Medical Microbiology and Infectious Diseases

Disentangling environmental, demographic and biological factors associated with transmission of SARS-CoV-2 in the households of healthcare workers

Supervisors: Professor Manish Pareek (manish.pareek@leicester.ac.uk), Professor Michael Barer (mrb19@leicester.ac.uk) and Dr Daniel Pan (dp440@leicester.ac.uk)

Transmission of SARS-CoV-2 continues to occur in highly vaccinated populations. Current vaccines against COVID-19 help reduce the impact of severe disease, but not the risk of infection or transmission.

Our group has developed a new technology to identify those who are most infectious with SARS-CoV-2, involving the use of specialised strips embedded within duckbilled facemasks (termed facemask sampling, FMS). Analysis of viral load from FMS shows a stronger relationship to household transmission in pilot studies, compared to upper respiratory tract sampling (URTS). Transmission of respiratory viruses however, is complex and depends on a combination of host, environmental and biological factors.

The ACF will undertake two main projects:

1: Systematic review and meta-analysis, investigating what are the main contributors to transmission of SARS-CoV-2 within highly vaccinated and infected populations.

2: Analysis of a routine household transmission study dataset containing FMS and URTS viral load, identify their contribution to transmission.

Ultimately, this data will be used to submit an application for a doctoral research fellowship. Analysis of the above data will identify key factors that are under-investigated so far – eg, host immunity in exhaled breath/mucosa; ethnic differences in household size; or quality of ventilation within the households. The candidate will then design a transmission study taking these factors into account in their application.

Understanding ethnic differences in the risk of SARS-CoV-2 breakthrough infection using analysis of SARS-CoV-2 antibody neutralisation assays

Supervisors: Professor Manish Pareek (manish.pareek@leicester.ac.uk) and Dr Christopher Martin (cm712@leicester.ac.uk)

SARS-CoV-2 continues to cause breakthrough infection, despite high levels of vaccination and previous infection. This is thought to be due to waning immunity to infection, and the constant emergence of new SARS-CoV-2 variants.

Our group has been on the forefront of research into ethnic differences in SARS-CoV-2 infection. We have a longitudinal dataset of >600 healthcare workers (HCWs) across four years; where repeated immunological measurements have been obtained across a period of one year shortly before, and following the HCW’s booster vaccine. 

The ACF will undertake two main projects:

1: Systematic review and meta-analysis, investigating ethnic differences in the risk of SARS-CoV-2 breakthrough infection and how immunology (quantitative antibodies, neutralisation data, T-cell data and mucosal immunology) may contribute to the differences in these outcomes

2: Analysis of the routine HCW dataset, to identify key immunological markers of SARS-CoV-2 breakthrough infection across different ethnic groups and how this may contribute to differences in breakthrough infection.

Ultimately, this data will be used to submit an application for a doctoral research fellowship, where the ACF will undertake prospective sampling studies to investigate whether immunological correlates of protection identified in their pilot work could be used to guide when HCWs receive their next booster vaccination.

Ethnic differences in the risk of cardio-metabolic comorbidities in people living with HIV

Supervisors: Professor Manish Pareek (manish.pareek@leicester.ac.uk) and Dr Joshua Nazareth (jn208@leicester.ac.uk)

HIV infection, alongside certain HIV medications, accelerates the development of cardiovascular disease (CVD) compared to HIV negative individuals. Furthermore, persons living with HIV (PLWH) often fail to achieve the evidence-based treatment goals for the prevention of CVD, and the reasons for this are currently poorly understood.

The infectious diseases team in Leicester looks after >1500 PLWH, which contains a high degree of ethnic diversity. It is well known that those from ethnic minority groups are often at higher risk of cardio-metabolic disease; therefore, identifying and understanding how ethnicity may contribute to cardio-metabolic disease in PLWH is of critical public health importance.

The ACF will undertake two main projects:

1: Systematic review and meta-analysis, investigating ethnic differences in HIV outcomes and how multimorbidity may contribute to these differences

2: Analysis of the routine HIV dataset, to identify ethnic differences in HIV outcomes and the reasons for this (including identification of key cardiometabolic comorbidities within our cohort)

Ultimately, this data will be used to submit an application for a doctoral research fellowship, where the ACF will undertake prospective studies to confirm their pilot data findings, and potentially implement a complex intervention to address these differences in outcomes.

Tuberculosis Research

Supervisor: Dr Pranab Haldar (ph62@le.ac.uk)

The Clinical Tuberculosis (TB) research programme at Leicester provides a diverse range opportunities for Academic Clinical Fellows. Projects may be quantitative or qualitative and focus on contributing research that addresses challenges associated with heterogeneity of M.tuberculosis infection. This is manifest in people with TB infection having a variable risk of developing disease in the future as well as those with disease expressing a breadth of clinical phenotypes. The host immune response play is a key driver of heterogeneity that underpins much of the research at Leicester.

Projects are available in the following areas:

1. Development and evaluation of novel biomarkers to support TB diagnosis and identify those at risk of developing the disease
2. Evaluating PET-CT as a novel tool for visualising M.tuberculosis infection;
3. Investigating epidemiological factors that associate with clinical disease expression;
4. Supporting development of new clinical pathways to improve TB care, including qualitative studies to understand the unmet health needs of this vulnerable patient group.

Development of Phage Therapy for the Treatment of Prosthetic Joint Infections

Supervisors: Dr Melissa Haines(mh508@leicester.ac.uk) and Mr Daniel Howard

Prosthetic Joint Infections (PJIs) are costly to the NHS – approximately £36,000 per infection, and they are difficult-to-treat in the long-term. A new collaboration between the University Hospitals of Leicester Orthopaedics Department and the Leicester Centre for Phage Research aims to support the development of promising alternative treatment options.  

Bacteriophages (phages) are a potential alternative treatment for infections caused by bacteria. The clinical use of phages to treat infections is known as phage therapy. Phages are currently being explored globally and the demand for phage therapy is increasing, in countries such as Australia, Belgium, France, Georgia, Poland and the USA. This project aims to bridge the gap between laboratory research/compassionate use and use within the NHS.

The Leicester Centre for Phage Centre has successfully built clinical collections for urinary tract infections, COPD, and C. diff infection. This project will involve building a collection of clinical bacterial strains taken from PJIs, laboratory experiments to find and assess the phages for effective killing of the PJIs from clinical isolate collection, and analysis of implant-associated biofilm breakdown. The resultant phage collection will have to potential to be used clinically.