Antibiotic Resistance Advance In Asia - Growing Resistance Of Paratyphoid Fever Bacterium

Main Category: MRSA / Drug Resistance
Also Included In: Infectious Diseases / Bacteria / Viruses;  Tropical Diseases
Article Date: 24 Feb 2006 - 22:00 PDT

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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 S. Typhi increased in the UK.

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

"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 IVI. "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 IVI, 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."

Enteric fever and antibiotic resistance

Full resistance to ciprofloxacin in S. enterica Serovar Paratyphi was first reported in 2004 by Professor Harish (Harish BN et al. (2004) J. Med. Microbiol. 53: 819. The research reported here describes the mutations in this original strain.
jmm.sgmjournals.org/cgi/content/full/53/8/819

Paratyphi accounted for more than 60% of enteric fever cases in Hechi City region, China. In four sites sampled (China; Karachi, Pakistan; Calcutta, India; North Jakarta, Indonesia) incidence of Paratyphi ranged from 14-64%.
cdc.gov/ncidod/EID/vol11no11/05-0168.htm

Successful typhoid vaccination in Thailand in the 1980s

On 16 February 2006, the UK's Health Protection Agency reported an increase in the number of confirmed cases of Salmonella Paratyphi A and Salmonella Typhi in England and Wales.
hpa.org.uk/cdr/pages/news.htm#paratyphi

Publication details

Nair S, Unnikrishnan M, Turner K, Parija SC, Churcher C, Wain J, Harish BM. (2006) Molecular analysis of fluoroquinolone-resistant Salmonella Paratyphi A isolate, India. Emerging Infectious Diseases [serial on the Internet] Available from
cdc.gov/ncidod/EID/vol12no03/05-0560.htm
Appeared online on 31 January and in print 1 March 2006

Participating Centres

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

Websites

-- Wain Lab:
http://www.sanger.ac.uk/Teams/Team100
-- JIPMER:
http://www.jipmer.edu/index.htm
-- IVI:
http://www.ivi.org

The Wellcome Trust Sanger Institute was founded in 1992 as the focus for the UK sequencing effort of the human and mouse genomes. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome and one-fifth of the mouse, The Institute is also a major contributor to the mapping and sequencing of the zebrafish genome and genomes of more than 90 disease-causing organisms, including TB and malaria. The Wellcome Trust Sanger Institute is based in Hinxton, Cambridge, UK.
http://www.sanger.ac.uk

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 foster and promote research with the aim of improving human and animal health.
http://www.wellcome.ac.uk
Henry Wellcome wellcome.ac.uk/node7120.html

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. http://www.ivi.org

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.
jipmer.edu/index.htm

http://www.sanger.ac.uk

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