Elsevier

The Lancet

Volume 393, Issue 10181, 20–26 April 2019, Pages 1642-1656
The Lancet

Seminar
Tuberculosis

https://doi.org/10.1016/S0140-6736(19)30308-3Get rights and content

Summary

Tuberculosis remains the leading cause of death from an infectious disease among adults worldwide, with more than 10 million people becoming newly sick from tuberculosis each year. Advances in diagnosis, including the use of rapid molecular testing and whole-genome sequencing in both sputum and non-sputum samples, could change this situation. Although little has changed in the treatment of drug-susceptible tuberculosis, data on increased efficacy with new and repurposed drugs have led WHO to recommend all-oral therapy for drug-resistant tuberculosis for the first time ever in 2018. Studies have shown that shorter latent tuberculosis prevention regimens containing rifampicin or rifapentine are as effective as longer, isoniazid-based regimens, and there is a promising vaccine candidate to prevent the progression of infection to the disease. But new tools alone are not sufficient. Advances must be made in providing high-quality, people-centred care for tuberculosis. Renewed political will, coupled with improved access to quality care, could relegate the morbidity, mortality, and stigma long associated with tuberculosis, to the past.

Introduction

Tuberculosis—the leading cause of death worldwide from an infectious disease among adults—has been considered a global public health emergency for the past 25 years.1 Although public health approaches to tuberculosis have saved tens of millions of lives, modest progress has been made to control (let alone to end) tuberculosis. Drug-resistant forms of tuberculosis are currently on course to be the world's deadliest pathogens, responsible for a quarter of deaths due to antimicrobial resistance.2 Great ambition and radical action are needed to tackle this completely curable pathogen, which remains one of the greatest health problems in the world.

The global tuberculosis situation is dire, but now is also a time of great promise and discovery for the disease. Numerous advances have been made in our understanding of the epidemiology, risk factors, and pathophysiology of tuberculosis, and new diagnostics and treatment for all forms of tuberculosis infection and disease are appearing on the horizon. Access to these innovations remains a substantial challenge for the majority of people living with the disease, but if the political will that seems to be building in the tuberculosis community and beyond3 is put into action, with a focus on the rights of people affected by the disease, the next decade might finally see the devastation caused by this age-old disease start to abate.

Section snippets

Epidemiology, pathogenesis, and risk factors

Tuberculosis continues to cause considerable morbidity and mortality globally. According to WHO,4 an estimated 10 million people became newly sick with tuberculosis in 2017; 8·7 million (87%) of these individuals reside in 30 high-burden countries. Among these 10 million individuals, only 6·4 million were diagnosed and officially notified. 1·3 million people are estimated to die from tuberculosis each year.4

Tuberculosis is a disease of poverty. Although most high-income countries have estimated

Diagnosis

Although multiple advances have been made in the diagnosis of tuberculosis, no reliable, simple, point-of-care test exists to definitively diagnose the disease. Clinicians often seek bacteriological diagnosis, but this evidence is also supplemented by clinical findings, radiological evidence, and tests for bacterial products that indicate the presence of M tuberculosis. WHO currently endorses a range of diagnostic and drug susceptibility tests (appendix).

New developments exist for the use of

Treatment

The treatment landscape for tuberculosis has changed dramatically over the past 5 years, with the introduction of two new drugs, bedaquiline and delamanid, and multiple clinical trials whose results are being used to radically alter the care of people with all forms of tuberculosis.57 More tuberculosis treatment studies are happening than ever before in the history of the disease, and not only will these studies help improve the care of people living with tuberculosis, but they should also help

Support for successful outcomes

Adherence support aimed at ensuring successful tuberculosis treatment has historically relied on the use of directly observed therapy (DOT). The use of DOT has shown mixed results in multiple studies and meta-analyses, largely because the term appears to be a catch-all phrase for radically different treatment support approaches. When coupled with emotional support, nutritional supplementation, and other types of enablers, DOT can be a way to ensure daily contact with vulnerable individuals and

Prevention

Prevention efforts have focused on tuberculosis vaccination and the treatment of latent tuberculosis or tuberculosis infection. Immunisation with the BCG vaccine is known to protect children from severe and disseminated forms of disease, decrease infection by 30%, and potentially offer some protection to adult populations.164 In general, the vaccine is not thought to be immunogenic enough to induce long-term immunity, although some studies show that intrapulmonary administration might be more

How to modernise tuberculosis care

For too long, tuberculosis care has relied on antiquated tools that are no longer fit for purpose. This can and must change.175 As described in this Seminar, many new tools and solutions already exist in some form (figure 2); however, these developments have not come together to serve those who need them the most. For some improvements to be made, such as the development of a better vaccine or a shorter drug therapy, new investments are urgently needed. High-quality systems for data management

Political will to end tuberculosis

On Sept 26, 2018, a UN meeting focused on tuberculosis was held in New York, NY, USA.178 The pledges made by multiple, high-level delegations, including heads of state from high burden tuberculosis countries, such as South Africa, could herald a new level of political commitment in the fight against tuberculosis. Although similar meetings held to discuss HIV and Ebola led to substantial increases in funding for research and treatment, the effects of the UN tuberculosis meeting are not yet

Conclusions

Although tuberculosis continues to be one of the most important public health problems of the 21st century, clinical and scientific advances exist that stand to revolutionise the diagnosis, treatment, and prevention of all forms of this disease. Access to these diagnostic and therapeutic advances must be guaranteed for all as part of a human rights-based approach to tuberculosis. The political will to eliminate tuberculosis is stronger than ever; this intention must be matched with unparalleled

Search strategy and selection criteria

We searched the Cochrane library, PubMed, and Ovid for items published between Jan 1, 1946, and Nov 21, 2018. We used the search terms “tuberculosis” in combination with “epidemiology”, “pathophysiology”, “risks”, “diagnosis”, “test”, “treatment”, “prevention”, “vaccine”, “infection”, “quality”, “political will”, “patient-centered”, “person-centered”, “drug-resistant”, “drugs”, “access”, and “prognosis”. We prioritised research published since 2014, but we also included other papers of

References (178)

  • TM Walker et al.

    Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study

    Lancet Infect Dis

    (2013)
  • M Ruhwald et al.

    Safety and efficacy of the C-TB skin test to diagnose Mycobacterium tuberculosis infection, compared with interferon γ release assay and the tuberculin skin test: a phase 3, randomised, double-blind controlled trial

    Lancet

    (2017)
  • H Getahun et al.

    Active case finding for TB in the community: time to act

    Lancet

    (2010)
  • GL Calligaro et al.

    Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicenter, randomised controlled trial

    Lancet

    (2017)
  • AI Zumla et al.

    New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects

    Lancet Infect Dis

    (2014)
  • KW Jo et al.

    Risk factors for 1-year relapse of pulmonary tuberculosis treated with a 6-month daily regimen

    Respir Medi

    (2014)
  • MJ Boeree et al.

    High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial

    Lancet Infect Dis

    (2017)
  • JY Chien et al.

    Treatment outcome of patients with isoniazid mono-resistant tuberculosis

    Clin Microbiol Infect

    (2015)
  • J-Y Chien et al.

    Isoniazid-resistant tuberculosis treatment with first-line drugs

    Lancet Infect Dis

    (2017)
  • N Ismail et al.

    Defining bedaquiline susceptibility, resistance, cross resistance, and associated genetic determinants: a retrospective cohort study

    EBioMedicine

    (2018)
  • A Kunkel et al.

    Population implications of the use of bedaquiline in people with extensively drug-resistant tuberculosis: are fears of resistance justified

    Lancet Infect Dis

    (2017)
  • J Andrews

    To be or not to be exclusive: the sutezolid story

    Lancet Glob Health

    (2016)
  • RR Nathavitharana et al.

    A tale of two global emergencies: tuberculosis control efforts can learn from the Ebola outbreak

    Eur Respir J

    (2015)
  • Tackling drug-resistant infections globally: final report and recommendations

  • Scope, modalities, format and organization on the high-level meeting on the fight against tuberculosis

  • Global tuberculosis report 2018

  • The global burden of tuberculosis: results from the Global Burden of Disease Study 2015

    Lancet Infect Dis

    (2018)
  • Global, regional, and national burden of tuberculosis, 1990–2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study

    Lancet Infect Dis

    (2018)
  • M Mehra et al.

    Assessment of tuberculosis burden in China using a dynamic disease simulation model

    Int J Tuberc Lung Dis

    (2013)
  • I Comas et al.

    Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans

    Nature Genet

    (2013)
  • RM Houben et al.

    The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling

    PLoS Med

    (2016)
  • M Pai et al.

    Tuberculosis

    Nat Rev Dis Primers

    (2016)
  • P Drain et al.

    Incipient and sub-clinical tuberculosis: a clinical review of early stages and progression of infection

    Clinical Microbiol Rev

    (2018)
  • SW Michelsen et al.

    The dynamics of immune responses to Mycobacterium tuberculosis during different stages of natural infection: a longitudinal study among Greenlanders

    PLoS One

    (2017)
  • C Seshadri et al.

    Transcriptional networks are associated with resistance to Mycobacterium tuberculosis infection

    PLoS One

    (2017)
  • NS Shah et al.

    Transmission of extensively drug-resistant tuberculosis in South Africa

    N Engl J Med

    (2017)
  • K Dheda et al.

    Drug penetration gradients associated with acquired drug resistance in patients with tuberculosis

    Am J Respir Crit Care Med

    (2018)
  • M Behr et al.

    Revisiting the time table of tuberculosis

    BMJ

    (2018)
  • O Oxlade et al.

    Tuberculosis and poverty: why are the poor at greater risk in India?

    PLoS One

    (2012)
  • Batista JdL, de Albuquerque Mde F, Maruza M, et al. Incidence and risk factors for tuberculosis in people living with...
  • T Pande et al.

    Computer-aided detection of pulmonary tuberculosis on digital chest radiographs: a systematic review

    Int J Tuberc Ling Dis

    (2016)
  • Chest radiography in tuberculosis detection: summary of current WHO recommendations and guidance on programmatic approaches

  • S Lawn et al.

    Detection of lipoarabanomanna (LAM) in urine is indicative of disseminated tuberculosis with renal involvement in patients living with HIV and advanced immunodeficiency

    Trans R Soc Trop Med Hyg

    (2016)
  • SD Lawn

    Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review

    BMC Infect Dis

    (2012)
  • The use of the lateral flow urine lipoarabanomannan assay (LF-LAM) for the diagnosis and screening of active tuberculosis in people living with HIV

  • G Sigal et al.

    A novel, sensitive immunoassay targeting the MTB-lipoarabanaomannan epitope meets the WHO's performance target for tuberculosis diagnosis

    J Clin Microbiol

    (2018)
  • L Paris et al.

    Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity

    Sci Transl Med

    (2017)
  • D Goletti et al.

    Update on tuberculosis biomarkers: from correlates of risk to correlates of active disease and of cure from disease

    Respirology

    (2018)
  • MP La Manna et al.

    Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease

    PLoS One

    (2018)
  • TO Togun et al.

    Biomarkers for diagnosis of childhood tuberculosis: a systematic review

    PLoS One

    (2018)
  • Cited by (531)

    View all citing articles on Scopus
    View full text