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In these short interviews, Anna Kordala and Jane Millar talk about the research they do at the Department of Paediatrics.
Placental transfer of SARS-CoV-2 antibodies in mother-neonate pairs: a prospective nested cohort study.
BACKGROUND: Newborns depend on the transfer of IgG across the placenta to acquire protection against pathogens. We assessed the placental transfer of SARS-CoV-2 antibodies, primarily derived from infection, from seropositive pregnant women enrolled in a pregnancy cohort in Kilifi, Kenya. METHODS: The study was nested within a prospective observational multi-country cohort study. All available paired maternal delivery and cord blood samples were selected. Maternal sera were tested for SARS-CoV-2 receptor binding domain (RBD) IgM/IgG total antibodies using the Wantai assay. For positive samples, maternal and corresponding cord blood samples were tested for SARS-CoV-2 IgG antibodies against the spike (anti-spike) and nucleocapsid proteins (anti-NCP) using ELISA kits from Euroimmun. RESULTS: A total of 492 (56.1%) out of 877 maternal delivery samples were positive for RBD IgM/IgG total antibodies. Of these, 416 (84.6%) were seropositive for either anti-NCP IgG, anti-spike IgG antibodies or both. A total of 412 out of 496 (83%) cord blood samples tested positive for either anti-NCP or anti-spike antibodies. The geometric mean ratio was 1.04 (95% CI: 0.90, 1.21), indicating no significant difference between the anti-spike IgG concentration in cord and maternal blood samples. The log-transformed maternal and cord blood anti-spike IgG concentrations showed a weak positive correlation (r = 0.364, n = 496, p
Understanding the interaction of upper respiratory tract infection with respiratory syncytial virus and Streptococcus pneumoniae using a human challenge model: a multicenter, randomized controlled study protocol.
BACKGROUND: Streptococcus pneumoniae (pneumococcus) and respiratory syncytial virus (RSV) are major causes of respiratory infections globally. Viral and bacterial co-infections are commonly observed in respiratory infections and there is evidence that these pathogens interact synergistically to evade host responses and lead to more severe disease. Notably, RSV seasonal outbreaks are associated with increased hospitalization and a subsequent peak in invasive pneumococcal disease cases, particularly in pediatric populations. Here, we summarize a protocol for a controlled human infection model aiming to evaluate pathogen interaction dynamics and immune responses in a combined pneumococcus and RSV model. The primary objective is to determine whether primary RSV challenge increases the risk of secondary pneumococcal colonization. METHODS: This is an open-label, multi-center, randomized controlled human co-infection study, inclusive of a pilot phase. Individuals will be randomized to primary inoculation with either pneumococcus (serotype 6B) or RSV (subtype RSV-A) intra-nasally on day 0 followed by a reciprocal challenge on day 7. During pilot phase A up to 10 participants will be monitored in an in-patient facility for 7-10 days following RSV-A challenge. If there are no safety concerns, we will then progress to an outpatient phase where participants will self-isolate at home. Clinical samples to be taken from participants include nasal swabs and washes for pathogen detection; and nasal cells, nasal lining fluid, and blood samples to examine mucosal and systemic immune responses. DISCUSSION: This work will lead to important scientific knowledge on the interaction and dynamics between pneumococcus and RSV. This knowledge could help inform pneumococcal and RSV vaccination strategies, particularly for groups at risk of developing severe pneumococcal and RSV disease. TRIAL REGISTRATION: The study is registered on ISRCTN (The UKs Clinical Study Registry). DOI https://doi.org/10.1186/ISRCTN12036902.
Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy.
The North Star Ambulatory Assessment (NSAA) is a widely used functional endpoint in drug development for ambulatory patients with Duchenne muscular dystrophy (DMD). Accurately predicting NSAA total score trajectories is important for designing randomized trials for novel therapies in DMD and for contextualizing outcomes, especially over longer-term follow-up (>18 months) when placebo-controlled studies are infeasible. We developed a prognostic model for NSAA total score trajectories over at most 5 years of follow-up for patients with DMD aged 4 to <16 years who were initially ambulatory and receiving corticosteroids but no other disease-modifying therapies. The model was based on longitudinal data from four natural history databases: UZ Leuven, PRO-DMD-01 (provided by CureDuchenne), the North Star Clinical Network, and iMDEX. Candidate predictors included age, height, weight, body mass index, steroid type and regime, NSAA total score, rise from floor velocity, and 10-meter walk/run velocity, as well as DMD genotype class, index year, and data source. Among N = 416 patients at baseline, mean age was 8.2 years, mean NSAA total score was 24, and 61% were receiving prednisone and 39% deflazacort, with the majority having been treated with daily corticosteroid regimens (69%) relative to other regimens (31%). Patients had an average of four NSAA assessments post-baseline during a median follow-up of 2.6 years (inter-quartile range 1.9 to 3.6 years). The best-fitting model in the full study sample explained 39% of the variation in NSAA total score changes, with prediction errors of ±3.6, 5.1, 5.9, 7.5, 9.5 NSAA units during follow-up years 1-5, respectively. The most important predictors were baseline age, NSAA, rise from floor velocity, and 10-meter walk/run velocity. In conclusion, trajectories of ambulatory motor function in DMD, as measured by the NSAA total score, can be well-predicted using readily available baseline characteristics. We discuss applications of these predictions to DMD drug development.
Respiratory viral detection in children hospitalized with pneumonia during periods of major population disruptions in Nepal, 2014-2018.
BACKGROUND: Respiratory viruses commonly cause pneumonia in children. We aimed to identify respiratory viral nucleic acids in the nasopharynx of children admitted with pneumonia from 2014 to 2018, a period including a major earthquake (April 2015), PCV10 introduction (August 2015), and a fuel shortage (October 2015 to March 2016). METHODS: Children 2 months to 14 years admitted to Patan Hospital between March 2014 and February 2018 with a clinical diagnosis of pneumonia had nasopharyngeal swabs collected and tested with a multiplex panel for the presence of genetic material from 23 respiratory pathogens. RESULTS: Of 1343 children with pneumonia, 974 (72.5%) had the nucleic acids of at least one respiratory virus in the nasopharynx. The median age of children with any viral genetic material detected was lower than those without (1.18, IQR: 0.59-2.39 years; versus 2.01 years, IQR: 0.81-4.34 years; p<0.001). Commonly detected viral nucleic acids included those of RSV (21.0%), rhino/enterovirus (30.8%), and parainfluenza (7.4%). The odds of detecting any respiratory viral genetic material in children with pneumonia increased by 1.88 (95% confidence interval: 1.15, 3.06) in the year after the earthquake, when there were several aftershocks and a fuel crisis, relative to other periods and accounting for other potential confounding factors. CONCLUSIONS: These findings highlight the importance of viral diagnostics in pediatric pneumonia and suggest that public health measures addressing environmental conditions during disasters might help reduce respiratory infections.
Predictive Performance of Cardiovascular Risk Scores in Cancer Survivors From the UK Biobank.
BACKGROUND: Cardiovascular preventive strategies are guided by risk scores with unknown validity in cancer cohorts. OBJECTIVES: This study aimed to evaluate the predictive performance of 7 established cardiovascular risk scores in cancer survivors from the UK Biobank. METHODS: The predictive performance of QRISK3, Systematic Coronary Risk Evaluation 2 (SCORE2)/Systematic Coronary Risk Evaluation for Older Persons (SCORE-OP), Framingham Risk Score, Pooled Cohort equations to Prevent Heart Failure (PCP-HF), CHARGE-AF, QStroke, and CHA2DS2-VASc was calculated in participants with and without a history of cancer. Participants were propensity matched on age, sex, deprivation, health behaviors, family history, and metabolic conditions. Analyses were stratified into any cancer, breast, lung, prostate, brain/central nervous system, hematologic malignancies, Hodgkin lymphoma, and non-Hodgkin lymphoma. Incident cardiovascular events were tracked through health record linkage over 10 years of follow-up. The area under the receiver operating curve, balanced accuracy, and sensitivity were reported. RESULTS: The analysis included 31,534 cancer survivors and 126,136 covariate-matched controls. Risk score distributions were near identical in cases and controls. Participants with any cancer had a significantly higher incidence of all cardiovascular outcomes than matched controls. Performance metrics were significantly worse for all risk scores in cancer cases than in matched controls. The most notable differences were among participants with a history of hematologic malignancies who had significantly higher outcome rates and poorer risk score performance than their matched controls. The performance of risk scores for predicting stroke in participants with brain/central nervous system cancer was very poor, with predictive accuracy more than 30% lower than noncancer controls. CONCLUSIONS: Existing cardiovascular risk scores have significantly worse predictive accuracy in cancer survivors compared with noncancer comparators, leading to an underestimation of risk in this cohort.