Researchers, led by the NIHR Oxford Biomedical Research Centre, the Health Protection Agency in Birmingham and the Wellcome Trust Sanger Institute in Cambridge, have pioneered the whole genome sequencing (WGS) method through a study of 254 TB cases in the Midlands.
The method, published online in the Lancet Infectious Diseases (15.11.12) Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study compares the genetic information from the TB germs of each patient to determine with a high degree of accuracy whether cases are isolated, or if there is an outbreak of the potentially fatal disease.
By genetically mapping the spread of infection it can also show who has given the disease to whom and help identify potential "super spreaders" before any information has been collected from patients.
Armed with this data, public health bodies can assess how much transmission is taking place and thereby target efforts quickly, efficiently and effectively to where it is needed most.
Lead investigator Professor Tim Peto, at the NIHR Oxford Biomedical Research Centre, a partnership between the Oxford University Hospitals NHS Trust and the University of Oxford, said: "This will result in a major rebalancing of the public health approach to the spread of TB.
"It will make them far more focused on where the problems are and make them more efficient and effective."
Co-investigators Drs. Grace Smith and Philip Monk, senior members of the HPA TB control programme, described the research as a "revolution in TB control." Dr Monk added "at present you have to put a lot of work into contact tracing to find links between cases. This is extremely difficult particularly when people often lead such chaotic lives.
"By identifying so-called super spreaders we can target our work effectively. In terms of the public health management of TB, that is a major paradigm shift."
TB cases in the UK remain relatively low. However, the number of cases has risen slightly over the past decade, with 8,963 cases reported in 2011 (source: Health Protection Agency). Many cases are isolated, but there have been numerous outbreaks across the country over recent years.
Current practice sees public health bodies depend on people with TB volunteering information about their movements, family and friends, to identify further cases and piece together the potential spread of the disease. Until now this approach has been aided by limited genetic typing techniques that are only able to rule out transmission between cases, and not reliably confirm transmission.
The process of identifying outbreaks has therefore been time consuming, relying on the information people are able to give and occasionally throwing up "false connections," leading to wasted effort by health bodies.
By sequencing the whole genome the new technique allows linking of cases and the mapping of outbreaks, and has the ability to predict the existence of undiagnosed cases.
WGS is used to measure the genetic distance between TB strains to accurately link cases before any additional patient data has been collected. By analysing the evolving pattern of mutations it is possible to work out the direction of transmission and identify potential "super-spreaders."
Prof Peto said: "This work gives a level of certainty you could never have before about who belongs to a transmission chain.
"The information is in the germ, and it speaks for itself."
The study was supported by:
The NIHR Oxford Biomedical Research Centre is a partnership between the research expertise of the Oxford University Hospitals NHS Trust and the University of Oxford. Its main aim is to enable clinical research for patient benefit and foster innovation to improve healthcare. It is funded by the National Institute for Health Research (NIHR). The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world class facilities (both NHS and university), and conducting leading edge research focused on the needs of patients. www.oxfordbrc.nihr.ac.uk
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK's top-ranked medical school.
From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.
A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.
UK CRC Modernising Medical Microbiology Consortium is a UK wide consortium funded by the Wellcome Trust and MRC, between the University of Oxford, Health Protection Agency (HPA) and the Wellcome Trust Sanger Institute; to establish how revolutionary new technologies can be optimally integrated into microbiology research and service strategic vision. www.modmedmicro.ac.uk
The Health Protection Agency is an independent UK organisation that was set up by the government in 2003 to protect the public from threats to their health from infectious diseases and environmental hazards. In April 2013, subject to the usual approvals procedures for establishing new bodies, the Health Protection Agency will become part of a new organisation called Public Health England, an executive agency of the Department of Health. To find out more, visit our website: www.hpa.org.uk or follow us on Twitter @HPAuk.
Journal
The Lancet Infectious Diseases