The group at OUCRU focuses on the microbiology, genetics, epidemiology and treatment of enteric infections in low-income countries in South and Southeast Asia. The pathogens we focus on include Shigella spp., which causes dysentery, and Salmonella Typhi, and the primary agent of typhoid fever. Our current work combines microbiological, immunological and geographical information to investigate the transmission of organisms in urban environments and how this interplay can be used to design and implement vaccination strategies. Areas of particular interest include:
- Evolutionary adaptation and clonal replacement of gastrointestinal pathogens
- Molecular diagnostics of bacterial pathogens
- The impact of antimicrobial resistance
- Horizontal gene transfer
- Epidemiological and clinical aspects of gastrointestinal infections
- Randomised controlled trials for enteric infections
- Serological markers of infection and pathogen exposure
- Genome sequencing and pathogen genotyping
The Enterobacteriaceae are a family of Gram-negative bacteria, which incorporates a number of enteric pathogens, including pathogenic variants of E. coli (the most common cause of community-acquired diarrhoea),Shigella spp., the cause of shigellosis, and the many serovars of Salmonella enterica, including S. Typhi and S.Paratyphi A, which cause enteric (typhoid) fever. The natural environment for the Enterobacteriaceae is the gut of warm and cold-blooded animals and transmission frequently occurs via faecal contamination of food, water and the environment. The risk of infection with pathogenic members of the Enterobacteriaceae is higher in areas with poor sanitation and hygiene. This is a significant global problem, as acute infectious diarrhoea is the second biggest killer of children, accounting for 21% (~2.5 million annually) of childhood deaths worldwide. S. Typhi and S. Paratyphi A are estimated to cause >25,000,000 new infections annually with >200,000 deaths.
The importance of enteric infections research in Viet Nam.
Viet Nam is an industrialising country in Southeast Asia. It has an increasing and urbanising population, a high infectious disease burden and uncontrolled antibiotic usage, making it a dynamic setting for the study of emerging enteric pathogens. We have long-standing collaborations with several healthcare facilities in Ho Chi Minh City (HCMC), across Viet Nam and within the region. Amongst these are three of the largest infectious disease hospitals in the city; HTD, Children’s Hospital One (CH1) and Children’s Hospital Two (CH2). These hospitals are located in central HCMC, within 5km of OUCRU. Annually, these hospitals jointly admit over 200,000 children from across HCMC. Of these, more than 20,000 admissions are for diarrhoea, 10% of which are associated with dysentery. Therefore, by studying the causes, epidemiology and the treatment of these infections, we aim to substantially reduce the burden of disease in this setting. Additionally, although enteric fever is now less of a public health problem in Viet Nam, tin other parts of South and Southeast Asia. We therefore continue our commitment in enteric fever research through our unit in Kathmandu, Nepal. Here we focus specifically on the epidemiology, microbiology and treatment for enteric fever in this high burden, high transmission setting.
- Dr Stephen Baker
- Mr. Duy Pham Thanh
- Ms. Nhu Nguyen Thi Khanh
- Ms. Nga Tran Vu Thieu
- Ms. Dung Tran Thi Ngoc
- Ms. Tu Le Thi Phuong
- Mr. Phat Voong Vinh
- Mr. Hao Chung The
- Dr. My Phan Vu Tra
- Ms. Phuc Tran My
- Ms. Corrine Thompson
- Dr. Christiane Dolecek
- Dr. Amit Aryal
- Dr. Buddha Basnyat
- Dr. Abhilasha Karkey
- Ms. Sabina Dongol
What we’re doing to improve outcomes for enteric patients
A lack of an appropriate diagnosis and antimicrobial resistance in Gram-negative bacteria hampers effective treatment and disease management. Our work in Viet Nam and Nepal aims to develop better diagnostics, enhance understanding of disease and identify appropriate treatment regimes to combat antibiotic resistance in all enteric infections.
What we’re doing to understand enteric infections better
One of our current flagship projects is studying the epidemiology, genomics and longitudinal immune response of Shigella infections in Vietnamese children. The four species of the Gram-negative bacterial genus Shigella (boydii, dysenteriae, flexneri, and sonnei) are amongst the most common causes of dysenteric diarrhoea, with more than 164 million infections annually. However, the burden of Shigella is disproportionately distributed between the species. S.flexneri has historically been responsible for the majority of disease in developing countries, whilst S.sonnei has dominated in developed countries. This pattern, however, is changing with S.sonnei replacing S.flexneri as the primary agent of dysentery in many countries. We need to control S.sonnei and tackle the dramatic emergence of this pathogen in industrialising countries. Yet, there are extensive knowledge gaps regarding disease distribution, incidence and exposure. Furthermore, there is a limited understanding of the effect of uncontrolled antibiotic usage on the international spread and dynamics of pathogens like Shigella. Vaccines and diagnostics are in development, but are compromised by a lack of understanding of how Shigella specific immune responses emerge in children.
We are using prospective investigations, existing data and current high-throughput technologies to link the epidemiology, microbial population structure and host response to S.sonnei. Specifically, over the next three years we aim to answer these questions:
- What is the age specific incidence of S.sonnei infection in HCMC?
- What is the population structure of S.sonnei in HCMC and can phylogeny be used to understand transmission, selection, geographical distribution and the impact of antimicrobial resistance?
- What are the longitudinal serological responses to S.sonnei O-antigen, pan-Shigella antigens and antigens in developmental S.sonnei vaccine preparations before, during and after natural infection?
Our enteric infections research locations
- Ho Chi Minh City, Vietnam
- Dong Thap, Vietnam
- Hue, Vietnam
- Khanh Hoa, Vietnam
- Daklak, Vietnam
- Kathmandu, Nepal
- Siem Reap, Cambodia
- Vientiane, PDR Laos
Our enteric infections research collaborations/partnerships
- Children’s Hospital One, Ho Chi Minh City, Vietnam
- Children’s Hospital Two, Ho Chi Minh City, Vietnam
- The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
- Dong Thap Provincial Hospital, Cao Lanh, Vietnam
- The University of Oxford, UK
- The Wellcome Trust Sanger Institute, Cambridge, UK
- The London School of Hygiene and Tropical Medicine, UK
- The University of California, Irvine, USA
- Yale University, USA
- Princeton University, USA
- The University of Melbourne, Australia
- Cambodia Oxford Medical Research Unit, Siem Reap, Cambodia
- The Wellcome Trust-Mahosot-Oxford University Tropical Medicine Research Unit, PDR Laos
- The Novartis Vaccines Institute for Global Health (NVGH), Siena, Italy
- The University of Queensland, Australia
- Imperial College, London, UK
- Armed Forces Research Institute of the Medical Sciences, Bangkok, Thailand
- Murdoch Children’s Hospital, Melbourne, Australia
Key milestones in our enteric infection research
Research highlights on the Wellcome Trust, and Oxford University websites:
- http://www.wellcome.ac.uk/News/2012/News/ WTVM056062.htm
Article on Typhoid diagnostics of the USAID website:
Radio and newspaper (Le Monde) interviews related to science policy:
Grants and awards
- Grand challenges. Typhoid fever diagnostics. The Bill and Melinda Gates foundation, USA.
- Sir Henry Dale Fellowship. The epidemiology, genomics and longitudinal immune response of Shigella infections in Vietnamese children. The Wellcome Trust and the Royal Society, UK.
- The Wellcome Trust – Vietnam Initiative on Zoonotic Infections (WT-VIZIONS). The Wellcome Trust, UK.
Other key activities
- WHO typhoid treatment guidelines
- Providing data for changing fluoroquinolone breakpoints for enteric fever treatment
- Largest ever clinical trials in enteric fever