A5033152609- Salmonella and Campylobacter epidemiology
- Viral gastroenteritis research and epidemiology
- Vibrio bacteria research studies
- COVID-19 Clinical Research Studies
- Viral Infections and Outbreaks Research
- SARS-CoV-2 and COVID-19 Research
- Escherichia coli research studies
- Long-Term Effects of COVID-19
- Neutropenia and Cancer Infections
- Vaccine Coverage and Hesitancy
- Hepatitis B Virus Studies
- Bacteriophages and microbial interactions
- Antibiotic Use and Resistance
- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Viral Infections and Vectors
- Intensive Care Unit Cognitive Disorders
- Clostridium difficile and Clostridium perfringens research
- SARS-CoV-2 detection and testing
- Pneumonia and Respiratory Infections
- Hepatitis Viruses Studies and Epidemiology
- Pneumocystis jirovecii pneumonia detection and treatment
- Cancer Research and Treatments
- Respiratory Support and Mechanisms
- Global Security and Public Health
Imperial College London
2019-2024
Imperial College Healthcare NHS Trust
2014-2024
Oxford BioMedica (United Kingdom)
2016-2023
University of Oxford
2015-2023
Emory University
2023
National Health Service
2019-2022
Northwick Park Hospital
2014-2022
London North West Healthcare NHS Trust
2022
National Institute for Health Research
2015-2020
Chelsea and Westminster Hospital
2020
The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. development an effective vaccine is a priority for control future outbreak.
<h3>Importance</h3> Developing effective vaccines against Ebola virus is a global priority. <h3>Objective</h3> To evaluate an adenovirus type 26 vector vaccine encoding glycoprotein (Ad26.ZEBOV) and modified vaccinia Ankara vaccine, glycoproteins from virus, Sudan Marburg Tai Forest nucleoprotein (MVA-BN-Filo). <h3>Design, Setting, Participants</h3> Single-center, randomized, placebo-controlled, observer-blind, phase 1 trial performed in Oxford, United Kingdom, enrolling healthy 18- to...
Salmonella enterica serovar Typhi (S Typhi) is responsible for an estimated 20 million infections and 200 000 deaths each year in resource poor regions of the world. Capsular Vi-polysaccharide-protein conjugate vaccines (Vi-conjugate vaccines) are immunogenic can be used from infancy but there no efficacy data leading candidate vaccine being considered widespread use. To address this knowledge gap, we assessed a Vi-tetanus toxoid using established human infection model S Typhi.
Access to rapid diagnosis is key the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing current standard care but usually requires a centralised laboratory significant infrastructure. We describe our diagnostic accuracy assessment novel, point-of-care real time CovidNudge test, which no handling or sample pre-processing.
Abstract Mucosal-associated invariant T (MAIT) cells are innate-like that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, MAIT activated during infection, an effect maintained even after antibiotic treatment. At the peak cell T-cell receptor (TCR)β clonotypes over-represented prior to transiently contract. Select TCRβ expand have stronger TCR-dependent activation than do...
Controlled human infection model (CHIM) studies have pivotal importance in vaccine development, being useful for proof of concept, pathogenesis, down-selection and immunogenicity studies. To date, however, they seldom been carried out low middle income countries (LMIC), which is where the greatest burden preventable illness found. This workshop discussed benefits barriers to CHIM Malawi. Benefits include improved effectiveness host country capacity development clinical, laboratory governance...
To expedite the evaluation of vaccines against paratyphoid fever, we aimed to develop first human challenge model Salmonella enterica serovar Paratyphi A infection.Two groups 20 participants underwent oral with S. following sodium bicarbonate pretreatment at 1 2 dose levels (group 1: 1-5 × 103 colony-forming units [CFU] and group 2: 0.5-1 CFU). Participants were monitored in an outpatient setting daily clinical review collection blood stool cultures. Antibiotic treatment was started when...
Typhoid fever is estimated to cause between 11.9-26.9 million infections globally each year with 129,000-216,510 deaths. Access improved water sources have reduced disease incidence in parts of the world but use efficacious vaccines seen as an important public health tool for countries a high burden. A new generation Vi typhoid conjugate (TCVs), licensed young children and expected provide longer lasting protection than previous vaccines, are now available. The WHO Strategic Advisory Group...
Typhoid Vi vaccines have been shown to be efficacious in children living endemic regions; however, a widely accepted correlate of protection remains established. We applied systems serology approach identify Vi-specific serological correlates using samples obtained from participants enrolled an experimental controlled human infection study. Participants were vaccinated with Vi-tetanus toxoid conjugate (Vi-TT) or unconjugated Vi-polysaccharide (Vi-PS) and subsequently challenged Salmonella...
Salmonella Typhi is a human host-restricted pathogen that responsible for typhoid fever in approximately 10.9 million people annually1. The toxin postulated to have central role disease pathogenesis, the establishment of chronic infection and host restriction2–6. However, its precise humans not fully defined. We studied acute using randomized, double-blind S. challenge model7. Forty healthy volunteers were randomized (1:1) oral with 104 colony-forming units wild-type or an isogenic deletion...
Many aspects of Controlled Human Infection Models (CHIMs, also known as human challenge studies and infection studies) have been discussed extensively, including Good Manufacturing Practice (GMP) production the agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising incentives, pre-existing immunity, clinical, immunological, microbiological endpoints. The fourth meeting focused on regulation studies, bringing together scientists regulators from high-,...
Background The treatment of enteric fever is complicated by the emergence antimicrobial resistant Salmonella Typhi. Azithromycin commonly used for first-line uncomplicated fever, but response to may be sub-optimal in some patient groups when compared with fluoroquinolones. Methods We performed an analysis responses azithromycin (500mg once-daily, 14 days) or ciprofloxacin twice-daily, healthy UK volunteers (18–60 years) enrolled into two controlled human infection studies. Study A was a...
Enteric fever is a systemic infection caused by Salmonella Typhi or Paratyphi A. In many endemic areas, these serovars co-circulate and can cause multiple infection-episodes in childhood. Prior exposure thought to confer partial, but incomplete, protection against subsequent attacks of enteric fever. Empirical data support this hypothesis are limited, there few studies describing the occurrence heterologous-protection between closely related serovars. We performed challenge-re-challenge...
ObjectivesSince May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in nonendemic countries. Our aim was to characterize diagnostic features patients confirmed and possible guide future risk stratification describe a virtual care model.MethodsWe performed retrospective case-control study 140 assessed screened for suspected monkeypox; on hMPXV polymerase chain reaction testing, 70 were positive, negative. Data compared generate...
ABSTRACT Invasive nontyphoidal Salmonella (iNTS) disease remains a major public health challenge in sub-Saharan Africa. Typhimurium (STm) is responsible for the majority of cases, with specific lineages being associated increased risk bloodstream infection. We have recently developed STm controlled human infection model (CHIM) to better understand pathogenesis and provide platform test candidate vaccines. Selecting appropriate strains central design consideration developing protocols....
ABSTRACT MenB-4C is a meningococcal vaccine for the prevention of serogroup B disease. The contains factor H binding protein (FHbp) and three other antigens that can elicit serum bactericidal antibodies (SBA). For licensure, efficacy was inferred from SBA responses against antigen-specific indicator strains. relation between those results broad protection circulating genetically diverse strains not known. Twenty adults were immunized with two doses given 1 to 2 months apart. activity 3...
Shedding of Salmonella Typhi or Paratyphi in the stool urine leads to contamination food water, which is a prerequisite for transmission enteric fever. Currently, there are limited data on effect vaccination prior exposure shedding.Six human challenge studies were conducted between 2011 and 2017. Participants either unvaccinated vaccinated with 1 4 vaccines: Vi-polysaccharide (Vi-PS), Vi-tetanus-toxoid conjugate vaccine (Vi-TT), live oral Ty21a vaccine, an experimental (M01ZH09). Daily...
Introduction Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, enterica serovar Typhimurium accounts for two-thirds and is associated with an estimated case fatality rate 15%–20%. Several iNTS vaccine candidates early-stage assessment which—if found effective—would provide valuable public health tool to reduce disease burden. The CHANTS study aims develop first-in-human controlled...
Misdiagnosis of enteric fever is a major global health problem, resulting in patient mismanagement, antimicrobial misuse and inaccurate disease burden estimates. Applying machine learning algorithm to host gene expression profiles, we identified diagnostic signature, which could distinguish culture-confirmed cases from other febrile illnesses (area under receiver operating characteristic curve > 95%). this signature culture-negative suspected cohort Nepal further 12.6% as likely true cases....
BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have been developed based on surface Vi-capsular polysaccharide of S. Typhi; these include plain-polysaccharide-based vaccine, ViPS, glycoconjugate ViTT. To understand immune responses to vaccines their vaccine-induced immunological protection, molecular signatures were analyzed using bioinformatic approaches.METHODSBulk RNA-Seq...