) 2023 15 (8) 2294 Simple Summary: This study identified a set of 73 microRNAs (miRNAs) that can accurately detect lung cancer tumors from normal lung tissues. Based on the consistent expression patterns associated with patient survival outcomes and in tumors vs. normal lung tissues, 10 miRNAs were considered to be putatively tumor suppressive and 4 miRNAs were deemed as oncogenic in lung cancer. From the list of genes that were targeted by the 73 diagnostic miRNAs, DGKE and WDR47 had significant associations with responses to both systemic therapies and radiotherapy in lung cancer. Based on our identified miRNA-regulated network, we discovered three drugs—BX-912, daunorubicin, and midostaurin—that can be repositioned to treat lung cancer, which was not known before. The majority of lung cancer patients are diagnosed with metastatic disease. This study identified a set of 73 microRNAs (miRNAs) that classified lung cancer tumors from normal lung tissues with an overall accuracy of 96.3% in the training patient cohort (n = 109) and 91.7% in unsupervised classification and 92.3% in supervised classification in the validation set (n = 375). Based on association with patient survival (n = 1016), 10 miRNAs were identified as potential tumor suppressors (hsa-miR-144, hsa-miR-195, hsa-miR-223, hsa-miR-30a, hsa-miR-30b, hsa-miR-30d, hsa-miR-335, hsa-miR-363, hsa-miR-451, and hsa-miR-99a), and 4 were identified as potential oncogenes (hsa-miR-21, hsa-miR-31, hsa-miR-411, and hsa-miR-494) in lung cancer. Experimentally confirmed target genes were identified for the 73 diagnostic miRNAs, from which proliferation genes were selected from CRISPR-Cas9/RNA interference (RNAi) screening assays. Pansensitive and panresistant genes to 21 NCCN-recommended drugs with concordant mRNA and protein expression were identified. DGKE and WDR47 were found with significant associations with responses to both systemic therapies and radiotherapy in lung cancer. Based on our identified miRNA-regulated molecular machinery, an inhibitor of PDK1/Akt BX-912, an anthracycline antibiotic daunorubicin, and a multi-targeted protein kinase inhibitor midostaurin were discovered as potential repositioning drugs for treating lung cancer. These findings have implications for improving lung cancer diagnosis, optimizing treatment selection, and discovering new drug options for better patient outcomes. |
Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo
Pittman PR , Martin JW , Kingebeni PM , Tamfum JM , Mwema G , Wan Q , Ewala P , Alonga J , Bilulu G , Reynolds MG , Quinn X , Norris S , Townsend MB , Satheshkumar PS , Wadding J , Soltis B , Honko A , Güereña FB , Korman L , Patterson K , Schwartz DA , Huggins JW . PLoS Negl Trop Dis 2023 17 (4) e0010384 We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Seours Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT. |
Development of an international glossary for clinical guidelines collaboration
Christensen RE , Yi MD , Kang BY , Ibrahim SA , Anvery N , Dirr M , Adams S , Amer YS , Bisdorff A , Bradfield L , Brown S , Earley A , Fatheree LA , Fayoux P , Getchius T , Ginex P , Graham A , Green CR , Gresele P , Hanson H , Haynes N , Hegedüs L , Hussein H , Jakhmola P , Kantorova L , Krishnasamy R , Krist A , Landry G , Lease ED , Ley L , Marsden G , Meek T , Meremikwu M , Moga C , Mokrane S , Mujoomdar A , Newton S , O'Flynn N , Perkins GD , Smith EJ , Prematunge C , Rychert J , Saraco M , Schünemann HJ , Senerth E , Sinclair A , Shwayder J , Stec C , Tanni S , Taske N , Temple-Smolkin RL , Thomas L , Thomas S , Tonnessen B , Turner AS , Van Dam A , van Doormaal M , Wan YL , Ventura CB , McFarlane E , Morgan RL , Ogunremi T , Alam M . J Clin Epidemiol 2023 158 84-91 OBJECTIVE: Clinical practice guidelines are often created through collaboration among organizations. Use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development. STUDY DESIGN AND SETTING: A literature review of collaborative guidelines was performed to develop an initial list of terms related to guideline collaboration. The list of terms was presented to the members of the Guideline International Network Guidelines Collaboration Working Group, who provided presumptive definitions for each term and proposed additional terms to be included. The revised list was subsequently reviewed by an international, multidisciplinary panel of expert stakeholders. Recommendations received during this pre-Delphi review were implemented to augment an initial draft glossary. The glossary was then critically evaluated and refined through two rounds of Delphi surveys and a virtual consensus meeting with all panel members as Delphi participants. RESULTS: Forty-nine experts participated in the pre-Delphi survey and 44 participated in the two-round Delphi process. Consensus was reached for 37 terms and definitions. CONCLUSION: Uptake and utilization of this guideline collaboration glossary by key organizations and stakeholder groups may facilitate collaboration among guideline-producing organizations by improving communication, minimizing conflicts, and increasing guideline development efficiency. |
Multiple introductions and recombination events underlie the emergence of a hyper-transmissible Cryptosporidium hominis subtype in the USA.
Huang W , Guo Y , Lysen C , Wang Y , Tang K , Seabolt MH , Yang F , Cebelinski E , Gonzalez-Moreno O , Hou T , Chen C , Chen M , Wan M , Li N , Hlavsa MC , Roellig DM , Feng Y , Xiao L . Cell Host Microbe 2022 31 (1) 112-123 e4 The parasite Cryptosporidium hominis is a leading cause of the diarrheal disease cryptosporidiosis, whose incidence in the United States has increased since 2005. Here, we show that the newly emerged and hyper-transmissible subtype IfA12G1R5 is now dominant in the United States. In a comparative analysis of 127 newly sequenced and 95 published C. hominis genomes, IfA12G1R5 isolates from the United States place into three of the 14 clusters (Pop6, Pop13, and Pop14), indicating that this subtype has multiple ancestral origins. Pop6 (IfA12G1R5a) has an East Africa origin and has recombined with autochthonous subtypes after its arrival. Pop13 (IfA12G1R5b) is imported from Europe, where it has recombined with the prevalent local subtype, whereas Pop14 (IfA12G1R5c) is a progeny of secondary recombination between Pop6 and Pop13. Selective sweeps in invasion-associated genes have accompanied the emergence of the dominant Pop14. These observations offer insights into the emergence and evolution of hyper-transmissible pathogens. |
The power, potential, benefits, and challenges of implementing high-throughput sequencing in food safety systems.
Imanian B , Donaghy J , Jackson T , Gummalla S , Ganesan B , Baker RC , Henderson M , Butler EK , Hong Y , Ring B , Thorp C , Khaksar R , Samadpour M , Lawless KA , MacLaren-Lee I , Carleton HA , Tian R , Zhang W , Wan J . NPJ Sci Food 2022 6 (1) 35 The development and application of modern sequencing technologies have led to many new improvements in food safety and public health. With unprecedented resolution and big data, high-throughput sequencing (HTS) has enabled food safety specialists to sequence marker genes, whole genomes, and transcriptomes of microorganisms almost in real-time. These data reveal not only the identity of a pathogen or an organism of interest in the food supply but its virulence potential and functional characteristics. HTS of amplicons, allow better characterization of the microbial communities associated with food and the environment. New and powerful bioinformatics tools, algorithms, and machine learning allow for development of new models to predict and tackle important events such as foodborne disease outbreaks. Despite its potential, the integration of HTS into current food safety systems is far from complete. Government agencies have embraced this new technology, and use it for disease diagnostics, food safety inspections, and outbreak investigations. However, adoption and application of HTS by the food industry have been comparatively slow, sporadic, and fragmented. Incorporation of HTS by food manufacturers in their food safety programs could reinforce the design and verification of effectiveness of control measures by providing greater insight into the characteristics, origin, relatedness, and evolution of microorganisms in our foods and environment. Here, we discuss this new technology, its power, and potential. A brief history of implementation by public health agencies is presented, as are the benefits and challenges for the food industry, and its future in the context of food safety. |
HIV testing, diagnosis of HIV infection, linkage to medical care, and interview for partner services among transgender persons - United States, 2012-2017
Mulatu MS , Wang G , Song W , Keatley J , Kudon HZ , Wan C , Rao S . J Acquir Immune Defic Syndr 2020 Publish Ahead of Print (5) 530-535 BACKGROUND: Transgender persons are at high risk for HIV infection. Testing is a key component of the national effort to end the HIV epidemic in the United States. SETTING: Sixty-one local and state health departments (HDs) and 150 community-based organizations (CBOs) funded by the Centers for Disease Control and Prevention (CDC) to conduct HIV testing programs. METHODS: We analyzed HIV testing data submitted to CDC by funded HDs and CBOs during 2012-2017. Descriptive analysis examined patterns of HIV testing and key outcomes (diagnosis of HIV infection, linkage to HIV medical care, and interview for partner services) among transgender persons. Multivariate robust Poisson regression was used to assess associations between HIV testing outcomes and demographic characteristics, census region, and test setting. RESULTS: A total of 82,818 HIV tests were provided to transgender persons. Of these, 2,280 (2.8%) transgender persons were diagnosed with HIV infection; 1,556 (1.9%) received a new and 724 (0.9%) a previous diagnosis with HIV infection. The highest percentage of new HIV diagnosis was found among persons tested in correctional settings (4.6%), non-Hispanic Blacks (3.5%) and transgender women (2.4%).Among newly diagnosed persons, 85.0% were linked to HIV medical care ≤90 days after diagnosis and 63.5% were interviewed for partner services. CONCLUSIONS: HIV positivity was high, and the delivery of partner services was low, among transgender persons. HIV testing outcomes among transgender persons varied significantly by demographic characteristics and test setting. HIV prevention programs that are responsive to the needs of transgender persons may address gender-related disparities in HIV testing outcomes. |
Characterizations of Enterocytozoon bieneusi at new genetic loci reveal a lack of strict host specificity among common genotypes and the existence of a canine-adapted Enterocytozoon species.
Ou Y , Jiang W , Roellig DM , Wan Z , Li N , Guo Y , Feng Y , Xiao L . Int J Parasitol 2020 51 215-223 Molecular characterizations of the microsporidian pathogen Enterocytozoon bieneusi at the ribosomal internal transcribed spacer (ITS) locus have identified nearly 500 genotypes in 11 phylogenetic groups with different host ranges. Among those, one unique group of genotypes, Group 11, is commonly found in dogs. Genetic characterizations of those and many divergent E. bieneusi genotypes at other genetic loci are thus far impossible. In this study, we sequenced 151 E. bieneusi isolates from several ITS genotype groups at the 16S rRNA locus and two new semi-conservative genetic markers (casein kinase 1 (ck1) and spore wall protein 1 (swp1)). Comparison of the near full (~1,200 bp) 16S rRNA sequences showed mostly two to three nucleotide substitutions between Group 1 and Group 2 genotypes, while Group 11 isolates differed from those by 26 (2.2%) nucleotides. Sequence analyses of the ck1 and swp1 loci confirmed the genetic uniqueness of Group 11 genotypes, which produced sequences very divergent from other groups. In contrast, genotypes in Groups 1 and 2 produced similar nucleotide sequences at these genetic loci, and there was discordant placement of ITS genotypes among loci in phylogenetic analyses of sequences. These results suggest that the canine-adapted Group 11 genotypes are genetically divergent from other genotype groups of E. bieneusi, possibly representing a different Enterocytozoon sp. They also indicate that there is no clear genetic differentiation of ITS Groups 1 and 2 at other genetic loci, supporting the conclusion on the lack of strict host specificity in both groups. Data and genetic markers from the study should facilitate population genetic characterizations of E. bieneusi isolates and improve our understanding of the zoonotic potential of E. bieneusi in domestic animals. |
Cross-protection by inactivated H5 pre-pandemic vaccine seed strains against diverse Goose/Guangdong lineage H5N1 highly pathogenic avian influenza viruses.
Criado MF , Sá ESilva M , Lee DH , de Lima Salge CA , Spackman E , Donis R , Wan XF , Swayne DE . J Virol 2020 94 (24) The highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 lineage (Gs/GD) is endemic in poultry across several countries in the world, and has caused lethal, sporadic infections in humans. Vaccines are important in HPAI control for both poultry and in pre-pandemic preparedness in humans. This study assessed inactivated pre-pandemic vaccine strains in a One Health framework, focusing on the genetic and antigenic diversity of field H5N1 Gs/GD viruses from the agricultural sector and assessing cross protection in a chicken challenge model. Nearly half (47.92%) of the forty-eight combinations of vaccine/challenge viruses examined had bird protection of 80% or above. Most vaccinated groups had prolonged mean death time (MDT) and the virus shedding titers were significantly lower compared to the sham group (p≤ 0.05). The antibody titers in the pre-challenge sera were not predictive of protection. Although vaccinated birds had higher titers of hemagglutination inhibiting (HI) antibodies against homologous vaccine antigen, most of them also had lower or no antibody titer against the challenge antigen. The comparison of all parameters, homologous or closely related vaccine and challenge viruses, gave the best prediction protection. Through additional analysis, we identified a pattern of epitopes substitutions in the hemagglutinin (HA) of each challenge virus that impacted protection, regardless of the vaccine used. These changes were situated in the antigenic sites and/or reported epitopes associated with virus escape from antibody neutralization. As a result, this study highlights virus diversity, immune response complexity, and the importance of strain selection for vaccine development to control H5N1 HPAIV in the agricultural sector and for human pre-pandemic preparedness. We suggest that the engineering of specific antigenic sites can improve the immunogenicity of H5 vaccines.ImportanceThe sustained circulation of highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 lineage (Gs/GD) in the agricultural sector and some wild birds has led to the evolution and selection of distinct viral lineages involved in the escape from vaccine protection. Our results using inactivated vaccine candidates from the human pandemic preparedness program in a chicken challenge model identified critical antigenic conformational epitopes on the H5 hemagglutinin (HA) from different clades that were associated with antibody recognition and escape. Even though other investigators have reported epitope mapping in the H5 HA, much of this information pertains to epitopes reactive towards mouse antibodies. Our findings validate changes in antigenic epitopes of HA associated with virus escape from antibody neutralization in chickens, which has direct relevance to field protection and virus evolution. Therefore, the knowledge of these immunodominant regions is essential to proactively develop diagnostic tests, improve surveillance platforms to monitor AIV outbreaks, and design more efficient and broad-spectrum agricultural and human prepandemic vaccines. |
Population-based prevalence and incidence estimates of primary discoid lupus erythematosus from the Manhattan Lupus Surveillance Program
Izmirly P , Buyon J , Belmont HM , Sahl S , Wan I , Salmon J , Askanase A , Bathon JM , Geraldino-Pardilla L , Ali Y , Ginzler E , Putterman C , Gordon C , Helmick C , Parton H . Lupus Sci Med 2019 6 (1) e000344 Objective Epidemiological data for primary discoid lupus erythematosus (pDLE) remain limited, particularly for racial/ethnic populations in the USA. The Manhattan Lupus Surveillance Program (MLSP) is a population-based retrospective registry of cases with SLE and related diseases including pDLE in Manhattan and was used to provide estimates of the prevalence and incidence of pDLE across major racial/ethnic populations. Methods MLSP cases were identified from rheumatologists, hospitals and population databases. Two case definitions were used for pDLE: the primary case definition which was any physician diagnosis found in the chart and a secondary case definition which was limited to cases diagnosed by a rheumatologist and/or dermatologist. Rates among Manhattan residents were age-adjusted, and capture-recapture analyses were conducted to assess case under-ascertainment. Results Based on the primary definition, age-adjusted overall prevalence and incidence rates of pDLE among Manhattan residents were 6.5 and 0.8 per 100 000 person-years, which increased to 9.0 and 1.3 after capture-recapture adjustment. Prevalence and incidence rates were approximately two and six times higher, respectively, among women compared with men (p<0.0001). Higher prevalence was also found among non-Latino blacks (23.5) and Latinos (8.2) compared with non-Latino whites (1.8) and non-Latino Asians (0.6) (p<0.0001). Incidence was highest among non-Latino blacks (2.4) compared with all other racial/ethnic groups. Similar relationships were observed for the secondary case definition. Conclusion Data from the MLSP provide epidemiological estimates for pDLE among the major racial/ethnic populations in the USA and reveal disparities in pDLE prevalence and incidence by sex and race/ethnicity among Manhattan residents. |
Dose effect of influenza vaccine on protection against laboratory-confirmed influenza illness among children aged 6 months to 8 years of age in southern China, 2013/14-2015/16 seasons: a matched case control study
Fu C , Greene CM , He Q , Liao Y , Wan Y , Shen J , Rong C , Zhou S . Hum Vaccin Immunother 2019 16 (3) 595-601 Background We conducted a matched case control study in China during the 2013/14-2015/16 influenza seasons to estimate influenza vaccine effectiveness (VE) by dose among children aged 6 months to 8 years. Methods Cases were laboratory-confirmed influenza infections identified through the influenza-like illness sentinel surveillance network in Guangzhou. Age and sex matched community controls were randomly selected through the expanded immunization program database. We defined priming as receipt of >/=1 dose of influenza vaccine during the immediate prior season. Results In total, 4,185 case-control pairs were analyzed. Among children 6-35 months, VE for current season dose(s) across the three seasons during 2013/14-2015/16 were 59% (95% Confidence Interval: 44-71%), 12% (-11%,30%), 54% (32-69%); among unprimed children 6-35 months, VE for 1 vs 2 current season doses were 45% (8-67%) vs 65% (46-78%), -2% (-53%,32%) vs 19% (-11%,40%), and 37% (-24%,68%) vs 61% (32-78%). Among children aged 3-8 years, VE for current season dose(s) across study seasons were 62% (36-78%), 43% (22-58%), 32% (1-53%). VE for unprimed children receiving 1 dose only in current season was insignificant or lower than among all children. Conclusion Findings support utility of providing second dose ("booster dose") of seasonal influenza vaccine to unprimed children aged 6-35 months, and the need to study further dose effect of a booster dose among unprimed children aged 3-8 years in China. |
The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain
Wan H , Gao J , Yang H , Yang S , Harvey R , Chen YQ , Zheng NY , Chang J , Carney PJ , Li X , Plant E , Jiang L , Couzens L , Wang C , Strohmeier S , Wu WW , Shen RF , Krammer F , Cipollo JF , Wilson PC , Stevens J , Wan XF , Eichelberger MC , Ye Z . Nat Microbiol 2019 4 (12) 2216-2225 A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown. Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain. This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468. As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished. This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge. X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding. Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines. |
Comparison of self-reported female condom failure and biomarker-confirmed semen exposure
Walsh TL , Snead MC , St Claire BJ , Schwartz JL , Mauck CK , Frezieres RG , Blithe DL , Archer DF , Barnhart KT , Jensen JT , Nelson AL , Thomas MA , Wan LS , Weaver MA . Contraception 2019 100 (5) 406-412 OBJECTIVE: To investigate whether rates of self-reported Woman's Condom (WC) clinical failure and semen exposure from a functionality study are comparable to results from a contraceptive efficacy substudy. STUDY DESIGN: We structured our comparative analysis to assess whether functionality studies might credibly supplant contraceptive efficacy studies when evaluating new female condom products. Couples not at risk of pregnancy in the functionality (breakage/slippage/invagination/penile misdirection) study and women in the contraceptive efficacy study completed condom self-reports and collected pre and postcoital vaginal samples for up to four uses of the WC. Both studies used nearly identical self-report questions and the same self-sampling procedures and laboratory for prostatic specific antigen (PSA), a well-studied semen biomarker. We compared condom failure and semen exposure proportions using generalized estimating equations methods accounting for within-couple correlation. RESULTS: Ninety-five (95) efficacy substudy participants used 334 WC and 408 functionality participants used 1572 WC. Based on self-report, 19.2% WC (64 condoms) clinically failed in the efficacy substudy compared to 12.3% WC (194 condoms) in the functionality study (p-value=0.030). Of the 207 WC efficacy uses with evaluable post-coital PSA levels, 14.5% (30 uses) resulted in semen exposure compared to 14.2% (184 uses) of the 1293 evaluable WC functionality study uses. CONCLUSIONS: When evaluating the ability of an experimental condom to prevent semen exposure, the rate of clinical condom failure reported by participants risking pregnancy in an efficacy substudy was significantly higher than the rate reported by participants not risking pregnancy in a functionality study. The rate of semen exposure, assessed by an objective biomarker was nearly identical for the two studies. IMPLICATIONS: Our results suggest that an objective marker of semen exposure in functionality studies could provide a reasonable alternative to contraceptive efficacy studies in evaluating risk of unintended pregnancy and inferring protection from sexually transmitted infection than condom failure rates based on self-report. |
Antigenic drift of the influenza A(H1N1)pdm09 virus neuraminidase results in reduced effectiveness of A/California/7/2009 (H1N1pdm09)-specific antibodies
Gao J , Couzens L , Burke DF , Wan H , Wilson P , Memoli MJ , Xu X , Harvey R , Wrammert J , Ahmed R , Taubenberger JK , Smith DJ , Fouchier RAM , Eichelberger MC . mBio 2019 10 (2) The effectiveness of influenza vaccines against circulating A(H1N1)pdm09 viruses was modest for several seasons despite the absence of antigenic drift of hemagglutinin (HA), the primary vaccine component. Since antibodies against HA and neuraminidase (NA) contribute independently to protection against disease, antigenic changes in NA may allow A(H1N1)pdm09 viruses to escape from vaccine-induced immunity. In this study, analysis of the specificities of human NA-specific monoclonal antibodies identified antigenic sites that have changed over time. The impact of these differences on in vitro inhibition of enzyme activity was not evident for polyclonal antisera until viruses emerged in 2013 without a predicted glycosylation site at amino acid 386 in NA. Phylogenetic and antigenic cartography demonstrated significant antigenic changes that in most cases aligned with genetic differences. Typical of NA drift, the antigenic difference is observed in one direction, with antibodies against conserved antigenic domains in A/California/7/2009 (CA/09) continuing to inhibit NA of recent A(H1N1)pdm09 viruses reasonably well. However, ferret CA/09-specific antiserum that inhibited the NA of A/Michigan/45/2015 (MI/15) very well in vitro, protected mice against lethal MI/15 infection poorly. These data show that antiserum against the homologous antigen is most effective and suggest the antigenic properties of NA should not be overlooked when selecting viruses for vaccine production.IMPORTANCE The effectiveness of seasonal influenza vaccines against circulating A(H1N1)pdm09 viruses has been modest in recent years, despite the absence of antigenic drift of HA, the primary vaccine component. Human monoclonal antibodies identified antigenic sites in NA that changed early after the new pandemic virus emerged. The reactivity of ferret antisera demonstrated antigenic drift of A(H1N1)pdm09 NA from 2013 onward. Passive transfer of serum raised against A/California/7/2009 was less effective than ferret serum against the homologous virus in protecting mice against a virus with the NA of more recent virus, A/Michigan/45/2015. Given the long-standing observation that NA-inhibiting antibodies are associated with resistance against disease in humans, these data demonstrate the importance of evaluating NA drift and suggest that vaccine effectiveness might be improved by selecting viruses for vaccine production that have NAs antigenically similar to those of circulating influenza viruses. |
Prospective investigation of folic acid supplements before and during early pregnancy and paediatric and adult cancers in the Chinese children and families cohort: a pilot study in a sample of rural and urban families
Linet MS , Wang L , Wang N , Berry RJ , Chao A , Hao L , Li Z , Fang L , Yin P , Potischman N , Sun X , Meng F , Yang R , Cong S , Fan J , Kitahara CM , Liang X , Liu F , Lu X , Lv F , Mu C , Sampson J , Tang Y , Wan W , Wang B , Wang H , Zhang L , Wang Y . BMJ Open 2018 8 (7) e022394 OBJECTIVE: To determine the feasibility of long-term prospective follow-up and ascertainment of cancer in offspring and mothers from the 1993-1995 Chinese Community Intervention Program that provided folic acid supplements before and during early pregnancy to reduce neural tube defects. DESIGN: Feasibility pilot study for a prospective cohort study. SETTING: Families residing during 2012-2013 in one rural and one urban county from 21 counties in 3 provinces in China included in the Community Intervention Program campaign. PARTICIPANTS: The feasibility study targeted 560 families, including 280 from the rural and 280 from the urban county included in the large original study; about half of mothers in each group had taken and half had not taken folic acid supplements. INTERVENTION: The planned new study is observational. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary: incidence of paediatric cancers in offspring; secondary: other chronic diseases in offspring and chronic diseases in mothers RESULTS: Only 3.4% of pilot study families could not be found, 3.9% had moved out of the study area and 8.8% refused to participate. Interviews were completed by 82% of mothers, 79% of fathers and 83% of offspring in the 560 families. Almost all mothers and offspring who were interviewed also participated in anthropometric measurements. We found notable urban-rural differences in sociodemographic and lifestyle characteristics of the parents, but fewer differences among the offspring. In eight catchment area hospitals, we identified a broad range of paediatric cancers diagnosed during 1994-2013, although paediatric brain tumours, lymphomas and rarer cancers were likely under-represented. CONCLUSIONS: Overall, 20 years after the original Community Intervention Program, the pilot study achieved high levels of follow-up and family member interview participation, and identified substantial numbers of paediatric malignancies during 1994-2013 in catchment area hospitals. Next steps and strategies for overcoming limitations are described. |
The incidence and prevalence of adult primary Sjogren's syndrome in New York County
Izmirly PM , Buyon JP , Wan I , Belmont HM , Sahl S , Salmon JE , Askanase A , Bathon JM , Geraldino-Pardilla L , Ali Y , Ginzler EM , Putterman C , Gordon C , Helmick CG , Parton H . Arthritis Care Res (Hoboken) 2018 71 (7) 949-960 OBJECTIVE: Extant epidemiologic data of primary Sjogren's Syndrome (pSS) remains limited, particularly for racial/ethnic populations in the United States (US). The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of cases with Systemic Lupus Erythematosus and related diseases including pSS in Manhattan, was used to provide estimates of the incidence and prevalence of pSS across major racial/ethnic populations. METHODS: MLSP cases were identified from hospitals, rheumatologists, and population databases. Three case definitions were used for pSS: physician diagnosis, rheumatologist diagnosis, and modified pSS criteria. Rates among Manhattan residents were age-adjusted, and capture-recapture analyses were conducted to assess case under-ascertainment. RESULTS: By physician diagnosis, age-adjusted overall incidence and prevalence rates of pSS among adult Manhattan residents were 3.5 and 13.1 per 100,000 person-years. Capture-recapture adjustment increased incidence and prevalence rates (4.1 and 14.2). Based on physician diagnosis, incidence and prevalence rates were approximately 6 times higher among women than men (p<0.01). Incidence of pSS was statistically higher among non-Latina Asian (10.5) and non-Latina White women (6.2) compared with Latina women (3.2). Incidence was also higher among non-Latina Asian women compared with non-Latina Black women (3.3). Prevalence of pSS did not differ by race/ethnicity. Similar trends were observed when more restrictive case definitions were applied. CONCLUSION: Data from the MLSP revealed disparities in pSS incidence and prevalence by sex among Manhattan residents and differences in pSS incidence by race/ethnicity among women. These data also provided epidemiologic estimates for the major racial/ethnic populations in the US. This article is protected by copyright. All rights reserved. |
The incidence and prevalence of systemic lupus erythematosus in New York County (Manhattan), New York: The Manhattan Lupus Surveillance Program
Izmirly PM , Wan I , Sahl S , Buyon JP , Belmont HM , Salmon JE , Askanase A , Bathon JM , Geraldino-Pardilla L , Ali Y , Ginzler EM , Putterman C , Gordon C , Helmick CG , Parton H . Arthritis Rheumatol 2017 69 (10) 2006-2017 OBJECTIVE: The Manhattan Lupus Surveillance Program (MLSP) is a population-based registry designed to determine the prevalence of systemic lupus erythematosus (SLE) in 2007 and the incidence from 2007 to 2009 among residents of New York County (Manhattan), New York, and to characterize cases by race/ethnicity, including Asians and Hispanics, for whom data are lacking. METHODS: We identified possible SLE cases from hospital records, rheumatologist records, and administrative databases. Cases were defined according to the American College of Rheumatology (ACR) classification criteria, the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, or the treating rheumatologist's diagnosis. Rates among Manhattan residents were age-standardized, and capture-recapture analyses were conducted to assess case underascertainment. RESULTS: By the ACR definition, the age-standardized prevalence and incidence rates of SLE were 62.2 and 4.6 per 100,000 person-years, respectively. Rates were approximately 9 times higher in women than in men for prevalence (107.4 versus 12.5) and incidence (7.9 versus 1.0). Compared with non-Hispanic white women (64.3), prevalence was higher among non-Hispanic black (210.9), Hispanic (138.3), and non-Hispanic Asian (91.2) women. Incidence rates were higher among non-Hispanic black women (15.7) compared with non-Hispanic Asian (6.6), Hispanic (6.5), and non-Hispanic white (6.5) women. Capture-recapture adjustment increased the prevalence and incidence rates (75.9 and 6.0, respectively). Alternate SLE definitions without capture-recapture adjustment revealed higher age-standardized prevalence and incidence rates (73.8 and 6.2, respectively, by the SLICC definition and 72.6 and 5.0 by the rheumatologist definition) than the ACR definition, with similar patterns by sex and race/ethnicity. CONCLUSION: The MLSP confirms findings from other registries on disparities by sex and race/ethnicity, provides new estimates among Asians and Hispanics, and provides estimates using the SLICC criteria. |
Clonal Evolution of Enterocytozoon bieneusi Populations in Swine and Genetic Differentiation in Subpopulations between Isolates from Swine and Humans.
Wan Q , Xiao L , Zhang X , Li Y , Lu Y , Song M , Li W . PLoS Negl Trop Dis 2016 10 (8) e0004966 Enterocytozoon bieneusi is a widespread parasite with high genetic diversity among hosts. Its natural reservoir remains elusive and data on population structure are available only in isolates from primates. Here we describe a population genetic study of 101 E. bieneusi isolates from pigs using sequence analysis of the ribosomal internal transcribed spacer (ITS) and four mini- and microsatellite markers. The presence of strong linkage disequilibrium (LD) and limited genetic recombination indicated a clonal structure for the population. Bayesian inference of phylogeny, structural analysis, and principal coordinates analysis separated the overall population into three subpopulations (SP3 to SP5) with genetic segregation of the isolates at some geographic level. Comparative analysis showed the differentiation of SP3 to SP5 from the two known E. bieneusi subpopulations (SP1 and SP2) from primates. The placement of a human E. bieneusi isolate in pig subpopulation SP4 supported the zoonotic potential of some E. bieneusi isolates. Network analysis showed directed evolution of SP5 to SP3/SP4 and SP1 to SP2. The high LD and low number of inferred recombination events are consistent with the possibility of host adaptation in SP2, SP3, and SP4. In contrast, the reduced LD and high genetic diversity in SP1 and SP5 might be results of broad host range and adaptation to new host environment. The data provide evidence of the potential occurrence of host adaptation in some of E. bieneusi isolates that belong to the zoonotic ITS Group 1. |
Genetic variation of mini- and microsatellites and a clonal structure in Enterocytozoon bieneusi population in foxes and raccoon dogs and population differentiation of the parasite between fur animals and humans.
Li W , Wan Q , Yu Q , Yang Y , Tao W , Jiang Y , Xiao L . Parasitol Res 2016 115 (7) 2899-904 Enterocytozoon bieneusi is an obligate intracellular protozoan parasite that infects a wide range of mammal hosts and birds. Previous genotypic surveys were limited to measure the polymorphisms at the ribosomal internal transcribed spacer (ITS) that evolved slowly. Data on population structure are available only on E. bieneusi isolates from primates. This study explored the genotypic and phylogenetic characteristics of four mini- and microsatellites and performed a population genetic analysis in 39 E. bieneusi isolates of potentially zoonotic ITS genotype D from farmed foxes and raccoon dogs in China. Sequence polymorphisms facilitated determination of six, two, four, and five genotypes at markers MS1, MS3, MS4, and MS7, respectively. Patterns of phylogeny revealed different levels of diversity within and among the genetic markers. Clear genotypic and phylogenetic divergences between E. bieneusi isolates of ITS genotype D from fur animals and humans were observed at individual markers. Complete linkage disequilibrium and very limited recombination in subsequent population genetic analysis supported a clonal structure for E. bieneusi population from fur animals (FID). Phylogenetic analysis, genetic network, and measures of F ST and gene flow demonstrated population differentiation of FID from two known human E. bieneusi populations HID (with a clonal structure) and HIA (with an epidemic structure). The data indicated an ideal resolving power of MLST compared to the previously widely used ITS genotyping and confirmed the clonal nature and population differentiation of E. bieneusi in various hosts. |
Health department HIV prevention programs that support the national HIV/AIDS strategy: the enhanced comprehensive HIV prevention planning project, 2010–2013
Fisher HH , Hoyte T , Purcell DW , van Handel M , Williams W , Krueger A , Dietz P , Stratford D , Heitgerd J , Dunbar E , Wan C , Linley LA , Flores SA . Public Health Rep 2016 131 (1) 185-194 OBJECTIVE: The Enhanced Comprehensive HIV Prevention Planning project was the first initiative of the Centers for Disease Control and Prevention (CDC) to address the goals of the National HIV/AIDS Strategy (NHAS). Health departments in 12 U.S. cities with a high prevalence of AIDS conducted comprehensive program planning and implemented cost-effective, scalable HIV prevention interventions that targeted high-risk populations. We examined trends in health department HIV prevention programs in these cities during the project. METHODS: We analyzed the number of people who received partner services, condoms distributed, and people tested for HIV, as well as funding allocations for selected HIV prevention programs by year and by site from October 2010 through September 2013. We assessed trends in the proportional change in services and allocations during the project period using generalized estimating equations. We also conducted thematic coding of program activities that targeted people living with HIV infection (PLWH). RESULTS: We found significant increases in funding allocations for HIV testing and condom distribution. All HIV partner services indicators, condom distribution, and HIV testing of African American and Hispanic/Latino populations significantly increased. HIV tests associated with a new diagnosis increased significantly among those self-identifying as Hispanic/Latino but significantly decreased among African Americans. For programs targeting PLWH, health department activities included implementing new program models, improving local data use, and building local capacity to enhance linkage to HIV medical care, retention in care, and treatment adherence. CONCLUSIONS: Overall, these findings indicate that health departments in areas with a high burden of AIDS successfully shifted their HIV prevention resources to scale up important HIV programs and make progress toward NHAS goals. © 2016 Association of Schools and Programs of Public Health. |
A Bayesian method for analyzing combinations of continuous, ordinal, and nominal categorical data with missing values
Zhang X , Boscardin W , Belin TR , Wan X , He Y , Zhang K . J Multivar Anal 2015 135 43-58 From a Bayesian perspective, we propose a general method for analyzing a combination of continuous, ordinal (including binary), and categorical/nominal multivariate measures with missing values. We assume multivariate normal linear regression models for multivariate continuous measures, multivariate probit models for correlated ordinal measures, and multivariate multinomial probit models for multivariate categorical/nominal measures. Then we assume a multivariate normal linear model on the continuous vector comprised of continuous variables and those underlying normal variables for ordinal variables from multivariate probit models and for categorical variables from multinomial probit models. We develop a Markov chain Monte Carlo (MCMC) algorithm to estimate unknown parameters including regression parameters, cut-points for ordinal data from the multivariate probit models, and the covariance matrix encompassing both continuous variables and the underlying normal latent variables. Combining the continuous variables and the normal latent variables allows us to model combinations of continuous, ordinal, and categorical multivariate data simultaneously. The framework incorporates flexible priors for the covariance matrix, provides a foundation for inference about the underlying covariance structure, and imputes missing data where needed. The method is illustrated through simulated examples and two real data applications. |
Centers for Disease Control and Prevention funding for HIV testing associated with higher state percentage of persons tested
Hayek S , Dietz PM , Van Handel M , Zhang J , Shrestha RK , Huang YL , Wan C , Mermin J . J Public Health Manag Pract 2015 21 (6) 531-7 OBJECTIVES: To assess the association between state per capita allocations of Centers for Disease Control and Prevention (CDC) funding for HIV testing and the percentage of persons tested for HIV. SETTING AND PARTICIPANTS: We examined data from 2 sources: 2011 Behavioral Risk Factor Surveillance System and 2010-2011 State HIV Budget Allocations Reports. Behavioral Risk Factor Surveillance System data were used to estimate the percentage of persons aged 18 to 64 years who had reported testing for HIV in the last 2 years in the United States by state. State HIV Budget Allocations Reports were used to calculate the state mean annual per capita allocations for CDC-funded HIV testing reported by state and local health departments in the United States. DESIGN: The association between the state fixed-effect per capita allocations for CDC-funded HIV testing and self-reported HIV testing in the last 2 years among persons aged 18 to 64 years was assessed with a hierarchical logistic regression model adjusting for individual-level characteristics. MAIN OUTCOME: The percentage of persons tested for HIV in the last 2 years. RESULTS: In 2011, 18.7% (95% confidence interval = 18.4-19.0) of persons reported being tested for HIV in last 2 years (state range, 9.7%-28.2%). During 2010-2011, the state mean annual per capita allocation for CDC-funded HIV testing was $0.34 (state range, $0.04-$1.04). A $0.30 increase in per capita allocation for CDC-funded HIV testing was associated with an increase of 2.4 percentage points (14.0% vs 16.4%) in the percentage of persons tested for HIV per state. CONCLUSIONS: Providing HIV testing resources to health departments was associated with an increased percentage of state residents tested for HIV. |
Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers
Wan H , Yang H , Shore DA , Garten RJ , Couzens L , Gao J , Jiang L , Carney PJ , Villanueva J , Stevens J , Eichelberger MC . Nat Commun 2015 6 6114 A(H1N1)pdm09 influenza A viruses predominated in the 2013-2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses. |
Prevalence and genetic characteristics of Cryptosporidium, Enterocytozoon bieneusi and Giardia duodenalis in cats and dogs in Heilongjiang province, China.
Li W , Li Y , Song M , Lu Y , Yang J , Tao W , Jiang Y , Wan Q , Zhang S , Xiao L . Vet Parasitol 2015 208 125-34 This study investigated 319 fecal specimens of cats (n=52) and dogs (n=267) from Heilongjiang province, China for the prevalence and genetic characteristics of Cryptosporidium, Enterocytozoon bieneusi, and Giardia duodenalis. PCR and DNA sequence analysis of the small subunit rRNA gene identified C. felis and C. parvum in one cat each (3.8%) and C. canis and C. ubiquitum in 6 dogs (2.2%). Polymorphisms in the ribosomal internal transcribed spacer and phylogenetic analysis characterized zoonotic E. bieneusi genotypes D, EbpC, NED1, and NED2 and host-adapted ones NED3, NED4, and PtEb IX in 18 dogs (6.7%) and human-pathogenic genotypes D and IV in 3 cats (5.8%). Genotyping based on the hypermutation of G. duodenalis triosephosphate isomerase gene (TPI) facilitated identification of assemblage F in a cat (1.9%) and assemblages C and E in 12 dogs (4.5%). Subtypes of G. duodenalis isolates were determined by measuring the diversity of both TPI nucleotide and amino acid sequences. C. canis, C. felis, C. parvum, E. bieneusi genotypes D, EbpC, and IV, and G. duodenalis assemblage C identified herein have been documented in human infections in China. C. canis, C. parvum, C. ubiquitum, and E. bieneusi genotypes D, EbpC, and IV carried by cats or dogs also existed in wastewater in China. The finding suggested pet animals could be reservoirs for human cryptosporidiosis, microsporidiosis, and giardiasis and potential sources of water contamination in China. |
Genomic analysis of the causative agents of coccidiosis in domestic chickens.
Reid AJ , Blake DP , Ansari HR , Billington K , Browne HP , Bryant JM , Dunn M , Hung SS , Kawahara F , Miranda-Saavedra D , Malas T , Mourier T , Naghra H , Nair M , Otto TD , Rawlings ND , Rivailler P , Sanchez-Flores A , Sanders M , Subramaniam C , Tay YL , Woo Y , Wu X , Barrell B , Dear PH , Doerig C , Gruber A , Ivens AC , Parkinson J , Rajandream MA , Shirley MW , Wan KL , Berriman M , Tomley FM , Pain A . Genome Res 2014 24 (10) 1676-85 Global production of chickens has trebled in the past two decades and they are now the most important source of dietary animal protein worldwide. Chickens are subject to many infectious diseases that reduce their performance and productivity. Coccidiosis, caused by apicomplexan protozoa of the genus Eimeria, is one of the most important poultry diseases. Understanding the biology of Eimeria parasites underpins development of new drugs and vaccines needed to improve global food security. We have produced annotated genome sequences of all seven species of Eimeria that infect domestic chickens, which reveal the full extent of previously described repeat-rich and repeat-poor regions and show that these parasites possess the most repeat-rich proteomes ever described. Furthermore, while no other apicomplexan has been found to possess retrotransposons, Eimeria is home to a family of chromoviruses. Analysis of Eimeria genes involved in basic biology and host-parasite interaction highlights adaptations to a relatively simple developmental life cycle and a complex array of co-expressed surface proteins involved in host cell binding. |
The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells.
Pacurari M , Addison JB , Bondalapati N , Wan YW , Luo D , Qian Y , Castranova V , Ivanov AV , Guo NL . Int J Oncol 2013 43 (2) 548-60 Lung cancer remains the leading cause of cancer-related mortality for both men and women. Tumor recurrence and metastasis is the major cause of lung cancer treatment failure and death. The microRNA200 (miR-200) family is a powerful regulator of the epithelial-mesenchymal transition (EMT) process, which is essential in tumor metastasis. Nevertheless, miR-200 family target genes that promote metastasis in non-small cell lung cancer (NSCLC) remain largely unknown. Here, we sought to investigate whether the microRNA-200 family regulates our previously identified NSCLC prognostic marker genes associated with metastasis, as potential molecular targets. Novel miRNA targets were predicted using bioinformatics tools based on correlation analyses of miRNA and mRNA expression in 57 squamous cell lung cancer tumor samples. The predicted target genes were validated with quantitative RT-PCR assays and western blot analysis following re-expression of miR-200a, -200b and -200c in the metastatic NSCLC H1299 cell line. The results show that restoring miR-200a or miR-200c in H1299 cells induces downregulation of DLC1, ATRX and HFE. Reinforced miR-200b expression results in downregulation of DLC1, HNRNPA3 and HFE. Additionally, miR-200 family downregulates HNRNPR3, HFE and ATRX in BEAS-2B immortalized lung epithelial cells in quantitative RT-PCR and western blot assays. The miR-200 family and these potential targets are functionally involved in canonical pathways of immune response, molecular mechanisms of cancer, metastasis signaling, cell-cell communication, proliferation and DNA repair in Ingenuity pathway analysis (IPA). These results indicate that re-expression of miR-200 downregulates our previously identified NSCLC prognostic biomarkers in metastatic NSCLC cells. These results provide new insights into miR-200 regulation in lung cancer metastasis and consequent clinical outcome, and may provide a potential basis for innovative therapeutic approaches for the treatment of this deadly disease. |
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