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  1. Article ; Online: Impact of respiratory viral infections on nasopharyngeal pneumococcal colonization dynamics in children.

    Howard, Leigh M / Grijalva, Carlos G

    Current opinion in infectious diseases

    2024  Volume 37, Issue 3, Page(s) 170–175

    Abstract: Purpose of review: Prevention of acute respiratory illnesses (ARI) in children is a global health priority, as these remain a leading cause of pediatric morbidity and mortality throughout the world. As new products and strategies to prevent respiratory ... ...

    Abstract Purpose of review: Prevention of acute respiratory illnesses (ARI) in children is a global health priority, as these remain a leading cause of pediatric morbidity and mortality throughout the world. As new products and strategies to prevent respiratory infections caused by important pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, respiratory syncytial virus and pneumococcus are advancing, increasing evidence suggests that these and other respiratory viruses and pneumococci may exhibit interactions that are associated with altered colonization and disease dynamics. We aim to review recent data evaluating interactions between respiratory viruses and pneumococci in the upper respiratory tract and their potential impact on pneumococcal colonization patterns and disease outcomes.
    Recent findings: While interactions between influenza infection and subsequent increased susceptibility and transmissibility of colonizing pneumococci have been widely reported in the literature, emerging evidence suggests that human rhinovirus, SARS-CoV-2, and other viruses may also exhibit interactions with pneumococci and alter pneumococcal colonization patterns. Additionally, colonizing pneumococci may play a role in modifying outcomes associated with respiratory viral infections. Recent evidence suggests that vaccination with pneumococcal conjugate vaccines, and prevention of colonization with pneumococcal serotypes included in these vaccines, may be associated with reducing the risk of subsequent viral infection and the severity of the associated illnesses.
    Summary: Understanding the direction and dynamics of viral-pneumococcal interactions may elucidate the potential effects of existing and emerging viral and bacterial vaccines and other preventive strategies on the health impact of these important respiratory pathogens.
    MeSH term(s) Humans ; Respiratory Tract Infections/microbiology ; Respiratory Tract Infections/virology ; Streptococcus pneumoniae ; Child ; Pneumococcal Infections/prevention & control ; Pneumococcal Infections/microbiology ; Nasopharynx/microbiology ; Nasopharynx/virology ; COVID-19/microbiology ; SARS-CoV-2 ; Pneumococcal Vaccines ; Child, Preschool ; Coinfection/microbiology ; Virus Diseases
    Chemical Substances Pneumococcal Vaccines
    Language English
    Publishing date 2024-03-04
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 645085-4
    ISSN 1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
    ISSN (online) 1473-6527 ; 1535-3877
    ISSN 0951-7375 ; 1355-834X
    DOI 10.1097/QCO.0000000000001008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Is There an Association Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae?

    Howard, Leigh M

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2020  Volume 72, Issue 5, Page(s) e76–e78

    MeSH term(s) COVID-19 ; Cohort Studies ; England ; Humans ; Pandemics ; Pneumococcal Infections ; Prospective Studies ; SARS-CoV-2 ; Streptococcus pneumoniae
    Language English
    Publishing date 2020-09-01
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciaa1812
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The central role of pneumococcal colonization in the pathogenesis and control of pneumococcal diseases.

    Howard, Leigh M / Grijalva, Carlos G

    Future microbiology

    2018  Volume 13, Page(s) 1453–1456

    MeSH term(s) Adult ; Animals ; Carrier State/microbiology ; Carrier State/pathology ; Carrier State/prevention & control ; Carrier State/therapy ; Child ; Disease Models, Animal ; Humans ; Microbiota ; Nasopharynx/microbiology ; Nasopharynx/pathology ; Pneumococcal Infections/complications ; Pneumococcal Infections/microbiology ; Pneumococcal Infections/prevention & control ; Pneumococcal Infections/therapy ; Pneumococcal Vaccines/therapeutic use ; Serotyping ; Streptococcus pneumoniae/classification ; Streptococcus pneumoniae/pathogenicity ; Vaccines, Conjugate/therapeutic use ; Virulence ; Virus Diseases/complications
    Chemical Substances Pneumococcal Vaccines ; Vaccines, Conjugate
    Language English
    Publishing date 2018-10-12
    Publishing country England
    Document type Editorial
    ISSN 1746-0921
    ISSN (online) 1746-0921
    DOI 10.2217/fmb-2018-0198
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Unraveling the Impact of Pneumococcal Conjugate Vaccines on Bacterial Conjunctivitis in Children.

    Howard, Leigh M / de St Maurice, Annabelle

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2020  Volume 72, Issue 7, Page(s) 1208–1210

    MeSH term(s) Bacteriology ; Child ; Conjunctivitis, Bacterial/epidemiology ; Conjunctivitis, Bacterial/prevention & control ; Humans ; Incidence ; Pneumococcal Vaccines ; Prospective Studies ; Vaccines, Conjugate
    Chemical Substances Pneumococcal Vaccines ; Vaccines, Conjugate
    Language English
    Publishing date 2020-03-12
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciaa202
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Pooling of six respiratory samples for the detection of SARS-CoV-2: A validation and cost study in a cohort in Lima, Peru.

    Ochoa, Mayra / Peña, Bia / Flores, Omar / Gil, Ana I / Ecker, Lucie / Cornejo, Rubelio / Howard, Leigh M / Grijalva, Carlos G / Lanata, Claudio F

    Heliyon

    2023  Volume 9, Issue 8, Page(s) e18904

    Abstract: Background: The continuous evolution of the SARS-CoV-2 pandemic has led to a high demand for diagnostic testing and major shortages in testing materials, especially in low- and middle-income countries. As an alternative to testing individual samples, ... ...

    Abstract Background: The continuous evolution of the SARS-CoV-2 pandemic has led to a high demand for diagnostic testing and major shortages in testing materials, especially in low- and middle-income countries. As an alternative to testing individual samples, pooling of respiratory samples has been suggested. Previous studies have assessed performance of pooling, mainly using nasopharyngeal samples for the detection of SARS-CoV-2, but few studies have examined the performance of pooling the more practical nasal swabs or saliva samples.
    Objective: To evaluate the sensitivity, specificity, and potential cost reduction of pooling of nasal swab (NS) and saliva (SL) samples for detection of SARS-CoV-2 in a community-based cohort study in Lima, Peru.
    Study design: A prospective cohort study was conducted in a community setting in San Juan de Lurigancho, Lima-Peru. NS and SL samples were collected from 132 participants twice-a-week for a 2-month period. Pools of 2 to 12 samples of the same type, from participants of the same household, were tested by RT-PCR. After pooled testing, all individual samples from positive pools and all individual samples from randomly chosen negative pools were evaluated. For assessment of diagnostic performance, pool testing results were compared with results from individual testing, which served as reference, and concordance in pooled and individual test detections was evaluated. Laboratory costs for both types of samples and testing were compared.
    Results: A total of 2008 NS and 2002 SL samples were collected from 132 study participants. We tested 329 NS and 333 SL pools. The mean pool size for NS and SL pools was 6.22 (SD = 0.92) and 6.39 (SD = 1.71), respectively. Using individual testing as reference, NS pooling of 6 had a sensitivity and specificity of 94% and 100%, respectively, with kappa of 0.97 (CI 95%: 0.93-1.00). The corresponding values for SL pooling of 6 were 83%, 100%, and 0.90 (CI 95%: 0.83-0.97). Compared with individual testing, pooling resulted in a cost reduction of 74.8% for NS and 72.4% for SL samples.
    Conclusions: Pooling easy-to-collect respiratory samples, especially NS, demonstrated very high diagnostic performance for detection of SARS-CoV-2 with substantial cost savings. This approach could be considered in large population screening programs, especially in LMIC.
    Language English
    Publishing date 2023-08-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2023.e18904
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients.

    Howard, Leigh M / Jensen, Travis L / Goll, Johannes B / Gelber, Casey E / Bradley, Matthew D / Sherrod, Stacy D / Hoek, Kristen L / Yoder, Sandra / Jimenez-Truque, Natalia / Edwards, Kathryn / Creech, C Buddy

    The Journal of infectious diseases

    2024  

    Abstract: Background: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants.: Methods: Twenty healthy men and women (18-49 years of age) were ... ...

    Abstract Background: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants.
    Methods: Twenty healthy men and women (18-49 years of age) were randomized to receive two doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) one month apart. Urine and serum samples were collected on day 0 and on days 1, 3, and 7 following first vaccination and subjected to metabolomics analyses to identify metabolites, metabolic pathways, and metabolite clusters associated with immunization.
    Results: Seventy-three differentially abundant (DA) serum and 88 urine metabolites were identified for any post-vaccination day comparison. Pathway analysis revealed enrichment of tryptophan, tyrosine and nicotinate metabolism in urine and serum among IIV-AS03 recipients. Increased urine abundance of 4-vinylphenol sulfate on Day 1 was associated with serologic response based on hemagglutination inhibition responses. In addition, 9 DA urine metabolites were identified in participants with malaise compared to those without.
    Conclusions: Our findings suggest that tryptophan, tyrosine, and nicotinate metabolism are upregulated among IIV-AS03 recipients compared with IIV alone. Metabolites within these pathways may serve as measures of immunogenicity and may provide mechanistic insights for adjuvanted vaccines.
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad611
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Epidemiologic trends and characteristics of SARS-CoV-2 infections among children in the United States.

    Rankin, Danielle A / Talj, Rana / Howard, Leigh M / Halasa, Natasha B

    Current opinion in pediatrics

    2020  Volume 33, Issue 1, Page(s) 114–121

    Abstract: Purpose of review: To review the epidemiological characteristics and clinical features associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children in the United States.: Recent findings: In the United States, ...

    Abstract Purpose of review: To review the epidemiological characteristics and clinical features associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children in the United States.
    Recent findings: In the United States, the majority of SARS-CoV-2 infections in children have been mild illnesses, with those 5-17 years of age having the highest frequency. Specifically, the incidence of SARS-CoV-2 in children is two times higher in adolescents (12-17 years) than younger school-aged children (5-11 years). Despite the higher case counts in older children, 10% of pediatric hospitalizations have been in infants less than one year. In addition, severe respiratory and renal complications, hospitalization, and even death have been documented in children.
    Summary: Clinical manifestations of SARS-CoV-2 infection in children range from asymptomatic to severe respiratory distress, with mild nonspecific symptoms being the most commonly reported. The broad clinical presentation and the frequency of asymptomatic or minimally symptomatic infections in children pose challenges for controlling and detecting SARS-CoV-2. However, severe disease has been noted in children with associated medical complications and death. Thus, additional active surveillance and research is needed to understand the burden children contribute to the SARS-CoV-2 pandemic in the United States.
    MeSH term(s) Adolescent ; COVID-19 ; Child ; Child, Preschool ; Hospitalization ; Humans ; Incidence ; Pandemics ; SARS-CoV-2 ; United States/epidemiology
    Language English
    Publishing date 2020-12-05
    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.0000000000000971
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Rapid Changes in Nasopharyngeal Antibiotic Resistance Gene Profiles After Short Courses of Antibiotics in a Pilot Study of Ambulatory Young Children.

    Howard, Leigh M / Dantuluri, Keerti L / Soper, Nicole / Thomsen, Isaac P / Grijalva, Carlos G

    Open forum infectious diseases

    2021  Volume 8, Issue 11, Page(s) ofab519

    Abstract: We quantified antibiotic resistance genes before and after short antibiotic courses in nasopharyngeal specimens from ambulatory children. Carriage of certain bacteria and resistance genes was common before antibiotics. After antibiotics, we observed ... ...

    Abstract We quantified antibiotic resistance genes before and after short antibiotic courses in nasopharyngeal specimens from ambulatory children. Carriage of certain bacteria and resistance genes was common before antibiotics. After antibiotics, we observed substantial reductions in pneumococcal and
    Language English
    Publishing date 2021-10-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofab519
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Concordance in RT-PCR detection of SARS-CoV-2 between samples preserved in viral and bacterial transport medium.

    Peña, Bia / Ochoa, Mayra / Flores, Omar / Gil, Ana I / Ecker, Lucie / Cornejo, Rubelio / Lanata, Claudio F / Howard, Leigh M / Grijalva, Carlos G

    Journal of virological methods

    2022  Volume 304, Page(s) 114522

    Abstract: Background: While the detection of SARS-CoV-2 in samples preserved in viral transport medium (VTM) by RT-PCR is a standard diagnostic method, this may preclude the study of bacterial respiratory pathogens from the same specimen. It is unclear if the use ...

    Abstract Background: While the detection of SARS-CoV-2 in samples preserved in viral transport medium (VTM) by RT-PCR is a standard diagnostic method, this may preclude the study of bacterial respiratory pathogens from the same specimen. It is unclear if the use of skim milk, tryptone, glucose, and glycerin (STGG) transport media, used for study of respiratory bacteria, allows an efficient and concurrent study of SARS-CoV-2 infections.
    Objectives: To determine the concordance in SARS-CoV-2 detection by real time RT-PCR between paired nasopharyngeal (NP) swabs preserved in STGG and nasal (NS) swabs preserved in VTM.
    Study design: Paired samples of NP and NS swabs were collected between December 2020 and March 2021 from a prospective longitudinal cohort study of 44 households and 132 participants from a peri-urban community (Lima, Peru). NP and NS swabs were taken from all participants once and twice per week, respectively, independent of respiratory symptoms. STGG medium was used for NP samples and VTM for NS samples. Samples were analyzed for SARS-CoV-2 by RT-PCR for N, S and ORF1ab targets. We calculated the concordance in detections between sample types and compared the RT-PCR cycle thresholds (Ct).
    Results: Among the 148 paired samples, we observed a high concordance in detections between NP and NS samples (agreement = 94.59%; Kappa = 0.79). Median Ct values were statistically similar between sample types for each RT-PCR target: N, S and ORF1ab (p = 0.11, p = 0.71 and p = 0.11, respectively).
    Conclusions: NP swabs collected in STGG medium are reliable alternatives to nasal swabs collected in VTM for the study of SARS-CoV-2.
    MeSH term(s) COVID-19/diagnosis ; Humans ; Longitudinal Studies ; Nasopharynx/microbiology ; Prospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; SARS-CoV-2/genetics ; Sensitivity and Specificity ; Specimen Handling/methods
    Language English
    Publishing date 2022-03-09
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 8013-5
    ISSN 1879-0984 ; 0166-0934
    ISSN (online) 1879-0984
    ISSN 0166-0934
    DOI 10.1016/j.jviromet.2022.114522
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: COVID-19 and Acute Neurologic Complications in Children.

    Antoon, James W / Hall, Matt / Howard, Leigh M / Herndon, Alison / Freundlich, Katherine L / Grijalva, Carlos G / Williams, Derek J

    Pediatrics

    2022  Volume 150, Issue 5

    Abstract: Background: Little is known about the epidemiology and outcomes of neurologic complications associated with coronavirus disease 2019 (COVID-19) in children.: Methods: We performed a cross-sectional study of children 2 months to <18 years of age with ... ...

    Abstract Background: Little is known about the epidemiology and outcomes of neurologic complications associated with coronavirus disease 2019 (COVID-19) in children.
    Methods: We performed a cross-sectional study of children 2 months to <18 years of age with COVID-19 discharged from 52 children's hospitals from March 2020 to March 2022. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye's syndrome, and cerebral infarction. We assessed length of stay (LOS), ICU admission, 30 day readmissions, deaths, and hospital costs. We used multivariable logistic regression to identify factors associated with neurologic complications.
    Results: Of 15 137 children hospitalized with COVID-19, 1060 (7.0%) had a concurrent diagnosis of a neurologic complication. The most frequent neurologic complications were febrile seizures (3.9%), nonfebrile seizures (2.3%), and encephalopathy (2.2%). Hospital LOS, ICU admission, ICU LOS, 30 day readmissions, deaths, and hospital costs were higher in children with neurologic complications compared with those without complications. Factors associated with lower odds of neurologic complications included: younger age (adjusted odds ratio [aOR]: 0.97; 95% confidence interval [CI]: 0.96-0.98), occurrence during delta variant predominant time period (aOR: 0.71; 95% CI: 0.57-0.87), presence of a nonneurologic complex chronic condition (aOR: 0.80; 95% CI: 0.69-0.94). The presence of a neurologic complex chronic condition was associated with higher odds of neurologic complication (aOR 4.14, 95% CI 3.48-4.92).
    Conclusions: Neurologic complications are common in children hospitalized with COVID-19 and are associated with worse hospital outcomes. Our findings emphasize the importance of COVID-19 immunization in children, especially in high-risk populations, such as those with neurologic comorbidity.
    MeSH term(s) Child ; Humans ; COVID-19/complications ; COVID-19/epidemiology ; SARS-CoV-2 ; Cross-Sectional Studies ; Nervous System Diseases/etiology ; Nervous System Diseases/complications ; Hospitalization ; Chronic Disease ; Brain Diseases/complications ; Retrospective Studies
    Language English
    Publishing date 2022-08-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 207677-9
    ISSN 1098-4275 ; 0031-4005
    ISSN (online) 1098-4275
    ISSN 0031-4005
    DOI 10.1542/peds.2022-058167
    Database MEDical Literature Analysis and Retrieval System OnLINE

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