Objective
In 4‐ to 8‐year‐old Zambian children (n = 744), we evaluated the effects of adjusting for inflammation (α1‐acid glycoprotein >1 g/l), with or without additional adjustment for malaria, on ...prevalence estimates of iron deficiency (ID) and iron deficiency anaemia (IDA) during low malaria (LowM) and high malaria (HighM) transmission seasons.
Methods
To estimate adjustment factors, children were classified as: (i) reference (malaria negative without inflammation), (ii) inflammation without malaria (I), (iii) malaria without inflammation (M) and (iv) inflammation with malaria (IM). We estimated the unadjusted ID or IDA prevalence, and then adjusted for inflammation alone (IDI or IDAI) or inflammation and malaria (IDIM or IDAIM).
Results
Mean ferritin was 38 (reference), 45 (I), 43 (M) and 54 μg/l (IM) in LowM, increasing to 44, 56, 96 and 167 μg/l, respectively, in HighM. Corresponding mean sTfR was 6.4, 6.9, 7.9 and 8.4 mg/l in LowM, increasing to 8.2, 9.2. 8.7 and 9.7 mg/l in HighM. Ferritin‐based ID, IDI and IDIM were 7.8%, 8.7% or 9.1%, respectively, in LowM and 4.6%, 10.0% or 11.7%, respectively, in HighM. Corresponding soluble transferrin receptor (sTfR)‐based estimates were 27.0%, 24.1% and 19.1%, respectively, in LowM, increasing to 53.6%, 46.5% and 45.3%, respectively, in HighM. Additional adjustment for malaria resulted in a ~1‐ to 2‐percentage point change in IDA, depending on biomarker and season.
Conclusions
In this population, malaria substantially increased ferritin and sTfR concentrations, with modest effects on ID and IDA prevalence estimates.
Objectif
Chez les enfants zambiens de 4 à 8 ans (n = 744), nous avons évalué les effets de l'ajustement pour l'inflammation (α1‐glycoprotéine acide > 1 g/L), avec ou sans ajustement additionnel pour le paludisme, sur les estimations de prévalence de la carence en fer (CF) et l'anémie ferriprive (AF) lors des saisons de transmission faible (LowM) et élevée (HighM) du paludisme.
Méthodes
Pour estimer les facteurs d'ajustement, les enfants ont été classés en: a) référence (paludisme négatif sans inflammation), b) inflammation sans paludisme (I), c) paludisme sans inflammation (M), et d) inflammation avec paludisme (IM). Nous avons estimé la prévalence non ajustée de la CF ou de l’AF, puis avons ajusté pour l'inflammation seule (CFI ou AFI) ou l'inflammation avec le paludisme (CFIM ou AFIM).
Résultats
La ferritine moyenne était de 38 (référence), 45 (I), 43 (M) et 54 (IM) μg/L dans la LowM, augmentant à 44, 56, 96 et 167 μg/L respectivement, dans la HighM. Les valeurs moyennes correspondantes du récepteur soluble de la transferrine (sTfR) étaient de 6,4; 6,9; 7,9 et 8,4 mg/L dans la LowM, augmentant à 8,2; 9,2; 8,7 et 9,7 mg/L dans la HighM. Les CF sur base de la ferritine, de CFI et CFIM étaient respectivement de 7,8%, 8,7% et 9,1% dans la LowM et de 4,6%, 10,0% et 11,7% respectivement, dans la HighM. Les estimations correspondantes du sTfR étaient respectivement de 27,0%, 24,1% et 19,1% dans la LowM, augmentant à 53,6%, 46,5% et 45,3%, respectivement, dans la HighM. Des ajustements supplémentaires pour le paludisme ont entraîné une variation d'environ 1 à 2 points de pourcentage de l’AF selon le biomarqueur et la saison.
Conclusions
Dans cette population, le paludisme a considérablement augmenté les concentrations de ferritine et du sTfR, avec des effets modestes sur les estimations de prévalence la CF et de l'AF.
Breath Biomarkers of Influenza Infection Danaher, Patrick J; Phillips, Michael; Schmitt, Peter ...
Open forum infectious diseases,
10/2022, Volume:
9, Issue:
10
Journal Article
Peer reviewed
Open access
Abstract
Background
Volatile organic compounds (VOCs) are produced systemically due to varied physiological states such as oxidative stress and are excreted through the lungs. Benchtop and ...preliminary clinical data suggest that breath testing may be a useful diagnostic modality for viral respiratory tract infections.
Methods
Patients with influenza-like illness (ILI) presenting to a single clinic in San Antonio, Texas, from 3/2017 to 3/2019 submitted a 2-minute breath sample in addition to a nasopharyngeal swab collected for polymerase chain reaction (PCR) assay for respiratory pathogens. VOCs were assayed with gas chromatography–mass spectrometry (GC-MS), and data were analyzed to identify breath VOC biomarkers that discriminated between ILI patients with and without a polymerase chain reaction (PCR) assay that was positive for influenza.
Results
Demographic, clinical, PCR, and breath data were available for 237 episodes of ILI, among which 32 episodes (13.5%) were PCR positive for influenza. Twenty candidate VOCs identified patients with influenza with greater than random accuracy. A predictive algorithm using 4 candidate biomarkers identified this group with 78% accuracy (74% sensitivity, 70% specificity). Based on their mass spectra, most of these biomarkers were n-alkane derivatives, consistent with products of oxidative stress.
Conclusions
A breath test for VOC biomarkers accurately identified ILI patients with PCR-proven influenza. These findings bolster those of others that a rapid, accurate, universal point-of-care influenza diagnostic test based on assay of exhaled-breath VOCs may be feasible. The next step will be a study of patients with ILI using a simplified method of breath collection that would facilitate translation for use in clinical practice.
Despite vaccine efforts, influenza outbreaks pose a significant threat to global public health. There are two commercially available seasonal influenza vaccines in the United States: the trivalent ...inactivated vaccine (TIV), delivered parenterally, and the live attenuated influenza vaccine (LAIV), delivered intranasally. Although both vaccines are generally efficacious, the immunologic mechanisms which contribute to protective immunity are incompletely understood. Thus, we investigated the protracted effects of TIV and LAIV on serum cytokine profiles at 14 and 28days post-vaccination (when antibody titers are peak) in healthy adults over two influenza seasons. Vaccination with TIV was associated with a small, yet significant, decrease in the levels of both IL-8 and TNF-α at 14 and 28days post-vaccination. LAIV, however, had no impact on serum cytokine levels. Similarly, analysis of serum antibody titers indicated that TIV recipients had a significantly higher sero-response rate compared to LAIV recipients, as has been previously shown. Finally, we examined the relationship between baseline serum cytokine levels and antibody responses to TIV (LAIV recipients were excluded due to the poor sero-response rate). Interestingly, in TIV recipients pre-vaccination levels of IL-8 were higher in sero-responders compared to non-responders. Collectively, these data suggest that cytokines may influence vaccine outcomes and indicate that parenteral immunization with TIV induces a sustained, systemic cytokine response which lasts for weeks.
•Higher serum TNF-α concentration was associated with reduced oral HPV clearance.•The association of TNF-α with oral HPV clearance was stronger among men than women.•Results are consistent with ...studies of TNF-α and decreased cervical HPV clearance.
Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored.
From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count.
Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio aHR=0.52, 95% CI=0.34–0.79) and women (aHR=0.76, 95% confidence interval CI=0.55–1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50–0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4<500 cells/μl) among HIV-infected participants. No other cytokines were associated with clearance.
High serum TNF-α is associated with reduced clearance of oral HPV infection.
Inflammation-induced hyporetinolemia (IIH), a reduction in serum retinol (SR) during inflammation, may bias population estimates of vitamin A deficiency (VAD). The optimal adjustment for IIH depends ...on the type and extent of inflammation. In rural Zambian children (4–8 years, N = 886), we compared three models for defining inflammation: α-1-acid glycoprotein (AGP) only (inflammation present if > 1 g/L or normal if otherwise), C-reactive protein (CRP) only (moderate inflammation, 5–15 mg/L; high inflammation, > 15 mg/L; or normal if otherwise) and a combined model using both AGP and CRP to delineate stages of infectious episode. Models were compared with respect to 1) the variance in SR explained and 2) comparability of inflammation-adjusted VAD estimated in low and high malaria seasons. Linear regression was used to estimate the variance in SR explained by each model and in estimating the adjustment factors used in generating adjusted VAD (retinol < 0.7 μmol/L). The variance in SR explained were 2% (AGP-only), 11% (CRP-only), and 11% (AGP–CRP) in the low malaria season; and 2% (AGP-only), 15% (CRP-only), and 12% (AGP–CRP) in the high malaria season. Adjusted VAD estimates in the low and high malaria seasons differed significantly for the AGP (8.2 versus 13.1%) and combined (5.5 versus 9.1%) models but not the CRP-only model (6.1 versus 6.3%). In the multivariate regression, a decline in SR was observed with rising CRP (but not AGP), in both malaria seasons (slope = −0.06; P < 0.001). In this malaria endemic setting, CRP alone, as opposed to CRP and AGP, emerged as the most appropriate model for quantifying IIH.
Abstract
Introduction
Since the influenza A/H1N1 pandemic of 2009 to 2010, numerous studies have described the clinical course and outcome of the different subtypes of influenza (A/H1N1, A/H3N2, and ...B). A recent systematic literature review concluded that there were no appreciable differences in either clinical presentation or disease severity among these subtypes, but study parameters limit the applicability of these results to military populations. We sought to evaluate differences in disease severity among influenza subtypes in a cohort of healthy, primarily outpatient adult U.S. Department of Defense beneficiaries.
Materials and Methods
From 2009 to 2014, we enrolled otherwise healthy adults age 18 to 65 years with influenza-like illness in an observational cohort study based in 5 U.S. military medical centers. Serial nasopharyngeal swabs were collected for determination of etiology and viral shedding by polymerase chain reaction. The presence and severity of symptoms was assessed by interview and patient diary.
Results
Over a 5-year period, a total of 157 adults with laboratory-confirmed influenza and influenza subtype were enrolled. Of these, 69 (44%) were positive for influenza A(H1N1), 69 (44%) for influenza A(H3N2), and 19 (12%) for influenza B. About 61% were male, 64% were active duty military personnel, and 72% had received influenza vaccine in the past 8 months. Almost 10% were hospitalized with influenza. Seasonal influenza virus distribution among enrollees mirrored that of nationwide trends each year of study. Individuals with A/H1N1 had upper respiratory composite scores that were lower than those with A/H3N2. Multivariate models indicated that individuals with A(H1N1) and B had increased lower respiratory symptom scores when compared to influenza A(H3N2) (AH1N1: 1.51 95% CI 0.47, 2.55; B: 1.46 95% CI 0.09, 2.83), whereas no other differences in symptom severity scores among influenza A(H1N1), influenza A(H3N2), and influenza B infection were observed. Overall, influenza season (maximum in 2012–2013 season) and female sex of the participant were found to be associated with increased influenza symptom severity.
Conclusions
Our study of influenza in a cohort of otherwise healthy, outpatient adult Department of Defense beneficiaries over 5 influenza seasons revealed few differences between influenza A(H1N1), influenza A(H3N2), and influenza B infection with respect to self-reported disease severity or clinical outcomes. This study highlights the importance of routine, active, and laboratory-based surveillance to monitor ongoing trends and severity of influenza in various populations to inform prevention measures.
BACKGROUND:Severe pneumonia remains a leading cause of morbidity and mortality in undernourished young children in developing countries. OBJECTIVE:This study evaluated the effect of adjuvant zinc ...therapy on recovery from severe pneumonia by hospitalized children in southern India who were receiving standard antibiotic therapy. DESIGN:This randomized, double-blind, placebo-controlled clinical trial was conducted at the Christian Medical College Hospital, an 1800-bed teaching hospital in Tamilnadu, India. Enrollment and follow-up occurred between September 2003 and August 2004. Children aged 2-23 mo (n = 299) who were hospitalized with severe pneumonia were randomly assigned to receive 10-mg tablets of zinc sulfate or placebo twice a day during hospitalization, along with standard therapy for severe pneumonia. All clinical signs and symptoms of pneumonia were assessed and recorded at 8-h intervals. RESULTS:There were no clinical or statistically significant differences in the duration of tachypnea, hypoxia, chest indrawing, inability to feed, lethargy, severe illness, or hospitalization. Zinc supplementation was associated with a significantly longer duration of pneumonia in the hot season (P = 0.015). CONCLUSIONS:Zinc supplementation had no overall effect on the duration of hospitalization or of clinical signs associated with severe infection in young children hospitalized for severe pneumonia in southern India. This finding differs from the results of 2 previously reported trials wherein zinc supplementation was associated with a shorter period of recovery from severe pneumonia. Given the conflicting results, further research in representative settings is required to help clarify the role of zinc in the treatment of severe pneumonia.
The stability of the
populations in the human gastrointestinal tract is not fully appreciated, and represents a significant knowledge gap regarding gastrointestinal community structure, as well as ...resistance to incoming pathogenic bacterial species and antibiotic treatment. The current study examines the genomic content of 240
isolates from 30 children, aged 2 to 35 months old, in Tanzania. The
strains were isolated from three time points spanning a six-month time period, with and without antibiotic treatment. The resulting isolates were sequenced, and the genomes compared. The findings in this study highlight the transient nature of
strains in the gastrointestinal tract of these children, as during a six-month interval, no one individual contained phylogenomically related isolates at all three time points. While the majority of the isolates at any one time point were phylogenomically similar, most individuals did not contain phylogenomically similar isolates at more than two time points. Examination of global genome content, canonical
virulence factors, multilocus sequence type, serotype, and antimicrobial resistance genes identified diversity even among phylogenomically similar strains. There was no apparent increase in the antimicrobial resistance gene content after antibiotic treatment. The examination of the
from longitudinal samples from multiple children in Tanzania provides insight into the genomic diversity and population variability of resident
within the rapidly changing environment of the gastrointestinal tract of these children.
This study increases the number of resident
genome sequences, and explores
diversity through longitudinal sampling. We investigate the genomes of
isolated from human gastrointestinal tracts as part of an antibiotic treatment program among rural Tanzanian children. Phylogenomics demonstrates that resident
are diverse, even within a single host. Though the
isolates of the gastrointestinal community tend to be phylogenomically similar at a given time, they differed across the interrogated time points, demonstrating the variability of the members of the
community in these subjects. Exposure to antibiotic treatment did not have an apparent impact on the
community or the presence of resistance and virulence genes within
genomes. The findings of this study highlight the variable nature of specific bacterial members of the human gastrointestinal tract.
Purpose
Persistent oral human papillomavirus (HPV) infection increases risk for oropharyngeal carcinoma, and people living with HIV have higher rates of oral HPV infection and related cancers. Some ...prescription medications have immunomodulatory effects, but the impact of medication use on oral HPV natural history is unknown.
Methods
Scope
®
oral rinse-and-gargle samples were collected semi-annually from 1,666 participants and tested for 37 types of oral HPV DNA using PCR; 594 HPV-infected participants with 1,358 type-specific oral HPV infections were identified. Data were collected on recent (past 6 months) use of medications. The relationship between medication use and oral HPV clearance was evaluated using Wei–Lin–Weissfeld regression, adjusting for biologic sex, prevalent versus incident infection, age, HIV status and CD4+ T cell count.
Results
Out of 11 medications examined, oral HPV clearance was significantly reduced in participants reporting recent use of antipsychotics (HR 0.75, 95% CI 0.57–0.99), anxiolytics/sedatives (HR 0.78, 95% CI 0.63–0.96) and antidepressants (HR 0.82, 95% CI 0.67–0.999). Among antipsychotics users, effect modification by HIV status was observed, with reduced clearance in HIV-infected (HR 0.67, 95% CI 0.49–0.91), but not HIV-uninfected participants (
p
-interaction = 0.009). After adjusted analysis, antipsychotic use remained significantly associated with reduced oral HPV clearance overall (aHR 0.75, 95% CI 0.57–0.99), and when restricted to only HIV-infected participants (aHR 0.66, 95% CI 0.48–0.90). After adjustment, anxiolytic/sedative use and antidepressant use were no longer significantly associated with reduced oral HPV clearance.
Conclusions
Some medications were associated with decreased oral HPV clearance, most notably antipsychotic medications. These medications are prescribed for conditions that may have immunomodulating effects, so characteristics of underlying illness may have partially contributed to reduced oral HPV clearance.
Nasopharyngeal (NP) carriage of S. pneumoniae (Spn) is a risk factor for pneumococcal disease and its transmission. We assessed the impact of vitamin A (VA) supplementation shortly after birth in ...reducing Spn colonization in early infancy in rural Bangladesh. We recruited 500 infants participating in a cluster-randomized trial that reported a 15% reduction in mortality following receipt of an oral dose of VA (52.25 μmol) compared to placebo. NP specimens were collected at the age of 3 mo to study the effect of VA on the prevalence of culture-confirmed Spn. Analyses were conducted by intention to treat. Spn carriage prevalence did not differ between VA and placebo recipients OR = 0.83 (95% CI: 0.55-1.27); P = 0.390. Spn carriage at the age of 3 mo was not lowered by VA given at birth. Results are similar to those from an Indian study in which impact on Spn carriage was assessed at the age of 4 mo OR = 0.73 (95% CI: 0.48-1.10); P = 0.128. The point estimate of the pooled effect size for the 2 studies is OR = 0.78 (95% CI: 0.58-1.04); P = 0.095, which may imply a modest impact on carriage. If so, then the evidence thus far would suggest that Spn carriage reduction is unlikely to be a primary ancillary benefit of newborn VA supplementation.
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