Philippa C Matthews

The Francis Crick Institute

The Tropical Medicine Notebook provides a concise overview of the key topics in tropical medicine using short notes, diagrams, maps, and tables. The book is divided into eight sections. The first five cover infections caused by bacteria, viruses, fungi, protozoa, and helminths. The following three present the topics of vector biology, disease syndr...

Increased clinical and scientific scrutiny is being applied to hepatitis B virus (HBV), with focus on the development of new therapeutic approaches, ultimately aiming for cure. Defining the optimum natural CD8+ T cell immune responses that arise in HBV, mediated by HLA class I epitope presentation, may help to inform novel immunotherapeutic strateg...

Anti-Retroviral Therapy (ART) has dramatically reduced morbidity and mortality associated with HIV/AIDS. However, this has left a niche for the emergence of liver disease in HIV-positive individuals co-infected with HBV. Despite the geographical overlap between highly endemic HBV and HIV in Southern Africa, there is a wide range in the prevalence o...

Human immunodeficiency virus (HIV), Hepatitis B (HBV) and Hepatitis C (HCV) are blood-borne viruses with potentially shared routes of transmission. In high-income settings, the impact of antiretroviral therapy (ART) on survival has unmasked chronic liver disease from viral hepatitis B or hepatitis C as a leading cause of morbidity and mortality in...

Background: In South Africa, the first HBV vaccine dose is administered at age 6 weeks, leaving a potential window for vertical transmission. Insights into HBV seroprevalence in the vulnerable HIV-infected group are important to drive improvements in surveillance, treatment and prevention. Objectives: We set out to implement a screening program...

We undertook a point of care test (POCT) for hepatitis B core related antigen (HBcrAg) on adults living with HBV in Kilifi, Kenya. A positive test identified all those with HBV VL >200,000 IU/ml, who were HBeAg positive, and correlated well with abnormal ALT, APRI and elastography scores.

Background The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%–12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug...

Hepatitis B virus (HBV) whole genome sequencing (WGS) is currently limited as the DNA viral loads (VL) of many clinical samples are below the threshold required to generate full genomes using current sequencing methods. We developed two pan-genotypic viral enrichment methods, using probe-based capture and tiled amplicon PCR (HEP-TILE) for HBV WGS....

Whilst many lessons were learned from the COVID-19 pandemic, ongoing reflection is needed to develop and maintain preparedness for future outbreaks. Within the field of infectious disease and public health there remain silos and hierarchies in interdisciplinary work, with the risk that humanities and social sciences remain on the epistemological pe...

Introduction Better understanding of hepatitis B virus (HBV) biomarkers is needed. We evaluated Hepatitis B core related antigen (HBcrAg), in the United Kingdom (UK) and South Africa (SA). Methods We undertook a cross-sectional retrospective observational study of adults with chronic HBV infection from the UK (n=142) and SA (n=211). We recorded cl...

Background An outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 was subsequently linked to infections with adenovirus-associated virus 2 and other ‘helper viruses’, including human adenovirus. It is possible that evidence of such an outbreak could be identified at a population level based on routine data ca...

Background The WHO’s global hepatitis strategy aims to achieve viral hepatitis elimination by 2030. Migrant children and pregnant persons represent an important target group for prevention strategies. However, evidence on the burden of chronic hepatitis B (CHB) infection and the factors affecting its incidence is lacking. Methods EMBASE, Global He...

Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys are potentially impacted by biases arising from differences in participation rates across key groups. Here, we used spatio-tem...

Introduction The World Health Organisation (WHO) has set targets for the elimination of Hepatitis B virus (HBV), which include preventing new infections and reducing deaths. We explored beliefs, behaviours and barriers to diagnosis, prevention and treatment for people living with HBV infection (PLWHB) and those with liver disease in a rural South A...

Detecting and quantifying changes in growth rates of infectious diseases is vital to informing public health strategy and can inform policymakers’ rationale for implementing or continuing interventions aimed at reducing impact. Substantial changes in SARS-CoV-2 prevalence with emergence of variants provides opportunity to investigate different meth...

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer...

This protocol describes the HEP-TILE tiled amplicon protocol for whole genome sequencing of Hepatitis B virus (HBV) on the nanopore MinION. We developed a pan-genotypic (genotypes A-J) HBV scheme using an early version of PrimalScheme3, a web-based primer design tool for developing multiplex primer schemes. PrimalScheme3 is a successor to PrimalSch...

Unstructured Summary The WHO Africa region bears a disproportionate burden of morbidity and mortality related to chronic Hepatitis B Virus (HBV), accounting for an estimated 70% of new infections worldwide. We investigated the extent to which HBV clinical trials (CT) represent populations in this region. Through analysis of CT registries, we identi...

Aim: Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) particularly in African populations, in whom malignancy frequently presents at an advanced stage with poor outcomes. We derived HBV whole genome sequences (WGS) from individuals with HCC and compared them to sequences from individuals without HC...

Background We investigated how social and contextual factors shape perceptions and attitudes of rural and urban dwellers towards vaccines in South Africa. We assessed the views, acceptance, and uptake of vaccines for a range of infectious diseases, in the light of the experiences of the COVID-19 pandemic. Methods We conducted 30 in-depth face-to-f...

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the...

Background & Aims The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos/tide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes. Methods Utilising large scale, routinely collected elec...

Background To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load). Methods We used anonymized electronic h...

Background: An outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 has subsequently been linked to infections by adenovirus-associated virus 2 and other ‘helper viruses’, including human adenovirus. It is possible that evidence of such an outbreak could be identified at a population level based on routine dat...

BACKGROUND Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause. METHODS The prospective China Kadoorie Biobank included >500 000 adults...

Background: As nucleos/tide analogue (NA) therapy for chronic Hepatitis B virus (HBV) infection becomes more widely indicated and available, understanding drug resistance is essential. We performed a systematic review and meta-analysis to estimate the risk of genotypic resistance to tenofovir and entecavir. Methods: We searched nine databases up to...

There are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir...

Introduction Hepatitis B Virus (HBV) infection is a major global health concern, leading the World Health Organization to set targets to eliminate HBV as a public health threat by 2030. Very few countries are on target to meet elimination targets, and a UKHSA report published in 2023 highlights areas in which the UK needs to accelerate progress.One...

Respiratory viral infections are a major global clinical problem, and rapid, cheap, scalable and agnostic diagnostic tests that capture genome-level information on viral variation are urgently needed. Metagenomic approaches would be ideal, but remain currently limited in that much of the genetic content in respiratory samples is human, and amplifyi...

Background HIV and hepatitis B virus (HBV) prevalence are high in KwaZulu-Natal, South Africa. HIV co-infection negatively impacts HBV prognosis, and can increase likelihood of HBV mother-to-child-transmission (MTCT). In an early HIV infant treatment intervention cohort of HIV-transmitting mother-child pairs in KwaZulu-Natal, we characterised mater...

Introduction: Chronic hepatitis B virus (HBV) infection is associated with significant global morbidity and mortality. Low treatment rates are observed in patients living with HBV; the reasons for this are unclear. This study sought to describe patients' demographic, clinical and biochemical characteristics across three continents and their associ...

Background Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-...

SARS-CoV-2 reinfections increased substantially after Omicron variants emerged. Large-scale community-based comparisons across multiple Omicron waves of reinfection characteristics, risk factors, and protection afforded by previous infection and vaccination, are limited, especially after widespread national testing stopped. We studied 245,895 adult...

Background: An outbreak of severe acute hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 has subsequently been linked to infections by adenovirus-associated virus 2 (AAV2) and other 'helper viruses', including human adenovirus (HAdV). Aim: We investigated clinical characteristics and temporal distribution of acute hepatitis with u...

The physiological effects of vaccination against SARS-CoV-2 (COVID-19) are well documented, yet the behavioural effects not well known. Risk compensation suggests that gains in personal safety, as a result of vaccination, are offset by increases in risky behaviour, such as socialising, commuting and working outside the home. This is potentially imp...

Following primary SARS-CoV-2 vaccination, whether boosters or breakthrough infections provide greater protection against SARS-CoV-2 infection is incompletely understood. Here we investigated SARS-CoV-2 antibody correlates of protection against new Omicron BA.4/5 (re-)infections and anti-spike IgG antibody trajectories after a third/booster vaccinat...

Background Liver cancer has one of the fastest rising incidence and mortality rates among all cancers in the UK, but it receives little attention. This study aims to understand the disparities in epidemiology and clinical pathways of primary liver cancer and identify the gaps for early detection and diagnosis of liver cancer in England. Methods Th...

Hepatitis B virus (HBV) is one of the smallest human DNA viruses and its 3.2 Kb genome encodes multiple overlapping open reading frames, making its viral transcriptome challenging to dissect. Previous studies have combined quantitative PCR and Next Generation Sequencing to identify viral transcripts and splice junctions, however the fragmentation a...

Approximately 80 million people live with chronic hepatitis B virus (HBV) infection in the WHO Africa Region. The natural history of HBV infection in this population is poorly characterised, and may differ from patterns observed elsewhere due to differences in prevailing genotypes, environmental exposures, co-infections, and host genetics. Existing...

Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-expo...

Background: HIV and hepatitis B virus (HBV) prevalence are high in KwaZulu-Natal (KZN), South Africa. HIV co-infection negatively impacts HBV prognosis, and can increase likelihood of HBV mother-to-child-transmission (MTCT). In an established early treatment intervention cohort of HIV-transmitting mother-child pairs in KZN, we characterised HBV ser...

Background The COVID-19 pandemic is rapidly evolving, with emerging variants and fluctuating control policies. Real-time population screening and identification of groups in whom positivity is highest could help monitor spread and inform public health messaging and strategy.

Background: HBV is the leading global cause of cirrhosis and primary liver cancer. However, the UK HBV population has not been well characterised, and estimates of UK HBV prevalence and/or incidence vary widely between sources. We aimed to i) extract and summarise existing national HBV prevalence estimates, ii) add a new estimate based on primary c...

High profile international goals have been set for the elimination of hepatitis B virus (HBV) infection as a public health threat by the year 2030. Developing and expanding equitable, accessible translational HBV research programmes that represent real-world populations are therefore an urgent priority for clinical and academic communities. We pres...

Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys are potentially impacted by biases arising from differences in participation rates across key groups. Here, we use spatio-temp...

Hepatitis B Virus (HBV) genome sequencing can be used to provide more complete genetic information at the population and individual level to shed light on the limitations of current interventions, and inform new strategies for elimination. HBV sequencing is challenging due to the partially dsDNA genome, high diversity, low viral loads and presence...

Hepatitis B virus (HBV) infection represents a significant global health threat, accounting for 300 million chronic infections and up to 1 million deaths each year. HBV disproportionately affects people who are under-served by health systems due to social exclusion, and can further amplify inequities through its impact on physical and mental health...

Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs...

The aim of this systematic review and meta-analysis is to evaluate available prevalence and viral sequencing data representing chronic hepatitis B (CHB) infection in Kenya. More than 20% of the global disease burden from CHB is in Africa, however there is minimal high quality seroprevalence data from individual countries and little viral sequencing...

In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index...

Hepatitis B viruses (HBVs) are compact viruses with circular genomes of ∼3.2 kb in length. Four genes (HBx, Core, Surface, and Polymerase) generating seven products are encoded on overlapping reading frames. Ten HBV genotypes have been characterised (A-J), which may account for differences in transmission, outcomes of infection, and treatment respo...

The increasing frequency and magnitude of viral outbreaks in recent decades, epitomized by the COVID-19 pandemic, has resulted in an urgent need for rapid and sensitive diagnostic methods. Here, we present a methodology for virus detection and identification that uses a convolutional neural network to distinguish between microscopy images of fluore...

Hepatitis B viruses (HBV) are compact viruses with circular genomes of ~3.2kb in length. Four genes (HBx, Core, Surface and Polymerase) generating seven products are encoded on overlapping reading frames. Ten HBV genotypes have been characterised (A-J), which may account for differences in transmission, outcomes of infection, and treatment response...

Following primary SARS-CoV-2 vaccination, understanding the relative extent of protection against SARS-CoV-2 infection from boosters or from breakthrough infections (i.e. infection in the context of previous vaccination) has important implications for vaccine policy. In this study, we investigated correlates of protection against Omicron BA.4/5 inf...

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and wor...