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Antibiotic-resistant typhoid likely to spread despite drug control programmes

10 December 2013

Typhoid bacteria sm
Restricting the use of antibiotics is unlikely to stop the spread of drug resistance in typhoid fever, according to a study funded by the Wellcome Trust and published in the journal 'eLife'.

The findings reveal that antibiotic-resistant strains of Salmonella Typhi bacteria can outcompete drug-sensitive strains when grown in the laboratory, even in the absence of antibiotics.

Typhoid fever is transmitted by consuming food or drink that is contaminated with Salmonella Typhi bacteria, and the disease is linked to poor sanitation and limited access to clean drinking water. The disease can be treated, but there is widespread drug resistance to common antibiotics and resistance to the recommended, more specialised antibiotic therapy for typhoid fever is increasing.

Researchers at the Oxford University Clinical Research Unit, Wellcome Trust Vietnam Research Programme, created 12 laboratory strains of Salmonella Typhi bacteria with one or more genetic mutations that confer resistance to the recommended antibiotic therapy for typhoid fever, fluoroquinolone. Typically, developing antibiotic resistance comes at a cost for bacteria, and when the drug is absent they are usually weaker and less able to compete for food and resources than strains that are not resistant.

Dr Maciej Boni, a Sir Henry Dale Fellow funded jointly by the Wellcome Trust and the Royal Society at the Oxford University Clinical Research Unit in Vietnam, who co-led the study, said: "When we grew different strains of Salmonella Typhi in the lab, we found that half of the antibiotic-resistant strains had a growth advantage over their parent strain, even in the absence of antibiotic, enabling them to predominate in the population."

Dr Stephen Baker, also a Sir Henry Dale Fellow in the Oxford University Clinical Research Unit, said: "Currently, the control of typhoid across Asia and Africa relies on treatment with fluoroquinolones, but resistance is rising. Withdrawing or restricting the use of this class of antibiotics is one approach to try and combat the spread of resistance. However, the results of this study suggest that we need to think beyond this, as antibiotic resistance will likely continue to rise even if these strategies are implemented.”

Dr Jimmy Whitworth, Head of International Activities at the Wellcome Trust, said: "These important findings from researchers in Vietnam are very worrying. If confirmed, one of our main strategies for controlling drug resistance in typhoid will be ineffective. We will need to concentrate on developing more effective and affordable vaccines and improving water supplies and sanitation, a Herculean task for low- and middle-income countries."

There are an estimated 21 million cases of typhoid fever around the world each year. If left untreated, it's estimated that up to one in five people with the disease will die; of those who survive, some will have permanent physical or mental disabilities. According to a World Health Organization report, 90 per cent of the world's typhoid deaths occur in Asia and the disease persists mainly in children under five years.

Typhoid infects the gut and bloodstream, causing fever that can reach temperatures of 40°C and constipation or diarrhoea. The disease can be associated with other characteristics, including rose-coloured spots on the chest, confusion and perforation of the gut.
 

Image: An electron microscope image of bacteria responsible for typhoid fever. Credit: Sanofi Pasteur on Flickr.

Contact

Jen Middleton
Senior Media Officer, Wellcome Trust
T +44 (0) 20 7611 7262
E j.middleton@wellcome.ac.uk 

Notes for editors

Reference
Baker S et al. Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure. eLife 2013.

About the Wellcome Trust Vietnam Research Programme
Established in 1991 in Ho Chi Minh City and Hanoi in 2006, the Wellcome Trust Vietnam Research Programme aims to tackle national health problems and improve the prevention, diagnosis and treatment of infectious and non-infectious diseases - many of which are also challenging global health issues. The Programme is hosted by the Hospital for Tropical Diseases in Ho Chi Minh City and the National Hospital for Tropical Diseases in Hanoi, and it is home to the Oxford University Clinical Research Unit (OUCRU). The Programme collaborates widely across Vietnam and with research groups in Cambodia, China, Indonesia, Malaysia, the Philippines, Nepal, Singapore and Latin America.

About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. 

About Oxford University’s Medical Sciences Division
Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK’s top-ranked medical school.

From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.

A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.
 

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