Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame.

The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio

Changes in the intestinal microbiota following the administration of azithromycin in a randomised placebo-controlled trial among infants in south India.

Macrolides are among the most widely prescribed antibiotics worldwide. However, their impact on the gut's bacterial microbiota remains uncertain. We characterised the intestinal microbiota in 6-11 month-old infants in India who received a 3-day course of azithromycin or placebo during a randomised trial of oral poliovirus vaccine immunogenicity (CTRI/2014/05/004588). In 60 infants per study arm, we sequenced the V4 region of the bacterial 16S rRNA gene in stool samples collected before and 12 days after finishing treatment. We also tested for the presence of common bacterial, viral, and eukaryotic enteropathogens in the same samples using real-time PCR in a Taqman array card (TAC) format. Azithromycin induced a modest decline in microbiota richness and a shift in taxonomic composition driven by a reduction in the relative abundance of Proteobacteria and Verrucomicrobia (specifically Akkermansia muciniphila). The former phylum includes pathogenic strains of Escherichia coli and Campylobacter spp. that declined in prevalence based on the TAC assay. These findings differ from previous observations among older children and adults in Europe and North America, suggesting that the effects of azithromycin on the bacterial microbiota may be specific to the age and geographic setting of its recipients

FUT2 Secretor Status Is Not Associated With Oral Poliovirus Vaccine Immunogenicity in South Indian Infants.

FUT2 determines whether histo-blood group antigens are secreted at mucosal surfaces. Secretor status influences susceptibility to enteric viruses, potentially including oral poliovirus vaccine (OPV). We performed a nested case-control study to determine the association between FUT2 genotype (single-nucleotide polymorphisms G428A, C302T, and A385T) and seroconversion among Indian infants who received a single dose of monovalent type 3 OPV. Secretor prevalence was 75% (89 of 118) in infants who seroconverted and 80% (97 of 122) in infants who did not seroconvert (odds ratio, 0.79; 95% confidence interval, .43-1.45). Our findings suggest that FUT2 genotype is not a key determinant of variation in OPV immunogenicity

Identification of patients undergoing chronic kidney replacement therapy in primary and secondary care data: validation study based on OpenSAFELY and UK Renal Registry

Objective: To validate primary and secondary care codes in electronic health records to identify people receiving chronic kidney replacement therapy based on gold standard registry data. Design: Validation study using data from OpenSAFELY and the UK Renal Registry, with the approval of NHS England. Setting: Primary and secondary care electronic health records from people registered at 45% of general practices in England on 1 January 2020, linked to data from the UK Renal Registry (UKRR) within the OpenSAFELY-TPP platform, part of the NHS England OpenSAFELY covid-19 service. Participants: 38 745 prevalent patients (recorded as receiving kidney replacement therapy on 1 January 2020 in UKRR data, or primary or secondary care data) and 10 730 incident patients (starting kidney replacement therapy during 2020), from a population of 19 million people alive and registered with a general practice in England on 1 January 2020. Main outcome measures: Sensitivity and positive predictive values of primary and secondary care code lists for identifying prevalent and incident kidney replacement therapy cohorts compared with the gold standard UKRR data on chronic kidney replacement therapy. Agreement across the data sources overall, and by treatment modality (transplantation or dialysis) and personal characteristics. Results: Primary and secondary care code lists were sensitive for identifying the UKRR prevalent cohort (91.2% (95% confidence interval (CI) 90.8% to 91.6%) and 92.0% (91.6% to 92.4%), respectively), but not the incident cohort (52.3% (50.3% to 54.3%) and 67.9% (66.1% to 69.7%)). Positive predictive values were low (77.7% (77.2% to 78.2%) for primary care data and 64.7% (64.1% to 65.3%) for secondary care data), particularly for chronic dialysis (53.7% (52.9% to 54.5%) for primary care data and 49.1% (48.0% to 50.2%) for secondary care data). Sensitivity decreased with age and index of multiple deprivation in primary care data, but the opposite was true in secondary care data. Agreement was lower in children, with 30% (295/980) featuring in all three datasets. Half (1165/2315) of the incident patients receiving dialysis in UKRR data had a kidney replacement therapy code in the primary care data within three months of the start date of the kidney replacement therapy. No codes existed whose exclusion would substantially improve the positive predictive value without a decrease in sensitivity. Conclusions: Codes used in primary and secondary care data failed to identify a small proportion of prevalent patients receiving kidney replacement therapy. Codes also identified many patients who were not recipients of chronic kidney replacement therapy in UKRR data, particularly dialysis codes. Linkage with UKRR kidney replacement therapy data facilitated more accurate identification of incident and prevalent kidney replacement therapy cohorts for research into this vulnerable population. Poor coding has implications for any patient care (including eligibility for vaccination, resourcing, and health policy responses in future pandemics) that relies on accurate reporting of kidney replacement therapy in primary and secondary care data

Bias assessment of a test-negative design study of COVID-19 vaccine effectiveness used in national policymaking

National test-negative-case-control (TNCC) studies are used to monitor COVID-19 vaccine effectiveness in the UK. A questionnaire was sent to participants from the first published TNCC COVID-19 vaccine effectiveness study conducted by the UK Health Security Agency, to assess for potential biases and changes in behaviour related to vaccination. The original study included symptomatic adults aged ≥70 years testing for COVID-19 between 08/12/2020 and 21/02/2021. A questionnaire was sent to cases and controls tested from 1-21 February 2021. In this study, 8648 individuals responded to the questionnaire (36.5% response). Using information from the questionnaire to produce a combined estimate that accounted for all potential biases decreased the original vaccine effectiveness estimate after two doses of BNT162b2 from 88% (95% CI: 79-94%) to 85% (95% CI: 68-94%). Self-reported behaviour demonstrated minimal evidence of riskier behaviour after vaccination. These findings offer reassurance to policy makers and clinicians making decisions based on COVID-19 vaccine effectiveness TNCC studies

Quantifying movement patterns and vaccination status of high risk mobile populations in Pakistan and Afghanistan to inform poliovirus risk and vaccination strategy.

BACKGROUND: Stopping serotype 1 wild poliovirus transmission in Pakistan and Afghanistan requires ensuring all children 90% across HRMP type, ethnic group, language and mobility means. CONCLUSION: Large numbers of HRMPs were found across Pakistan, with substantial links throughout the country and with Afghanistan. While vaccination coverage of HRMPs was high, ensuring these populations are consistently vaccinated remains a priority

Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP

Objective To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England. Design Matched cohort study, emulating a comparative effectiveness trial. Setting Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant. Participants 3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1. Intervention Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose. Main outcome measures Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose. Results 1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras. Conclusions This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance