Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission: a prospective cohort study in England

Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated the effectiveness of Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford AstraZeneca adenovirus vector vaccine (ChAdOx1) vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: Households were recruited based on adult purported index cases testing positive after reverse transcription-quantitative (RT-q)PCR testing of oral-nasal swabs. Purported index cases and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment and a subset of the PCR-positive swabs underwent genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Results: Between 2 February 2021 and 10 September 2021, 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained, of whom 113 (41%) became PCR positive. Delta lineages had 1.53 times the risk (95% Credible Interval: 1.04 – 2.20) of transmission than Alpha; contacts older than 18 years old were 1.48 (1.20 – 1.91) and 1.02 (0.93 – 1.16) times more likely to acquire an Alpha or Delta infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 36% (-1%, 66%) and 49% (18%, 73%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 69% (9%, 95%) vs. 18% (-11%, 59%), respectively, for BNT162b2 and 24% (-41%, 72%) vs. 9% (-15%, 42%), respectively, for ChAdOx1.Conclusions: BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting, although their protection against infection within this setting is low

Phylogenetic inference of pneumococcal transmission from cross-sectional data, a pilot study.

Background: Inference on pneumococcal transmission has mostly relied on longitudinal studies which are costly and resource intensive. Therefore, we conducted a pilot study to test the ability to infer who infected whom from cross-sectional pneumococcal sequences using phylogenetic inference. Methods: Five suspected transmission pairs, for which there was epidemiological evidence of who infected whom, were selected from a household study. For each pair, Streptococcus pneumoniae full genomes were sequenced from nasopharyngeal swabs collected on the same day. The within-host genetic diversity of the pneumococcal population was used to infer the transmission direction and then cross-validated with the direction suggested by the epidemiological records. Results: The pneumococcal genomes clustered into the five households from which the samples were taken. The proportion of concordantly inferred transmission direction generally increased with increasing minimum genome fragment size and single nucleotide polymorphisms. We observed a larger proportion of unique polymorphic sites in the source bacterial population compared to that of the recipient in four of the five pairs, as expected in the case of a transmission bottleneck. The only pair that did not exhibit this effect was also the pair that had consistent discordant transmission direction compared to the epidemiological records suggesting potential misdirection as a result of false-negative sampling. Conclusions: This pilot provided support for further studies to test if the direction of pneumococcal transmission can be reliably inferred from cross-sectional samples if sequenced with sufficient depth and fragment length

Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission

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Bacterial and Fungal Microbiota Changes Distinguish C. difficile Infection from Other Forms of Diarrhea: Results of a Prospective Inpatient Study.

This study sought to characterize the bacterial and fungal microbiota changes associated with Clostridium difficile infection (CDI) among inpatients with diarrhea, in order to further explain the pathogenesis of this infection as well as to potentially guide new CDI therapies. Twenty-four inpatients with diarrhea were enrolled, 12 of whom had CDI. Each patient underwent stool testing for CDI prior to being treated with difficile-directed antibiotics, when appropriate. Clinical data was obtained from the medical record, while each stool sample underwent 16S rRNA and ITS sequencing for bacterial and fungal elements. An analysis of microbial community structures distinct to the CDI population was also performed. The results demonstrated no difference between the CDI and non-CDI cohorts with respect to any previously reported CDI risk factors. Butyrogenic bacteria were enriched in both CDI and non-CDI patients. A previously unreported finding of increased numbers of Akkermansia muciniphila in CDI patients was observed, an organism which degrades mucin and which therefore may provide a selective advantage toward CDI. Fungal elements of the genus Penicillium were predominant in CDI; these organisms produce antibacterial chemicals which may resist recovery of healthy microbiota. The most frequent CDI microbial community networks involved Peptostreptococcaceae and Enterococcus, with decreased population density of Bacteroides. These results suggest that the development of CDI is associated with microbiota changes which are consistently associated with CDI in human subjects. These gut taxa contribute to the intestinal dysbiosis associated with C. difficile infection

Antibiotic Treatments for Clostridium difficile Infection Are Associated with Distinct Bacterial and Fungal Community Structures

ABSTRACT Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by C. difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI. Analyzing tissue ex vivo and in duplicate, CDI and non-CDI fecal samples (n = 176) were either not antibiotic treated or treated with metronidazole, vancomycin, or fidaxomicin, the three most common CDI therapies. The microbial community composition, interactions, and predicted metabolic functions were assessed by 16S rRNA gene and internal transcribed spacer sequencing, bipartite network analysis, and phylogenetic investigation of communities by reconstruction of unobserved states. Our results demonstrate that while all C. difficile-directed antibiotics were associated with similar reductions in alpha diversity, beta diversity significantly differed on the basis of the particular antibiotic, with differentiating relative abundances of bacterial and fungal assemblages. With the exception of fidaxomicin, each antibiotic was associated with the emergence of potentially pathogenic fungal operational taxonomic units, with predicted bacterial functions enriched for xenobiotic metabolism that could perpetuate the dysbiosis driving CDI. Toxin-independent mechanisms of colitis related to the relative abundance of pathogenic bacteria and fungi were also noted. This study suggests that a transkingdom interaction between fungi and bacteria may be important in CDI pathophysiology, including being a factor in the historically high persistence and recurrence rates associated with this disease. IMPORTANCE Using human fecal samples and including sequencing for both bacterial and fungal taxa, this study compared the conventional antibiotics used to treat C. difficile infection (CDI) from the perspective of the microbiome, which is particularly relevant, given the relationship between dysbiotic states and the development of CDI. Sequencing and imputed functional analyses suggest that C. difficile-directed antibiotics are associated with distinct forms of dysbiosis that may be influential in the course of CDI. Further, a role for fungal organisms in the perpetuation of the causal dysbiosis of CDI is discussed, suggesting a previously unappreciated, clinically relevant transkingdom interaction that warrants further study