Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-9 (of 9 Records) |
Query Trace: Ende Z [original query] |
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Antiviral Approaches against Influenza Virus.
Kumari R , Sharma SD , Kumar A , Ende Z , Mishina M , Wang Y , Falls Z , Samudrala R , Pohl J , Knight PR , Sambhara S . Clin Microbiol Rev 2023 36 (1) e0004022 Preventing and controlling influenza virus infection remains a global public health challenge, as it causes seasonal epidemics to unexpected pandemics. These infections are responsible for high morbidity, mortality, and substantial economic impact. Vaccines are the prophylaxis mainstay in the fight against influenza. However, vaccination fails to confer complete protection due to inadequate vaccination coverages, vaccine shortages, and mismatches with circulating strains. Antivirals represent an important prophylactic and therapeutic measure to reduce influenza-associated morbidity and mortality, particularly in high-risk populations. Here, we review current FDA-approved influenza antivirals with their mechanisms of action, and different viral- and host-directed influenza antiviral approaches, including immunomodulatory interventions in clinical development. Furthermore, we also illustrate the potential utility of machine learning in developing next-generation antivirals against influenza. |
Phylogenetic Structure and Comparative Genomics of Multi-National Invasive Haemophilus influenzae Serotype a Isolates.
Topaz N , Tsang R , Deghmane AE , Claus H , Lâm TT , Litt D , Bajanca-Lavado MP , Pérez-Vázquez M , Vestrheim D , Giufrè M , Van Der Ende A , Gaillot O , Kuch A , McElligott M , Taha MK , Wang X . Front Microbiol 2022 13 856884 Recent reports have indicated a rise of invasive disease caused by Haemophilus influenzae serotype a (Hia) in North America and some European countries. The whole-genome sequences for a total of 410 invasive Hia isolates were obtained from 12 countries spanning the years of 1998 to 2019 and underwent phylogenetic and comparative genomic analysis in order to characterize the major strains causing disease and the genetic variation present among factors contributing to virulence and antimicrobial resistance. Among 410 isolate sequences received, 408 passed our quality control and underwent genomic analysis. Phylogenetic analysis revealed that the Hia isolates formed four genetically distinct clades: clade 1 (n = 336), clade 2 (n = 13), clade 3 (n = 3) and clade 4 (n = 56). A low diversity subclade 1.1 was found in clade 1 and contained almost exclusively North American isolates. The predominant sequence types in the Hia collection were ST-56 (n = 125), ST-23 (n = 98) and ST-576 (n = 51), which belonged to clade 1, and ST-62 (n = 54), which belonged to clade 4. Clades 1 and 4 contained predominantly North American isolates, and clades 2 and 3 predominantly contained European isolates. Evidence of the presence of capsule duplication was detected in clade 1 and 2 isolates. Seven of the virulence genes involved in endotoxin biosynthesis were absent from all Hia isolates. In general, the presence of known factors contributing to β-lactam antibiotic resistance was low among Hia isolates. Further tests for virulence and antibiotic susceptibility would be required to determine the impact of these variations among the isolates. |
Influenza Virus Infects and Depletes Activated Adaptive Immune Responders
Bohannon CD , Ende Z , Cao W , Mboko WP , Ranjan P , Kumar A , Mishina M , Amoah S , Gangappa S , Mittal SK , Lovell JF , García-Sastre A , Pfeifer BA , Davidson BA , Knight P , Sambhara S . Adv Sci (Weinh) 2021 8 (16) e2100693 Influenza infections cause several million cases of severe respiratory illness, hospitalizations, and hundreds of thousands of deaths globally. Secondary infections are a leading cause of influenza's high morbidity and mortality, and significantly factored into the severity of the 1918, 1968, and 2009 pandemics. Furthermore, there is an increased incidence of other respiratory infections even in vaccinated individuals during influenza season. Putative mechanisms responsible for vaccine failures against influenza as well as other respiratory infections during influenza season are investigated. Peripheral blood mononuclear cells (PBMCs) are used from influenza vaccinated individuals to assess antigen-specific responses to influenza, measles, and varicella. The observations made in humans to a mouse model to unravel the mechanism is confirmed and extended. Infection with influenza virus suppresses an ongoing adaptive response to vaccination against influenza as well as other respiratory pathogens, i.e., Adenovirus and Streptococcus pneumoniae by preferentially infecting and killing activated lymphocytes which express elevated levels of sialic acid receptors. These findings propose a new mechanism for the high incidence of secondary respiratory infections due to bacteria and other viruses as well as vaccine failures to influenza and other respiratory pathogens even in immune individuals due to influenza viral infections. |
Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study
Horváth-Puhó E , van Kassel MN , Gonçalves BP , de Gier B , Procter SR , Paul P , van der Ende A , Søgaard KK , Hahné SJM , Chandna J , Schrag SJ , van de Beek D , Jit M , Sørensen HT , Bijlsma MW , Lawn JE . Lancet Child Adolesc Health 2021 5 (6) 398-407 BACKGROUND: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands. METHODS: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts. FINDINGS: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], p<0·0001) and hospital admissions (1·33 [1·27-1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts. INTERPRETATION: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATIONS: For the Dutch and Danish translations of the abstract see Supplementary Materials section. |
Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection - United Kingdom and United States, March-August 2020.
Morris SB , Schwartz NG , Patel P , Abbo L , Beauchamps L , Balan S , Lee EH , Paneth-Pollak R , Geevarughese A , Lash MK , Dorsinville MS , Ballen V , Eiras DP , Newton-Cheh C , Smith E , Robinson S , Stogsdill P , Lim S , Fox SE , Richardson G , Hand J , Oliver NT , Kofman A , Bryant B , Ende Z , Datta D , Belay E , Godfred-Cato S . MMWR Morb Mortal Wkly Rep 2020 69 (40) 1450-1456 During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition. |
The Global Meningitis Genome Partnership.
Rodgers E , Bentley SD , Borrow R , Bratcher HB , Brisse S , Brueggemann AB , Caugant DA , Findlow J , Fox L , Glennie L , Harrison LH , Harrison OB , Heyderman RS , van Rensburg MJ , Jolley KA , Kwambana-Adams B , Ladhani S , LaForce M , Levin M , Lucidarme J , MacAlasdair N , Maclennan J , Maiden MCJ , Maynard-Smith L , Muzzi A , Oster P , Rodrigues CMC , Serino ORL , Smith V , van der Ende A , Vazquez J , Wang X , Yezli S , Stuart JM . J Infect 2020 81 (4) 510-520 Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1,935), Sa (9,026); The Wellcome Sanger Institute: Nm (13,711), Sp (>24,000), Sa (6,200), Hi (1738); and BMGAP: Nm (8,785), Hi (2,030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data. |
The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: a systematic review and meta-analysis
Balsells E , Dagan R , Yildirim I , Gounder PP , Steens A , Munoz-Almagro C , Mameli C , Kandasamy R , Lavi NG , Daprai L , van der Ende A , Trzcinski K , Nzenze S , Meiring S , Foster D , Bulkow LR , Rudolph K , Valero-Rello A , Ducker S , Vestrheim DF , von Gottberg A , Pelton SI , Zuccotti G , Pollard AJ , Sanders EAM , Campbell H , Madhi SA , Nair H , Kyaw MH . J Infect 2018 77 (5) 368-378 OBJECTIVES: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV). METHODS: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes. RESULTS: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR>5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0*1-0*3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum. CONCLUSIONS: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines. |
It's not as simple as it sounds: problems and solutions in accessing and using administrative child welfare data for evaluating the impact of early childhood interventions
Green BL , Ayoub C , Bartlett JD , Furrer C , Von Ende A , Chazan-Cohen R , Klevens J , Nygren P . Child Youth Serv Rev 2015 57 40-49 In recent years, there has been increasing interest in using administrative data collected by state child welfare agencies as a source of information for research and evaluation. The challenges of obtaining access to and using these data, however, have not been well documented. This study describes the processes used to access child welfare records in six different states and the approach to combining and using the information gathered to evaluate the impact of the Early Head Start program on children's involvement with the child welfare system from birth through age eleven. We provide "lessons learned" for researchers who are attempting to use this information, including being prepared for long delays in access to information, the need for deep understanding of how child welfare agencies record and code information, and for considerable data management work for translating agency records into analysis-ready datasets. While accessing and using this information is not easy, and the data have a number of limitations, we suggest that the benefits can outweigh the challenges and that these records can be a useful source of information for policy-relevant child welfare research. |
The effect of Early Head Start on child welfare system involvement: a first look at longitudinal child maltreatment outcomes
Green BL , Ayoub C , Bartlett JD , Von Ende A , Furrer C , Chazan-Cohen R , Vallotton C , Klevens J . Child Youth Serv Rev 2014 42 127-135 The high societal and personal costs of child maltreatment make identification of effective early prevention programs a high research priority. Early Head Start (EHS), a dual generational program serving low-income families with children prenatally through age three years, is one of the largest federally funded programs for infants and toddlers in the United States. A national randomized trial found EHS to be effective in improving parent and child outcomes, but its effectiveness in reducing child maltreatment was not assessed. The current study used administrative data from state child welfare agencies to examine the impact of EHS on documented abuse and neglect among children from seven of the original seventeen programs in the national EHS randomized controlled trial. Results indicated that children in EHS had significantly fewer child welfare encounters between the ages of five and nine years than did children in the control group, and that EHS slowed the rate of subsequent encounters. Additionally, compared to children in the control group, children in EHS were less likely to have a substantiated report of physical or sexual abuse, but more likely to have a substantiated report of neglect. These findings suggest that EHS may be effective in reducing child maltreatment among low-income children, in particular, physical and sexual abuse. |
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