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Background

Why is our project important?

Many infectious diseases that are common in the developing world receive little research funding because these diseases are rare in developed countries. However, these diseases can cause serious health problems and hundreds of thousands of fatalities a year – especially when coupled with a lack of access to high-quality medical care. It is estimated that over a billion people in developing countries are at risk of such diseases (Bill & Melinda Gates Foundation, 2015).

Over the past two decades, changes in global travel patterns and lifestyles has led to the emergence of new infectious diseases in the developing world and re-emergence of old infectious diseases in the developed world. Coupled with the global spread of antibiotic resistance, this has made the emergence of new infectious diseases a truly global concern.

We got Dr. Sanjib Bhakta, Director of Mycobacteria Research Laboratory at the Institute of Structural and Molecular Biology, Birkbeck, University of London and UCL to share his expertise of TB with us in order to shed some light on our rationale for designing a quick diagnostic tool in the wider international fight against this infamous bacterial infection.

According to the World Health Organisation, one of the main ways of addressing infectious diseases is through a strong surveillance system to monitor the spread of different diseases (WHO, 2015). Improved detection and surveillance can help in prioritising public health resources and research funding to combat these diseases more efficiently.

Diagnosis of many infectious diseases relies on expensive medical or laboratory technology, which additionally requires trained personnel to operate. In remote areas of the developing world these facilities may be out of reach for the most vulnerable people. This can be due to a lack of effective infrastructure to enable people to travel the often long distances to hospitals that are usually based in urban areas, and also because of the relatively high cost of accessing healthcare. As a result traditional medicine is still heavily relied upon. Not only do these issues prevent people from accessing quick and effective treatment, they also create “blind spots” in the global surveillance of disease transmission.

How can we apply virus-based diagnostics in the real world?

The major health challenges faced by the developing world differ considerably from those encountered in developed countries, caused by a combination of factors including lack of funding, poor access to medical care and different environmental conditions. These issues are contributing to the ongoing spread of bacterial diseases including tuberculosis (TB), leprosy, syphilis and yaws. Different problems have emerged in the fight against these diseases: in the cases of leprosy (caused by Mycobacterium leprae or M. lepromatosis), syphilis (Treponema pallidum pallidum) and yaws (T. pallidum pervenue) conclusive diagnosis remains difficult, as these bacteria have not been successfully cultured under lab conditions. TB, caused by the bacterium M. tuberculosis, now displays widespread drug resistance, with some areas even facing multi-drug resistant TB (MDR-TB) (Fig. 1), meaning the bacteria are immune to at least isoniazid and rifampicin. Additionally, extensively-drug resistant TB (XDR-TB), in which the bacteria are resistant to all first and second-line drugs, making the disease incredibly difficult to treat, is becoming a growing problem around the world. As a result of developments such as these, antibiotic resistance has been identified as ‘one of the greatest challenges to global public health today’ (WHO 2015).

Fig 1. Multi-drug resistant TB prevalence around the world. Drug resistance has become a major problem among the Russian prison population in the wake of the fall of the Soviet Union (Kenyon 2009); meanwhile, drug resistance remains under-reported in many developing countries due to lack of monitoring and diagnostic facilities.

Fig 2. Occurrence of XDR-TB around the world. It should be noted that many cases of XDR-TB are thought to remain unreported due to a lack of diagnostic and monitoring facilities in the developing world. (Data: WHO)

M. tuberculosis is notoriously slow-growing, making positive diagnosis of TB a lengthy process, with drug resistance even slower to confirm: although faster diagnostic methods for MDR-TB have been developed in recent years (WHO 2014), these remain expensive and rare, so even in areas with access to modern technology the time to diagnosis is usually 2-4 weeks. In developing nations, and especially in rural communities without access to laboratories, equipment for the growth and analysis of liquid cultures is not available and a significant percentage of drug-resistant TB goes undiagnosed. Therefore, a bacteriophage-based diagnostic tool that does not require advanced training or equipment could significantly improve rates of diagnosis, which could lead to better treatment and improved monitoring of the spread of drug resistance. Such a method was first proposed by Hemvani et al (2012) using plaque assays of mycobacteriophage D29 to identify bacterial viability after exposure to the five most common TB medications. Although this study was carried out on concentrated M. tuberculosis cultures, the rapid and extensive proliferation of bacteriophages in the presence of host cells could enable the test to be performed on sputum samples of affected patients, with diagnosis requiring no more than 48 hours. Furthermore, the addition of a chromoprotein marker to the phage capsid would simplify the process of resistance identification by local medics or healers with minimal training. Such a tool would offer a considerable improvement on current diagnostic methods in much of the developing world.

References

Gates Foundation (2015) Neglected infectious diseases strategy overview [online]. Available at: http://www.gatesfoundation.org/What-We-Do/Global-Health/Neglected-Infectious-Diseases. [Accessed 27 July 2015]

N Hemvani, V. Patidar, D.S. Chitnis (2012) In-house, simple & economical phage technique for rapid detection of rifampicin, isoniazid, ethambutol, streptomycin & ciprofloxacin drug resistance using Mycobacterium tuberculosis isolates, Indian Journal of Medical Research, Volume 135, pp 783-787.

G. Kenyon (2009) Russia's prisons fuel drug-resistant tuberculosis, The Lancet, Volume 9(10), pp 594.

World Health Organisation (2014) Progress in diagnosing multidrug-resistant tuberculosis [online]. Available at: http://www.who.int/mediacentre/news/releases/2014/tb-day/en/. [Accessed 30 July 2015]

World Health Organisation (2015) Worldwide country situation analysis: response to antimicrobial resistance [online]. Available at: http://apps.who.int/iris/bitstream/10665/163473/1/WHO_HSE_PED_AIP_2015.1_eng.pdf?ua=1. [Accessed 30 July 2015]

World Health Organisation (2015) Global infectious disease surveillance [online]. Available at: http://www.who.int/mediacentre/factsheets/fs200/en/. [Accessed 27 July 2015]

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