Typhoid fever bug sequence raises hope of complete eradication

Scientists from Britain, Denmark and Vietnam have deciphered the genetic code of the bacterium responsible for typhoid fever, Salmonella typhi.

Their achievement, reported in the magazine Nature today, raises hope for the prospects of completely eradicating typhoid, which currently claims 600,000 lives a year globally.

Scientists are already using the sequence data, which is freely available on the web, to design new drugs to combat the disease, and improve understanding of the way the bacteria spreads in communities and the mechanisms by which it causes disease.

The researchers unravelled the sequence of a strain of Salmonella typhi known as “CT18”, which is resistant to all cheap antibiotics and is close to becoming untreatable.

“The genetic blueprint of Salmonella is already leading to new methods of treatment and control, and better diagnostic tests. It provides enormous amounts of information and clues as to how it causes disease and spreads in the environment and food chain.”

Professor Gordon Dougan of Imperial College One of the leaders of the UKP 390,000 project funded by the Wellcome Trust

“By studying such a lethal strain of Salmonella, this research also has major implications for public health threats beyond typhoid, because it is an ideal model for the evolution of drug resistance in many diseases.”

“There is a real threat of untreatable typhoid emerging in the next few years in some countries. Already 90 per cent of strains in Vietnam are reported to be resistant to most available drugs – even those which have only just been developed.”

Dr Jeremy Farrar of the University of Oxford-Wellcome Trust Clinical Research Unit Vietnam

“In recent years there have been major outbreaks in Asia and Africa and an increasing incidence in Europe and the USA. That is why this collaborative sequencing project has been so vitally important. Hopefully it will lead to a vaccine that everyone can afford.”

Publication of the research marks the end of a three year sequencing effort, involving 41 scientists based at five centres:

• The Wellcome Trust Sanger Institute, Cambridge, UK
• Imperial College, London, UK
• University of Oxford-Wellcome Trust Clinical Research Unit, Vietnam
• Technical University of Denmark

Analysis of the genetic blueprint of S. typhi has also led to optimism over the chances of completely eradicating typhoid.

In the details of its code they discovered a quantity of “pseudogenes” – sequences of code very similar to working genes but which are seemingly functionless.

This indicates that the bacterium is likely to be restricted to survival in just one species of host – humankind.

“We now know that typhoid emerged only once in human history, at some time in the last 20,000 years, most likely during early settlements. Because there is no animal reservoir for typhoid, if we can eliminate it from humans it would likely eradicate the disease altogether as typhoid could not emerge from other Salmonella easily.”

Professor Gordon Dougan

The strain CT18 was isolated from a 9-year-old boy in December 1993 at the Cho Quan hospital, Ho Chi Minh City, Vietnam.

• Affects 17 million people worldwide every year with approximately 600,000 deaths
• 107 different strains of the bacteria, but all very closely related
• Symptoms are: sustained fever, severe headache, nausea, severe loss of appetite, constipation or diarrhoea
• Without therapy the illness may last for between three to four weeks and death rates range between 12 per cent and 30 per cent
• Typhoid fever is contracted when people eat food or drink water that has been infected with Salmonella typhi
• In 1880 Karl J. Erberth first isolated the causal organism for typhoid fever
• The best known carrier was ‘typhoid Mary’: Mary Mallon was a cook in Oyster Bay, New York in 1906, known to have infected 53 people, 5 of whom died
• In Vietnam 90 per cent of strains are reported to be resistant to several antibiotics (multi resistant) including recently developed ones
• In the war against South Africa in the late nineteenth century British troops lost 13,000 men to typhoid as opposed to 8000 battle deaths
• In regions where typhoid fever is common, school children and young adults are most frequently affected, though in some densely populated regions the peak incidence of typhoid fever may occur at 2-5 years of age

Notes to Editor

1. Internet resources:
   • CDC information on Typhoid (Centers for Disease Control, US)
   • WHO (World Health Organisation) info
   • Vaccines and Typhoid
   • Typhoid Mary
   • Sanger Institute Typhoid sequencing web page
2. The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, is one of the world’s leading genome sequencing centres. Both the Sanger Institute and the Wellcome Trust have been at the forefront of efforts to keep sequence data in the public domain. The Institute employs nearly 600 people in the purpose-built campus at Hinxton. The Institute is a leading partner in the Human Genome Project, and is responsible for sequencing one-third of the human genome sequence. A major focus of the Institute’s work is in national and international projects to sequence the genomes of disease-causing organisms. Details of sequencing projects at the Sanger Institute can be found on the sequencing pages.
3. The Wellcome Trust is an independent research-funding charity, established under the will of Sir Henry Wellcome in 1936. It is funded from a private endowment which is managed with long-term stability and growth in mind. The Trust’s mission is to promote research with the aim of improving human and animal health.
4. Imperial College of Science, Technology and Medicine is the largest applied science, technology and medicine university institution in the UK. It is consistently rated in the top three UK university institutions for research quality, with one of the largest annual turnovers (UKP339 million in 1999-2000) and research incomes (UKP176 million in 1999-2000).