Tom Harrison is a Professor of Infectious Diseases and Medicine.
His research focuses on the fungal disease cryptococcal meningitis, in particular the pathological mechanisms, the human immune response, and clinical prevention and management of disease. He also works on the development of new clinical treatments for tuberculosis.
Professor Harrison’s group’s research addresses the pathophysiology, immunology, management, and prevention of cryptococcal meningitis. In Thailand, in the first study of its kind, using serial quantitative cultures of cerebrospinal fluid, the fungicidal activities of different drug treatments for cryptococcal meningitis were directly compared to determine the rate of clearance of infection. The technique was shown to be much more powerful than prior markers of response, opening the way for more rapid assessment of novel treatments. Follow up trials have been completed in Cape Town, Uganda and Malawi, that have had a significant impact on international guidelines for treatment and led to a major, Medical Research Council-funded, phase III study recently started in Malawi and Zambia.
Associated laboratory projects are examining the effects of pathogen and host factors on the outcome of infection. Genotypic and phenotypic pathogen studies are led by Dr Tihana Bicanic within the group. Regarding host immune responses to cryptococcal infection, a pro-inflammatory cytokine response was shown to be protective and interferon-gamma was shown to determine the rate of clearance of cryptococcal infection in patients. A recently completed trial of short course adjunctive immunotherapy with interferon gamma demonstrated for the first time a significant acceleration of killing with adjunctive immune therapy.
The feasibility of preventing many cases of HIV-associated cryptococcal meningitis through screening for sub-clinical infection and pre-emptive therapy has been demonstrated, and, with collaborators from industry and the University of Nevada, a novel point-of-care test for immunodiagnosis validated, that will make screening for subclinical infection feasible, and will allow earlier, primary care-based diagnosis of symptomatic cases. Cost effectiveness analysis of the screening strategy in South Africa showed that it would save both lives and costs compared to current practice, and screening has subsequently been adopted as policy by the Department of Health in South Africa.
With colleagues in the InterTB Group at St George’s (Dr Amina Jindani and Professor Dennis Mitchison and Professor Philip Butcher), phase II and III trials of chemotherapy for tuberculosis are examining the efficacy of high dose rifamycins in pulmonary tuberculosis. A major phase III trial has recently completed, demonstrating for the first time that a once weekly continuation phase regimen, based on high dose rifapentine and moxifloxacin, is equivalent to standard short course chemotherapy. The use of rapid genotypic testing for drug sensitivity of tuberculosis isolates is being explored, and novel assays developed, with Professor Philip Butcher and colleagues at St George’s.
After studying natural sciences at Christ’s College Cambridge, Prof Harrison studied medicine at St George’s. Following this he undertook postgraduate training in Infectious Diseases in London and through an Infectious Disease fellowship in Boston, USA. His initial research training was in the laboratory of Professor Stuart Levitz in Boston, investigating immune responses to Cryptococcus neoformans, a globally important cause of adult meningitis. He undertook clinical research training in Clinical Effectiveness and International Health at Harvard Medical School. On returning to the UK in 1997, further laboratory studies were combined with clinical trial work, developed first in Thailand, and subsequently in Africa.
Awards and honours include:
- Infectious Diseases Society of America Division Fellowship in Medical Mycology
- NIH/Fogarty HIV, Aids and Related Illnesses Collaboration Award
- Advanced Training Fellowship, The Wellcome Trust
- MRC: Infection and Immunity Board member
- MRC panel member: Global Health Challenges Foundation Call; African Research Leader Scheme; Sub-Committees for MRC Gambia and Entebbe Units; Scientific Advisory Board, Aberdeen MRC Centre in Medical Mycology
- WHO, Infectious Diseases Society of America, and Southern African HIV Clinician’s Society expert panel member
Longley N, Jarvis JN, Meintjes G, Boulle A, Cross A, Kelly N, Govender NP, Bekker LG, Wood R, Harrison TS. Cryptococcal Antigen Screening in Patients Initiating ART In South Africa: A Prospective Cohort Study. Clin Infect Dis 2016; 62:581-7
Mfinanga S, Chanda D, Lesikari S, Guinness L, Bottomley C, Chijoka C, Masasi A, Kimaro G, Ngowi B, Kahwa A, Mwaba P, Harrison TS, Egwaga S, Jaffar S. Cryptococcal meningitis screening and community-based early adherence support reduces all-cause mortality among HIV-infected people initiating antiretroviral therapy with advanced disease: a randomised-controlled trial in Tanzania and Zambia. Lancet 2015 385:2173-82.
Jarvis JN, Meintjes G, Bicanic T, Buffa V, Hogan L, Mo S, Tomlinson G, Kropf P, Noursadeghi M, Harrison TS. Cerebrospinal fluid cytokine profiles in patients with HIV-associated cryptococcal meningitis comprise two principal components that separately predict survival and immune reconstitution inflammatory syndrome. PLoS Pathogens 2015; 11:e1004754
Jarvis JN, Bicanic T, Loyse A, Namarika D, Jackson A, Nussbaum J, Longley N, Muzoora C, Phulusa J, Taseera K, Kanyembe C, Wilson W, Hosseinipour MC, Brouwer A, Limmathurotsakul D, White N, van der Horst C, Wood W, Meintjes G, Jaffar S, Harrison TS. Determinants of Mortality in a Combined Cohort of 523 Patients with HIV-associated Cryptococcal Meningitis: Implications for Improving Outcomes. Clinical Infectious Diseases 2014 58:736-45.
Jindani A, Harrison TS, Nunn A, et al. RIFAQUIN: A multicentre randomised controlled clinical trial to evaluate high dose rifapentine and a quinolone in the treatment of pulmonary tuberculosis. New England J Med 2014; 371:1599-1608.
Loyse A, Thangaraj H, Easterbrook P, Ford N, Roy M, Chiller T, Govender N, Harrison TS, Bicanic T. Cryptococcal meningitis: improving access to essential antifungal medicines in resource poor countries. Lancet Infectious Diseases 2013; May 31st Epub ahead of print
Jarvis JN, Casazza JP, Stone H, Meintjes G, Lawn SD, Levitz SM, Harrison TS*, Koup RA* (* = equal contribution). The Phenotype of the Cryptococcus-specific CD4 Memory T-cell Response is Associated with Disease Severity and Outcome in HIV-associated Cryptococcal Meningitis. J Infect Dis 2013; 207:1817-28.
Jarvis JN, Meintjes G, Rebe K, Williams GN, Bicanic T, Williams A, Schutz C, Bekker L-G, Wood R, Harrison TS. Adjunctive Interferon- Immunotherapy for the Treatment of HIV-associated Cryptococcal Meningitis: A Randomized Controlled Trial. AIDS 2012; 26:1105-13
Jackson A, Nussbaum J, Phulusa J, Namarika D, Chikasema M, Kenyemba C, Jarvis J, Jaffar S, Hosseinipour MC, van der Horst C, Harrison TS. A Randomised Controlled Trial Adding Oral Flucytosine to High Dose Fluconazole, with or without Short-course Amphotericin B, for Cryptococcal Meningitis in Malawi – a Role for Triple Therapy? AIDS 2012; 26:1363-1370
Loyse A, Wilson D, Meintjes G, Jarvis JN, Bicanic T , Bishop L, Rebe K, Williams A, Jaffar S, Bekker L-G, Wood R, Harrison TS. Comparison of the early fungicidal activity of high dose fluconazole, voriconazole, and flucytosine, as second drugs given in combination with amphotericin B, for the treatment of HIV-associated cryptococcal meningitis. Clin Infect Dis 2012; 54:121-8.
Jarvis JN, Percival A, Bauman S, Pelfrey J, Meintjes G, Williams GN, Longley N, Harrison TS, Kozel TR. Evaluation of a Novel Point of Care Cryptococcal Antigen (CRAG) Test on Serum, Plasma and Urine from Patients with HIV-associated Cryptococcal Meningitis. Clin Infect Dis 2011; 53:1019-23.
A.E. Brouwer, A. Rajanuwong, W. Chierakul, G.E. Griffin, R.A. Larsen, N.J. White, T.S. Harrison. Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomized trial. The Lancet 2004; 363:1764-67.
A. Siddiqui, A. Brouwer, V. Wuthiekanun, S. Jaffar, R. Shattock, D. Irving, J. Sheldon, W. Chierakul, S. Peacock, N. Day, N.J.White, T.S. Harrison. Interferon-gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis. Journal of Immunology 2005; 174:1746-50.
J.N Jarvis, S.D. Lawn, M. Vogt, N. Bangani, R. Wood, T.S Harrison. Screening for Cryptococcal Antigenaemia in Patients Accessing an Antiretroviral Treatment Program in South Africa. Clinical Infectious Diseases 2009; 48:856-62
T. Bicanic, C. Muzoora, A.E Brouwer, G. Meintjes, N. Longley, K. Taseera, Rebe K, Loyse A, Jarvis J, L-G Bekker, R. Wood, D Limmathurotsakul, W. Chierakul, K Stepniewska N.White, S. Jaffar, T.S Harrison.. Rate of clearance of infection is independently associated with clinical outcome in HIV-associated cryptococcal meningitis: analysis of a combined cohort of 262 patients. Clinical Infectious Diseases 2009; 49:702-9.
Harry Thangaraj: Access to antifungal drugs in resource limited settings.
InterTB: Dr Amina Jindani, Professor Denis Mitchison, Professor Philip Butcher – Clinical Trials Tuberculosis Chemotherapy; Genetic and phenotypic drug sensitivity testing in MDR / XDR Tuberculosis.
Shabbar Jaffar (London School Hygiene and Tropical Medicine).
Graeme Meintjes (University of Cape Town).
Charles van der Horst, Mina Hosseinipour, Cecilia Kayemba (UNC Project, and Kamuzu Central Hospital, Lilongwe, Malawi).
Shabir Lhaki, Duncan Chanda (University Teaching Hospital, Lusaka, Zambia).
Conrad Muzoora, Taseera Kabanda (Mbarara University Hospital, Uganda).
Douglas Wilson (Edendale Hospital, KZN, South Africa).
Rick Koup (National Institutes of Health USA).
Stuart Levitz (University of Massachusetts).
Matthew Fisher (Imperial College, London).
Tom Kozel (University of Nevada).
Sean Bauman (Immuno-Mycologics, Oklahoma, USA) .
Tom Chiller, (Centers for Disease Control and Prevention, Atlanta).
John Perfect (Duke University).
William Hope (Liverpool University).
June Kwon-Chung, (National Institutes of Health, USA)
Antifungal resistance and pharmacokinetics in cryptococcal meningitis.
Robert Larsen (University College Los Angeles).
Olivier Lortholary (Institut Pasteur).
Professor Harrison gives clinical firm teaching and teaches special study modules.
Professor Harrison supervises PhD/MD(Res) students and gives specialist registrar training in infection.