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Article ; Online: The Role of Punctuated Evolution in the Pathogenicity of Influenza Viruses.

McCullers, Jonathan A

Microbiology spectrum

2016 Volume 4, Issue 2

Abstract: Influenza is an acute respiratory disease caused by influenza viruses. Evolutionarily, all influenza viruses are zoonoses, arising in the animal reservoir and spilling over into the human population. Several times a century, one of these zoonotic events ... ...

Abstract	Influenza is an acute respiratory disease caused by influenza viruses. Evolutionarily, all influenza viruses are zoonoses, arising in the animal reservoir and spilling over into the human population. Several times a century, one of these zoonotic events results in a new influenza virus lineage becoming established in humans and circulating for years or decades as an endemic strain. The worldwide pandemic that occurs shortly after the nascent virus becomes established can have a profound impact on morbidity and mortality. Because influenza viruses continually evolve and the illness they engender can vary considerably based on characteristics of the strain, the weather, other circulating or endemic pathogens, as well as the number of susceptible hosts, the impact of each season on human health is unpredictable. Over time, the general pattern is for pandemic strains to adapt and gradually take on characteristics of seasonal strains with lower virulence and a diminished synergism with bacterial pathogens. Study of this punctuated evolution yields a number of insights into the overall pathogenicity of influenza viruses.
MeSH term(s)	Animals ; Biological Evolution ; Birds ; Disease Outbreaks ; Evolution, Molecular ; Humans ; Influenza A virus/genetics ; Influenza A virus/pathogenicity ; Influenza in Birds/epidemiology ; Influenza in Birds/virology ; Influenza, Human/epidemiology ; Influenza, Human/virology ; Orthomyxoviridae/genetics ; Orthomyxoviridae/pathogenicity ; Virulence
Keywords	covid19
Language	English
Publishing date	2016-05-17
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2165-0497
ISSN (online)	2165-0497
DOI	10.1128/microbiolspec.EI10-0001-2015
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Article ; Online: Whole Child Well-Child Visits: Implementing ACEs and SDOH Screenings in Primary Care.

Yaun, Jason A / Rogers, Lisa W / Marshall, August / McCullers, Jonathan A / Madubuonwu, Sandra

Clinical pediatrics

2022 Volume 61, Issue 8, Page(s) 542–550

Abstract: Adverse childhood experiences (ACEs) and social determinants of health (SDOH) negatively affect health outcomes. This program was developed to screen for ACEs and SDOH in the primary care setting in families with children 9 months to 5 years of age at ... ...

Abstract	Adverse childhood experiences (ACEs) and social determinants of health (SDOH) negatively affect health outcomes. This program was developed to screen for ACEs and SDOH in the primary care setting in families with children 9 months to 5 years of age at well-child checks and provide interventions that support families and build resiliency. Programmatic criteria were identified, referral resources were developed, and a database was implemented, with 246 families enrolled in year 1; 56.9% of caregivers reported 1 or more ACEs for their child, 63% of caregivers reported an SDOH need, and 39.4% of caregivers reported both. The average number of ACEs was 0.94. This program was created to address ACEs and SDOH, to empower families, build resiliency, and provide buffers to mitigate and prevent ACEs. It provides a model that can be implemented in a primary care setting while providing wraparound resources, including integrated mental health resources and referrals, to measure the success of these interventions.
MeSH term(s)	Adverse Childhood Experiences ; Family/psychology ; Humans ; Primary Health Care ; Social Determinants of Health ; Surveys and Questionnaires
Language	English
Publishing date	2022-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207678-0
ISSN	1938-2707 ; 0009-9228
ISSN (online)	1938-2707
ISSN	0009-9228
DOI	10.1177/00099228221093279
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Zs.A 454: Show issues

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Article ; Online: Utility of Induced Sputum in Assessing Bacterial Etiology for Community-Acquired Pneumonia in Hospitalized Children.

Green, Amanda / Cockroft, Jody L / Kaufman, Robert A / McCullers, Jonathan A / Arnold, Sandra R

Journal of the Pediatric Infectious Diseases Society

2022 Volume 11, Issue 6, Page(s) 274–282

Abstract: Background: Diagnostic testing for bacterial etiology of community-acquired pneumonia (CAP) is insensitive. Induced sputum (IS) is an attractive option for the evaluation of the lower respiratory tract.: Methods: Children aged 0-18 years with CAP ... ...

Abstract	Background: Diagnostic testing for bacterial etiology of community-acquired pneumonia (CAP) is insensitive. Induced sputum (IS) is an attractive option for the evaluation of the lower respiratory tract. Methods: Children aged 0-18 years with CAP were enrolled in the Etiology of Pneumonia in the Community (EPIC) study between 2010 and 2012. Blood and respiratory specimens were assessed by culture and polymerase chain reaction (PCR). The radiographic CAP was determined by a study radiologist. Sputum was induced with hypertonic saline. IS specimen was high quality (HQ) if Gram stain showed >25 white blood and <10 epithelial cells per low-powered field; all others were low quality (LQ). We compared IS pathogen prevalence between HQ and LQ IS, and by radiographic pneumonia. Pathogen concordance with EPIC etiology was assessed. Length of stay (LOS) was compared by receipt of IS pathogen-concordant antibiotics. Results: Out of 977 children, 916 (94%) children enrolled in Memphis, Tennessee, produced IS; 794 (87%) had radiographic CAP and 174 (19%) were HQ. HQ IS yielded pathogenic bacteria more often than LQ (64% vs 44%; P < .01); however, pathogens were isolated at similar rates in HQ IS in patients with and without radiographic CAP (64% vs. 63%; P = .6). Pathogens from study specimens matched an IS pathogen in only 9/42 (21%) patients with radiographic CAP. Median LOS was similar among patients with radiographic CAP regardless of receipt of IS pathogen-concordant antibiotics (3.1 days), non-pathogen-concordant antibiotics (2.7 days), or no antibiotics (3.2 days; P = .5). Conclusions: Bacterial pathogens were isolated from most IS cultures regardless of radiographic CAP and quality of IS. IS cultures infrequently corresponded with sterile site cultures. Isolation of pathogens from pediatric IS reflects oropharyngeal carriage and is insufficient to determine bacterial etiology of CAP.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Bacteria ; Child ; Child, Hospitalized ; Community-Acquired Infections/diagnosis ; Community-Acquired Infections/microbiology ; Humans ; Pneumonia/diagnostic imaging ; Pneumonia/etiology ; Sputum/microbiology
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2022-04-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2668791-4
ISSN	2048-7207 ; 2048-7193
ISSN (online)	2048-7207
ISSN	2048-7193
DOI	10.1093/jpids/piac014
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Article ; Online: The public health policy implications of understanding metabiosis.

McCullers, Jonathan A

Cell host & microbe

2014 Volume 16, Issue 1, Page(s) 3–4

Abstract: In this issue of Cell Host & Microbe, Siegel et al. (2014) report that colonization of Streptococcus pneumoniae is facilitated by coinfection with influenza virus through utilization of sialic acids cleaved by the viral neuraminidase. The implications of ...

Abstract	In this issue of Cell Host & Microbe, Siegel et al. (2014) report that colonization of Streptococcus pneumoniae is facilitated by coinfection with influenza virus through utilization of sialic acids cleaved by the viral neuraminidase. The implications of this finding for use of influenza antivirals to prevent flu-related complications are discussed.
MeSH term(s)	Animals ; Coinfection/pathology ; Microbial Interactions ; Orthomyxoviridae/growth & development ; Orthomyxoviridae Infections/complications ; Pneumonia, Pneumococcal/complications ; Sialic Acids/metabolism ; Streptococcus pneumoniae/growth & development
Chemical Substances	Sialic Acids
Language	English
Publishing date	2014-07-10
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2014.06.010
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Zs.A 6578: Show issues

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Article ; Online: The co-pathogenesis of influenza viruses with bacteria in the lung.

McCullers, Jonathan A

Nature reviews. Microbiology

2014 Volume 12, Issue 4, Page(s) 252–262

Abstract: Concern that a highly pathogenic virus might cause the next influenza pandemic has spurred recent research into influenza and its complications. Bacterial superinfection in the lungs of people suffering from influenza is a key element that promotes ... ...

Abstract	Concern that a highly pathogenic virus might cause the next influenza pandemic has spurred recent research into influenza and its complications. Bacterial superinfection in the lungs of people suffering from influenza is a key element that promotes severe disease and mortality. This co-pathogenesis is characterized by complex interactions between co-infecting pathogens and the host, leading to the disruption of physical barriers, dysregulation of immune responses and delays in a return to homeostasis. The net effect of this cascade can be the outgrowth of the pathogens, immune-mediated pathology and increased morbidity. In this Review, advances in our understanding of the underlying mechanisms are discussed, and the key questions that will drive the field forwards are articulated.
MeSH term(s)	Bacterial Infections/etiology ; Bacterial Infections/microbiology ; Bacterial Infections/virology ; Coinfection/microbiology ; Coinfection/virology ; Humans ; Influenza, Human/complications ; Influenza, Human/microbiology ; Influenza, Human/virology ; Lung/microbiology ; Lung/pathology ; Lung/virology ; Pneumonia, Bacterial/etiology ; Pneumonia, Bacterial/microbiology ; Pneumonia, Bacterial/virology ; Pneumonia, Viral/complications ; Pneumonia, Viral/microbiology ; Pneumonia, Viral/virology ; Superinfection/microbiology ; Superinfection/virology
Language	English
Publishing date	2014-03-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/nrmicro3231
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Zs.A 5865: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 74: Show issues

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Article ; Online: Influenza: annual seasonal severity.

Gavigan, Patrick / McCullers, Jonathan A

Current opinion in pediatrics

2018 Volume 31, Issue 1, Page(s) 112–118

Abstract: Purpose of review: Influenza remains a major cause of morbidity and mortality. The 2017-2018 season was one of the most severe in the past decade. The exact factors determining the severity of a particular influenza season are complex and often poorly ... ...

Abstract	Purpose of review: Influenza remains a major cause of morbidity and mortality. The 2017-2018 season was one of the most severe in the past decade. The exact factors determining the severity of a particular influenza season are complex and often poorly understood. Recent findings: Factors impacting annual influenza severity include characteristics of the specific virus, influenza vaccination, and antiviral use. Although viral virulence factors are important in this context and our knowledge of these is growing, there is a complex interplay between expression of these factors and their impact on a particular patient population. Vaccination has demonstrated efficacy in preventing disease, but vaccination rates remain sub-optimal and vaccine effectiveness can vary significantly between influenza strains and patient populations. Finally, while antiviral treatment is available and has shown benefits, many patients with influenza do not receive treatment. Summary: Strides have been made in recent years towards understanding the many factors that contribute to the severity of any particular influenza season. Obvious areas for improvement include improved vaccination rates and antiviral use. Additionally, a more complete understanding of reasons for poor strain and population-specific vaccine effectiveness may help reduce the severity of future influenza seasons.
MeSH term(s)	Antiviral Agents/therapeutic use ; Humans ; Influenza Vaccines ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Influenza, Human/therapy ; Seasons ; Vaccination
Chemical Substances	Antiviral Agents ; Influenza Vaccines
Language	English
Publishing date	2018-11-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1049374-8
ISSN	1531-698X ; 1040-8703
ISSN (online)	1531-698X
ISSN	1040-8703
DOI	10.1097/MOP.0000000000000712
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Zs.A 3049: Show issues

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Article ; Online: Effect of Vitamin A Deficiency in Dysregulating Immune Responses to Influenza Virus and Increasing Mortality Rates After Bacterial Coinfections.

Penkert, Rhiannon R / Smith, Amanda P / Hrincius, Eike R / McCullers, Jonathan A / Vogel, Peter / Smith, Amber M / Hurwitz, Julia L

The Journal of infectious diseases

2020 Volume 223, Issue 10, Page(s) 1806–1816

Abstract: Background: Secondary bacterial coinfections are ranked as a leading cause of hospitalization and morbid conditions associated with influenza. Because vitamin A deficiency (VAD) and insufficiency are frequent in both developed and developing countries, ... ...

Abstract	Background: Secondary bacterial coinfections are ranked as a leading cause of hospitalization and morbid conditions associated with influenza. Because vitamin A deficiency (VAD) and insufficiency are frequent in both developed and developing countries, we asked how VAD influences coinfection severity. Methods: VAD and control mice were infected with influenza virus for evaluation of inflammatory cytokines, cellular immune responses, and viral clearance. Influenza-infected mice were coinfected with Streptococcus pneumoniae to study weight loss and survival. Results: Naive VAD mouse lungs exhibited dysregulated immune function. Neutrophils were enhanced in frequency and there was a significant reduction in RANTES (regulated on activation of normal T cells expressed and secreted), a chemokine instrumental in T-cell homing and recruitment. After influenza virus infection, VAD mice experienced failures in CD4+ T-cell recruitment and B-cell organization into lymphoid structures in the lung. VAD mice exhibited higher viral titers than controls and slow viral clearance. There were elevated levels of inflammatory cytokines and innate cell subsets in the lungs. However, arginase, a marker of alternatively activated M2 macrophages, was rare. When influenza-infected VAD animals were exposed to bacteria, they experienced a 100% mortality rate. Conclusion: Data showed that VAD dysregulated the immune response. Consequently, secondary bacterial infections were 100% lethal in influenza-infected VAD mice.
MeSH term(s)	Animals ; Coinfection ; Cytokines ; Immunity ; Lung ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae ; Orthomyxoviridae Infections/complications ; Pneumococcal Infections/complications ; Pneumococcal Infections/mortality ; Streptococcus pneumoniae ; Vitamin A Deficiency/complications
Chemical Substances	Cytokines
Language	English
Publishing date	2020-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiaa597
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Zs.MO 445: Show issues

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Article ; Online: Preventing and treating secondary bacterial infections with antiviral agents.

McCullers, Jonathan A

Antiviral therapy

2011 Volume 16, Issue 2, Page(s) 123–135

Abstract: Bacterial super-infections contribute to the significant morbidity and mortality associated with influenza and other respiratory virus infections. There are robust animal model data, but only limited clinical information on the effectiveness of licensed ... ...

Abstract	Bacterial super-infections contribute to the significant morbidity and mortality associated with influenza and other respiratory virus infections. There are robust animal model data, but only limited clinical information on the effectiveness of licensed antiviral agents for the treatment of bacterial complications of influenza. The association of secondary bacterial pathogens with fatal pneumonia during the recent H1N1 influenza pandemic highlights the need for new development in this area. Basic and clinical research into viral-bacterial interactions over the past decade has revealed several mechanisms that underlie this synergism. By applying these insights to antiviral drug development, the potential exists to improve outcomes by means other than direct inhibition of the virus.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Bacterial Infections/complications ; Bacterial Infections/drug therapy ; Bacterial Infections/prevention & control ; Child, Preschool ; Disease Models, Animal ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/complications ; Influenza, Human/drug therapy ; Influenza, Human/virology ; Mice ; Oseltamivir/therapeutic use ; Pneumonia, Bacterial/complications ; Pneumonia, Bacterial/drug therapy ; Pneumonia, Bacterial/prevention & control ; Randomized Controlled Trials as Topic ; Treatment Outcome
Chemical Substances	Antiviral Agents ; Oseltamivir (20O93L6F9H)
Keywords	covid19
Language	English
Publishing date	2011-04-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1339842-8
ISSN	2040-2058 ; 1359-6535
ISSN (online)	2040-2058
ISSN	1359-6535
DOI	10.3851/IMP1730
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Zs.A 4877: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Particulate matter exposure predicts residence in high-risk areas for community acquired pneumonia among hospitalized children.

Oyana, Tonny J / Minso, Jagila / Jones, Tamekia L / McCullers, Jonathan A / Arnold, Sandra R / Cormier, Stephania A

Experimental biology and medicine (Maywood, N.J.)

2021 Volume 246, Issue 17, Page(s) 1907–1916

Abstract: Particulate matter exposure is a risk factor for lower respiratory tract infection in children. Here, we investigated the geospatial patterns of community-acquired pneumonia and the impact of ... ...

Abstract	Particulate matter exposure is a risk factor for lower respiratory tract infection in children. Here, we investigated the geospatial patterns of community-acquired pneumonia and the impact of PM
MeSH term(s)	Adolescent ; Child ; Child, Hospitalized/statistics & numerical data ; Child, Preschool ; Environmental Exposure/adverse effects ; Humans ; Incidence ; Infant ; Male ; Particulate Matter/adverse effects ; Pneumonia/chemically induced ; Pneumonia/epidemiology ; Pneumonia/etiology ; Risk Factors
Chemical Substances	Particulate Matter
Language	English
Publishing date	2021-05-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/15353702211014456
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Article ; Online: Association of Radiology Findings with Etiology of Community Acquired Pneumonia among Children.

Arnold, Sandra R / Jain, Seema / Dansie, David / Kan, Herman / Williams, Derek J / Ampofo, Krow / Anderson, Evan J / Grijalva, Carlos G / Bramley, Anna M / Pavia, Andrew T / Edwards, Kathryn M / Nolan, Vikki G / McCullers, Jonathan A / Kaufman, Robert A

The Journal of pediatrics

2023 Volume 261, Page(s) 113333

Abstract: Objective: To evaluate the association between consolidation on chest radiograph and typical bacterial etiology of childhood community acquired pneumonia (CAP) in the Etiology of Pneumonia in the Community study.: Study design: Hospitalized children < ...

Abstract	Objective: To evaluate the association between consolidation on chest radiograph and typical bacterial etiology of childhood community acquired pneumonia (CAP) in the Etiology of Pneumonia in the Community study. Study design: Hospitalized children <18 years of age with CAP enrolled in the Etiology of Pneumonia in the Community study at 3 children's hospitals between January 2010 and June 2012 were included. Testing of blood and respiratory specimens used multiple modalities to identify typical and atypical bacterial, or viral infection. Study radiologists classified chest radiographs (consolidation, other infiltrates [interstitial and/or alveolar], pleural effusion) using modified World Health Organization pneumonia criteria. Infiltrate patterns were compared according to etiology of CAP. Results: Among 2212 children, there were 1302 (59%) with consolidation with or without other infiltrates, 910 (41%) with other infiltrates, and 296 (13%) with pleural effusion. In 1795 children, at least 1 pathogen was detected. Among these patients, consolidation (74%) was the most frequently observed pattern (74% in typical bacterial CAP, 58% in atypical bacterial CAP, and 54% in viral CAP). Positive and negative predictive values of consolidation for typical bacterial CAP were 12% (95% CI 10%-15%) and 96% (95% CI 95%-97%) respectively. In a multivariable model, typical bacterial CAP was associated with pleural effusion (OR 7.3, 95% CI 4.7-11.2) and white blood cell ≥15 000/mL (OR 3.2, 95% CI 2.2-4.9), and absence of wheeze (OR 0.5, 95% CI 0.3-0.8) or viral detection (OR 0.2, 95% CI 0.1-0.4). Conclusions: Consolidation predicted typical bacterial CAP poorly, but its absence made typical bacterial CAP unlikely. Pleural effusion was the best predictor of typical bacterial infection, but too uncommon to aid etiology prediction.
MeSH term(s)	Humans ; Child ; Pneumonia/diagnostic imaging ; Pneumonia/epidemiology ; Pneumonia/etiology ; Radiography ; Pleural Effusion/diagnostic imaging ; Pleural Effusion/etiology ; Causality ; Community-Acquired Infections/diagnostic imaging ; Community-Acquired Infections/etiology ; Radiology
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2023.01.010
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