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Introduction
My current research interests have been focused in two main areas: (1) evolution of the antigenic profile of a virus under selective pressure of host and population (herd) immunity, and (2) the virus-host interactions made during the early stages of infection.
This work has led to a model of evolution for norovirus, and the identification of putative key epitope sites on the virus surface.
Additional affiliations
January 2017 - present
November 2014 - December 2016
November 2009 - November 2014
Independent Researcher
Position
- PostDoc Position
Education
August 2005 - December 2008
October 2002 - July 2005
Publications
Publications (79)
Human norovirus is the leading cause of acute gastroenteritis. Young children and the elderly bear the greatest burden of disease, representing more than 200,000 deaths annually. Infection prevalence peaks at younger than 2 years and is driven by novel GII.4 variants that emerge and spread globally. Using a surrogate neutralization assay, we charac...
In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree.
Aims:
Norovirus remains the most significant virological risk that is transmitted via food and the environment to cause acute gastroenteritis. This study aimed to investigate the hypothesis that the contamination of the commercial food production environment with norovirus will be higher in premises that have recently reported a foodborne noroviru...
Standardised molecular methods are available for the detection of norovirus from water and specific food items. Detection of norovirus from stool samples also relies on molecular methods, but differences exist between nucleic acid extraction, reverse transcription, and amplification strategies recommended by the ISO 15216-1:2017, and those employed...
Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibo...
Background
To reduce the coronavirus disease burden in England, along with many other countries, the government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting...
Background: To reduce the coronavirus disease burden in England, along with many other countries, the Government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting...
Foodborne outbreaks associated with transmission of norovirus are increasingly becoming a public health concern. Foods can be contaminated with faecal material at the point of production or during food preparation, in both the home and in commercial premises. Transmission of norovirus occurs through the faecal-oral route, either via person-to-perso...
Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread of the tick-borne viruses. However, African strains of CCHFV are poorly represented in sequence databases. In addition, almost all sequence data collected to date have been obtained from cases of human disease, while information regarding the circulation of the viru...
Human noroviruses (HuNoVs) circulate globally, affect all age groups and place a substantial burden upon health services. High genetic diversity leading to antigenic variation plays a significant role in HuNoV epidemiology, driving periodic global emergence of epidemic variants. Studies have suggested that immunocompromised individuals may be a res...
Crimean-Congo haemorrhagic fever virus (CCHFV) is the most geographically widespread tick-borne virus. However, African strains are poorly represented in sequence databases. In addition, almost all sequence data have been obtained from cases of human disease, while information regarding circulation of the virus in tick and animal reservoirs is seve...
Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensi...
Objective
To describe infants with acute gastroenteritis symptoms in primary and secondary care who have the Rotarix vaccine-derived G1P[8] rotavirus strain identified in their stools.
Design
This is a prospective national surveillance conducted by Public Health England (PHE). Rotavirus-positive samples from vaccine-eligible children are routinely...
Background: Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely to have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions and sample dates, combined with pathogen genomic informatio...
Background: Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely to have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions and sample dates, combined with pathogen genomic informatio...
During October and November 2016, over 1,000 customers
and staff reported gastroenteritis after eating
at all 23 branches of a restaurant group in the United
Kingdom. The outbreak coincided with a new menu
launch and norovirus was identified as the causative
agent. We conducted four retrospective cohort studies;
one among all restaurant staff and t...
Background:
The monovalent oral rotavirus vaccine Rotarix® was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme.
Methods:
We used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for ro...
IntroductionRotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England in July 2013. Since then, there have been significant reductions in rotavirus gastroenteritis incidence.AimWe assessed the vaccine's impact on rotavirus genotype distribution and diversity 3 year...
Abstract Background Norovirus is the commonest cause of infectious intestinal disease (IID) worldwide. In the UK community incidence of norovirus has been estimated at 59/1000 population, equating to four million cases a year. Whilst norovirus infects people of all ages, a substantial burden occurs in infants and young children. The population of v...
Objectives
This study aimed to prospectively collect detailed clinical information for all enterovirus (EV) and human parechovirus (HPeV) meningitis cases in infants aged <90 days in the UK and Ireland.
Participants, design and setting
Prospective, active national surveillance during July 2014 to July 2015 through the British Paediatric Surveillan...
Background:
Oral poliovirus vaccine (OPV) is less immunogenic in LMIC countries. We tested whether bacterial and viral components of the intestinal microbiota are associated with this phenomenon.
Methods:
We assessed prevalence of enteropathogens using TaqMan array cards 14 days before and at vaccination in 704 Indian infants (6-11 months) recei...
Enterovirus (EV) infections (n=102) in paediatric and adult patients, presenting with hand-foot-and-mouth disease (HFMD), suspected sepsis or viral meningitis during Jan 2014 to Dec 2016 were characterised. Coxsackie A6 was the predominant EV type in HFMD, Coxsackie B viruses caused more severe infections than echoviruses, based on laboratory param...
Comparison of children hospitalized with enterovirus (EV) or human parechovirus (HPeV) detected in their cerebrospinal fluid (CSF) revealed that HPeV infections presented with more persistent fever, irritability and feeding problems, more frequent leukopenia and lymphopenia, and higher admission rates to high dependency or intensive care units. Few...
Background
Human parechovirus (HPeV), like enteroviruses, usually causes mild self-limiting respiratory and gastrointestinal symptoms. In infants, HPeV can occasionally cause serious illnesses, including sepsis-like syndrome and encephalitis. In summer 2016, Public Health England (PHE) received increasing reports of severe HPeV infections nationall...
Human parechovirus (HPeV), like enteroviruses, usually causes mild self-limiting respiratory and gastrointestinal symptoms. In infants, HPeV can occasionally cause serious illnesses, including sepsis-like syndrome and encephalitis. In summer 2016, Public Health England (PHE) received increasing reports of severe HPeV infections nationally. We, ther...
Background:
Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With s...
Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate...
Background:
The development of a vaccine for norovirus requires a detailed understanding of global genetic diversity of noroviruses. We analysed their epidemiology and diversity using surveillance data from the NoroNet network.
Methods:
We included genetic sequences of norovirus specimens obtained from outbreak investigations and sporadic gastro...
Background:
Environmental surveillance (ES) is a sensitive method for detecting human enterovirus (HEV) circulation and it is used worldwide to support global polio eradication. We describe a novel ES approach using next generation sequencing (NGS) to identify HEVs in sewage samples taken in London, UK, from June-2016 to May-2017.
Methods and res...
Introduction
Noroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quan...
Norovirus is the commonest cause of gastrointestinal disease worldwide in. Infections with norovirus occur in all age groups, however, the highest incidence is in children aged less than five years. Surveillance of norovirus is complicated because most people do not contact medical services when they are ill. Nevertheless, Public health laboratory...
Noroviruses are a leading cause of human gastroenteritis worldwide. The norovirus genotype GII.4 is the most prevalent genotype in the human population and has caused six pandemics since 1995. A novel norovirus lineage containing the GII.P16 polymerase and pandemic GII.4 Sydney 2012 capsid was recently detected in Asia and Germany. We demonstrate t...
Alignment of GII.4 Sydney 2012 capsid sequences.
This alignment was used to reconstruct the GII.4 Sydney 2012 phylogenetic trees in Fig 2.
(FASTA)
Alignment of GII.P16 RdRp sequences.
This alignment was used to reconstruct the GII.P16 phylogenetic tree in Fig 1.
(FASTA)
BEAST XML file for GII.P16 analysis.
(XML)
Phylogenetic tree of GII.P16 RdRp sequences.
The BEAST maximum clade credibility tree used in Fig 1.
(NEX)
Phylogenetic tree of GII.4 Sydney 2012 sequences.
The BEAST maximum clade credibility tree used in Fig 2.
(NEX)
BEAST XML file for GII.4 Sydney 2012 analysis.
(XML)
We report a number of cases (n=102) of enterovirus (EV) infections in paediatric and adult patients, admitted with suspected sepsis or meningitis in UK Midlands during Jan 2014 to Dec 2016. Although clinically impossible to differentiate on admission, we show that Coxsackie B viruses appear to cause more severe infections than echoviruses, on the b...
Nucleic-acid-based matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) applications for the detection and identification of viruses use specific or broad-range polymerase chain reaction (PCR) primers in combination with different post-PCR biochemistries. The most widely used biochemistry and variations thereo...
In autumn 2014, enterovirus D68 (EV-D68) cases presenting with severe respiratory or neurological disease were described in countries worldwide. To describe the epidemiology and virological characteristics of EV-D68 in England, we collected clinical information on laboratory-confirmed EV-D68 cases detected in secondary care (hospitals), between Sep...
In August 2015 a gastroenteritis outbreak occurred following a wedding. An outbreak investigation was undertaken and a cohort study was conducted using an online survey. Of 140 guests, 134 received the survey and 113 responded (84·3% response rate). Seventy respondents met the case definition of vomiting and/or diarrhoea within 72 h of the wedding...
Importance:
Human noroviruses are the main cause of viral diarrhea worldwide in people of all ages. Noroviruses can infect individuals who had been previously exposed to the same or different norovirus genotypes. Norovirus genotype GII.4 has been reported to be the most prevalent during the last 40 years. In the present study, we describe a novel...
Background/objectives:
Enteroviruses are the most common cause of aseptic or lymphocytic meningitis, particularly in children. With reports of unusually severe neurological disease in some patients infected with enterovirus D68 in North America, and a recent increase in the number of paediatric enterovirus meningitis cases presenting in this UK Mi...
Background:
Human noroviruses (NoVs) are the main cause of gastroenteritis worldwide. The most commonly detected NoV strains belong to the genetically diverse GII.4 genotype, with new pandemic variants emerging periodically. Despite extensive efforts, NoV investigation has been hampered by the lack of an effective in vitro cell culture system. How...
Noroviruses are endemic in the human population, and are recognised as a leading cause of acute gastroenteritis worldwide. Although they are a highly diverse group of viruses, genogroup-II genotype-4 (GII-4) noroviruses are the most frequently identified strains worldwide. The predominance of GII-4 norovirus strains is driven by the periodic emerge...
The impact of routine rotavirus vaccination on community-acquired (CA) and healthcare-associated (HA) rotavirus gastroenteritis (RVGE) at a large paediatric hospital, UK, was investigated over a 13-year period. A total of 1644 hospitalized children aged 0‒15 years tested positive for rotavirus between July 2002 and June 2015. Interrupted time-serie...
Background:
The oral infant rotavirus vaccine, Rotarix, was introduced in England and Wales in July 2013. We estimated the impact on laboratory-confirmed rotavirus infections and hospitalizations for all-cause acute gastroenteritis (AGE) during the first year after introduction.
Methods:
We extracted data on laboratory-confirmed rotavirus infect...
The aim of the study was to explore the potential use of mass spectrometry for identification of norovirus in clinical specimens.
Norovirus Virus-like particles were spiked into norovirus-negative stool samples. The purification of the viral proteins was performed magnetic beads coated with porcine gastric mucin, followed by one-dimensional gel el...
Norovirus is the commonest cause of acute gastrointestinal disease and is the main aetiological agent of outbreaks of gastroenteritis, particularly in semi-closed environments. Norovirus infections in England typically peak between December and March each year. The most commonly detected norovirus strains belong to the genetically diverse genogroup...
SUMMARY A new surveillance system for outbreaks of norovirus in English hospitals, the hospital norovirus outbreak reporting system (HNORS), was launched in January 2009. On site investigators were enabled to enter data on outbreaks of norovirus directly onto a tailored system via an internet-based front end. A standard dataset was designed to coll...
Noroviruses are the commonest cause of infectious intestinal disease, and are frequently associated with outbreaks of gastroenteritis, mainly in healthcare-associated settings, but also in outbreaks associated with contaminated food and/or water. The contamination of foods can occur during production, preparation, and/or service, or, more rarely by...
The Moloney murine leukaemia virus (Mo-MLV) gag gene encodes three main structural proteins, matrix, capsid and nucleocapsid and a protein called p12. In addition to its role during the late stages of infection, p12 has an essential, but undefined, function during early post-entry events. As these stages of retroviral infection remain poorly unders...
Infectivity of particles used in TRIM5alpha and Fv1 saturation assays (Figure4). (A) LacZ-encoding N-MLV tester viruses, with or without p12 mutations, or B-MLV were synthesized in 293T cells and used in TRIM5alpha and Fv1b abrogation assays (Figure
4A and
4B). Equal RT-units of VLPs were used to challenge D17, TE671 and B3T3 cells and infectivity...
Activity of p12 mutants in a panel of cell lines. Wild type Mo-MLV or p12 mutants 5, 6, 8 and 13 VLPs were produced in 293T cells by transient transfection and virus production was quantified by RT-ELISA. Equivalent RT-units of VLPs were used to challenge a panel of cell lines from different species and productive infection was measured after 48 ho...
Immunoblot analysis of Mo-MLV/GaLV chimeras. LacZ-encoding Mo-MLV/GaLV p12 chimeric VLPs (A) and GaLV/Mo-MLV p12 chimeric VLPs (B) were produced by transfection of 293T cells (as in Figure
7). Equal RT-units of particles were concentrated through 20% (w/v) sucrose cushions and lysed in SDS loading dye. Viral proteins were separated on a 10% polyacr...
Site directed mutagenesis primer sequences used to construct different gammaretroviral p12 alanine substitution mutations.
Site directed mutagenesis primer sequences used to construct single amino acid changes in p12.
Quantification of viral cDNA levels in D17 cells. Wild type and mutant N-MLV VLPs were produced in 293T cells by transient transfection and equal RT-units of VLPs were used to challenge D17 cells. Total DNA was isolated at various times post infection as indicated, and the relative amounts of second strand extension were measured using qPCR. Result...
Background
Human Noroviruses (NoV) are the major cause of acute nonbacterial gastroenteritis and the leading cause of outbreaks of gastroenteritis worldwide. Genotype II-4 (GII-4) NoV has been shown to spread rapidly and is the most commonly detected strain worldwide, particularly in association with outbreaks. Previously, we have shown that circul...
List of accession numbers for GII-4 norovirus strains used in this study. A total of 250 GII-4 NoV sequences from strains isolated 1974–2009 that were available from Genbank were included in our analysis. These were a mixture of full-length genome, full-length capsid (ORF2) and partial capsid sequences.
(PPT)
Observed GII-4 norovirus strain replacement events. The figure shows the frequencies of detection in each year for the five most commonly detected Site A/B motif combinations (Figure 2). Strain replacement events (where the most frequently detected Site A/B motif combination in that year was different from that in the previous year) are indicated a...
