Tuberculosis (TB) is a contagious, airborne, but curable bacterial disease that affects primarily the developing world. It exerts a significant economic burden on developing-world countries.
1.5 million deaths due to TB were reported in 2014, with 9.6 million new cases in the same year.
Most impacted are those in low- and lower-middle-income countries in Asia and Africa, with a particular impact on people in those regions co-infected with human immunodeficiency virus (HIV).
According to a World Health Organization (WHO) study in 2008, the global cost of managing TB was reported to be $3.1 billion for TB control activities. This does not include the value of lost productivity and life impacted by the disease. The economic cost of TB-related deaths in Africa alone was estimated at $519 billion for the period from 2006—2015 in a World Bank study commissioned by The Bill & Melinda Gates Foundation. (“Economic Benefit of TB Control” The World Bank, Human Development Network, 2007). There are clear gains in both human and economic terms to support investment in controlling TB.
For decades, sputum smear tests and clinical observation have been used to diagnose TB infection. However, these methods have serious deficiencies in performance, cost, and time to result. Microscopic techniques are available and affordable but have poor sensitivity, particularly in HIV co-infected patients. Additionally, sputum smear tests are not able to distinguish resistant strains, which significantly impacts treatment. Microbiological culture techniques are also available at low cost and can additionally detect resistant TB, but they can take days to perform and require infrastructure and skilled analysts. Improvements on these tests would save money and lives and move closer to TB eradication.
The goal of the Diagnostics Program’s TB portfolio is to better align TB diagnostic products with the needs of low-resource settings. In addition to assay development, a particular challenge is to create tools that improve the systems and techniques associated with existing diagnostics to better integrate them into low-resource settings. This is being pursued both through user needs assessments as well as incremental improvements at several critical points in the work flows surrounding TB diagnosis.
Areas of focus
The focus of the Diagnostics Program TB portfolio is to evaluate, develop, and implement diagnostic assays and supporting tools. Areas of specific interest and ongoing project work are described below.
Field assessment of tuberculosis screening technologies
The Diagnostics Program TB portfolio is working with the PATH HIV/TB program and its extensive field presence to assess the performance of the Xpert MTB/RIF, a cartridge-based, automated diagnostic test that can identify Mycobacterium tuberculosis and resistance to rifampicin. Specifically, PATH is assessing the impact of introduction of the test in Tanzania and the Democratic Republic of the Congo. Also of interest is cooperative evaluation of multiple countries for introduction of an assay for drug susceptibility testing.
Tuberculosis and diabetes co-morbidity
The dual burden of TB and type 2 diabetes is a pressing public health issue in low resource countries. The PATH HIV/TB program, in collaboration with the Diagnostics Program, is assessing novel point-of-care screening technologies in a TB and type 2 diabetes bidirectional screening project. The programmatic aspects of the project will provide evidence for an effective bidirectional screening model.
Drug susceptibility testing via TB MODS
A significant gap in TB diagnostics in low-resource settings involves identifying drug resistant strains of TB to allow for proper treatment. PATH is involved in an effort to commercialize a liquid TB culture assay in a fully inclusive kit designed for low-resource settings.
Evaluation and performance assessment of tuberculosis tools in China
PATH is involved in a consortium of global diagnostics experts and the Chinese TB control program to determine the operational feasibility, cost-effectiveness, and impact of innovative new TB diagnostic tools. These include an improved microscopy method and several nucleic acid amplification technologies for the rapid diagnosis of TB and the identification of genetic markers of first-line drug resistance.
Tuberculosis DNA amplification tools
Isothermal amplification of nucleic acid sequences is a powerful tool in rapidly detecting the presence of pathogens in clinical samples. This is particularly true in low-resource settings where there is minimal infrastructure to support instrument-based molecular diagnostics. The Diagnostics Program TB portfolio has ongoing projects with multiple commercial partners to develop and introduce point-of-care TB diagnostics with these technologies.
Landscaping New and Emerging Diagnostic Technologies
PATH, in collaboration with McGill University, are contracted to draft annual and semiannual reports describing the status of diagnostic tools in use or intended to enter the TB diagnostics market. These reports also include global market updates and changes to policy guidelines from the WHO.
David Boyle, Tuberculosis Diagnostics Portfolio Leader