Formula supplementation remains a risk for cow's milk allergy in breast-fed infants.

BACKGROUND: Many breastfed babies in Ireland receive formula supplementation within 24 hours of birth. We explored (a) impact of formula supplementation on the likelihood of developing cow's milk protein allergy (CMPA) and (b) current practice of formula supplementation (<24 hours) among mothers intending to breastfeed. METHOD: Fifty-five CMPA-diagnosed children, fed at <24 hours of age (breast only, formula only or breast with formula supplementation), were recruited, and 55 milk-tolerant age- and sex-matched controls were identified retrospectively in Cork University Maternity Hospital. Two logistic regressions (LoR) examined neonatal feed types on likelihood of developing CMPA while controlling for parental atopy and infant sex. Formula supplementation was then prospectively measured among a separate group of 179 breastfeeding mothers. Linear regression (LiR) analysis was used to examine the subjective and objective reasons for formula supplementation, in addition to examining pre-existing factors. RESULTS: Two LoR examined the infant groups: exclusively breastfed, exclusively formula-fed or breastfed with formula supplementation. The first LoR model which showed only formula supplementation was significant in prediction of development of CMPA (χ2 (3) = 25.74, P < .05), with 74% diagnostic accuracy when parental atopy and infant sex were controlled for. Breastfed infants given formula supplements were 7.03 (95% CI, 1.82-27.25) times more likely to exhibit CMPA than those who were exclusively breastfed. Formula supplementation was significant (OR 16.62, 95% CI 3.89-71.11), indicating that breastfed infants who were given formula supplements were 16 times more likely to exhibit CMPA than those who were exclusively bottle-fed. Exclusively formula-fed infants (odds ratio 0.42, 95% CI, 0.16-1.07) were not significantly more likely to exhibit CMPA than those who were exclusively breastfed in either model (P > .05). About 45.8% of breastfed infants (<24 hours) received supplemental formula. LiR investigated importance of the subjective and objective reasons, in predicting formula supplementation. This model was significant F(8,170) = 66.95, P < .05) explaining 75% of total variance. The subjective factors 'no latch' and 'mum unwell' were the strongest predictors (ß > .45). Objective factors and pre-existing factors had lower ß values with only mode of delivery and infant hypoglycaemia being significant. CONCLUSION: Breastfed babies are still being put at significantly increased risk of CMPA by receiving supplemental formula in the first 24 hours of life, despite the major predictors of supplementation being subjective and remediable in other ways. Mothers and healthcare providers should be better educated on the benefits of exclusive breastfeeding and resourced adequately to avoid unnecessary formula supplementation to reduce risk of development of CMPA.

Reactogenicity, immunogenicity and breakthrough infections following heterologous or fractional second dose COVID-19 vaccination in adolescents (Com-COV3): A randomised controlled trial.

BACKGROUND: This was the first study to investigate the reactogenicity and immunogenicity of heterologous or fractional second dose COVID-19 vaccine regimens in adolescents. METHODS: A phase II, single-blind, multi-centre, randomised-controlled trial recruited across seven UK sites from September to November 2021, with follow-up visits to August 2022. Healthy 12-to-16 years olds were randomised (1:1:1) to either 30 µg BNT162b2 (BNT-30), 10 µg BNT162b2 (BNT-10), or NVX-CoV2373 (NVX), 8 weeks after a first 30 µg dose of BNT162b2. The primary outcome was solicited systemic reactions in the week following vaccination. Secondary outcomes included immunogenicity and safety. 'Breakthrough infection' analyses were exploratory. FINDINGS: 148 participants were recruited (median age 14 years old, 62% female, 26% anti-nucleocapsid IgG seropositive pre-second dose); 132 participants received a second dose. Reactions were mostly mild-to-moderate, with lower rates in BNT-10 recipients. No vaccine-related serious adverse events occurred. Compared to BNT-30, at 28 days post-second dose anti-spike antibody responses were similar for NVX (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI): 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI: 0.61, 0.99]). For Omicron BA.1 and BA.2, the neutralising antibody titres for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI: 0.65, 1.54] and 1.02 [95% CI: 0.71, 1.48], respectively), but higher for NVX (aGMR 1.7 [95% CI: 1.07, 2.69] and 1.43 [95% CI: 0.96, 2.12], respectively). Compared to BNT-30, cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI: 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI: 0.37, 1.15]) at 14 days post-second dose. Cellular responses were similar across the study arms by day 236 post-second dose. Amongst SARS-CoV-2 infection naïve participants, NVX participants had an 89% reduction in risk of self-reported 'breakthrough infection' compared to BNT-30 (adjusted hazard ratio [aHR] 0.11 [95% CI: 0.01, 0.86]) up until day 132 after second dose. BNT-10 recipients were more likely to have a 'breakthrough infection' compared to BNT-30 (aHR 2.14 [95% CI: 1.02, 4.51]) up to day 132 and day 236 post-second dose. Antibody responses at 132 and 236 days after second dose were similar for all vaccine schedules. INTERPRETATION: Heterologous and fractional dose COVID-19 vaccine schedules in adolescents are safe, well-tolerated and immunogenic. The enhanced performance of the heterologous schedule using NVX-CoV2373 against the Omicron SARS-CoV-2 variant suggests this mRNA prime and protein-subunit boost schedule may provide a greater breadth of protection than the licensed homologous schedule. FUNDING: National Institute for Health Research and Vaccine Task Force. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry: 12348322.

Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness.

BACKGROUND: Infectious diseases play a significant role in the global burden of disease. The gold standard for the diagnosis of bacterial infection, bacterial culture, can lead to diagnostic delays and inappropriate antibiotic use. The advent of high- throughput technologies has led to the discovery of host-based genomic biomarkers of infection, capable of differentiating bacterial from other causes of infection, but few have achieved validation for use in a clinical setting. METHODS: A systematic review was performed. PubMed/Ovid Medline, Ovid Embase and Scopus databases were searched for relevant studies from inception up to 30/03/2022 with forward and backward citation searching of key references. Studies assessing the diagnostic performance of human host genomic biomarkers of bacterial infection were included. Study selection and assessment of quality were conducted by two independent reviewers. A meta-analysis was undertaken using a diagnostic random-effects model. The review was registered with PROSPERO (ID: CRD42021208462). FINDINGS: Seventy-two studies evaluating the performance of 116 biomarkers in 16,216 patients were included. Forty-six studies examined TB-specific biomarker performance and twenty-four studies assessed biomarker performance in a paediatric population. The results of pooled sensitivity, specificity, negative and positive likelihood ratio, and diagnostic odds ratio of genomic biomarkers of bacterial infection were 0.80 (95% CI 0.78 to 0.82), 0.86 (95% CI 0.84 to 0.88), 0.18 (95% CI 0.16 to 0.21), 5.5 (95% CI 4.9 to 6.3), 30.1 (95% CI 24 to 37), respectively. Significant between-study heterogeneity (I2 77%) was present. INTERPRETATION: Host derived genomic biomarkers show significant potential for clinical use as diagnostic tests of bacterial infection however, further validation and attention to test platform is warranted before clinical implementation can be achieved. FUNDING: No funding received.

SARS-CoV-2 infection in general practice in Ireland: a seroprevalence study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing in community settings may help us better understand the immune response to this virus and, therefore, help guide public health efforts. AIM: To conduct a seroprevalence study of immunoglobulin G (IgG) antibodies in Irish GP clinics. DESIGN & SETTING: Participants were 172 staff and 799 patients from 15 general practices in the Midwest region of Ireland. METHOD: This seroprevalence study utilised two manufacturers' point-of-care (POC) SARS-CoV-2 immunoglobulin M (IgM)-IgG combined antibody tests, which were offered to patients and staff in general practice from 15 June to 10 July 2020. RESULTS: IgG seroprevalence was 12.6% in patients attending general practice and 11.1% in staff working in general practice, with administrative staff having the lowest seroprevalence at 2.5% and nursing staff having the highest at 17.6%. Previous symptoms suggestive of COVID-19 and history of a polymerase chain reaction (PCR) test were associated with higher seroprevalence. IgG antibodies were detected in approximately 80% of participants who had a previous PCR-confirmed infection. Average length of time between participants' positive PCR test and positive IgG antibody test was 83 days. CONCLUSION: Patients and healthcare staff in general practice in Ireland had relatively high rates of IgG to SARS-CoV-2 compared with the national average between 15 June and 10 July 2020 (1.7%). Four-fifths of participants with a history of confirmed COVID-19 disease still had detectable antibodies an average of 12 weeks post-infection. While not proof of immunity, SARS-CoV-2 POC testing can be used to estimate IgG seroprevalence in general practice settings.