Microfluidic qPCR for detection of 21 common respiratory viruses in children with influenza-like illness.

Multiple respiratory viruses lead to high morbidity and mortality, yet global surveillance platforms focus primarily on seasonal influenza viruses. The COVID-19 pandemic and new RSV vaccines highlight the importance of a broader approach. Upper respiratory tract swabs from children aged 24-59 months presenting with influenza-like illness in The Gambia were collected during follow-up of a live-attenuated influenza vaccine randomised controlled trial in 2017-18.

Unraveling Cecal Alterations in Colonized Mice through Comprehensive Metabolic Profiling.

The disruption of gut microbiota caused by antibiotics favors the intestinal colonization of - a Gram-positive, spore-forming anaerobic bacterium that causes potentially fatal gastrointestinal infections. In an endeavor to elucidate the complexities of the gut-brain axis in the context of infection (CDI), a murine model has been used to investigate the potential effects of antibiotic administration and subsequent colonization by , as well as the impact of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the cecal metabolome for the first time. This follows our previous research which highlighted the metabolic effect of CDI and these treatments in the brain and employs the same four different metabolomics-based methods (targeted GC-MS/MS, targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS and untargeted GC-MS).

Molecular methods enhance the detection of pyoderma-related Streptococcus pyogenes and emm-type distribution in children.

Background: Streptococcus pyogenes-related skin infections are increasingly implicated in the development of rheumatic heart disease (RHD) in lower-resourced settings, where they are often associated with scabies. The true prevalence of S. pyogenes-related pyoderma may be underestimated by bacterial culture.

Streptococcus pyogenes carriage and infection within households in The Gambia: a longitudinal cohort study.

Background: Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S pyogenes skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both S pyogenes asymptomatic carriage and infection in a high-burden setting.

Health-seeking behaviour and beliefs around sore throat in The Gambia: A qualitative study.

Group A Streptococcus (Strep A) bacteria causes a broad spectrum of diseases. The most common manifestations of Strep A infection are sore throat and pus-producing skin infections such as impetigo. Complications of Strep A infection can lead to inflammation in the bones, muscles, joints, and internal organs causing acute rheumatic fever and rheumatic heart disease (RHD).

carriage acquisition, persistence and transmission dynamics within households in The Gambia (SpyCATS): protocol for a longitudinal household cohort study.

Background: (StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year, predominantly in low- and middle-income countries (LMIC). Superficial StrepA infections of the skin and pharynx can lead to rheumatic heart disease, the largest cause of StrepA-related deaths in LMIC.

CXCR3 Provides a Competitive Advantage for Retention of -Specific Tissue-Resident Memory T Cells Following a Mucosal Tuberculosis Vaccine.

is a major human pathogen, and new vaccines are needed to prevent transmission. Mucosal vaccination may confer protection against by stimulating tissue-resident memory (T) CD4 T cells in the lungs. The chemokine receptor CXCR3 promotes lung recruitment of T cells, but its role in T development is unknown.

Streptococcus pyogenes Colonization in Children Aged 24-59 Months in the Gambia: Impact of Live Attenuated Influenza Vaccine and Associated Serological Responses.

Background: Immunity to Streptococcus pyogenes in high burden settings is poorly understood. We explored S. pyogenes nasopharyngeal colonization after intranasal live attenuated influenza vaccine (LAIV) among Gambian children aged 24-59 months, and resulting serological response to 7 antigens.

Metabolic Phenotyping Study of Mouse Brain Following Microbiome Disruption by Colonization.

infection (CDI) is responsible for an increasing number of cases of post-antibiotic diarrhea worldwide, which has high severity and mortality among hospitalized elderly patients. The disruption of gut microbiota due to antibacterial medication facilitates the intestinal colonization of . In the present study, a murine model was used to investigate the potential effects of antibiotic administration and subsequent colonization by , as well as the effects of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the brain metabolome for the first time.

Erratum: Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children.

[This corrects the article DOI: 10.1016/j.xcrm.

Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children.

In children lacking influenza-specific adaptive immunity, upper respiratory tract innate immune responses may influence viral replication and disease outcome. We use trivalent live attenuated influenza vaccine (LAIV) as a surrogate challenge model in children aged 24-59 months to identify pre-infection mucosal transcriptomic signatures associated with subsequent viral shedding. Upregulation of interferon signaling pathways prior to LAIV is significantly associated with lower strain-specific viral loads (VLs) at days 2 and 7.

The effect of live attenuated influenza vaccine on pneumococcal colonisation densities among children aged 24-59 months in The Gambia: a phase 4, open label, randomised, controlled trial.

Background: Influenza and other respiratory viruses promote proliferation in the upper respiratory tract. We sought to investigate for what we believe is the first time, the effect of intranasal live attenuated influenza vaccine (LAIV) on nasopharyngeal density in a low-income to middle-income country population with high pneumococcal carriage rates.

Methods: In an open-label, randomised, controlled trial in The Gambia, 330 healthy children aged 24-59 months were randomly assigned 2:1 to receive one trivalent LAIV dose at enrolment (day 0, intervention) or at the end of active follow-up (day 21, control).

The Epidermal Growth Factor Ligand Spitz Modulates Macrophage Efferocytosis, Wound Responses and Migration Dynamics During Embryogenesis.

How multifunctional cells such as macrophages interpret the different cues within their environment and undertake an appropriate response is a key question in developmental biology. Understanding how cues are prioritized is critical to answering this - both the clearance of apoptotic cells (efferocytosis) and the migration toward damaged tissue is dependent on macrophages being able to interpret and prioritize multiple chemoattractants, polarize, and then undertake an appropriate migratory response. Here, we investigate the role of Spitz, the cardinal epidermal growth factor (EGF) ligand, in regulation of macrophage behavior in the developing fly embryo, using activated variants with differential diffusion properties.

Identification of functionally distinct macrophage subpopulations in .

Vertebrate macrophages are a highly heterogeneous cell population, but while blood is dominated by a macrophage-like lineage (plasmatocytes), until very recently these cells were considered to represent a homogeneous population. Here, we present our identification of enhancer elements labelling plasmatocyte subpopulations, which vary in abundance across development. These subpopulations exhibit functional differences compared to the overall population, including more potent injury responses and differential localisation and dynamics in pupae and adults.

Metabolic consequences for mice lacking Endosialin: LC-MS/MS-based metabolic phenotyping of serum from C56Bl/6J Control and CD248 knock-out mice.

Introduction: The Endosialin/CD248/TEM1 protein is expressed in adipose tissue and its expression increases with obesity. Recently, genetic deletion of CD248 has been shown to protect mice against atherosclerosis on a high fat diet.

Objectives: We investigated the effect of high fat diet feeding on visceral fat pads and circulating lipid profiles in CD248 knockout mice compared to controls.

Overexposure to apoptosis via disrupted glial specification perturbs Drosophila macrophage function and reveals roles of the CNS during injury.

Apoptotic cell clearance by phagocytes is a fundamental process during development, homeostasis and the resolution of inflammation. However, the demands placed on phagocytic cells such as macrophages by this process, and the limitations these interactions impose on subsequent cellular behaviours are not yet clear. Here, we seek to understand how apoptotic cells affect macrophage function in the context of a genetically tractable Drosophila model in which macrophages encounter excessive amounts of apoptotic cells.

Metabolic Phenotyping Study of Mouse Brains Following Acute or Chronic Exposures to Ethanol.

The chronic and acute effect of ethanol administration on the metabolic phenotype of mouse brain was studied in a C57BL/6 mouse model of ethanol abuse using both untargeted and targeted ultra performance liquid chromatography-tandem mass spectrometry. Two experiments based on either chronic (8 week) exposure to ethanol of both male and female mice or acute exposure of male mice for 11 days, plus 2 oral gavage doses of 25% ethanol, were undertaken. Marked differences were found in amino acids, nucleotides, nucleosides, and related metabolites as well as a number of different lipids.

Estimation of Seasonal Influenza Attack Rates and Antibody Dynamics in Children Using Cross-Sectional Serological Data.

Directly measuring evidence of influenza infections is difficult, especially in low-surveillance settings such as sub-Saharan Africa. Using a Bayesian model, we estimated unobserved infection times and underlying antibody responses to influenza A/H3N2, using cross-sectional serum antibody responses to 4 strains in children aged 24-60 months. Among the 242 individuals, we estimated a variable seasonal attack rate and found that most children had ≥1 infection before 2 years of age.

Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia: an open-label, observational, phase 4 study.

Background: The efficacy and effectiveness of the pandemic H1N1 (pH1N1) component in live attenuated influenza vaccine (LAIV) is poor. The reasons for this paucity are unclear but could be due to impaired replicative fitness of pH1N1 A/California/07/2009-like (Cal09) strains. We assessed whether an updated pH1N1 strain in the Russian-backbone trivalent LAIV resulted in greater shedding and immunogenicity compared with LAIV with Cal09.

Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution.

Macrophages encounter and clear apoptotic cells during normal development and homeostasis, including at numerous sites of pathology. Clearance of apoptotic cells has been intensively studied, but the effects of macrophage-apoptotic cell interactions on macrophage behaviour are poorly understood. Using Drosophila embryos, we have exploited the ease of manipulating cell death and apoptotic cell clearance in this model to identify that the loss of the apoptotic cell clearance receptor Six-microns-under (Simu) leads to perturbation of macrophage migration and inflammatory responses via pathological levels of apoptotic cells.

CXCR6-Deficiency Improves the Control of Pulmonary and Influenza Infection Independent of T-Lymphocyte Recruitment to the Lungs.

T-lymphocytes are critical for protection against respiratory infections, such as and influenza virus, with chemokine receptors playing an important role in directing these cells to the lungs. CXCR6 is expressed by activated T-lymphocytes and its ligand, CXCL16, is constitutively expressed by the bronchial epithelia, suggesting a role in T-lymphocyte recruitment and retention. However, it is unknown whether CXCR6 is required in responses to pulmonary infection, particularly on CD4 T-lymphocytes.

The efficacy, effectiveness, and immunogenicity of influenza vaccines in Africa: a systematic review.

The burden of influenza in Africa is substantial and underappreciated. Although surveillance has increased, the medical community's understanding of seasonal influenza vaccine performance remains limited. We did a systematic review, using PRISMA guidelines (PROSPERO CRD42017058107), on the efficacy, effectiveness, and immunogenicity of influenza vaccines in populations within Africa with the aim of identifying key data gaps to help direct future research.

Natural variation in tolerance to sub-zero temperatures among populations of Arabidopsis lyrata ssp. petraea.

Background: Temperature is one of the most important abiotic factors limiting plant growth and productivity. Many plants exhibit cold acclimation to prepare for the likelihood of freezing as temperatures decrease towards 0 °C. The physiological mechanisms associated with enabling increased tolerance to sub-zero temperatures vary between species and genotypes.