Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy

Aims Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin, vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. We now aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well itpredicted gastric pathology. Methods Gastric biopsies were donated by 39 H. pylori-infected patients attending for endoscopy at Queen’s Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative polymerase chain reaction. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. Results vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (

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

Association between COVID-19 Vaccination and SARS-CoV-2 Infection among Household Contacts of Infected Individuals: A Prospective Household Study in England.

BACKGROUND: We investigated whether COVID-19 vaccination reduced SARS-CoV-2 infection risk among adult household contacts of COVID-19 index cases during the Alpha, Delta, and Omicron waves in England. METHODS: Between February 2021 and February 2022, SARS-CoV-2 RT-PCR nasal swabs were collected from COVID-19-confirmed index cases aged ≥20 years and their household contacts at enrolment and three and seven days thereafter. Generalized Estimating Equations models were fitted with SARS-CoV-2 positivity as the outcome and household contacts' vaccination status as the main exposure while adjusting for confounders. RESULTS: SARS-CoV-2 infection was confirmed in 238/472 household contacts (50.4%) aged ≥20 years. The adjusted relative risk (95% confidence interval) of infection in vaccinated versus unvaccinated household contacts was 0.50 (0.35-0.72) and 0.69 (0.53-0.90) for receipt of two doses 8-90 and >90 days ago, respectively, and 0.34 (0.23-0.50) for vaccination with three doses 8-151 days ago. Primary vaccination protected household contacts against infection during the Alpha and Delta waves, but only three doses protected during the Omicron wave. Vaccination with three doses in the index case independently reduced contacts' infection risk: 0.45 (0.23-0.89). CONCLUSIONS: Vaccination of household contacts reduces their risk of infection under conditions of household exposure though, for Omicron, only after a booster dose

Transmission dynamics of COVID-19 in household and community settings in the United Kingdom

AbstractBackgroundHouseholds appear to be the highest risk setting for transmission of COVID-19. Large household transmission studies were reported in the early stages of the pandemic in Asia with secondary attack rates ranging from 5–30% but few large scale household transmission studies have been conducted outside of Asia.MethodsA prospective case ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. Household secondary attack rates and serial intervals were estimated. Individual and household basic reproduction numbers were also estimated. The incubation period was estimated using known point source exposures that resulted in secondary cases.ResultsA total of 233 households with two or more people were included with a total of 472 contacts. The overall household SAR was 37% (95% CI 31–43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. We find lower secondary attack rates in larger households. SARs were highest when the primary case was a child. We estimate a mean incubation period of around 4.5 days.ConclusionsHigh rates of household transmission of COVID-19 were found in the UK emphasising the need for preventative measures in this setting. Careful monitoring of schools reopening is needed to monitor transmission from children.</jats:sec

Effectiveness of filtering or decontaminating air to reduce or prevent respiratory infections: A systematic review

Installation of technologies to remove or deactivate respiratory pathogens from indoor air is a plausible non-pharmaceutical infectious disease control strategy. OBJECTIVE: We undertook a systematic review of worldwide observational and experimental studies, published 1970-2022, to synthesise evidence about the effectiveness of suitable indoor air treatment technologies to prevent respiratory or gastrointestinal infections. METHODS: We searched for data about infection and symptom outcomes for persons who spent minimum 20 hours/week in shared indoor spaces subjected to air treatment strategies hypothesised to change risk of respiratory or gastrointestinal infections or symptoms. RESULTS: Pooled data from 32 included studies suggested no net benefits of air treatment technologies for symptom severity or symptom presence, in absence of confirmed infection. Infection incidence was lower in three cohort studies for persons exposed to high efficiency particulate air filtration (RR 0.4, 95%CI 0.28-0.58, p<0.001) and in one cohort study that combined ionisers with electrostatic nano filtration (RR 0.08, 95%CI 0.01-0.60, p=0.01); other types of air treatment technologies and air treatment in other study designs were not strongly linked to fewer infections. The infection outcome data exhibited strong publication bias. CONCLUSIONS: Although environmental and surface samples are reduced after air treatment by several air treatment strategies, especially germicidal lights and high efficiency particulate air filtration, robust evidence has yet to emerge that these technologies are effective at reducing respiratory or gastrointestinal infections in real world settings. Data from several randomised trials have yet to report and will be welcome to the evidence base

Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy

Aims Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin, vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. We now aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well it predicted gastric pathology. Methods Gastric biopsies were donated by 39 H. pylori-infected patients attending for endoscopy at Queen’s Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative polymerase chain reaction. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. Results vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (p<0.02), neutrophil infiltration (p<0.005), and the presence of atrophy (p<0.01). A polymorphism at nucleotide +28 near the base of a potential stem- loop structure within the 5’ untranslated region was significantly associated with vacA transcript level and inflammation. Conclusions Increased gastric vacA expression during H. pylori infection is associated with inflammation and premalignant pathology. The +28 nucleotide within the vacA 5’ stem-loop stratifies disease risk amongst toxic vacA i1-type strains

Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy

Aims Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin, vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. We now aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well it predicted gastric pathology. Methods Gastric biopsies were donated by 39 H. pylori-infected patients attending for endoscopy at Queen’s Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative polymerase chain reaction. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. Results vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (p<0.02), neutrophil infiltration (p<0.005), and the presence of atrophy (p<0.01). A polymorphism at nucleotide +28 near the base of a potential stem- loop structure within the 5’ untranslated region was significantly associated with vacA transcript level and inflammation. Conclusions Increased gastric vacA expression during H. pylori infection is associated with inflammation and premalignant pathology. The +28 nucleotide within the vacA 5’ stem-loop stratifies disease risk amongst toxic vacA i1-type strains

Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy

Aims Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin, vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. We now aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well it predicted gastric pathology. Methods Gastric biopsies were donated by 39 H. pylori-infected patients attending for endoscopy at Queen’s Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative polymerase chain reaction. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. Results vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (p<0.02), neutrophil infiltration (p<0.005), and the presence of atrophy (p<0.01). A polymorphism at nucleotide +28 near the base of a potential stem- loop structure within the 5’ untranslated region was significantly associated with vacA transcript level and inflammation. Conclusions Increased gastric vacA expression during H. pylori infection is associated with inflammation and premalignant pathology. The +28 nucleotide within the vacA 5’ stem-loop stratifies disease risk amongst toxic vacA i1-type strains

Association between COVID-19 Vaccination and SARS-CoV-2 Infection among Household Contacts of Infected Individuals: A Prospective Household Study in England

Background: We investigated whether COVID-19 vaccination reduced SARS-CoV-2 infection risk among adult household contacts of COVID-19 index cases during the Alpha, Delta, and Omicron waves in England. Methods: Between February 2021 and February 2022, SARS-CoV-2 RT-PCR nasal swabs were collected from COVID-19-confirmed index cases aged ≥20 years and their household contacts at enrolment and three and seven days thereafter. Generalized Estimating Equations models were fitted with SARS-CoV-2 positivity as the outcome and household contacts’ vaccination status as the main exposure while adjusting for confounders. Results: SARS-CoV-2 infection was confirmed in 238/472 household contacts (50.4%) aged ≥20 years. The adjusted relative risk (95% confidence interval) of infection in vaccinated versus unvaccinated household contacts was 0.50 (0.35–0.72) and 0.69 (0.53–0.90) for receipt of two doses 8–90 and >90 days ago, respectively, and 0.34 (0.23–0.50) for vaccination with three doses 8–151 days ago. Primary vaccination protected household contacts against infection during the Alpha and Delta waves, but only three doses protected during the Omicron wave. Vaccination with three doses in the index case independently reduced contacts’ infection risk: 0.45 (0.23–0.89). Conclusions: Vaccination of household contacts reduces their risk of infection under conditions of household exposure though, for Omicron, only after a booster dose