A partnership between the Universities of Brighton and Sussex with the NHS

 

infection and inflammation

Name: Dr Martin Llewelyn

Academic position: Senior Lecturer in Infectious Diseases and Therapeutics

Research: Bacterial superantigens and Gram positive sepsis

Contact details:

Brighton and Sussex Medical School
Medical Research Building
University of Sussex
Falmer
Brighton
BN1 9PS

Tel: 01273 876671
Fax: 01273 877884

E-mail:

Biography:

• BSc (Human Physiology) 1989 University of London
• MB BS 1992 University of London
• MRCP 1996
• DTMH 1998
• MRC Clinical Research Fellow, Imperial College (Hammersmith Hospital) 2000-2003
• PhD (Immunology) 2004 University of London.
• FRCP 2008

Teaching focus:

As senior lecturer in infectious diseases, I teach our students throughout their time as BSMS. In module 102 I teach microbiology and about the role of host and pathogen in the outcome of infection. In module 302 I teach the scientific basis of infectious diseases and the immune response to infection. In the fourth year specialist rotation in infectious diseases I teach the diagnosis and management of common infectious diseases.  Each year I supervise medical students undertaking both clinical and laboratory based individual research projects

Research focus:

My research is driven by a desire to improve the outcome of patients with common, life-threatening infections. I have focused on bacterial infections I encounter commonly in my clinical practice such as Streptococcus pyogenes, Staphylococcus aureus and Clostridium difficile. There are two main themes to my work. First I am interested in better understanding the immune response to the infections I study with the aim of identifying new approaches to diagnosis and treatment. Second I am interested in their clinical management; diagnosis, assessment and treatment. 

Current research:

The role of bacterial superantigens in autoimmunity.

There is a wealth of circumstantial evidence that superantigen exotoxins of S. pyogenes may be involved in the various autoimmune phenomena which sometimes follow S. pyogenes infection such as psoriasis, rheumatic fever and Sydenham’s chorea. My post-doc Amanda Taylor is studying regulatory T cell responses to bacterial superantigens to test the hypothesis that superantigens may alter regulation of immune autoreactivity either arising spontaneously or as a consequence of cross-reactivity between self and bacterial antigens (so called ‘molecular mimicry’).

Invasive Staphylococcus aureus infection; clinical outcomes and microbial epidemiology. Invasive infection by S. aureus including MRSA is common and associated with high mortality and morbidity. In view of the high burden of invasive S. aureus infection in the UK and specifically in Brighton we are looking at the role of bacterial virulence in determining clinical outcome of S. aureus bacteraemia. Identification of specific virulence factors associated with severe or complicated invasive infection would suggest novel therapeutic targets in this disease.

UK Clinical Infection Research Network; Management of Staphylococcus aureus bacteraemia in the UK. The UK CIRN is a collaboration of UK based infection specialists set up in 2008 with the aim of performing large, pragmatic intervention studies to define the optimal management of common UK-acquired infections. We have a service evaluation of the management of S. aureus bacteraemia underway which is already the largest UK study of its kind and will form the basis of an intervention study to define the optimal duration of treatment of S. aureus bacteraemia. 

Clostridium difficile infection; determinants of outcome.  C. difficile infection has emerged rapidly in the last 10 years as a major form of healthcare associated infection. As with other forms of HCAI, considerable attention has been given to reducing CDI rates but little work has been undertaken to optimise management. We are undertaking a cohort study of CDI cases to identify the clinical, microbiological and management factors associated with outcome to better guide risk assessment in clinical practice and support the design of future intervention studies.

Immune responses in C. difficile carriage and infection. As a consequence partly of the relatively recent emergence of C. difficile as an important pathogen and partly of diagnostic limitations, comparatively little is known about the role of the host immune response to C. difficile in determining susceptibility and outcome. Dr Kate Nambiar, a research fellow funded by Brighton and Sussex University Hospitals NHS Trust Clinical Investigation Unit is, in collaboration with Prof Kern, undertaking a series of cohort studies employing peptide array and multi-parameter flow cytometry to understand how the immune system targets C. difficile in different patient groups.

Key/recent publications:

Clinical and microbiological determinants of outcome in Staphylococcus aureus bacteraemia. Price J, Baker G, Heath I, Walker-Bone K, Cubbon M, Curtis S. Enright MC, Lindsay J, Paul J, Llewelyn M. International Journal of Microbiology 2010 in press

The diagnosis of Clostridium difficile infection is associated with a small increased risk of death in elderly in-patients. Tangiisuran B, Davies JG, Cheek, E, Rajkumar, C, Llewelyn M. Journal of Hospital Infection 2010 in press

Impact of an intervention to control Clostridium difficile infection on hospital and community onset disease; an interrupted time series analysis. Price J, Cheek E, Lippett S, Cubbon, M, Gerding DN, Sambol, SP, Citron DM, Llewelyn M. Clinical Microbiology and Infection 2009;  in press.

Paradoxical relationship between the clinical outcome of Staphylococcus aureus bacteremia and the minimum inhibitory concentration of vancomycin. Price J, Atkinson S, Llewelyn M, Paul J. Clinical Infectious Diseases 2009; 48: 997-8

The T cell receptor Vβ signature of bacterial superantigens spreads with stimulus strength Llewelyn M, Sriskandan S, Cohen J, Altmann.DM. International Immunology 2006; 18:1433-41.

HLA class II haplotypes which protect or predispose for Streptococcal Toxic Shock. Llewelyn M. Clinical Infectious Diseases. 2005; 41: S445-8.

Diagnostic utility of bone marrow sampling in HIV positive patients since the advent of HAART. Llewelyn M, Noursedeghi M, Dogan A, Edwards SG, Miller RF. International Journal of STD and AIDS. 2005; 10:686-90.

HLA Class II Polymorphisms Determine Responses to Bacterial Superantigens. Llewelyn M, Sriskandan S, Peakman M, Ambrozak DR, Douek DC, Kwok WW,  Cohen J, and Altmann DM. Journal of Immunology. 2004; 172: 1719 - 1726.

Superantigens; microbial agents that corrupt immunity. Llewelyn M, Cohen J. Lancet Infectious Diseases. 2002; 2:156-162.

Recent insights into the pathogenesis and treatment of sepsis. Llewelyn M, Cohen J. Current Clinical Topics in Infectious Diseases. 2001; 21: 148-171.

Superantigen antagonist peptides. Llewelyn M, Cohen J. Critical Care 2001; 5: 53-55.

Tuberculosis diagnosed during pregnancy; a prospective study from London. Llewelyn M, Cropley I, Wilkinson R, Davidson RN. Thorax. 2000; 55: 129-32.

Influence of vitamin D deficiency and vitamin D receptor polymorphism on tuberculosis amongst Gujarati Asians in West London: a case control study. Wilkinson RJ, Llewelyn M, Toosi Z, Patel P, Pasvol G, Lavani A, Wright D, Latif M, Davidson RN. Lancet. 2000; 355: 618-621.

Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and interleukin IL-1b on tuberculosis. Wilkinson RJ, Patel P, Llewelyn M, Hirsch CS, Pasvol G, Snounou G, Davidson RN, Toossi Z. Journal of Experimental Medicine. 1999; 189: 1863-1873.

Antiendotoxin antibodies in sepsis: a critical evaluation. Llewelyn M, Cohen J. Sepsis. 1999; 3: 39-45.

 

Funding:

Dunhill Medical Trust

Hospital Infection Society