Overview

Tom Harrison leads a research programme on the prevention and treatment of cryptococcal meningitis, the most common cause of meningitis in Africa, and responsible for an estimated 180,000 deaths per year and 10-20% of all HIV-related deaths, with colleagues from St George’s, and in collaboration with other UK institutions, and colleagues across study sites in Sub-Saharan Africa.

A series of phase II trials using serial quantitative cultures of cerebrospinal fluid to assess the rate of clearance of infection, or fungicidal activities, of different drug treatments for cryptococcal meningitis, were completed in centres in Africa, which led to the MRC-funded, phase III ACTA trial. The regimens studied in ACTA were associated with improved survival, have led to rapid revision of WHO guidelines, and are driving world-wide access to flucytosine one of the key antifungal drugs involved.

Current studies are examining use of liposomal amphotericin, which is better tolerated than conventional amphotericin B deoxycholate. A phase III trial is ongoing, comparing a single high dose of liposomal amphotericin, plus fluconazole and flucytosine, against the new (based on ACTA) WHO standard of one-week of amphotericin B plus flucytosine.

A retrospective study conducted in Cape Town demonstrated the value of cryptococcal antigen (CrAg) detection in blood as a sensitive and specific screening tool to identify those HIV-infected patients at risk of developing clinical cryptococcal meningitis. A point of care test to enable screening was jointly developed and tested with collaborators from Nevada and industry, and screening protocols developed. This test and pre-emptive treatment strategy was shown, together with antiretroviral adherence support, to lead to a 28% reduction in one year mortality in a phase III trial (REMSTART) in patients presenting with late stage HIV infection.

Laboratory projects, built around the clinical studies, examine pathogen evolution, virulence, and drug resistance, and host immunity, with the aim of developing novel management strategies.

Career

Tom Harrison studied Natural Sciences at Christ’s College Cambridge before studying Medicine at St Georges and training in Infectious Diseases in London and Boston, USA. In Boston, he trained in the laboratory of Stuart Levitz investigating host defense against Cryptococcus neoformans,

On returning to the UK in 1997, he obtained an Advanced Training Fellowship from The Wellcome Trust, and set up a series of ongoing clinical studies, first in Thailand and subsequently through a network of collaborating centres across Sub-Saharan Africa. Laboratory work focuses on host immunity and novel immunotherapeutic approaches and understanding pathogen virulence and evolution. In addition, with Dr Amina Jindani, he is helping drive clinical studies to simplify and shorten the treatment of tuberculosis; and leads the hospital service for multi-drug resistant TB.

He continues to work as a hospital consultant in the Infectious Diseases Department, and remains actively involved in the clinical and academic supervision of trainees in Infectious diseases from across London.

Professor Harrison has served on guidelines panels for WHO, IDSA, and the Southern African HIV Clinicians Society. He was a member of the MRC Infection and Immunity Board from 2014-18, and has served on many MRC panels in Global Health. He is an Adjunct Member at The Institute of Infectious Diseases and Molecular Medicine, University of Cape Town

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