Tuberculosis eradication: renewed commitment and global investment required
Authors: Helen Cox, Mark P Nicol
Journal: The Lancet Infectious Diseases (2017)

Despite centuries of scientific endeavour and social struggle, tuberculosis continues to claim more than 1·6 million lives each year.1WHOGlobal tuberculosis report 2017. World Health Organization, Geneva2017Google Scholar Tuberculosis has killed and continues to kill more people than any other infectious disease. In The Lancet Infectious Diseases, the GBD Tuberculosis Collaborators2GBD Tuberculosis CollaboratorsThe global burden of tuberculosis: results from the Global Burden of Disease Study 2015.Lancet Infect Dis. 2017; (published online Dec 5.)http://dx.doi.org/10.1016/S1473-3099(17)30703-XGoogle Scholar estimate that 10·2 million (95% uncertainty interval [95% UI] 9·2 million to 11·5 million) individuals developed tuberculosis in 2015. While this estimate represents a modest decline since peaking in the early years of this century, the continued high burden, along with a woefully inadequate response to drug-resistant tuberculosis,1WHOGlobal tuberculosis report 2017. World Health Organization, Geneva2017Google Scholar show a profound failure of public health globally. Tuberculosis programmes are often termed control programmes, suggesting that, if implemented as recommended, programme activities should reduce transmission and therefore the number of individuals developing active tuberculosis. However, the GBD Tuberculosis Collaborators estimate that tuberculosis incidence has fallen by only 1·6% (95% UI 1·2–1·9) annually between 2005 and 2015, similar to the rate of decline between 1990 and 2005 (−1·5% [−1·7 to −1·3], and far short of the 4–5% required to reach the global End TB Strategy targets.3WHOThe end TB strategy: global strategy and targets for tuberculosis prevention, care and control after 2015. World Health Organization, Geneva2016Google Scholar Additionally, the decline is inconsistent; countries in the lowest quintile of Socio-demographic Index (SDI) collectively show increasing incidence across 2005–15, after declining in the previous 15 years. Why has the tuberculosis epidemic not been curbed? Are programmes poorly implemented? The GBD Tuberculosis Collaborators2GBD Tuberculosis CollaboratorsThe global burden of tuberculosis: results from the Global Burden of Disease Study 2015.Lancet Infect Dis. 2017; (published online Dec 5.)http://dx.doi.org/10.1016/S1473-3099(17)30703-XGoogle Scholar conclude that strengthening health systems for early case detection and improved care quality across diagnosis and treatment are required. Clearly this strengthening is needed in some countries. An association between declining tuberculosis mortality and SDI overall shown by the GBD Tuberculosis Collaborators2GBD Tuberculosis CollaboratorsThe global burden of tuberculosis: results from the Global Burden of Disease Study 2015.Lancet Infect Dis. 2017; (published online Dec 5.)http://dx.doi.org/10.1016/S1473-3099(17)30703-XGoogle Scholar suggests that some countries should be doing better than at present given their socioeconomic status. Indeed, declines in tuberculosis mortality were substantially greater than for tuberculosis incidence, including in countries in the lowest SDI quintile. However, the overall slow decline in burden suggests that tuberculosis programmes, while reducing deaths, are insufficient to overcome poverty-related drivers and substantially impact the epidemic.4Ortblad KF Salomon JA Barnighausen T Atun R Stopping tuberculosis: a biosocial model for sustainable development.Lancet. 2015; 386: 2354-2362Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar Modelling suggests that, to avert transmission, we need to either identify individuals before they develop tuberculosis and provide effective preventive treatment or diagnose individuals with less infectious early tuberculosis and provide rapid disease treatment.5Oxlade O Piatek A Vincent C Menzies D Modeling the impact of tuberculosis interventions on epidemiologic outcomes and health system costs.BMC Public Health. 2015; 15: 141Crossref PubMed Scopus (9) Google Scholar, 6Arinaminpathy N Dowdy D Understanding the incremental value of novel diagnostic tests for tuberculosis.Nature. 2015; 528: S60-S67Crossref PubMed Scopus (14) Google Scholar We believe that currently available tools are insufficient to achieve these aims. Although substantial advances have occurred in diagnostic technology, many high-burden countries still rely on antiquated sputum smear microscopy; globally, only 57% of cases of tuberculosis are bacteriologically confirmed, with fewer still receiving drug susceptibility testing.1WHOGlobal tuberculosis report 2017. World Health Organization, Geneva2017Google Scholar Smear microscopy diagnoses tuberculosis only when a high bacterial burden exists, after individuals have probably transmitted the infection to others. Although more sensitive diagnostics than smear microscopy are available, such as Xpert MTB/RIF (Cepheid; Sunnyvale, CA, USA), high costs have restricted roll-out.7Albert H Nathavitharana RR Isaacs C Pai M Denkinger CM Boehme CC Development, roll-out and impact of Xpert MTB/RIF for tuberculosis: what lessons have we learnt and how can we do better?.Eur Respir J. 2016; 48: 516-525Crossref PubMed Scopus (195) Google Scholar Unfortunately, in tuberculosis, unlike HIV, only extremely cheap tools seem to be accepted, perhaps because most individuals with tuberculosis are poor. This reluctance is present despite estimates of the huge economic burden attributed to tuberculosis: approximately US$6·9 billion in Indonesia, for example.8Collins D Hafidz F Mustikawati D The economic burden of tuberculosis in Indonesia.Int J Tuberc Lung Dis. 2017; 21: 1041-1048Crossref PubMed Scopus (32) Google Scholar Encouragingly, research efforts are now being directed towards identification of improved biomarkers, such as blood gene signatures that identify active tuberculosis or predict high risk of development of active tuberculosis.9Zak DE Penn-Nicholson A Scriba TJ et al.A blood RNA signature for tuberculosis disease risk: a prospective cohort study.Lancet. 2016; 387: 2312-2322Summary Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 10Kaforou M Wright VJ Oni T et al.Detection of tuberculosis in HIV-infected and -uninfected African adults using whole blood RNA expression signatures: a case-control study.PLoS Med. 2013; 10: e1001538Crossref PubMed Scopus (236) Google Scholar These signatures are suboptimal, and the task of incorporation of biomarkers into a point-of-care test is formidable. However, such tests could revolutionise how tuberculosis is diagnosed—ie, through mass screening. Early identification of individuals with high risk of tuberculosis or early disease presupposes that safe, effective treatment is on offer. Current preventive therapy predominantly entails daily isoniazid treatment, but there is reluctance to scale-up preventive treatment in high-burden settings because of questions about duration and the risk of drug resistance if undiagnosed active tuberculosis is treated with a single drug.11Balcells ME Thomas SL Godfrey-Faussett P Grant AD Isoniazid preventive therapy and risk for resistant tuberculosis.Emerg Infect Dis. 2006; 12: 744-751Crossref PubMed Scopus (172) Google Scholar However, trials12Sterling TR Villarino ME Borisov AS et al.Three months of rifapentine and isoniazid for latent tuberculosis infection.N Engl J Med. 2011; 365: 2155-2166Crossref PubMed Scopus (672) Google Scholar have shown that short, multidrug-preventive regimens can be efficacious, and trials with new drugs are underway.13Frick M Gaudino A Harrington M et al.Pipeline report 2017: HIV, TB, HCV. Treatment Action Group, New York2017Google Scholar Finally, patients are still reliant on a universal, 6 month regimen for active drug-susceptible tuberculosis, a lengthy treatment that is difficult to maintain and results in catastrophic costs for many.14Wingfield T Boccia D Tovar M et al.Defining catastrophic costs and comparing their importance for adverse tuberculosis outcome with multi-drug resistance: a prospective cohort study, Peru.PLoS Med. 2014; 11: e1001675Crossref PubMed Scopus (146) Google Scholar Clearly, new patient-centred diagnostic and treatment tools are required. However, funding for tuberculosis research, from basic science through to implementation, has been sorely neglected. Globally, research funding fell by more than US$50 million between 2014 and 2015, just as the tuberculosis eradication targets were launched.3WHOThe end TB strategy: global strategy and targets for tuberculosis prevention, care and control after 2015. World Health Organization, Geneva2016Google Scholar, 15Frick M 2016 report on tuberculosis research funding trends, 2005–2015: no time to lose. Treatment Action Group, New York2016Google Scholar Overall, only a third of the research funding needed to meet the Stop TB Partnership's goals was invested during 2011–15 (figure).15Frick M 2016 report on tuberculosis research funding trends, 2005–2015: no time to lose. Treatment Action Group, New York2016Google Scholar More urgency, commitment, and funding than have been shown so far are needed if tuberculosis is really to be eradicated. HC has received grants from the Wellcome Trust, the UK Medical Research Council, and the National Research Foundation, South Africa. MPN has received grants from the Foundation for Innovative New Diagnostics and from the National Institutes of Health. The global burden of tuberculosis: results from the Global Burden of Disease Study 2015Despite a concerted global effort to reduce the burden of tuberculosis, it still causes a large disease burden globally. Strengthening of health systems for early detection of tuberculosis and improvement of the quality of tuberculosis care, including prompt and accurate diagnosis, early initiation of treatment, and regular follow-up, are priorities. Countries with higher than expected tuberculosis rates for their level of sociodemographic development should investigate the reasons for lagging behind and take remedial action. Full-Text PDF Open Access