Dr Sarah Dunstan - Head of Human Genetics, Oxford University Clinical Research Unit

Variation in the LTA4H gene has been identified to change a tuberculosis patients’ response to treatment.  Even though personalized medicine is becoming more widely known in cancer medicine, the idea of it in infectious diseases is much less established. Scientists and clinicians at the Oxford University Clinical Research Unit (OUCRU), the Hospital for Tropical Diseases, Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease in Vietnam, and the University of Washington in the USA published their findings in the international journal Cell this week (link to Tobin et al 2012).
Elegant experiments from the team at the University of Washington identified LTA4H as a hypersusceptibility gene for Mycobacterium infection in the zebrafish model, which was then confirmed in patients from Vietnam with the devastating disease, Tuberculous Meningitis (TBM; link to Tobin et 2010). Further experiments to unravel the mechanism found that the immune response to Mycobacterium infection could be either too inflammatory, not inflammatory enough, or just right, according to LTA4H genotype.  Previously, a randomized controlled trial conducted in Viet Nam established that adjunctive dexamethasone benefitted survival in patients with TBM (link to Thwaites et al NEJM) and steroid use became part of the standard treatment for TBM in Viet Nam.  These latest findings part-funded by the Wellcome Trust and reported in Cell (link to Tobin et al 2012) support the theory that steroid use in the treatment of TBM may only benefit some patients depending on their LTA4H genotype.  Further clinical and genetic studies in TBM patients are on-going at OUCRU to establish this.


For more information see :

Tobin D et al, Cell 148, 434–446, February 3, 2012

Lavani A et al, Cell 148, 389-391, February 3, 2012

Tobin D et al, Cell 140, 717–730, March 5, 2010

Thwaites G et al, N Engl J Med 351, 1741-51, 2004

http://www.wellcome.ac.uk/News/2012/News/WTVM054310.htm

http://www.ox.ac.uk/media/news_releases_for_journalists/120203.html

http://www.dailymail.co.uk/health/article-2095835/Goldilocks-gene-used-drug-treatment-just-right-TB-patients.html

Ms Ngoc Ha received an MSc from the University of Science, Ho Chi Minh City, in October 2011. Her research project, which was conducted in the TB group at OUCRU, has been developing a test for rapid detection of resistance to the drug ethambutol in the bacteria Mycobacterium tuberculosis. Drug resistance in Mycobacterium tuberculosis, which causes tuberculosis, is becoming more common worldwide and therefore rapid and accurate methods to detect resistance are urgently needed. Tuberculosis is usually treated with at least four drugs to prevent the emergence of drug resistant strains. Ethambutol is one of the drugs used in standard treatment for tuberculosis and it plays an important role in preventing the development of multi-drug resistant tuberculosis in patients infected with a strain already resistant to another drug. Her project evaluated the distribution of mutations in the emb gene, which are responsible for ethambutol resistance and then developed a multi allele specific PCR (MAS-PCR) to rapidly detect ethambutol resistance.

Dr Stephen Baker, Head of enteric infections, Oxford University Clinical Research Unit.

In October 2011 the genome sequence of Salmonella Typhi CT18 celebrated its tenth birthday. As a consequence of the publication and open access to genome sequences substantial advances have been made in understanding the biology of the organism. Yet as the sequence moves into adolescence, why are we no closer to a global solution for typhoid fever and can we modify our research focus to address this pressing issue? This is the question raised by Dr Stephen Baker, head of enteric infections here at Oxford University Clinical research unit, in a recent worldview piece in Nature and in an interview with the French national newspaper, Le Monde. Dr Baker suggests "unless we change our approach and invest in translational science beyond the bench in endemic countries, the genome will persist as a fascinating and luxurious academic advance, remaining largely useless in a public health context".

Heiman Wertheim and Mary Chambers

The forth Vietnamese National Scientific Conference on Infectious Diseases was recently held in Hanoi on the 16th and 17th of September 2011. The conference was hosted by the National Hospital of Tropical Diseases and the Vietnamese Association for Infectious Diseases and held at the International Conference Center in Hanoi. The meeting touched on various subjects pertinent to Viet Nam, including zoonoses, hospital acquired infections, antibiotic resistance and HIV/AIDS.
The meeting was attended by approximately 550 people, of which 60% were from Hanoi and the surrounding provinces. OUCRU-Vietnam and the Wellcome Trust UK gave travel fellowships for Vietnamese scientists outside of Hanoi to present their work at the meeting. Twenty-eight scientists received funds for this purpose: 11 from HCMC, 5 from Hue, 2 from Yen Bai, 2 from Nghe An, 2 from Binh Dinh, and the remaining from other areas of Viet Nam. Seven oral presentations were from OUCRU scientists and several others were from collaborative projects. There was a relative high interest for Streptococcus suis infections, with two presentations from Dr Ho Dang Trung Nghia from Hospital for Tropical Diseases HCMC, doing his PhD with OUCRU HCMC, and Mrs Vu Thi Lan Huong from OUCRU Hanoi. All presentations were given in English and Vietnamese, making this a useful meeting for foreigners as well as Vietnamese.
In addition to the academic content the National Infectious Disease Association held a congress meeting during which members voted for a new NID Steering Committee and Permanent Steering Committee. Dr Nguyen Van Vinh Chau, Director HTD, and Prof Nguyen Tran Chinh, former Director HTD, were voted on to this committee.