27 January 2015
Last week Public Health England (PHE) and NHS England (NHSE) announced their collaborative strategy for decreasing the number of tuberculosis (TB) cases in England, with the goal of ultimately eliminating TB as a public health problem.
The five-year strategy involves investing £11.5 million on all aspects of the TB care pathway, including improving diagnostics, setting up TB control boards to oversee TB control efforts, testing for latent TB infection and improving outreach services that focus on hard to reach populations.
The incidence of tuberculosis is higher in England than in most Western European countries, and four times higher than in the USA. There were 7,290 reported TB cases in 2013 (13.5 per 100,000 population), of which 68 were multi-drug resistant TB (MDR-TB). By comparison, Germany has 5.2 TB cases per 100,000 population. TB cases in England are focused in large urban centres such as London and Birmingham, and nearly three quarters of cases occur in people who were born abroad: of these cases, 85% occur in settled migrants who have reactivated latent infections that they acquired many years previously. There is also a strong association between TB and social deprivation, and 9% of cases have one social risk factor such as a history of substance abuse, homelessness or imprisonment.
The new strategy outlines how PHE and NHSE plan to strengthen current practice to tackle TB. In countries that have had success in reducing TB levels and maintaining low levels of incidence, control programmes have had adequate resources, rigorous monitoring measures, and clear leadership and lines of accountability. Features of the strategy, including the formation of formal TB control boards, aim to create this strong leadership and accountability, with coverage over the whole country, not just in areas of high incidence.
Three of the ten key strands of the strategy are to ensure universal access to high quality diagnostics; to reduce incidence of drug-resistant TB; and to strengthen surveillance and monitoring. Current diagnostic practice involves a series of phenotypic and genotypic tests to determine strain information and drug resistance and susceptibility, which can take many weeks (8+) to complete. There is evidence that genomics, particularly whole genome sequencing (WGS), has a role to play in the management of TB, particularly with reference to these three strategic priorities.
The advantage of WGS is that once enough bacteria have been grown in culture, which takes around a week in most cases, sequencing the bacterial genome and analysing the information it contains takes only around one week more. In the majority of cases no further tests are needed as strain, drug resistance and susceptibility information and transmission chains can be determined from the sequence. Steps are already being taken by PHE to investigate WGS, as they have listed running a pilot programme of WGS for TB as a goal in its key priorities for the next five years.
It is therefore possible that genomics will have a role to play in efforts to manage TB. Along with current research efforts investigating the use of WGS to detect TB more rapidly in clinical samples and in surveillance efforts, there are future plans to focus on emerging technologies (including genomics) that will lead to swifter diagnoses of TB.
Along with the benefits of quicker diagnosis listed above, WGS also provides better quality data and much more comprehensive information on the genetics of the disease. WGS already provides valuable insights into other areas of TB biology: one example is a recent study published in Nature Genetics where researchers sequenced thousands of isolates of one sub-type of tuberculosis known as the Beijing lineage, which is strongly associated with the spread of MDR-TB. Comparing the sequence of the isolates showed that this sub-type originated in east Asia around 6,600 years ago, before spreading around the globe. Increases in the size of the pathogen population were associated in recent times with historical events such as the Industrial Revolution, World War One and the emergence of HIV epidemics. Most recently, this type of MDR-TB is spreading in central Asia and former Soviet republics, due to failures in the public health system following the break-up of the Soviet Union. The increase in incidence of MDR-TB worldwide is a growing concern, and studies such as this help us to understand how diseases spread.
The increased volume of data that is becoming available about TB, both in the research and clinical context, is vital to efforts to combat a disease that every year causes disease in 9 million people and kills 1.5 million people worldwide, the second largest cause of death from infectious disease after HIV/AIDS. Not only will WGS data enhance surveillance efforts, when used in conjunction with clinical and epidemiological data, but it will also provide valuable information to clinicians about which drugs are most suitable for their patients. This reduces the chance of hospital admission and the development of drug resistance. The knowledge gained from implementing the TB strategy within the English health system and carrying out further research into TB should not only reduce incidence of the disease in the UK but also contribute to international efforts to combat the disease.