BIOINFORMATICS CASE STUDY:

Using Genomics To Improve Diagnosis And Treatment Of Tuberculosis

Tuberculosis (TB) may have a low profile in New Zealand, but it still infects 300 Kiwis every year – and at a disproportionately higher rate in Maori and Pacific populations.

Internationally, the annual figure is 9 million people and 1.5 million deaths. And it is no longer only ‘standard TB’ – the highly-infectious, nasty disease of old; there is a growing percentage of drug-resistant cases – even in New Zealand. While standard TB takes $26 and six months to treat, a drugresistant strain could take $5500 and two years. A recent drug-resistant TB case at Dunedin Hospital cost $180,000 to treat.

University of Otago Postdoctoral Fellow Dr Htin Lin Aung is from Myanmar – one of the world’s most TB-affected countries – where about 600 cases are diagnosed daily and, of those, approximately 10 per cent are already resistant to at least two of the standard TB drugs.

Dr Aung’s research is focussed on better diagnosis and treatment of TB, with an eye to addressing the disease more effectively in socioeconomically disadvantaged communities, where the disease and antibiotic resistance are most prevalent.

Dr Aung says faster, more accurate diagnosis is needed to curb the spread of resistant strains. He is working with NZGL to carry out whole genome sequencing of TB bacteria. Armed with this information, drug-resistant TB bacteria can be identified – including the specific antibiotic/s they are resistant to – significantly faster than with conventional diagnosis. Consequently, clinicians could action more effective treatment regimens and do so more quickly.

“Currently, treatment is standardised. This is a personalised approach. We anticipate treatment outcomes will be better for patients and we will reduce drug resistance.”

The next step is randomised clinical trials in his home country, Myanmar. “If we can pull this off, it will be a major breakthrough in tackling this global health threat,” Dr Aung says.

NZGL Services:2 lanes MiSeq; 20 hours bioinformatics, whole genomic sequencing

Dr Richard Fong, Massey University Genome Service

“Until recently, whole genome sequencing (WGS) studies of microbial genomes have been limited by the complexity of microbial ecosystems, inefficient DNA sequencing methodologies and unreliable genetic information. However, Illumina platforms – such as MiSeq and the Nextera XT protocol, which utilise rapid sequencing and ultra-low DNA input concentration – have promised improved opportunities for the investigation of microbial communities. WGS is becoming an important part of clinical and epidemiological investigations of infectious diseases, such as the M.tuberculosis (M.Tb) project conducted by Dr Aung. We helped Dr Aung develop a robust workflow that supported rapid and high-throughput sequencing at a reduced cost. We addressed the bottlenecks of next-generation sequencing library construction by using an in-house modified protocol, which harnessed the rapid library construction of the Nextera XT kit. This allowed rapid reproducible construction of M.Tb genome at a fraction of sequencing cost – greatly assisting the research into finding multiple drug resistance M.Tb (MDR-TB) profiles.”


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University of Otago research is using whole genome sequencing of the TB Bacteria to improve TB diagnosis and treatment, particularly in poorer communities, where the disease and its resistant strains are most prevalent.

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Ministry of Business, Innovation & Employment