Professor Susanna J Dunachie
- Wellcome Intermediate Clinical Fellow
- Honorary Consultant in Infectious Diseases and Medical Microbiology
People continue to die around the world from infections for which there is no vaccine. A greater understanding of immunity to a range of infectious diseases is desirable to improve treatments and vaccine design, especially for intra-cellular organisms which are harder to prevent and cure. My research establishes expertise in cellular immunology in tropical countries to address key questions that further vaccine discovery and immunogenicity monitoring. Current diseases of interest include melioidosis, scrub typhus and malaria.
Burkholderia pseudomallei is a Gram negative bacterium which causes melioidosis in humans. Melioidosis is a common cause of illness and death in some regions of South East Asia and Northern Australia yet its international profile is low. The known risk factors include diabetes, alcoholism and renal disease but not HIV. The range of presentations includes pneumonia, liver and splenic abscesses and septic shock. A vaccine is therefore urgently required. There is evidence of exposure to melioidosis in up to 80% of the population in North East Thailand but only some become unwell with sepsis carrying a mortality of 40%. The intracellular nature of the pathogen and its potential to show latency and relapse suggest T-cells play a major part in defense against disease, but to date there has been little research in this area.
Key questions currently being addressed include:
- Why are people with diabetes so susceptible to melioidosis, accounting for around 60% of hospital admissions?
- Which B. pseudomallei proteins and HLA Class I restricted CD8 epitopes do patients with acute melioidosis in Thailand respond to?
- What is the phenotype of cellular responses to B. pseudomallei?
- What is the role of functional antibody responses to B. pseudomallei?
- Are cellular responses important in host defence against Orientia tsutsugamushi, the causative bacteria for scrub typhus?
I have set up an immunology laboratory at the Mahidol Oxford Tropical Medicine Research Unit (MORU), and a satellite laboratory at Sappasithiprasong Hospital, Ubon Ratchathani in North East Thailand, which has around 400 annual admissions of culture-positive melioidosis (the highest in the world). A longitudinal study of 200 patients with acute melioidosis both with and without diabetes in Ubon Ratchathani completed in 2015 with a further study underway. PBMC have been isolated locally and used to evaluate T-cell by ex vivo IFN-ʏ ELISPOT to a panel of candidate proteins and peptides from B. pseudomallei, in collaboration with Prof Danny Altmann and Dr Rosemary Boyton at Imperial College. Cells from people with diabetes in the region and from exposed and unexposed healthy control subjects are used as controls. Techniques for assays in a field setting including low volume whole blood stimulation assays and plasma cytokine analysis are also in development.
Further work in Bangkok with Dr Daniel Paris has established assays to quantitate cellular responses to scrub typhus, and field studies of immunology to scrub typhus are underway in Chiang Rai, Northern Thailand.
The Tropical Immunology laboratory at the Peter Medawar Building in Oxford was established in late 2015 with support from Prof Paul Klenerman, and the team includes post-doctoral immunologist Dr Barbara Kronsteiner-Dobramysl and Commonwealth DPhil student Dr Fazle Rabbi Chowdhury. In this laboratory we use cutting-edge approaches to characterising the immune response to tropical pathogens, including multiparameter flow cytometry and Zellscanner with Dr Chris Willberg.
Capacity development is a key theme of my research programme and I twice delivered a popular course in basic immunology at MORU. Other activities include contributing to the Wellcome Trust’s “Foreign Bodies, Common Ground” exhibition and working with clinical microbiologists at multiple sites in South East Asia to standardise diagnostic microbiology lab SOPs for tropical settings.
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