24th February 2006

Antibiotic Resistance Advance in Asia

Growing Resistance of Paratyphoid Fever Bacterium

Immunisation programmes

Typhoid fever and paratyphoid fever are clinically indistinguishable diseases, collectively called enteric fever, that strike at the world's poorest. Although measures capable of controlling typhoid fever are available, the International Vaccine Institute has reported that paratyphoid fever is increasing across Asia. In a study published in Emerging Infectious Diseases, a team led by the Wellcome Trust Sanger Institute highlights the need for effective diagnosis of paratyphoid fever to postpone the increase in antibiotic resistance and to defend against the loss of confidence in vaccination programmes.

Each year there are an estimated 21 million cases of enteric fever as a result of infection by Salmonella Typhi (typhoid fever) or Salmonella Paratyphi A (paratyphoid fever). In the absence of treatment, as many as 20% of infected people will die, most are the very young. With successful diagnosis and treatment, those rates plummet to less than 1%.

Current, effective vaccines against typhoid fever do not work against paratyphoid fever and moreover some strains of Salmonella Paratyphi A have become resistant to the current antibiotics of choice, called fluoroquinolones. The importance of paratyphoid fever is likely to increase.

"Paratyphoid fever may emerge as a bigger threat than typhoid fever," commented Dr John Wain, Junior Fellow at the Wellcome Trust Sanger Institute, "and we are concerned about the increased drug resistance that we describe in this research, the lack of an effective vaccine and the poor diagnostic tools available to many clinics."

In the early 1980s, a typhoid immunisation programme in Thailand successfully eradicated typhoid fever without an increase in the level of paratyphoid fever. Yet recent surveillance in Asia shows an increase in paratyphoid fever and, in the first five weeks of 2006, the number of infections of Salmonella Paratyphi A and Salmonella Typhi increased in the UK.

So why are we seeing an increase in paratyphoid fever cases?

" Paratyphoid fever may emerge as a bigger threat than typhoid fever "

Dr John Wain

"There are three possibilities," continued Dr Wain. "First, it may be improved detection of paratyphoid fever. Second, it could be a real increase caused by a resistant strain. Third, we might be witnessing the emergence of a new and highly transmissible strain. The current work by the International Vaccine Institute, together with genetic studies at the Sanger Institute will help us sort out these possibilities. We expect that our results on changes in DNA sequence, together with the Asia-wide studies of the International Vaccine Institute, will help to develop and implement typing tools."

"So much is dependent on careful use of vaccines, antibiotics and diagnosis. If we cannot make all three work efficiently, then the number of cases of paratyphoid fever must increase. Although these are diseases of developing countries, in truth, all diseases are global concerns, and so we need to understand the increase in paratyphoid fever described by The International Vaccine Institute's studies."

The successful control of typhoid fever in Thailand shows how useful typhoid vaccines can be and the continued success of such campaigns depends on local perception of their effectiveness.

If we continue to use fluoroquinolones as a generic treatment for enteric fever, without specific knowledge of the infecting bacterial pathogen, we will encourage increase in resistance not only in Paratyphi, but in Typhi also.

"We must find reliable, swift and affordable methods to secure the accurate identification of the causes of enteric fever," said Leon Ochiai, Associate Research Scientist at the International Vaccine Institute. "That is the only way we can direct the most appropriate treatment to the most appropriate person. An understanding of the biology behind the increase in paratyphoid fever is of vital importance."

"From population-based studies conducted in Pakistan, India, Indonesia, and China, the proportion of paratyphoid fever ranged from 14% to 64% of enteric fever cases. This is alarming, as the protective effectiveness of currently available typhoid fever vaccines [Vi, Ty21a] against enteric fever may diminish, which could result in a loss of public confidence and public willingness to be vaccinated."

Dr Wain, supported by The Wellcome Trust, has worked with Leon Ochiai of the International Vaccine Institute, based in Seoul, Korea, to establish good laboratory facilities alongside the field epidemiology and vaccine implementation of the DOMI Programme (Diseases of the Most Impoverished, funded by the Bill and Melinda Gates Foundation).

Professor Myron Levine, Director of the University of Maryland School of Medicine Center for Vaccine Development, explained: "It can be too easy to blame clinicians for prescribing antibiotics that may lead to increased resistance. Where diagnosis is imprecise and the only available treatment results in a 20-fold reduction in case fatality, what choice is there?"

"We know that the long term solutions here lie in improved sanitation of water and food supplies. But we also know that improved diagnosis, appropriate use of antibiotics and an effective vaccine for paratyphoid fever are urgently needed, particularly in Asia."

Notes to Editors

  • Publication details

    • Molecular analysis of fluoroquinolone-resistant Salmonella Paratyphi A isolate, India.

      Nair S, Unnikrishnan M, Turner K, Parija SC, Churcher C, Wain J and Harish N

      Emerging infectious diseases 2006;12;3;489-91

    Participating Centres

    • Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    • Department of Microbiology, JIPMER, Pondicherry 605006, India

    The International Vaccine Institute

    The International Vaccine Institute contributes to the reduction of vaccine preventable diseases in developing countries by collaborative research that generates the evidence needed for rational introduction of vaccines, supported by programs of translational research, basic and applied laboratory research, product development, training, and technical assistance.

    Jawaharlal Institute of Post-graduate Medical Education and Research (JIPMER)

    seeks to impart quality education in Under-graduate and Post-graduate medical and paramedical courses; to set trends in medical research; and to offer patient care of high order. The staff strength of the institute is about 3000. The teaching faculty consists of 154 experienced teachers and 361 resident doctors. The institute is affiliated to Pondicherry University.


The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.


The Wellcome Trust and Its Founder

The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals. The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.


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