Publications by authors named "Angela Campbell"

133 Publications

Investigation of a Suspect SARS-CoV-2 and Influenza A Mixed Outbreak: Lessons Learned for Long-Term Care Facilities Nationwide.

Clin Infect Dis 2021 May 6. Epub 2021 May 6.

CDC COVID-19 Response Team.

A suspected outbreak of influenza A and SARS-CoV-2 at a long-term care facility in Los Angeles County was months later, determined to not involve influenza. To prevent inadvertent transmission of infections, facilities should use highly specific influenza diagnostics and follow CDC guidelines that specifically address infection control challenges.
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http://dx.doi.org/10.1093/cid/ciab372DOI Listing
May 2021

Effectiveness and cardiac safety of bedaquiline-based therapy for drug-resistant tuberculosis: a prospective cohort study.

Clin Infect Dis 2021 Apr 21. Epub 2021 Apr 21.

Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, and Department of Medicine, University of Cape Town, Cape Town, South Africa.

Background: Bedaquiline improves treatment outcomes in patients with rifampin-resistant TB (RR-TB) but prolongs the QT-interval and carries a black-box warning by the U.S. Food and Drug Administration. The World Health Organization recommends that all patients with RR-TB receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published.

Methods: We conducted an observational cohort study of RR-TB patients from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, including electrocardiograms (ECGs) performed in triplicate at four time points during bedaquiline therapy. Participants were followed until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT-prolongation, defined as any QTcF>500 ms or an absolute change from baseline (△ QTcF) >60 ms.

Results: We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant (XDR) TB. Most participants (97%) received concurrent clofazimine. 74% of participants were cured or successfully completed treatment, and outcomes did not differ by HIV status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase of 23.7 (SD 22.7) ms from baseline to month 6. Four participants experienced a QTcF>500 ms and 19 experienced a △QTcF>60 ms. Older age was independently associated with QT-prolongation. QT-prolongation was neither more common nor severe in participants receiving concurrent lopinavir-ritonavir.

Conclusions: Severe QT-prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close QT-monitoring may be advisable in older patients.
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http://dx.doi.org/10.1093/cid/ciab335DOI Listing
April 2021

Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic.

JAMA Pediatr 2021 Apr 6. Epub 2021 Apr 6.

US Centers for Disease Control and Prevention COVID-19 Response Team, Atlanta, Georgia.

Importance: Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic.

Objective: To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date.

Design, Setting, And Participants: Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition.

Main Outcomes And Measures: Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19.

Results: A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19-like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died.

Conclusions And Relevance: In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.
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http://dx.doi.org/10.1001/jamapediatrics.2021.0630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025123PMC
April 2021

Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study.

Lancet Child Adolesc Health 2021 05 10;5(5):323-331. Epub 2021 Mar 10.

CDC COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes.

Methods: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities.

Findings: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]).

Interpretation: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C.

Funding: None.
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http://dx.doi.org/10.1016/S2352-4642(21)00050-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943393PMC
May 2021

Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis in US Mothers and Children Aged 0-2: PREVAIL Cohort Study.

JMIR Res Protoc 2021 Feb 12;10(2):e22222. Epub 2021 Feb 12.

Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.

Background: Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development.

Objective: The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children.

Methods: Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody.

Results: Of the 245 enrolled mother-child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother-child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized.

Conclusions: The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing.

International Registered Report Identifier (irrid): RR1-10.2196/22222.
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http://dx.doi.org/10.2196/22222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910118PMC
February 2021

Effect of Vaccination on Preventing Influenza-Associated Hospitalizations Among Children During a Severe Season Associated with B/Victoria Viruses, 2019-2020.

Clin Infect Dis 2021 Jan 27. Epub 2021 Jan 27.

Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: The 2019-2020 influenza season was characterized by early onset with B/Victoria followed by A(H1N1)pdm09 viruses. Emergence of new B/Victoria viruses raised concerns about possible vaccine mismatch. We estimated vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department (ED) visits among U.S. children.

Methods: We assessed VE among children 6 months-17 years with acute respiratory illness and ≥10 days of symptoms enrolled at 7 pediatric medical centers in the New Vaccine Surveillance Network. Combined mid-turbinate/throat swabs were tested for influenza virus using molecular assays. Vaccination history was collected from parental report, state immunization information systems, and/or provider records. We estimated VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive versus negative for influenza.

Results: Among 2029 inpatients, 335 (17%) were influenza positive: 37% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone.VE was 62% (95% confidence interval [CI], 52%-71%) for influenza-related hospitalization, 54% (95% CI, 33%-69%) for B/Victoria viruses and 64% (95% CI, 49%-75%) for A(H1N1)pdm09. Among 2102 ED patients, 671 (32%) were influenza positive: 47% with influenza B/Victoria alone and 42% with influenza A(H1N1)pdm09 alone. VE was 56% (95% CI, 46%-65%) for an influenza-related ED visit, 55% (95% CI, 40%-66%) for B/Victoria viruses and 53% (95% CI, 37%-65%) for A(H1N1)pdm09.

Conclusions: Influenza vaccination provided significant protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the two predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus subclade.
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http://dx.doi.org/10.1093/cid/ciab060DOI Listing
January 2021

Obstructive sleep apnea risk factors and symptoms in children with a known parental obstructive sleep apnea diagnosis.

Sleep Med 2021 Feb 30;78:149-152. Epub 2020 Dec 30.

Departments of Paediatrics and Child Health, University of Otago Wellington, PO Box 7343, Wellington, 6242, New Zealand. Electronic address:

Objective: To document symptoms and risk factors of obstructive sleep apnea (OSA) in children who have a parent diagnosed with OSA and compare them to an age and sex matched sample where parents are low risk for OSA.

Methods: We recruited 25 children with a parent diagnosed with OSA (P-OSA) and 29 age and gender matched children from the community whose parents scored low risk for OSA (P-NOSA). Comparisons were made using the OSA-18 questionnaire, anthropometric measurements, and mallampati score. Statistical analysis included t-tests for OSA-18 score and BMI measures and non parametric analysis for mallampati score. OSA-18 domain scores were analysed using T-test and Bonferroni correction for multiple comparisons.

Results: Fifty-six percent of the P-OSA group had a mallampati score of III/IV compared to 11% in the P-NOSA sample (p = 0.005). There was a significant difference in BMI between the P-OSA sample (mean ± SD 19.5 ± 5.7 kg/m) and the P-NOSA sample (16.95 ± 2.08 kg/m, p = 0.002). Forty-four percent of P-OSA children were found to be either overweight or obese (BMI z-score). None of the P-NOSA children fell into this category. No significant difference was found between the P-OSA and P-NOSA samples on the OSA-18 score (P-OSA 36.5 ± 8.1, P-NOSA 29.2 ± 9.1, p = 0.07). Five children in the P-OSA sample scored >60 but no P-NOSA children scored >60.

Conclusions: This study suggests that children with a parent diagnosed with OSA are more likely to have risk factors of pediatric OSA compared to age and sex matched children of parents without OSA but do not have more symptoms.
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http://dx.doi.org/10.1016/j.sleep.2020.12.030DOI Listing
February 2021

Preference for sleep management strategies among prostate cancer patients: An Aotearoa/New Zealand perspective.

Cancer Treat Res Commun 2020 7;25:100219. Epub 2020 Oct 7.

Department of Anatomy, University of Otago, 270 Great King St, Dunedin, New Zealand - 9016. Electronic address:

Introduction: Many men with prostate cancer (PCa) experience insomnia symptoms post-treatment. We explore here PCa patients' preference for strategies to manage their sleep.

Patients And Methods: A brief online survey was launched on Facebook and promoted by Prostate Cancer Foundation New Zealand. The survey contained validated questionnaires on various sleep-related parameters, as well as questions about sleep management strategies.

Results: We recruited 82 PCa patients (67.9 ± 6.3 years old). Participants with high insomnia severity index (ISI) scores reported significantly worse daytime sleepiness, more severe fatigue, being less of a "morning person", and more frequent dreaming. Most participants (71-95%) were open to trying behavioural strategies for improving sleep hygiene, especially by improving their sleeping conditions and having a consistent sleep-wake schedule. Insomnia severity and past use of androgen deprivation therapy were significant predictors for the number of sleep treatments used. Participants with a high ISI were more likely to have used medication, CBT, and herbal remedies or supplements for treating sleep issues than those with low ISI. Furthermore, in patients who had not used these treatments options, those with a high ISI were more willing to try CBT and hypnosis compared to those with a low ISI. Reasons for not willing to try various sleep treatments were documented.

Conclusion: Most PCa patients are willing to adjust their behavior or lifestyle to improve their sleep habits/behaviours. Patients with severe insomnia are more likely to have both used and express willingness to try, interventions to improve sleep, with preferences for CBT and hypnosis.
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http://dx.doi.org/10.1016/j.ctarc.2020.100219DOI Listing
October 2020

Schistosoma mansoni Infection Is Associated With a Higher Probability of Tuberculosis Disease in HIV-Infected Adults in Kenya.

J Acquir Immune Defic Syndr 2021 Feb;86(2):157-163

Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA.

Background: Helminth infections can modulate immunity to Mycobacterium tuberculosis (Mtb). However, the effect of helminths, including Schistosoma mansoni (SM), on Mtb infection outcomes is less clear. Furthermore, HIV is a known risk factor for tuberculosis (TB) disease and has been implicated in SM pathogenesis. Therefore, it is important to evaluate whether HIV modifies the association between SM and Mtb infection.

Setting: HIV-infected and HIV-uninfected adults were enrolled in Kisumu County, Kenya, between 2014 and 2017 and categorized into 3 groups based on Mtb infection status: Mtb-uninfected healthy controls, latent TB infection (LTBI), and active TB disease. Participants were subsequently evaluated for infection with SM.

Methods: We used targeted minimum loss estimation and super learning to estimate a covariate-adjusted association between SM and Mtb infection outcomes, defined as the probability of being Mtb-uninfected healthy controls, LTBI, or TB. HIV status was evaluated as an effect modifier of this association.

Results: SM was not associated with differences in baseline demographic or clinical features of participants in this study, nor with additional parasitic infections. Covariate-adjusted analyses indicated that infection with SM was associated with a 4% higher estimated proportion of active TB cases in HIV-uninfected individuals and a 14% higher estimated proportion of active TB cases in HIV-infected individuals. There were no differences in estimated proportions of LTBI cases.

Conclusions: We provide evidence that SM infection is associated with a higher probability of active TB disease, particularly in HIV-infected individuals.
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http://dx.doi.org/10.1097/QAI.0000000000002536DOI Listing
February 2021

Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis.

PLoS Negl Trop Dis 2020 10 12;14(10):e0008764. Epub 2020 Oct 12.

Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.

Schistosoma mansoni (SM) is a parasitic helminth that infects over 200 million people and causes severe morbidity. It undergoes a multi-stage life cycle in human hosts and as such stimulates a stage-specific immune response. The human T cell response to SM is complex and varies throughout the life cycle of SM. Relative to the wealth of information regarding the immune response to SM eggs, little is known about the immune response to the adult worm. In addition, while a great deal of research has uncovered mechanisms by which co-infection with helminths modulates immunity to other pathogens, there is a paucity of data on the effect of pathogens on immunity to helminths. As such, we sought to characterize the breadth of the T cell response to SM and determine whether co-infection with Mycobacterium tuberculosis (Mtb) modifies SM-specific T cell responses in a cohort of HIV-uninfected adults in Kisumu, Kenya. SM-infected individuals were categorized into three groups by Mtb infection status: active TB (TB), Interferon-γ Release Assay positive (IGRA+), and Interferon-γ Release Assay negative (IGRA-). U.S. adults that were seronegative for SM antibodies served as naïve controls. We utilized flow cytometry to characterize the T cell repertoire to SM egg and worm antigens. We found that T cells had significantly higher proliferation and cytokine production in response to worm antigen than to egg antigen. The T cell response to SM was dominated by γδ T cells that produced TNFα and IFNγ. Furthermore, we found that in individuals infected with Mtb, γδ T cells proliferated less in response to SM worm antigens and had higher IL-4 production compared to naïve controls. Together these data demonstrate that γδ T cells respond robustly to SM worm antigens and that Mtb infection modifies the γδ T cell response to SM.
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http://dx.doi.org/10.1371/journal.pntd.0008764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580987PMC
October 2020

Comparison of Parental Report of Influenza Vaccination to Documented Records in Children Hospitalized With Acute Respiratory Illness, 2015-2016.

J Pediatric Infect Dis Soc 2021 Apr;10(4):389-397

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: Parent-reported influenza vaccination history may be valuable clinically and in influenza vaccine effectiveness (VE) studies. Few studies have assessed the validity of parental report among hospitalized children.

Methods: Parents of 2597 hospitalized children 6 months-17 years old were interviewed from November 1, 2015 to June 30, 2016, regarding their child's sociodemographic and influenza vaccination history. Parent-reported 2015-2016 influenza vaccination history was compared with documented vaccination records (considered the gold standard for analysis) obtained from medical records, immunization information systems, and providers. Multivariable logistic regression analyses were conducted to determine potential factors associated with discordance between the 2 sources of vaccination history. Using a test-negative design, we estimated VE using vaccination history obtained through parental report and documented records.

Results: According to parental report, 1718 (66%) children received the 2015-2016 influenza vaccine, and of those, 1432 (83%) had documentation of vaccine receipt. Percent agreement was 87%, with a sensitivity of 96% (95% confidence interval [CI], 95%-97%) and a specificity of 74% (95% CI, 72%-77%). In the multivariable logistic regression, study site and child's age 5-8 years were significant predictors of discordance. Adjusted VE among children who received ≥1 dose of the 2015-2016 influenza vaccine per parental report was 61% (95% CI, 43%-74%), whereas VE using documented records was 55% (95% CI, 33%-69%).

Conclusions: Parental report of influenza vaccination was sensitive but not as specific compared with documented records. However, VE against influenza-associated hospitalizations using either source of vaccination history did not differ substantially. Parental report is valuable for timely influenza VE studies.
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http://dx.doi.org/10.1093/jpids/piaa110DOI Listing
April 2021

Vaccine Effectiveness Against Pediatric Influenza Hospitalizations and Emergency Visits.

Pediatrics 2020 11 5;146(5). Epub 2020 Oct 5.

Influenza Division and.

Background: Influenza A(H1N1)pdm09 viruses initially predominated during the US 2018-2019 season, with antigenically drifted influenza A(H3N2) viruses peaking later. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits among children in the New Vaccine Surveillance Network.

Methods: We tested children 6 months to 17 years with acute respiratory illness for influenza using molecular assays at 7 pediatric hospitals (ED patients <5 years at 3 sites). Vaccination status sources were parental report, state immunization information systems and/or provider records for inpatients, and parental report alone for ED patients. We estimated VE using a test-negative design, comparing odds of vaccination among children testing positive versus negative for influenza using multivariable logistic regression.

Results: Of 1792 inpatients, 226 (13%) were influenza-positive: 47% for influenza A(H3N2), 36% for A(H1N1)pdm09, 9% for A (not subtyped), and 7% for B viruses. Among 1944 ED children, 420 (22%) were influenza-positive: 48% for A(H3N2), 35% for A(H1N1)pdm09, 11% for A (not subtyped), and 5% for B viruses. VE was 41% (95% confidence interval [CI], 20% to 56%) against any influenza-related hospitalizations, 41% (95% CI, 11% to 61%) for A(H3N2), and 47% (95% CI, 16% to 67%) for A(H1N1)pdm09. VE was 51% (95% CI, 38% to 62%) against any influenza-related ED visits, 39% (95% CI, 15% to 56%) against A(H3N2), and 61% (95% CI, 44% to 73%) against A(H1N1)pdm09.

Conclusions: The 2018-2019 influenza vaccine reduced pediatric influenza A-associated hospitalizations and ED visits by 40% to 60%, despite circulation of a drifted A(H3N2) clade.
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http://dx.doi.org/10.1542/peds.2020-1368DOI Listing
November 2020

Activation-Induced Marker Expression Identifies -Specific CD4 T Cells in a Cytokine-Independent Manner in HIV-Infected Individuals with Latent Tuberculosis.

Immunohorizons 2020 10 2;4(10):573-584. Epub 2020 Oct 2.

Emory Vaccine Center, Emory University, Atlanta, GA 30329;

HIV infection is a significant risk factor for reactivation of latent infection (LTBI) and progression to active tuberculosis disease, yet the mechanisms whereby HIV impairs T cell immunity to have not been fully defined. Evaluation of -specific CD4 T cells is commonly based on IFN-γ production, yet increasing evidence indicates the immune response to is heterogeneous and encompasses IFN-γ-independent responses. We hypothesized that upregulation of surface activation-induced markers (AIM) would facilitate detection of human -specific CD4 T cells in a cytokine-independent manner in HIV-infected and HIV-uninfected individuals with LTBI. PBMCs from HIV-infected and HIV-uninfected adults in Kenya were stimulated with CFP-10 and ESAT-6 peptides and evaluated by flow cytometry for upregulation of the activation markers CD25, OX40, CD69, and CD40L. Although -specific IFN-γ and IL-2 production was dampened in HIV-infected individuals, -specific CD25OX40 and CD69CD40L CD4 T cells were detectable in the AIM assay in both HIV-uninfected and HIV-infected individuals with LTBI. Importantly, the frequency of -specific AIM CD4 T cells was not directly impacted by HIV viral load or CD4 count, thus demonstrating the feasibility of AIM assays for analysis of -specific CD4 T cells across a spectrum of HIV infection states. These data indicate that AIM assays enable identification of -specific CD4 T cells in a cytokine-independent manner in HIV-uninfected and HIV-infected individuals with LTBI in a high-tuberculosis burden setting, thus facilitating studies to define novel T cell correlates of protection to and elucidate mechanisms of HIV-associated dysregulation of antimycobacterial immunity.
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http://dx.doi.org/10.4049/immunohorizons.2000051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585460PMC
October 2020

Fertility counseling information adequacy as a moderator of regret among adolescent and young adult breast cancer survivors.

Support Care Cancer 2021 May 26;29(5):2689-2697. Epub 2020 Sep 26.

The Pennsylvania State University, State College, PA, USA.

Purpose: Current literature disagrees on whether fertility counseling decreases or increases decision regret among young breast cancer survivors. This study investigates whether fertility counseling provided to pre-menopausal breast cancer patients regarding infertility due to treatment is associated with decision regret post-treatment, and how that relationship is moderated by information adequacy.

Methods: Breast cancer patients aged 18-35 listed in the Pennsylvania Cancer Registry as diagnosed between 2007 and 2012 were surveyed. Basic descriptive analyses were conducted, and linear regression models were estimated.

Results: Receipt of fertility counseling was not directly associated with decision regret. However, as fertility information adequacy increased, decision regret significantly decreased among women who received fertility counseling after finishing treatment or before and after finishing treatment. On average, a woman who receives fertility counseling before and after treatment with an information adequacy score of 1.5 had a regret score of 2.68. In contrast, a woman who received fertility counseling before and after treatment who had a fertility information adequacy score of 5 had a regret score of only 1.26 on average.

Conclusion: Information adequacy is a significant moderator in the relationship between fertility counseling and decision regret. This suggests a possible explanation for disagreement in the literature regarding the benefits of fertility counseling and highlights the need for an increased focus on the adequacy of the information provided.

Implications For Cancer Survivors: Fertility counseling should be pursued for young adult breast cancer patients and survivors, provided that their satisfaction with the information received is monitored and remains high.
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http://dx.doi.org/10.1007/s00520-020-05771-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984251PMC
May 2021

Children's Privacy Laws Must Be Strengthened and Enforced.

JAMA Pediatr 2020 Dec 7;174(12):e203393. Epub 2020 Dec 7.

Georgetown University Law Center, Washington, District of Columbia.

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http://dx.doi.org/10.1001/jamapediatrics.2020.3393DOI Listing
December 2020

Role of Human Bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients.

Clin Infect Dis 2020 Aug 9. Epub 2020 Aug 9.

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients.

Methods: In a longitudinal surveillance study among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then at least every 3 months through 1 year post-HCT at the Fred Hutch (2005-2010). Samples were tested by multiplex semi-quantitative PCR for 12 viruses. Plasma samples from BoV+ subjects were analyzed by PCR. Separately, we conducted a retrospective review of HCT recipients with BoV detected in lower respiratory tract specimens.

Results: Among 51 children and 420 adults in the prospective cohort, 21 distinct BoV respiratory tract infections (RTIs) were observed by 1 year post-HCT in 19 patients. Younger age and exposure to children were risk factors for BoV acquisition. Univariable models among patients with BoV RTI showed higher peak viral load in nasal samples (p=0.04) and presence of respiratory copathogens (p=0.03) were associated with presence of respiratory symptoms but BoV plasma detection was not. Only watery eyes and rhinorrhea were associated with BoV RTI in adjusted models. With additional chart review, we identified 6 HCT recipients with BoV detected in lower respiratory tract specimens [incidence rate of 0.4% (9/2509) per sample tested]. Although all cases presented with hypoxemia, 4 had respiratory copathogens or concomitant conditions that contributed to respiratory compromise.

Conclusions: BoV RTI is infrequent in transplant recipients and associated with mild symptoms. Our studies did not demonstrate convincing evidence that BoV is a serious respiratory pathogen.
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http://dx.doi.org/10.1093/cid/ciaa1149DOI Listing
August 2020

Respiratory Syncytial Virus-Associated Hospitalizations Among Young Children: 2015-2016.

Pediatrics 2020 07 16;146(1). Epub 2020 Jun 16.

Division of Viral Diseases and.

Background: Respiratory syncytial virus (RSV) is a major cause of hospitalized acute respiratory illness (ARI) among young children. With RSV vaccines and immunoprophylaxis agents in clinical development, we sought to update estimates of US pediatric RSV hospitalization burden.

Methods: Children <5 years old hospitalized for ARI were enrolled through active, prospective, population-based surveillance from November 1, 2015, to June 30, 2016, at 7 US pediatric hospital sites. Clinical information was obtained from parent interviews and medical records. Midturbinate nasal and throat flocked swabs were collected and tested for RSV by using molecular diagnostic assays at each site. We conducted descriptive analyses and calculated population-based rates of RSV-associated hospitalizations.

Results: Among 2969 hospitalized children included in analyses, 1043 (35%) tested RSV-positive; 903 (87%) children who were RSV-positive were <2 years old, and 526 (50%) were <6 months old. RSV-associated hospitalization rates were 2.9 per 1000 children <5 years old and 14.7 per 1000 children <6 months old; the highest age-specific rate was observed in 1-month-old infants (25.1 per 1000). Most children who were infected with RSV (67%) had no underlying comorbid conditions and no history of preterm birth.

Conclusions: During the 2015-2016 season, RSV infection was associated with one-third of ARI hospitalizations in our study population of young children. Hospitalization rates were highest in infants <6 months. Most children who were RSV-positive had no history of prematurity or underlying medical conditions, suggesting that all young children could benefit from targeted interventions against RSV.
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http://dx.doi.org/10.1542/peds.2019-3611DOI Listing
July 2020

Oseltamivir provides up to 3 days earlier time to recovery over usual care.

J Pediatr 2020 05;220:264-267

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.

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http://dx.doi.org/10.1016/j.jpeds.2020.02.064DOI Listing
May 2020

Distinct Human NK Cell Phenotypes and Functional Responses to in Adults From TB Endemic and Non-endemic Regions.

Front Cell Infect Microbiol 2020 24;10:120. Epub 2020 Mar 24.

Emory Vaccine Center, Emory University, Atlanta, GA, United States.

(Mtb) is the causative agent of tuberculosis (TB), which leads to an estimated 1. 5 million deaths worldwide each year. Although the immune correlates of protection against Mtb infection and TB disease have not been well-defined, natural killer (NK) cells are increasingly recognized as a key component of the innate immune response to Mtb and as a link between innate and adaptive immunity. In this study, we evaluated NK cell phenotypic and functional profiles in QuantiFERON-TB (QFT) and QFT adults in a TB endemic setting in Kisumu, Kenya, and compared their NK cell responses to those of Mtb-naïve healthy adult controls in the U.S. We used flow cytometry to define the phenotypic profile of NK cells and identified distinct CD56 NK cell phenotypes that differentiated the Kenyan and U.S. groups. Additionally, among Kenyan participants, NK cells from QFT individuals with latent Mtb infection (LTBI) were characterized by significant downregulation of the natural cytotoxicity receptor NKp46 and the inhibitory receptor TIGIT, compared with QFT individuals. Moreover, the distinct CD56 phenotypic profiles in Kenyan individuals correlated with dampened NK cell responses to tumor cells and diminished activation, degranulation, and cytokine production following stimulation with Mtb antigens, compared with Mtb-naïve U.S. healthy adult controls. Taken together, these data provide evidence that the phenotypic and functional profiles of NK cells are modified in TB endemic settings and will inform future studies aimed at defining NK cell-mediated immune correlates that may be protective against acquisition of Mtb infection and progression to TB disease.
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http://dx.doi.org/10.3389/fcimb.2020.00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105570PMC
March 2020

CD4 T Cells in and Co-infected Individuals Maintain Functional TH1 Responses.

Front Immunol 2020 7;11:127. Epub 2020 Feb 7.

Emory Vaccine Center, Emory University, Atlanta, GA, United States.

(Mtb) is a serious public health concern, infecting a quarter of the world and leading to 10 million cases of tuberculosis (TB) disease and 1. 5 million deaths annually. An effective type 1 CD4 T cell (TH1) immune response is necessary to control Mtb infection and defining factors that modulate Mtb-specific TH1 immunity is important to better define immune correlates of protection in Mtb infection. Helminths stimulate type 2 (TH2) immune responses, which antagonize TH1 cells. As such, we sought to evaluate whether co-infection with the parasitic helminth (SM) modifies CD4 T cell lineage profiles in a cohort of HIV-uninfected adults in Kisumu, Kenya. Individuals were categorized into six groups by Mtb and SM infection status: healthy controls (HC), latent Mtb infection (LTBI) and active tuberculosis (TB), with or without concomitant SM infection. We utilized flow cytometry to evaluate the TH1/TH2 functional and phenotypic lineage state of total CD4 T cells, as well as CD4 T cells specific for the Mtb antigens CFP-10 and ESAT-6. Total CD4 T cell lineage profiles were similar between SM and SM individuals in all Mtb infection groups. Furthermore, in both LTBI and TB groups, SM infection did not impair Mtb-specific TH1 cytokine production. In fact, SM LTBI individuals had higher frequencies of IFNγ Mtb-specific CD4 T cells than SM LTBI individuals. Mtb-specific CD4 T cells were characterized by expression of both classical TH1 markers, CXCR3 and T-bet, and TH2 markers, CCR4, and GATA3. The expression of these markers was similar between SM and SM individuals with LTBI. However, SM individuals with active TB had significantly higher frequencies of GATA3 CCR4 TH1 cytokine Mtb-specific CD4 T cells, compared with SM TB individuals. Together, these data indicate that Mtb-specific TH1 cytokine production capacity is maintained in SM-infected individuals, and that Mtb-specific TH1 cytokine CD4 T cells can express both TH1 and TH2 markers. In high pathogen burden settings where co-infection is common and reoccurring, plasticity of antigen-specific CD4 T cell responses may be important in preserving Mtb-specific TH1 responses.
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http://dx.doi.org/10.3389/fimmu.2020.00127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020828PMC
March 2021

Vaccine Effectiveness Against Influenza Hospitalization Among Children in the United States, 2015-2016.

J Pediatric Infect Dis Soc 2021 Mar;10(2):75-82

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: Annual United States (US) estimates of influenza vaccine effectiveness (VE) in children typically measure protection against outpatient medically attended influenza illness, with limited data evaluating VE against influenza hospitalizations. We estimated VE for preventing laboratory-confirmed influenza hospitalization among US children.

Methods: We included children aged 6 months-17 years with acute respiratory illness enrolled in the New Vaccine Surveillance Network during the 2015-2016 influenza season. Documented influenza vaccination status was obtained from state immunization information systems, the electronic medical record, and/or provider records. Midturbinate nasal and throat swabs were tested for influenza using molecular assays. We estimated VE as 100% × (1 - odds ratio), comparing the odds of vaccination among subjects testing influenza positive with subjects testing negative, using multivariable logistic regression.

Results: Of 1653 participants, 36 of 707 (5%) of those fully vaccinated, 18 of 226 (8%) of those partially vaccinated, and 85 of 720 (12%) of unvaccinated children tested positive for influenza. Of those vaccinated, almost 90% were documented to have received inactivated vaccine. The majority (81%) of influenza cases were in children ≤ 8 years of age. Of the 139 influenza-positive cases, 42% were A(H1N1)pdm09, 42% were B viruses, and 14% were A(H3N2). Overall, adjusted VE for fully vaccinated children was 56% (95% confidence interval [CI], 34%-71%) against any influenza-associated hospitalization, 68% (95% CI, 36%-84%) for A(H1N1)pdm09, and 44% (95% CI, -1% to 69%) for B viruses.

Conclusions: These findings demonstrate the importance of annual influenza vaccination in prevention of severe influenza disease and of reducing the number of children who remain unvaccinated or partially vaccinated against influenza.
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http://dx.doi.org/10.1093/jpids/piaa017DOI Listing
March 2021

Sleep in New Zealand children aged 7-9: associations with ethnicity, socioeconomic status, and achievement in reading and mathematics.

J Clin Sleep Med 2020 06;16(6):847-854

Department of Medicine, University of Otago, Wellington, New Zealand.

Study Objectives: The aims were (1) to investigate differences by ethnicity and socioeconomic status (SES) in objective measures of sleep in children aged 7-9 years and (2) determine whether measures of sleep predict child achievement in reading or mathematics after controlling for ethnicity and SES.

Methods: Four groups of parent-child dyads were recruited: Māori, low-SES schools (n = 18); Māori, high-SES schools (n = 17); New Zealand European, low-SES schools (n = 18); New Zealand European, high-SES schools (n = 17). Child sleep was measured by actigraphy. Parents and teachers reported child daytime sleepiness and behavior, and children completed a self-report of anxiety symptoms. Teachers also reported on child achievement in reading and mathematics.

Results: Children from low-SES schools went to bed later on school nights (F[1,68] = 12.150, P = .001) and woke later (F[1,68] = 15.978, P < .001) than children from high-SES schools but had similar sleep duration. There were no differences related to ethnicity. Children from low-SES schools were almost 3 times more likely to be below national standards for mathematics. Children not meeting academic standards in mathematics had a later sleep start time, lower sleep period efficiency, and a decreased total sleep time. However, when SES and sleep period efficiency were modeled together neither were found to significantly influence achievement in mathematics.

Conclusions: In this study, SES influenced sleep timing but not the quality and quantity of sleep in 7- to 9-year-old children, and a significant independent effect of sleep efficiency on learning could not be demonstrated.
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http://dx.doi.org/10.5664/jcsm.8342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849654PMC
June 2020

The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events.

J Acquir Immune Defic Syndr 2020 01;83(1):47-55

Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY.

Background: South Africa has among the highest incidence of multidrug-resistant tuberculosis (MDR-TB) and more than 70% of patients are HIV co-infected. MDR-TB treatment is associated with frequent adverse events (AEs). Although guidelines recommend concurrent treatment of MDR-TB and HIV, safety data on concurrent therapy are limited.

Methods: We conducted a prospective observational study of MDR-TB patients with and without HIV-coinfection in South Africa between 2011 and 2015. Participants received standardized MDR-TB and HIV regimens. Participants were followed monthly for the duration of MDR-TB therapy and screened for clinical and laboratory AEs. Audiometry was performed monthly during the intensive phase; color discrimination testing was performed every 2 months.

Results: We enrolled 150 HIV-infected and 56 HIV-uninfected participants. Nearly all experienced at least one clinical (93%) or laboratory (96%) AE. The most common clinical AEs were peripheral neuropathy (50%) and difficulty sleeping (48%); the most common laboratory AEs were hypokalemia (47%) and decreased creatinine clearance (46%). Among 19 clinical and lab AEs examined, there were no differences by HIV status, except for diarrhea (27% HIV-infected vs. 13% HIV-uninfected, P = 0.03). Hearing loss was experienced by 72% of participants (8% severe loss). Fourteen percent experienced color discrimination loss (4% severe loss). There were no differences in frequency or severity of hearing or vision loss by HIV status.

Conclusions: AEs were common, but not more frequent or severe among MDR-TB/HIV co-infected participants receiving concurrent antiretroviral therapy. Given the favorable treatment outcomes associated with concurrent treatment, antiretroviral therapy initiation should not be delayed in MDR-TB patients with HIV-coinfection.
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http://dx.doi.org/10.1097/QAI.0000000000002190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903405PMC
January 2020

Priming with MF59 adjuvanted versus nonadjuvanted seasonal influenza vaccines in children - A systematic review and a meta-analysis.

Vaccine 2020 01 15;38(3):608-619. Epub 2019 Nov 15.

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Identifying optimal priming strategies for children <2 years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal influenza vaccines were designed to promote a better immune response among young vaccine-naïve children.

Methods: We systematically reviewed randomized trials to assess hemagglutination inhibition (HAI) antibody response to MF59-adjuvanted inactivated influenza vaccine (aIIV) versus nonadjuvanted IIV among children. We estimated pooled ratios of post-vaccination HAI geometric mean titer (GMT) for aIIV versus IIV and confidence intervals (CIs) using the pooled variances derived from reported CIs.

Results: Mean age was 28 months (range, 6-72 months). Children received vaccines with either 7.5 μg (6-35 months) or 15 μg (≥36 months) hemagglutinin of each strain depending on age. Seven of eight trials administered trivalent vaccines and one used quadrivalent vaccine. Pooled post-vaccination GMT ratios against the three influenza vaccine strains were 2.5-3.5 fold higher after 2-dose-aIIV versus 2-dose-IIV among children 6-72 months, and point estimates were higher among children 6-35 months compared with older children. When comparing 1-dose-aIIV to 2-dose-IIV doses, pooled GMT ratios were not significantly different against A/H1N1 (1.0; 95% CI: 0.5-1.8; p = 0.90) and A/H3N2 viruses (1.0; 95% CI: 0.7-1.5; p = 0.81) and were significantly lower against B viruses (0.6; 95% CI: 0.4-0.8; p < 0.001) for both age groups. Notably, GMT ratios for vaccine-mismatched heterologous viruses after 2-dose-aIIV compared with 2-dose-IIV were higher against A/H1N1 (2.0; 95% CI: 1.1-3.4), A/H3N2 (2.9; 95% CI: 1.9-4.2), and B-lineage viruses (2.1; 95% CI: 1.8-2.6).

Conclusions: Two doses of adjuvanted IIV consistently induced better humoral immune responses against Type A and B influenza viruses compared with nonadjuvanted IIVs in young children, particularly among those 6-35 months. One adjuvanted IIV dose had a similar response to two nonadjuvanted IIV doses against Type A influenza viruses. Longer-term benefits from imprinting and cell-mediated immunity, including trials of clinical efficacy, are gaps that warrant investigation.
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http://dx.doi.org/10.1016/j.vaccine.2019.10.053DOI Listing
January 2020

Reported variability in healthcare facility policies regarding healthcare personnel working while experiencing influenza-like illnesses: An emerging infections network survey.

Infect Control Hosp Epidemiol 2020 01 14;41(1):80-85. Epub 2019 Nov 14.

University of Iowa Carver College of Medicine, Iowa City, Iowa.

Background: Presenteeism, or working while ill, by healthcare personnel (HCP) experiencing influenza-like illness (ILI) puts patients and coworkers at risk. However, hospital policies and practices may not consistently facilitate HCP staying home when ill.

Objective And Methods: We conducted a mixed-methods survey in March 2018 of Emerging Infections Network infectious diseases physicians, describing institutional experiences with and policies for HCP working with ILI.

Results: Of 715 physicians, 367 (51%) responded. Of 367, 135 (37%) were unaware of institutional policies. Of the remaining 232 respondents, 206 (89%) reported institutional policies regarding work restrictions for HCP with influenza or ILI, but only 145 (63%) said these were communicated at least annually. More than half of respondents (124, 53%) reported that adherence to work restrictions was not monitored or enforced. Work restrictions were most often not perceived to be enforced for physicians-in-training and attending physicians. Nearly all (223, 96%) reported that their facility tracked laboratory-confirmed influenza (LCI) in patients; 85 (37%) reported tracking ILI. For employees, 109 (47%) reported tracking of LCI and 53 (23%) reported tracking ILI. For independent physicians, not employed by the facility, 30 (13%) reported tracking LCI and 11 (5%) ILI.

Conclusion: More than one-third of respondents were unaware of whether their institutions had policies to prevent HCP with ILI from working; among those with knowledge of institutional policies, dissemination, monitoring, and enforcement of these policies was highly variable. Improving communication about work-restriction policies, as well as monitoring and enforcement, may help prevent the spread of infections from HCP to patients.
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http://dx.doi.org/10.1017/ice.2019.305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018563PMC
January 2020

Impact of type 1 diabetes mellitus, glucose levels, and glycemic control on sleep in children and adolescents: a case-control study.

Sleep 2020 02;43(2)

Department of Women's and Children's Health, University of Otago, Dunedin, New Zealand.

Study Objectives: To assess differences in habitual sleep patterns and sleep states between children and adolescents with type 1 diabetes mellitus (T1DM) and control subjects, and to explore the relationships between sleep, glucose levels, and glycemic control.

Methods: Participants included 82 children (5-18 years); 41 with T1DM (cases), and 41 healthy control subjects group matched for age and sex. Sleep was measured by 7-day actigraphy and single-night home-based polysomnography (PSG) recordings. Hemoglobin A1c (HbA1c) and 7 days of continuous glucose monitoring (CGM) data were collected in cases. Regression analyses were used to model all within- and between-group comparisons adjusted for age, sex, and BMI z-scores.

Results: There were no significant differences in sleep duration, efficiency, or awakenings as measured by actigraphy and PSG between cases and controls, nor sleep states measured by PSG. However, cases had significantly later sleep onset and offset than controls (both p < 0.05), partially moderated by age. Cases with suboptimal glycemic control (HbA1c ≥ 58 mmol/mol [≥7.5%]) had significantly shorter actigraphy-derived total sleep time (TST) (mean difference = -40 minutes; 95% confidence interval = -77, -3), with similar differences in TST measured by PSG. Cases with mean CGM glucose levels ≥10 mmol/L (≥180 mg/dL) on PSG night had significantly more stage N3 (%) sleep and less stage REM (%) sleep (both p < 0.05).

Conclusions: Short- and long-term suboptimal glycemic control in T1DM children appears to be associated with sleep alterations. Pediatric diabetes care teams should be aware of potential interrelationships between sleep and T1DM, including management and glycemic control.
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http://dx.doi.org/10.1093/sleep/zsz226DOI Listing
February 2020

HIV Infection Is Associated With Downregulation of BTLA Expression on -Specific CD4 T Cells in Active Tuberculosis Disease.

Front Immunol 2019 21;10:1983. Epub 2019 Aug 21.

Emory Vaccine Center, Emory University, Atlanta, GA, United States.

Nearly a quarter of the global population is infected with (Mtb), with 10 million people developing active tuberculosis (TB) annually. Co-infection with human immunodeficiency virus (HIV) has long been recognized as a significant risk factor for progression to TB disease, yet the mechanisms whereby HIV impairs T cell-mediated control of Mtb infection remain poorly defined. We hypothesized that HIV infection may promote upregulation of inhibitory receptors on Mtb-specific CD4 T cells, a mechanism that has been associated with antigen-specific T cell dysfunction in chronic infections. Using cohorts of HIV-infected and HIV-uninfected individuals with latent Mtb infection (LTBI) and with active TB disease, we stimulated peripheral blood mononuclear cells (PBMC) for 6 hours with Mtb peptide pools and evaluated co-expression profiles of the inhibitory receptors BTLA, CTLA-4, and PD-1 on IFN-γ/TNF-α Mtb-specific CD4 T cells. Mtb-specific CD4 T cells in all participant groups expressed predominately either one or no inhibitory receptors, unlike cytomegalovirus- and HIV-specific CD4 T cells circulating in the same individuals, which were predominately CTLA-4PD-1. There were no significant differences in inhibitory receptor expression profiles of Mtb-specific CD4 T cells between HIV-uninfected and HIV-infected individuals with LTBI. Surprisingly, BTLA expression, both alone and in combination with CTLA-4 and PD-1, was markedly downregulated on Mtb-specific CD4 T cells in HIV-infected individuals with active TB. Together, these data provide novel evidence that the majority of Mtb-specific CD4 T cells do not co-express multiple inhibitory receptors, regardless of HIV infection status; moreover, they highlight a previously unrecognized role of BTLA expression on Mtb-specific CD4 T cells that could be further explored as a potential biomarker of Mtb infection status, particularly in people living with HIV, the population at greatest risk for development of active TB disease.
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http://dx.doi.org/10.3389/fimmu.2019.01983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712065PMC
October 2020

Outcomes of Immunocompromised Adults Hospitalized With Laboratory-confirmed Influenza in the United States, 2011-2015.

Clin Infect Dis 2020 05;70(10):2121-2130

Emory University School of Medicine, Department of Pediatrics, Atlanta, Georgia.

Background: Hospitalized immunocompromised (IC) adults with influenza may have worse outcomes than hospitalized non-IC adults.

Methods: We identified adults hospitalized with laboratory-confirmed influenza during 2011-2015 seasons through CDC's Influenza Hospitalization Surveillance Network. IC patients had human immunodefiency virus (HIV)/AIDS, cancer, stem cell or organ transplantation, nonsteroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, and/or other rare conditions. We compared demographic and clinical characteristics of IC and non-IC adults using descriptive statistics. Multivariable logistic regression and Cox proportional hazards models controlled for confounding by patient demographic characteristics, pre-existing medical conditions, influenza vaccination, and other factors.

Results: Among 35 348 adults, 3633 (10%) were IC; cancer (44%), nonsteroid immunosuppressive therapy (44%), and HIV (18%) were most common. IC patients were more likely than non-IC patients to have received influenza vaccination (53% vs 46%; P < .001), and ~85% of both groups received antivirals. In multivariable analysis, IC adults had higher mortality (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.20-1.76). Intensive care was more likely among IC patients 65-79 years (aOR, 1.25; 95% CI, 1.06-1.48) and those >80 years (aOR, 1.35; 95% CI, 1.06-1.73) compared with non-IC patients in those age groups. IC patients were hospitalized longer (adjusted hazard ratio of discharge, 0.86; 95% CI, .83-.88) and more likely to require mechanical ventilation (aOR, 1.19; 95% CI, 1.05-1.36).

Conclusions: Substantial morbidity and mortality occurred among IC adults hospitalized with influenza. Influenza vaccination and antiviral administration could be increased in both IC and non-IC adults.
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http://dx.doi.org/10.1093/cid/ciz638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201407PMC
May 2020

Influenza Antiviral Prescribing Practices and the Influence of Rapid Testing Among Primary Care Providers in the US, 2009-2016.

Open Forum Infect Dis 2019 Jun 26;6(6):ofz192. Epub 2019 Apr 26.

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.

Background: Early influenza antiviral treatment within 2 days of illness onset can reduce illness severity and duration. Reliance on low sensitivity rapid influenza diagnostic tests (RIDTs) to guide antiviral prescribing has been reported. We describe antiviral prescribing practices among primary care providers from a large surveillance network in the United States.

Methods: From 2009-2016, a network of 36 to 68 outpatient clinics per year collected respiratory specimens and clinical data for patients with influenza-like illness (ILI). Specimens were tested for influenza using polymerase chain reaction (PCR). We used multivariable logistic regression to assess factors influencing antiviral prescribing.

Results: Among 13 540 patients with ILI, 2766 (20%) were prescribed antivirals. In age groups recommended to receive empiric antiviral treatment for suspected influenza, 11% of children <2 years and 23% of adults ≥65 years received a prescription. Among 3681 patients with a positive PCR test for influenza, 40% tested negative by RIDT. In multivariable analysis, prescription receipt was strongly associated with a positive RIDT (adjusted odds ratio [aOR] 12, 95% CI 11-14) and symptom onset ≤2 days before visit (aOR 4.3, 95% CI 3.8-4.9). Antiviral prescribing was also more frequent among pediatric and private family practice clinics compared with community health centers (aOR 1.9, 95% CI 1.6-2.2, and 1.3, 95% CI 1.1-1.5, respectively).

Conclusion: Primary care providers were more likely to prescribe antivirals to patients with a positive RIDT, but antivirals were prescribed infrequently even to patients in high-risk age groups. Understanding patient and provider characteristics associated with antiviral prescribing is important for communicating treatment recommendations.
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http://dx.doi.org/10.1093/ofid/ofz192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557305PMC
June 2019

Intermittent hypoxia in preterm infants: Measurement using the desaturation index.

Pediatr Pulmonol 2019 06 28;54(6):865-872. Epub 2019 Mar 28.

Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.

Objective: The aims of this study were to: (i) Determine in preterm infants at neonatal discharge the prevalence of intermittent hypoxia (IH), as measured by the oxygen desaturation index (DSI) recorded by pulse oximetry and (ii) Determine the change in values for very preterm infants at 1-month post discharge.

Methods: Preterm infants were recruited from the Wellington regional neonatal intensive care unit (NICU) and 24-h pulse oximetry recordings performed immediately before discharge. Infants born <32 weeks gestational age (GA) had repeat oximetry 1-month post discharge. Oxygenation measures included the 3% and 4% desaturation (DSI 3%, DSI 4%) indices.

Results: At discharge from the neonatal unit the median and interquartile range (IQR) for DSI 4% was 51 (31-74) events per hour with normal mean SpO (median of 97.9% [97.2-98.8 IQR]). Episodes of IH 1 month post discharge decreased with improvements of between 42% and 57% seen for the three DSI measures. Infants <32 weeks GA had higher median DSI 3 and 4% values at discharge but differences when compared with late preterm infants were not significant.

Conclusions: Preterm infants have frequent episodes of IH as measured by the 3% and 4% DSI when deemed otherwise ready for discharge home. Further research in a larger cohort of very preterm infants and also in term infants is needed to determine the significance of this finding.
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http://dx.doi.org/10.1002/ppul.24276DOI Listing
June 2019