The World Health Organization (WHO) End TB Strategy aims to end the global tuberculosis epidemic by 2030. Targets include a 90% reduction in tuberculosis mortality and an 80% reduction in tuberculosis incidence. Despite remarkable progress, with advances in disease detection and improvement in treatment success rates, tuberculosis is still common in several countries. Although the rates of tuberculosis incidence and tuberculosis-related mortality are declining worldwide, the disease continues to be an important public health issue.(1) In Latin America, the incidence rate has fallen by 1.7% per year since 2000, considerably less than the 5.3% annual decline needed in order to achieve the targets proposed in the WHO End TB Strategy.(2,3) In celebration of World TB Day, on March 24th, this issue of the JBP features several articles focusing on tuberculosis, to offer an overview of the various aspects of tuberculosis control.

To achieve its proposed targets, the WHO End TB Strategy has three pillars. One of the pillars (Pillar 2) is "bold policies and supportive systems", which includes regulatory frameworks for case notification.(1) In this issue of the JBP, an ecological time-series study(4) conducted in the city of Juazeiro, in the Brazilian state of Bahia, reported the behavior of the epidemiological indicators of tuberculosis. The results show the persistence of the disease burden in the municipality, identifying the local problems to be addressed and underscoring the importance of constant monitoring of epidemiological indicators.

Early diagnosis of tuberculosis is one of the components of Pillar 1 of the WHO End TB Strategy ("integrated, patient-centered care and prevention"). In our tuberculosis series, the diagnosis of tuberculosis is addressed in four original articles.(5-8) Since its introduction in 2010, the molecular test for Mycobacterium tuberculosis and its resistance to rifampin (Xpert MTB/RIF assay) is increasingly used as the initial diagnostic test for tuberculosis in many countries. (9,10) Two of the articles in our series addressed the use of the Xpert MTB/RIF assay.(5,6) In the first,(5) a retrospective study conducted at a tertiary referral center, the authors showed that the Xpert MTB/RIF assay is a highly accurate method of detecting tuberculosis and rifampin resistance in sputum, BAL fluid, and tracheal aspirate samples. In the second article,(6) the sensitivity and specificity of the Xpert MTB/RIF assay were evaluated in a population of indigenous Brazilians. That is an extremely important study, because it is the first to assess the performance of the test in such a population. Both articles emphasize that is essential to determine the effect of the Xpert MTB/RIF assay on the diagnosis of tuberculosis under programmatic conditions in Brazil.(11)

Improving the coverage and quality of diagnosis for individuals infected with drug-resistant tuberculosis is also relevant. In a cohort study conducted at a referral center for tuberculosis in the state of São Paulo, Brazil, between 2006 and 2010,(7) the authors found that early detection of infection with a drug-resistant strain of M. tuberculosis was associated with higher cure rates in patients without comorbidities and in patients with a higher body weight at the beginning of treatment (in comparison with the cure rates observed for those without comorbidities and for those with a lower body weight at the beginning of treatment). In another study conducted in the state of São Paulo,(8) the authors evaluated the diagnosis of multidrug-resistant tuberculosis (MDR-TB) using the GenoType MTBDRplus assay, version 2.0, which detects concomitant resistance to rifampin and isoniazid. The GenoType MTBDRplus assay has many advantages over phenotypic drug susceptibility testing, including excellent accuracy, reduced time to diagnosis, and fewer false results.

Another component of Pillar 1 of the WHO End TB Strategy is tuberculosis treatment. It is well-know that subtherapeutic concentrations of first-line antituberculosis drugs may contribute to treatment failure, relapse, acquired resistance, and death.(12) In a letter to the editor included in our tuberculosis series,(13) the investigators described the serum levels of pyrazinamide, as measured by HPLC, in 46 patients. They demonstrated that, at least in their sample, the therapeutic regimen in use in Brazil provides adequate exposure to pyrazinamide.

Yet another component of Pillar 1 of the WHO End TB Strategy is the preventive treatment of persons at high risk. Within that context, this issue of the JBP features an article focusing on the aspects related to latent tuberculosis infection in patients with rheumatologic diseases, especially those using tumor necrosis factor inhibitors, addressing the definition of latent tuberculosis infection, as well as the prevalence of the disease, the mechanisms involved in its pathogenesis, the medications in use, the screening criteria, its diagnosis, and its treatment.(14)

Even after adequate treatment and a microbiological cure, the sequelae of pulmonary tuberculosis can cause persistent symptoms, impairing lung function and quality of life. In a review article, Tiberi et al.(15) described the management of severe tuberculosis cases and their sequelae, discussing the importance of pharmacological and nonpharmacological interventions in the affected patients.

Finally, Pillar 3 of the WHO End TB Strategy is "intensified research and innovation".(1) In Latin America, there is a need to identify priorities in tuberculosis research and to increase the number of publications based on local data.(2,3) In this issue of the journal, Migliori et al.(16) report the results of a systematic review that identified studies on tuberculosis, drug-resistant tuberculosis and MDR-TB, published in priority countries of Latin America (Brazil, Peru, Mexico, Colombia, and Argentina). The authors found that the level of scientific production was highest in Brazil, Mexico, and Peru. They also found that there is still a lack of publications based on local data, showing that international collaborations would be quite helpful in scaling up scientific production in Latin America. The findings of that systematic review underscore the importance of building a pan-Latin American scientific network for research on tuberculosis. A regional network would enable the creation of more opportunities for collaborative research projects. In addition, scientific networks facilitate the recruitment of patients and allow the inclusion of patients from different settings. Furthermore, collaborations have overall positive effects on the number and quality of scientific manuscripts produced. Therefore, future perspectives include further collaboration incorporating relevant topics into the research agenda. The impact of international collaborations on the scientific landscape of Latin America has demonstrated the importance of a global approach to addressing the challenges of tuberculosis control.

We believe that this tuberculosis series, dedicated to the celebration of World TB Day, highlights the relevant advances in our understanding of many topics related to tuberculosis. It is important to focus on the three pillars of the WHO End TB Strategy, which was proposed in order to achieve the goal of ending the global tuberculosis epidemic.

ACKNOWLEDGMENTS

This article is part of the scientific activities of the WHO Collaborating Centre for Tuberculosis and Lung Diseases (Tradate, ITA-80, 2017-2020-GBM/RC/LDA) and of the Global Tuberculosis Network.

REFERENCES

1. World Health Organization. Global Tuberculosis report 2018. Geneva: World Health Organization; 2018.
2. Rendon A, Fuentes Z, Torres-Duque CA, Granado MD, Victoria J, Duarte R, et al. Roadmap for tuberculosis elimination in Latin American and Caribbean countries: a strategic alliance. Eur Respir J. 2016;48(5):1282-1287. https://doi.org/10.1183/13993003.01549-2016
3. Torres-Duque CA, Fuentes Alcalá ZM, Rendón A, Migliori GB. Roadmap for Tuberculosis Elimination in Latin America and the Caribbean. Arch Bronconeumol. 2018;54(1):7-9. https://doi.org/10.1016/j.arbres.2017.07.004
4. Souza CDF, Matos TS, Santos VS, Santos FGB. Tuberculosis surveillance in an endemic area of northeastern Brazil. What do the epidemiological indicators reveal? J Bras Pneumol. 2019;45(2): e20180257.
5. Silva TM, Soares VM, Ramos MG, Santos A. Accuracy of a rapid molecular test for tuberculosis in sputum samples, bronchoalveolar lavage fluid, and tracheal aspirate obtained from patients with suspected pulmonary tuberculosis at a tertiary referral hospital. J Bras Pneumol. 2019;45(2):e20170451.
6. Malacarne J, Heirich AS, Cunha EAT, Kolte IV, Souza-Santos R, Basta PC. Performance of diagnostic tests for pulmonary tuberculosis in indigenous populations in Brazil: the contribution of Rapid Molecular Testing. J Bras Pneumol. 2019;45(2):e20180185.
7. Savioli MTG, Morrone N, Santoro I. Primary bacillary resistance in multidrug-resistant tuberculosis and predictive factors associated with cure at a referral center in São Paulo, Brazil. J Bras Pneumol. 2019;45(2):e20180075.
8. Brandao AP, Pinhata JMW, Oliveira RS, Galesi VMN, Caiaffa-Filho HH, Ferrazoli L. Speeding up the diagnosis of multidrug-resistant tuberculosis in a high-burden region with the use of a commercial line probe assay. J Bras Pneumol. 2019;45(2):e20180128.
9. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010;363(11):1005-15. https://doi.org/10.1056/NEJMoa0907847
10. World Health Organization. Tuberculosis diagnostics: Xpert MTB/RIF test rollout update 2017. Geneva: World Health Organization; 2018.
11. Silva DR, Sotgiu G, D'Ambrosio L, Pereira GR, Barbosa MS, Dias NJD, et al. Diagnostic performances of the Xpert MTB/RIF in Brazil. Respir Med. 2018;134:12-15. https://doi.org/10.1016/j.rmed.2017.11.012
12. Park JS, Lee JY, Lee YJ, Kim SJ, Cho YJ, Yoon H. Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome. Antimicrob Agents Chemother. 2016;60(1):92-8. https://doi.org/10.1128/AAC.00693-15
13. Lucena SMA, Alberio CAA, Pinto ACG, Vieira JLF. Serum pyrazinamide concentrations in patients with pulmonary tuberculosis. J Bras Pneumol. 2019;45(2):e20180254.
14. Anton C, Machado FD, Ramirez JMA, Bernardi RM, Palominos PE, Brenol CV, Mello FCQ, Silva DR. Latent Tuberculosis Infection in Patients with Rheumatic Diseases. J Bras Pneumol. 2019;45(2):e20190023.
15. Tiberi S, Torrico MM, Rahman A, Krutikov M, Visca D, Silva DR, Kunst H, Migliori GB. Managing severe tuberculosis cases and their sequelae: from intensive care to surgery and rehabilitation. J Bras Pneumol. 2019;45(2):e20180324.
16. Migliori GB, Centis R, D'Ambrosio L, Silva DR, Rendon A. International collaboration among medical societies is an effective way to boost Latin American production of articles on tuberculosis. J Bras Pneumol. 2019;45(2):e20180420.