World Tuberculosis Day 2021 Theme — ‘The Clock is Ticking’ — and the world is running out of time to deliver the United Nations General Assembly commitments to End TB due to the COVID-19 pandemic

On March 24th 1882 Koch's announcement in Berlin of the discovery of the microbial cause of tuberculosis (TB), Mycobacterium tuberculosis, heralded a major breakthrough, bringing hope for a devastating disease which at that time caused the death of one in seven people in Europe and the Americas. (Wallstedt and Maeurer, 2015Wallstedt H. Maeurer M. The history of tuberculosis management in Sweden.Int J Infect Dis. 2015; 32: 179-182Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar). One hundred and twenty years later, and despite the availability of effective treatment for the past 6 decades, 1.4 million people die of TB annually (WHO, 2021aWHO Global tuberculosis report 2020. World Health Organization, 2021https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdfGoogle Scholar). Over the past 15 months, the unprecedented COVID-19 pandemic has disrupted health services globally (Cilloni et al., 2020Cilloni L. Fu H. Vesga J.F. Dowdy D. Pretorius C. Ahmedov S. et al.The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.EClinicalMedicine. 2020; 28100603https://doi.org/10.1016/j.eclinm.2020.100603Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar) and has negatively impacted on gains being made in global TB control efforts to achieve End TB targets (Sahu et al., 2020Sahu S. Ditiu L. Lawson L. Ntoumi F. Arakaki D. Zumla A. UN General Assembly tuberculosis targets: are we on track?.Lancet. 2020; 395: 928-930Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar; STOP TB, 2019). The theme of this year's World TB Day March 24th, 2021, 'The Clock is Ticking' (WHO, 2021bWHO World Tuberculosis Day 2021 The Clock is Ticking.2021https://www.who.int/campaigns/world-tb-day/world-tb-day-2021Google Scholar), conveys the sense of urgency that the world is running out of time to deliver the commitments to End TB made by global leaders at the United Nations General Assembly high level meeting on TB (UNGA, 2018UNGA United Nations General Assembly resolution A/RES/73/3; October 2018. Political declaration of the high-level meeting of the General Assembly on the fight against tuberculosis.2018https://www.un.org/en/ga/search/view_doc.asp?symbol=A/RES/73/3Google Scholar). This theme is particularly appropriate and critical in light of the devastating COVID-19 pandemic which is currently the top killer from an infectious disease globally, with TB now being shifted to second place (WHO, 2021aWHO Global tuberculosis report 2020. World Health Organization, 2021https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdfGoogle Scholar, WHO, 2021cWHO COVID-19 dashboard.2021https://covid19.who.int/Google Scholar). Since the end of December, 2019, when the WHO was made aware of several cases of atypical pneumonia in Wuhan, China, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as of March 15th 2021, there have been 119,603,761 confirmed COVID-19 cases, with 2,649,722 deaths, reported to WHO (WHO, 2021cWHO COVID-19 dashboard.2021https://covid19.who.int/Google Scholar). In commemoration of World TB Day March 24th, 2021, the International Journal of Infectious Diseases is once again publishing a specific TB Theme issue of 18 articles covering a range of topics. The October 2020 WHO Global TB report and the United Nations (UN) Secretary-General's 2020 progress report on TB, are reviewed by Chakaya et al., 2021Chakaya J. Khan M. Ntoumi F. Aklillu E. Fatima R. Mwaba P. et al.Global Tuberculosis Report 2020 — Reflections on the Global TB burden, treatment and prevention efforts.Int J Infect Dis. 2021; 113: S7-S12Abstract Full Text Full Text PDF Scopus (393) Google Scholar. They reflect on current TB control strategies in light of the United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York (UNGA, 2018UNGA United Nations General Assembly resolution A/RES/73/3; October 2018. Political declaration of the high-level meeting of the General Assembly on the fight against tuberculosis.2018https://www.un.org/en/ga/search/view_doc.asp?symbol=A/RES/73/3Google Scholar). Progress in achieving TB control targets has been very slow. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208,000 deaths among people living with HIV. In addition, preliminary assessments of how the unprecedented, devastating COVID-19 pandemic is affecting TB health services, interrupting and slowing down treatment and prevention efforts. It is anticipated that the End TB strategy target of ending TB by 2035 will not be met. The WHO 2020 TB Report (WHO, 2021aWHO Global tuberculosis report 2020. World Health Organization, 2021https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdfGoogle Scholar) states that a 50% drop in the number of people with TB detected, could result in up to 400,000 additional TB deaths in a year. Innovative plans are needed to maintain all TB services as well as access to these services, in the wake of the COVID-19 pandemic and investments in the development of low-cost rapid diagnostic tests for both COVID-19 and TB are urgently needed. There needs to be a rejuvenated, sustained, and concerted effort to identify and treat 'missing people with TB'. Governments of high TB incidence countries need to ensure there are rapid TB diagnostic services available in every health facility, so all TB cases can be reached. Global health inequities that underlie differences in TB disease burden, as well as daunting environmental health challenges, need to be addressed by multiple approaches and sectors. Fox et al., 2021Fox G.J. Nguyen T.A. Coleman M. Trajman A. Velen K. Marais B.J. Mycobacterium tuberculosis; latent tuberculosis; preventive therapy; prophylaxis; patient-centered care.Int J Infect Dis. 2021; 113: S13-S15Abstract Full Text Full Text PDF Scopus (4) Google Scholar highlight that latent tuberculosis infection affects one quarter of the world's population and that despite effective oral treatment regimens being available, scale-up and rollout of TB preventive treatment (TPT) remains limited. They describe strategies to support scale-up of TPT in high-prevalence settings, where the potential benefit for affected individuals is considerable and emphasise that patients must be at the centre of TPT policies. Addressing health system requirements for scale-up will be important to ensure that programs can deliver treatment safely, efficiently and sustainably. Nachega et al., 2021aNachega J.B. Kapata N. Sam-Agudu N.A. Decloedt E.H. Katoto P.D.M.C. Nagu T. et al.Minimizing the impact of the triple burden of COVID-19, tuberculosis and HIV on health services in sub-Saharan Africa.Int J Infect Dis. 2021; 113: S16-S21Abstract Full Text Full Text PDF Scopus (27) Google Scholar discuss the negative impact of COVID-19 on TB and HIV health services. They suggest approaches to mitigate the growing burden of these colliding epidemics in sub-Saharan Africa, which bear the highest proportions of TB and HIV cases worldwide. The COVID-19 pandemic has added an additional burden to already overstretched health systems, which, among many other things, were struggling to deal with the longstanding dual epidemics of TB and HIV. Knipper et al., 2021Knipper M. Sedas A.C. Keshavjee S. Abbara A. Almhawish N. Alashawi H. et al.The need for protecting and enhancing TB health policies and services for forcibly displaced and migrant populations during the ongoing COVID-19 pandemic.Int J Infect Dis. 2021; 113: S22-S27Abstract Full Text Full Text PDF Scopus (7) Google Scholar review the COVID-19 pandemic threat to derailing health services for forcibly displaced people and migrant populations, populations who face specific vulnerabilities placing them at increased risk of developing TB if they have LTBI, or not being diagnosed as having active TB. Highlighting three case studies as examples—from Peru, South Africa, and Syria—they illustrate the lived experience of forced migration and mobile populations, and the impact of COVID-19 on TB among these populations. They indicate that addressing TB, COVID-19 and migration from a syndemic perspective, not only draws systematic attention to comorbidity and the relevance of social and structural context, but also helps to find solutions. The true reality of syndemic interactions can only be fully understood by considering a particular population and bio-social context and ensuring that they receive the comprehensive care that they need. It also provides avenues for strengthening and expanding the existing infrastructure for TB care to tackle both COVID-19 and TB in migrants and refugees in an integrated and synergistic manner. Over a quarter of the individuals diagnosed with TB in the European Union region are born outside the EU and the proportion has been increasing steadily. Over 50% of TB cases in Italy are foreign born migrants. Goscé et al., 2021Goscé L. Girardi E. Allel K. Cirillo D.M. Barcellini L. Stancanelli G. et al.Tackling TB in migrants arriving at Europe's southern border.Int J Infect Dis. 2021; 113: S28-S32Abstract Full Text Full Text PDF Scopus (1) Google Scholar describe the EDETECT-TB project in Italy which implemented and evaluated active TB screening in the migrant population and their study confirmed that early case detection is a cost-effective intervention and that targeted post-arrival early screening ensures that potential further transmission is averted. Recurrent pulmonary TB is a growing, important and neglected problem affecting treated TB patients and TB health services across the world, particularly in sub-Saharan Africa and Asia. Analyses and identification of differences in clinical features between recurrent PTB and newly diagnosed PTB may lead to improved management recommendations. Nagu et al., 2021Nagu T.J. Mboka M.A. Nkrumbih Z.F. Shayo G. Mizinduko M.M. Komba E.V. et al.Clinical and imaging features of adults with recurrent pulmonary tuberculosis — a prospective case-controlled study.Int J Infect Dis. 2021; 113: S33-S39Abstract Full Text Full Text PDF Scopus (4) Google Scholar performed a prospective case-controlled study of clinical and imaging features of patients with recurrent pulmonary TB (RPTB) and compared them with those of newly diagnosed PTB cases. They found that hemoptysis, lung parenchymal damage, and patients being older than 45 years of age are significant features of RPTB, suggesting that management of TB cases should focus on risk factors for recurrence, and design a more holistic model of care to prevent long term lung injury. Kizny Gordon et al., 2021Kizny Gordon A. Marais B. Walker T.M. Sintchenko V. Clinical and public health utility of Mycobacterium tuberculosis whole genome sequencing.Int J Infect Dis. 2021; 113: S40-S42Abstract Full Text Full Text PDF Scopus (15) Google Scholar review the clinical and public health utility benefits of M. tuberculosis whole genome sequencing (WGS), including provision of more rapid and complete information on drug-resistance, detection of transmission clusters, contamination events, mixed infections, and to differentiate between re-infection and relapse. They also discuss future advances that have the potential to change the landscape of TB diagnostics and management, such as culture-free sequencing and surveillance of antimicrobial resistance to guide precision medicine approaches, as well as some of the challenges involved. Whole genome sequencing-based differentiation between re-infection and relapse in TB cases has important implications for public health, especially in patients with human immunodeficiency virus (HIV) co-infection. Shanmugam et al., 2021Shanmugam S. Bachmann N.L. Martinez E. Menon R. Narendran G. Narendran S. et al.Whole genome sequencing based differentiation between re-infection and relapse in Indian patients with tuberculosis recurrence, with and without HIV co-infection.Int J Infect Dis. 2021; 113: S43-S47Abstract Full Text Full Text PDF Scopus (8) Google Scholar compared Mycobacterial Interspersed Repeat Unit (MIRU) typing and spoligotyping with WGS to differentiate between relapse and re-infection and assessed the value of WGS to track acquired drug resistance in those with relapse after successful treatment. Comparing M. tuberculosis genomes, they found that 95% of TB recurrences in the HIV-negative cohort were due to relapse, while the majority of TB recurrences in the HIV-positive cohort were due to re-infection, highlighting the need for effective infection control in HIV care setting. WGS for M. tuberculosis drug resistance detection is now available in diagnostic and reference laboratories worldwide. Characterizing novel mutations and deletions associated with drug resistant M. tuberculosis could ultimately lead to better treatment outcomes. The additional value WGS provides in inferring drug resistance is discussed by Lam et al., 2021Lam C. Martinez E. Crighton T. Furlong C. Donnan E. Marais B.J. et al.Value of routine whole genome sequencing for Mycobacterium tuberculosis drug resistance detection.Int J Infect Dis. 2021; 113: S48-S54Abstract Full Text Full Text PDF Scopus (18) Google Scholar. They sequenced genomes from all M. tuberculosis isolates in NSW, Australia, collected between 2016 and 2019 and tracked the prevalence of drug resistance and circulation of predominant M. tuberculosis lineages. They demonstrated that WGS was able to capture an additional 20% of drug resistance mutations not detected by commercial diagnostic assays, signaling the additional value that WGS offers over existing genotypic drug resistance assays in terms of sensitivity. The Bandim TBscore is a clinical score that predicts treatment outcome in TB patients and may prove useful as an indicator of which healthcare-seeking adults to refer for sputum smear microcopy. Rudolf et al., 2021Rudolf F. Abate E. Moges B. Mendes A.M. Mengistu M.Y. Sifna A. et al.Increasing smear positive tuberculosis detection using a clinical score — A stepped wedge multicenter trial from Africa.Int J Infect Dis. 2021; 113: S55-S62Abstract Full Text Full Text PDF Scopus (3) Google Scholar conducted a stepped wedge cluster-randomized trial at six health centers in Bissau, Guinea-Bissau, and Gondar, Ethiopia. They conclude that it is an implementable approach and solution to an old and yet unresolved challenge. Using the TBscore for triage before smear microscopy may improve case detection and decrease mortality if there is sufficient laboratory capacity to increase sputum smears. Marais et al., 2021Marais B.J. Verkuijl S. Casenghi M. Triasih R. Hesseling A.C. Mandalakas A.M. et al.Paediatric tuberculosis — new advances to close persistent gaps.Int J Infect Dis. 2021; 113: S63-S67Abstract Full Text Full Text PDF Scopus (9) Google Scholar discuss new advances to close persistent gaps in the prevention and diagnosis of childhood TB. Almost all children estimated in the Global TB Report 2020 to have died from TB were never diagnosed or offered TB treatment. Thus new approaches are required to ensure that effective TB prevention strategies are implemented and to improve the accuracy of current and new diagnostic (rule-in and rule-out) tests. Reducing the major gaps in TB preventive treatment (TPT) will require strong political commitment and concerted effort, with major upscaling of household contact investigation. While widespread roll-out of Xpert MTB/RIF Ultra® should be supported and could improve case detection in young children, they caution that specimen collection remains difficult and test sensitivity low. The use of non-sputum specimens are essential to improve diagnostic access, but given the limited accuracy of all available tests and the excellent tolerance of TB drugs in children the global community may have to accept some over-treatment using the most feasible approaches available; if we are serious about closing the persistent case detection gap in young children. Zoonotic TB is evolving in an everchanging global landscape. Despite slow reductions in the annual burden of active TB cases, Zoonotic TB (zTB) remains a poorly monitored and poorly addressed global burden. Kock et al., 2021Kock R. Michel A.L. Yeboah-Manu D. Azhar E.I. Torrelles J.B. SI et al.Zoonotic tuberculosis — the changing landscape.Int J Infect Dis. 2021; 113: S68-S72Abstract Full Text Full Text PDF Scopus (16) Google Scholar in their zoonotic TB review highlight the higher incidence in some specific regions and countries, especially where close association exists between growing numbers of cattle (the major source of Mycobacterium bovis (M. bovis) and people, many suffering from poverty and where milk or dairy products are consumed un-pasteurized. Attention needs to be re-focused to prevent a rapid increase in zTB disease along with growing intensification of dairy production. Evidence of new zoonotic mycobacterial strains such as M. orygis, especially in South Asia and Africa warrants rapid assessment of drivers and risk, and the development of appropriate interventions. Control of M. bovis in cattle through early detection of infection and disease, as well as pasteurization of dairy products, remains the mainstay of reducing zTB risk to humans, while new point of care diagnostics will help to detect and appropriately treat human cases. Lipman et al., 2021Lipman M. Kunst H. Loebinger M.R. Milburn H.J. King M. Non tuberculous mycobacteria pulmonary disease: patients and clinicians working together to improve the evidence base for care.Int J Infect Dis. 2021; 113: S73-S77Abstract Full Text Full Text PDF Scopus (6) Google Scholar highlight that pulmonary disease caused by non-tuberculous mycobacteria (NTM) is often missed, is difficult to treat successfully in an often frail population with other chronic conditions such as bronchiectasis and COPD, is on the rise globally, and results in significant morbidity and even mortality. They identify and discuss key issues in NTM management. In addition to the need for research into epidemiology, immunology and treatment, they recommend an 8-point plan including greater use of patient and clinician networks to educate primary and secondary care clinicians and promote a multidisciplinary team approach with shared patient-clinician decision making throughout care. They also call for co-ordinated patient-focused research to improve what is often a limited evidence base to guide management. Nachega et al., 2021bNachega J.B. Maeurer M. Sam-Agudu N.A. Chakaya J. Katoto P.D.M. Zumla A. Bacille Calmette-Guérin (BCG) vaccine and potential cross-protection against SARS-CoV-2 infection — Assumptions, knowns, unknowns and need for developing an accurate scientific evidence base.Int J Infect Dis. 2021; 113: S78-S81Abstract Full Text Full Text PDF Scopus (7) Google Scholar re-ignite the century old controversies on the Bacille Calmette–Guérin (BCG) vaccine, which is yet again a focus of global time due to the global COVID-19 pandemic caused by on the knowns, unknowns and need for developing an accurate scientific evidence base for of potential cross-protection against SARS-CoV-2 studies have that human and with a developed high to vaccine has been to increase and on and these could be as against severe of They highlight that there are clinical in progress to the of for prevention of SARS-CoV-2 infection or to morbidity and mortality associated with from ongoing may light on the and could lead to improved increased tolerance of treatment, and identification of benefits and COVID-19 or other There are several ongoing studies which are the interactions between COVID-19 and TB. et al., L. E. V. G. G. P. et of tuberculosis and COVID-19 the to in to J Infect Dis. 2021; 113: Full Text Full Text PDF Scopus Google Scholar evaluated in whole after with in the or with from SARS-CoV-2 They demonstrated for the time that COVID-19 with TB or LTBI, have a to an to SARS-CoV-2 while the to to results may have important implications for the clinical management of COVID-19 individuals with Fatima et al., R. N. A. Khan better tuberculosis control in a from during the COVID-19 pandemic.Int J Infect Dis. 2021; 113: Full Text Full Text PDF Scopus Google Scholar focus on TB control in and discuss the of a approach for better TB control to with the of in all countries, COVID-19 is negatively in The COVID-19 has an in to some to TB care to increased investments in human and addressing and of for and Global health inequities TB epidemiology, including the and and as well as need to be addressed by multiple approaches and sectors. The WHO 2020 global TB Report that in 2019 there were an estimated cases of resistant TB of which only cases were and positive treatment were in of highlight the need for and treatment and patient services. et al., M.M. et at six in patients and regimens for the treatment of tuberculosis in J Infect Dis. 2021; 113: Full Text Full Text PDF Scopus (6) Google Scholar the study from on at six in patients and regimens for the treatment of et al., S. Zumla A. J. Zumla A. development of new TB treatment regimens in of a of resistant TB due to the COVID-19 pandemic.Int J Infect Dis. 2021; 113: Full Text Full Text PDF Scopus Google Scholar that the and negative of COVID-19 on health services including TB programs and TB services further to longstanding challenges for such as availability of rollout of TB diagnostics and TB of WHO for in light of COVID-19 of TB services will be difficult it is anticipated the numbers of cases will rise in 2021 and and will treatment more in development of new TB drugs and treatment regimens is required in of drug resistance to new TB drug and COVID-19 and and clinical capacity to rapid treatment and and ensuring availability of of TB drugs both and through improved and of TB et al., S. Ditiu L. Zumla A. from the impact of the pandemic and to achieving the United Nations General Assembly tuberculosis J Infect Dis. 2021; 113: Full Text Full Text PDF Scopus (15) Google Scholar that it has been over years global leaders the UN General Assembly high level meeting on TB declaration which to 15 for TB, for TB care and 2 for TB (UNGA, 2018UNGA United Nations General Assembly resolution A/RES/73/3; October 2018. Political declaration of the high-level meeting of the General Assembly on the fight against tuberculosis.2018https://www.un.org/en/ga/search/view_doc.asp?symbol=A/RES/73/3Google Scholar). They point out that the up October 2020 UN report (UNGA, UN General Assembly September 2020. Progress the of global tuberculosis targets and of the political declaration of the high level meeting of the General Assembly on the fight against Report of the Scholar) on progress of the political declaration on TB that high-level commitments and targets global and progress ending TB, and more investments and were especially in of the COVID-19 pandemic where associated public health and have disrupted health services The report out to the world on track to targets by all countries should to these and the Global needs to increase current commitment to the impact of COVID-19 on TB services to to Tuberculosis and Scholar). and are required to the of people with TB. should active with community and contact to of and to of TB, using and other diagnostic and an of TB drugs and care for all people with TB TB TB A TB commitments TB a report on progress the UN political declaration on the fight against TB and a call to to close the gaps in TB Scholar). On World TB Day 2021, every political and community and must the that it is time to global inequities as we a TB While there is a need to new prevention and treatment for TB, the required for of current TB diagnostic and management could TB control efforts. World leaders need to urgently and the and health services impact of the COVID-19 COVID-19 and public health to have an on slowing down the COVID-19 every effort must be made by to ensure that health services and prevention programs for TB are not The commitment of to the rapid development and rollout of COVID-19 is but it is important to ensure that is now time for them to with commitment to ending the TB that it can be if there is serious political will which is into in This is of a World Tuberculosis Day March 24th, Clock is with support from an from have a specific in Tuberculosis and have to articles in this issue for World TB Day other of Kock and and Kapata and are of the European and Clinical project on and Zumla is in of a of Health and is a 2020 Nachega is supported by the International numbers for Health and (the of in South and Maeurer is a of the of the