Tuberculosis (TB) - Public Health Presentation

We presented at the Healthcare Department, City, University of London, UK (as part of the Public Health Project).

1. TUBERCULOSIS (TB) Lead: Dr Sharanya Rajan Dr Shelly Coe Amy Fornah Anoosha Anoosha Lourena Ferreira Mendes Louise Hart Marya Salhab 1 Public Health Project

2. 1 - Introduction Tuberculosis (TB) is one of the world’s deadliest disease. One third of the world’s population is infected with TB. In 2014, 9.6 million people felt sick with TB worldwide and there were 1.5 million TB deaths worldwide. Source- (CDC,2014) 2

3. 2 - Identify public health problem Tuberculosis (TB), is an infectious disease caused by the bacillus Mycobacterium tuberculosis complex: Mycobacterium tuberculosis, africanum, and bovis. Pulmonary TB or Extrapulmonary TB INFECTION — Inhalation of aerosol droplets containing M. tuberculosis with subsequent deposition in the lungs. 5-15% of those infected with M. tuberculosis will develop TB in their lifetime (HORSBURGH, 2016) 3

4. 3 - Scope/Extent of problem Tuberculosis has killed roughly 1 billion people in the past two centuries (Dheda, 2016); Estimated 10.4 million new (incidence) TB cases worldwide (WHO,2016); 0.47:0.67 female-to-male ratio of TB cases globally (WHO, 2015); Mortality fell by 22% between 2000-2015, however TB remains in the top 10 causes of death worldwide (WHO,2016); In 2015, 480 000 new cases of multidrug-resistant (MDR-TB) tuberculosis were estimated to have occurred worldwide (WHO,2016); US$ 6.6 billion spent on TB care and prevention on LMIC in 2016 (WHO,2016). 4

5. Ratio of female to male TB cases notified globally is 0.47:0.67 (WHO., 2015) I n 2015, of the 10.4 million new (incident) TB cases worldwide, 5.9 million (56%) were among men, 3.5 million (34%) among women and 1.0 million (10%) among children. People living with HIV accounted for 1.2 million (11%) of all new TB cases. Table: Worldwide results of smear positive test in men and women in 2004 (WHO, 2015) 5

6. 4 - Who is affected Added slides- From slide 6 to 11 6

7. Who Is Affected By Tuberculosis ? High Risk Groups Low Socioeconomic Population Gender and Ethnicity Immunocompromised Individuals Children Prisoners and Immigrants Old History of Tuberculosis or Past History of Inadequately treated Tuberculosis Increased exposure to T.B infected individuals 7

8. Source- (WHO,2016) 8

9. Where are the people affected by TB located ? - TB Endemic Regions/Areas 9

10. 2015 TB INCIDENCE RATES 10 (WHO, 2016)

11. ( WHO, 2016) 11

12. 5 - Socio-economic determinants The population distribution of TB reflects the distribution of these social determinants; Food insecurity and malnutrition; Poor housing and environmental conditions; Financial, geographic, and cultural barriers to health care access; Financial impact; 12 (Reid, S., 2012; Murray, E.,2013)

13. Socio-economic determinants Unemployment; TB is more prevalent in younger age-group between the ages of 18-47 years; Stigma; Improved socioeconomic conditions have been accompanied by a decline in the tuberculosis burden; Investments in low and middle-income countries fall almost US$ 2 billion short of the US$ 8.3 billion needed in 2016; this annual gap will widen in 2020 13 (WHO, 2016; Lawn,S, 2011)

14. Justification of Importance Marya Salhab Shelly Coe 14

15. Curable Disease, Global Epidemic Leading cause of infectious death worldwide, especially in developing countries. 2nd most common cause death of adults worldwide. Economic Burden Huge financial costs for the people with TB, their families, and communities Drain on society’s resources due to treatment costs, patient costs, and productivity losses The Global burden of TB is approximately $12 billion annually Marya Salhab Shelly Coe JUSTIFICATION OF IMPORTANCE 15

16. WHO Priority Eradication of TB is included in the UN’s Millennium Development Goals (MDGs) 2000-2015. The Sustainable Development Goals (SDGs) for 2030 superseded the MDGs in 2015, with SDG 3.3 focused on ending the epidemic of TB. WHO’s Stop TB Strategy, now the End TB Strategy for 2016-2035, calls for: 90% reduction in TB deaths by 2030 80% reduction in TB incidence by 2030 No TB-affected households to face catastrophic costs by 2020 The rate of decline in TB incidence to accelerate from 1.5% to 4 – 5% annually by 2020 Marya Salhab Shelly Coe JUSTIFICATION OF IMPORTANCE 16

17. TB disproportionately affects poor and vulnerable populations, ethical principles of social justice and equity must be considered in the care of patients and control of the disease to ensure balance of individual rights and liberties. (WHO, 2011) Many of the moral and ethical issues raised by infectious diseases are related to the diseases’ powerful ability to “engender fear in individuals and panic in populations.” This fear can become a principal force in clinical and public health decision-making, leading to ethical issues concerning just distribution of resources and human rights. (Smith et al, 2004) MORAL AND ETHICAL CONSIDERATIONS Marya Salhab Shelly Coe 17

18. Governments have a responsibility to provide free TB Care Patients need to be fully informed and counselled about their treatment Health care providers have an obligation to support patients to complete therapy Health care workers have obligations to provide care, but also a right to adequate protection Involuntary isolation should never be a routine component of TB programmes Research on TB is necessary and should be conducted in an ethical manner The Current one-size fits all treatment interventions (DOTS) ISSUES Marya Salhab Shelly Coe (WHO, 2014) 18

19. Updated guidance from WHO emphasized a deeper focus on ethical issues related to: Pediatric TB TB treatment in prisons TB and migration Suboptimal treatment of MDR and XDR TB Promote the use of non-stigmatizing language In 2015, the Stop TB Partnership launched United to End TB: Every Word Counts which addressed the role of language in TB stigma. First language guide for TB partners and stakeholders Supports the Global End TB Strategy 2016-2035 Stigma Contagion, defect, disability Marya Salhab Shelly Coe (Frick, 2015) 19

20. Interventions 20

21. 21

22. TYPES OF INTERVENTIONS TB interventions could include focussing on: Preventing infection Halting progression from infection to active disease Treating active disease Addressing underlying systematic TB factors Two examples of TB interventions Vaccination programmes DOTS strategy 22

23. TB Vaccinations 23

24. DOTS 24

25. TB Vaccinations: Advantages Helps reduce infection rates Also reduces risk for those infected from developing active disease High protective efficacy against serious forms of disease in children Estimated averts one case of meningeal TB in the first 5 years of life per 3435 vaccinated children and one case of miliary TB for every 9314 vaccinations Cost effectiveness of intervention - costs $40-170 per DALYS gained 25

26. TB Vaccinations: Limitations and Challenges Efficacy Restricted use Health system requirements Logistical challenges Community concerns Effect on skin tests 26

27. DOTS: Advantages Efficacy Improved completion rates Cost-effectiveness Flexibility Face to Face support Source: WHO 2004 in Focus 27

28. DOTS: Limitations and Challenges Resourcing Patient inconvenience Stigma Non-compliance Suitability for context Suitability for complex cases Not tackling root causes 28

29. Conclusion 29

30. “Countries are failing to diagnose and treat millions of people with TB. Governments need to get their heads out of the sand and realize that TB is not a disease consigned to the 1800s; we see and treat TB in our clinics every day, and it's a deadly threat to all of us.” The governments are mainly failing because of shortage of funding. - WHO TB control leader 30

31. References Commission on Social Determinants of Health. Closing the gap in a generation: health equity through action on the social determinants of health. Geneva, Switzerland: WHO, 2008. http://whqlibdoc.who.int/publications/2008/9789241563703_ eng.pdf Accessed October 20, 2016 FRICK, M.W., 2015. Ethical Considerations in TB. San Antonio, TX: Heartland National TB Center. HORSBURGH, R.C., Sep 29, 2016, 2016-last update, Epidemiology of tuberculosis [Homepage of UpToDate], [Online]. Available: www.uptodate.com . Lönnroth K, Jaramillo E, Williams B, Dye C, Raviglione M. Tuberculosis: the role of risk factors and social determinants. In: Blas E, Sivasankara Kurup A, eds. Equity, social determinants and public health programmes. Geneva, Switzerland: WHO, 2010: pp 219–241. SMITH, C.B., BATTIN, M.P., JACOBSON, J.A., FRANCIS, L.P., BOTKIN, J.R., ASPLUND, E.P., DOMEK, G.J. and HAWKINS, B., 2004. Are there Characteristics of Infectious Diseases that Raise Special Ethical Issues? Developing World Bioethics, 4 (1), pp. 1-16. STOP TB PARTNERSHIP, November 4, 2015, 2015-last update, TB language guide: ‘United to End TB: Every Word Counts’ [Homepage of TB Online, Global Tuberculosis Community Advisory Board], [Online]. Available: http://www.tbonline.info/posts/2015/11/4/tb-language-guide-united-end-tb-every-word-counts/ Accessed [11/06, 2016]. 31

32. References WHO, 2016-last update, Trade, foreign policy, diplomacy and health: Tuberculosis control [Homepage of WHO], [Online]. Available: http://www.who.int/trade/distance_learning/gpgh/gpgh3/en/index7.html Accessed [11/11, 2016]. WHO, 2016-last update, Tuberculosis (TB): Addressing the needs of vulnerable populations [Homepage of WHO], [Online]. Available: http://www.who.int/tb/areas-of-work/population-groups/en/ Accessed [11/06, 2016]. WHO, 2016-last update, Tuberculosis (TB): Childhood TB [Homepage of WHO], [Online]. Available: http://www.who.int/tb/areas-of-work/children/en/ Accessed [11/06, 2016]. WHO, March 22, 2016, 2016-last update, WHO calls on countries and partners to "Unite to End Tuberculosis" [Homepage of WHO], [Online]. Available: http://who.int/mediacentre/news/statements/2016/tb-day/en/ [11/06, 2016]. WHO, 2014. ETHICAL ISSUES IN TUBERCULOSIS PREVENTION, CARE AND CONTROL. WHO’s Department of Knowledge, Ethics, and Research (KER) and the Global TB Programme (GTB). WHO, 2011. ETHICAL ISSUES IN TUBERCULOSIS PREVENTION, CARE AND CONTROL. WHO. WHO, 2010. Guidance on ethics of tuberculosis prevention, care and control. Switzerland: WHO. 32

33. REFERENCES Amo-Adjei, J., Kumi-Kyereme, A., Fosuah-Amo, H. and Awusabo-Asare, K. (2014) ' The politics of tuberculosis and HIV service integration in Ghana. ', Social Science and Medicine, 117 . Arnold, A. (2016) ' XDR-TB transmission in London: Case management and contact tracing investigation assisted by early whole genome sequencing ', The Journal of infection, 73 (3), . Bell, C., Duncan, G., Eang, R. and Saini, B. (2015) ' Stakeholder Perceptions of a Pharmacy-Initiated Tuberculosis Referral Program in Cambodia, 2005-2012', Asia-Pacific Journal of Public Health, 27 (2), . Berzkalns, A., Bates, J., Ye, W., Mukasa, L., France, A., Patil, N. and Yang, Z. (2014) 'The road to tuberculosis (Mycobacterium tuberculosis) elimination in Arkansas; a re-examination of risk groups', Public Library of Science, 9 . Brimnes, N. (1982) ' BCG vaccination and WHO's global strategy for tuberculosis control 1948–1983 ', Social science & medicine, 67 (5), pp.863. Chiang, C., Van Weezenbeek, C. and Mori, T. (2013) ' Challenges to the global control of tuberculosis ', Respirology, 18 (4), . D'Ambrosio, L., Centis, R., Sotgiu, G., Pontali, E., Spanevello, A. and Migliori, G. (2015) 'New anti-tuberculosis drugs and regimens: 2015 update', ERS Monograph, . Dheda, K. (2016) ' Tuberculosis ', The Lancet, 387 (10024), pp.1211. Elmi, O., Hasan, H., Abdullah, S., Mat Jeab, M., Bin Alwi, Z. and Naing, N. (2015) ' Multidrug-resistant tuberculosis and risk factors associated with its development: a retrospective study', Journal Of Infection In Developing Countries, 9 (10), . 33

34. REFERENCES Frieden, T. (2002) 'Can tuberculosis be controlled?', International Journal of Epidemiology, 31 (5), pp.894. Holloway, K., Staub, K., Ruhli, F. and Henneberg, M. (2014) 'Lessons from history of socioeconomic improvements: a new approach to treating multi-drug-resistant tuberculosis', Journal of biosocial science, 46 (5), . Interrante, J., Haddad, M., Kim, L. and Gandhi, N. (2015) 'Exogenous Reinfection as a Cause of Late Recurrent Tuberculosis in the United States', Annals Of The American Thoracic Society, 12 (11), . Lawn, S. and Zumla, A. (2011) 'Tuberculosis', The Lancet, 378 . Lobato, M., Sun, S., Moonan, P., Weis, S., Saiman, L., Reichard, A. and Feja, K. (2008) ' Underuse of Effective Measures to Prevent and Manage Pediatric Tuberculosis in the United States ', Archives of Pediatrics & Adolescent Medicine, 162 (5), . Mears, J., Abubakar, I., Crisp, D., Maguire, H. and Innes, J. (2014) 'Prospective evaluation of a complex public health intervention: lessons from an initial and follow-up cross-sectional survey of the tuberculosis strain typing service in England', BMC public health, 14 . Murray, E., Bond, V., Marais, B., Godfrey-Faussett, P., Ayles, H. and Beyers, N. (2013) ' High levels of vulnerability and anticipated stigma reduce the impetus for tuberculosis diagnosis in Cape Town, South Africa ', Health Policy and Planning, 28 (4), pp.410. Olfatifar, M., Karami, M., Hosseini, S. and Parvin, M. (2016) 'Clustering of pulmonary tuberculosis in Hamadan province, west of Iran: A population based cross sectional study (2005-2013)', Journal of Research in Health Sciences, 16 (3), . Onozuka, D. and Hagihara, A. (2015) ' The association of extreme temperatures and the incidence of tuberculosis in Japan', International Journal of Biometeorology, 59 (8), . Reid, S., Topp, S. and Turnbull, E. (2012) ' Tuberculosis and HIV Control in Sub-Saharan African Prisons: "Thinking Outside the Prison Cell"', The Journal of Infectious Diseases, 205 (2), . Simon, G. (2016) 'Impacts of neglected tropical disease on incidence and progression of HIV/AIDS, tuberculosis', International Journal of Infectious Diseases, 42 . White, C. and Veronica, L. (2002) ' Management of tuberculosis in a British inner ‐ city population ', Journal of public health medicine, 24 (1), . 34

35. REFERENCES White, P. and Abubakar, I. (2016) 'Improving control of tuberculosis in low-burden countries: Insights from mathematical modeling', Frontiers in Microbiology, 394 . Yasin, Y. (2015) ' Infection of the Invisible: Impressions of a Tuberculosis Intervention Program for Migrants in Istanbul ', Journal of immigrant and minority health, 17 (5), . Dye C, Lönnroth K, Jaramillo E, et al. Trends in tuberculosis incidence and their determinants in 134 countries. Bull World Health Organ 2009; 87:683. 27. Lienhardt C. From exposure to disease: the role of environmental factors in susceptibility to and development of tuberculosis. Epidemiol Rev 2001; 23:288 35

36. Not Harvard formatted • Case study of Hoa, Nguyen Binh et al. "National Survey Of Tuberculosis Prevalence In Viet Nam". Bulletin of the World Health Organization 88.4 (2010): 273-280. Web. • Dye C. Global epidemiology of tuberculosis. Lancet. 2006;367:938–40.[PubMed] • 9. Diwan VK, Thorson A. Sex, gender, and tuberculosis. Lancet. 1999;353:1000–1. [PubMed] • REF: World Health Organization. Use of high burden country lists for TB by WHO in the post-2015 era: Summary. Available at: http://www.who.int/tb/publications/global_report/high_tb_burdencountrylists2016-2020summary.pdf?ua=1 (Accessed on September 13, 2016). • Global Tuberculosis Report 2014. Geneva, World Health Organization, 2014. Copyright © 2014 World Health Organization. Available at: http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf?ua=1. (Accessed on January 12, 2015). • Zaman, K. "Tuberculosis: A Global Health Problem". J Health Popul Nutr 28.2 (2010): n. pag. Web 36

37. Slides to be deleted 37

38. Tuberculosis GLOBAL EPIDEMIC 38

39. Tuberculosis (TB), is an infectious disease caused by the bacillus Mycobacterium tuberculosis complex: Mycobacterium tuberculosis, africanum, and bovis. Typically affects the lungs (Pulmonary TB), but can affect other sites (Extrapulmonary TB) INFECTION — Inhalation of aerosol droplets containing M. tuberculosis with subsequent deposition in the lungs leads to one of four possible outcomes: ●Immediate clearance of the organism ●Primary disease: immediate onset of active disease ●Latent infection ●Reactivation disease: onset of active disease many years following a period of latent infection 5-15% of those infected with M. tuberculosis will develop TB in their lifetime, though higher if infected with HIV. 39

40. Disease 2nd most common cause of death in adults worldwide 40

41. Current treatment recommendations New cases drug-susceptible TB: 6 month regimen of four first-line drugs: Isoniazid, refampicin, ethambutol and pyrazinamide Treatment for muliti-drug resistant (MDR-TB) and refampicin-resistant (RR-TB) is 9-12 months. BCG vaccine used to prevent severe forms in children. 41

42. Epidemiology Scope and Extent of Burden of Disease 42

43. SCOPE Tuberculosis has killed roughly 1 billion people in the past two centuries estimated 10.4 million new (incident) TB cases worldwide Mortality fell by 22% between 2000-2015, TB remains in the top ten causes of death worldwide In 2015, 580 000 new cases of multidrug-resistant (MDR-TB) tuberculosis were estimated to have occurred worldwide Total number of people infected from TB: 43

44. Ratio of female to male TB cases notified globally is 0.47:0.67 (WHO., 2015) I n 2015, of the 10.4 million new (incident) TB cases worldwide, 5.9 million (56%) were among men, 3.5 million (34%) among women and 1.0 million (10%) among children. People living with HIV accounted for 1.2 million (11%) of all new TB cases. Table: Worldwide results of smear positive test in men and women in 2004 (WHO, 2015) 44

45. The future for TB The WHO and other health organisations have been working together to eradicate TB. The MDGs (2000–2015) have now been superseded by the Sustainable Development Goals (SDGs), which have an end date of 2030. The Sustainable Development Goals (SDGs) for 2030 were adopted by the United Nations, all member states, in 2015. Similarly, WHO’s Stop TB Strategy has been replaced by the End TB Strategy, which covers the period 2016–2035, and calls for a 90% reduction in TB deaths, and an 80% reduction in the TB incidence rate by 2030, compared with 2015. One of the targets is to end the global TB epidemic. SDG 3 Ensure healthy lives and promote well-being for all at all ages (3.3 By 2030,end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.) The rate of decline in TB incidence remained at only 1.5% from 2014 to 2015. This needs to accelerate to a 4–5% annual decline by 2020 to reach the first milestones of the End TB Strategy. 2020 milestones of the End TB Strategy are a 35% reduction in the absolute number of TB deaths and a 20% reduction in the TB incidence rate, compared with levels in 2015; and that no TB-affected households face catastrophic costs. (WHO, 2016) 45

46. SOCIO-ECONIMIC improved socioeconomic conditions have been accompanied by a decline in the tuberculosis burden in industrialized countries over the past century Food insecurity and malnutrition, poor housing and environmental conditions, and financial, geographic, and cultural barriers to health care access , including difficulties in transport to health facilities . In turn, the population distribution of TB reflects the distribution of these social determinants, which influence the 4 stages of TB pathogenesis: exposure to infection, progression to disease, late or inappropriate diagnosis and treatment, and poor treatment adherence and success . 46

47. SOCIO ECONOMIC GAP in reported cases and incident cases. In 2015, 6.1 million new TB cases were notified to national authorities and reported to WHO. However, globally there was a 4.3 million gap between incident and notified cases, with India, Indonesia and Nigeria accounting for almost half of this gap. GAP in MDR-TB detection and treatment. Of the 580K eligible for treatment, only 125K (20%) were enrolled. Investments in low and middle-income countries fall almost US$ 2 billion short of the US$ 8.3 billion needed in 2016. This annual gap will widen to US$ 6 billion in 2020 if current funding levels do not increase. Overall health financing needs improvement, since government expenditures on health are less than the WHO benchmark of 6% of the GDP in 150 countries, and OOP (out of pocket) expenditures exceeded 45% in 46 countries including 11 of the high TB burden countries. Research underfunded. 47

48. Interventions 48

49. DOT (direct observation of therapy) Strategy 49

50. 3 important interventions under the umbrella of DOT strategy: Direct observation of therapy (DOT) Effective drug supply (including BCG vaccines, ANTI-TB drugs and drugs for MDR-TB. Rapid Molecular testing (for accurate diagnosis) 50

51. Tuberculosis: scope/extent Modelling studies suggest that tuberculosis elimination is probably only achievable by 2050 if therapeutic and diagnostic interventions (early case detection and high cure rates) are combined with preventive strategies (vaccines and treatment of the latent tuberculosis reservoir in 2 billion people in high-burden and low-burden settings) Tuberculosis remains a disease of poverty, associated with overcrowding and undernutrition; HIV is the most potent of risk factors for TB; Heavy alcohol consumption, smoking, diabetes and imunosupressive drugs have long been associated with high risk of TB; LMIC relies heavily on sputum smear microscopy and chest radiology; unsatisfactory and unavailable at patients’ first point of contact with the health system; 51

52. Tuberculosis: scope/extent The only licensed vaccine, BCG, was first given to a human infant in 1921; it has done little to contain the current tuberculosis pandemic; the incidence of TB has been shown to be inversely related to per capita gross domestic product; Health system strengthening is indispensable for successful TB programmes and all health-care providers must be engaged; Human errors in prescribing inadequate regimens, inconsistent dosing and poor quality of drugs, resulting in the emergence of drug resistance and treatment failure 52

53. Tuberculosis: scope/extent Low confidence in patient confidentiality and anticipated HIV-related stigma act as direct deterrents to TB diagnosis and treatment; TB control policy relies on passive case finding (PCF)—the voluntary presentation of individuals to local health services; Treatment of MDR-TB infections is much more complicated and complex, less effective, leads to high toxicity, and is very costly compared with the treatment of patients infected with susceptible TB strains ; 53

54. scope/extent ?urbanization and an increase in the incidences of tuberculosis. Directly observed treatment of TB rapidly reduces mortality; death rates in DOTS programmes throughout the world are generally less than 5% community-based public health interventions targeting vulnerable populations when dealing with an infectious disease like TB. 54

55. TB PROGRAMS FINANCING US$ 6.6 billion was available for TB care and prevention in low and middle-income countries in 2016, of which 84% was from domestic sources; national TB programmes (NTPs) in low-income countries continue to rely on international donors for almost 90% of their financing; using national social protection platforms is a priority TB research and development remains severely underfunded Considerable inequalities among countries in access to TB diagnosis and treatment that need to be addressed The BRICS countries (Brazil, the Russian Federation, India, China and South Africa), which collectively account for about 50% of the world’s TB cases, rely mostly or exclusively (the exception is India) on domestic funding. Four diagnostic tests were reviewed and recommended by WHO: the loop-mediated isothermal ampli- fication test for TB (known as TB-LAMP), two line probe assays (LPAs) for the detection of resistance to the firstline anti-TB drugs isoniazid and rifampicin, and an LPA for the detection of resistance to second-line anti-TB drugs. 55

56. Mortality and incidence rates •World Health Assembly resolution recognized TB as a major global health problem in 1991. •Treatment developed by the WHO in the mid-1990: the five-element Directly Observed Therapy, Short-course (DOTS) strategy: 8 Million deaths averted. •Global decline. Four dimensions of tuberculosis (TB) elimination in low-incidence countries. 56

57. 57

58. Designated as a prior area by the WHO Spreads through air so hard to stop Affects lungs but can also spread to other areas such as brain Symptoms depend on where in the body the TB bacteria is growing: difficult to diagnose Difficult treatment People with immunodeficiency (HIV, drug resistance…) more likely to not survive treatments. TB is still an important cause of death in poor countries (ex: Africa). TB needs to be treated carefully because there is a risk of relapse. Zaman, K. "Tuberculosis: A Global Health Problem". J Health Popul Nutr 28.2 (2010): n. pag. Web. 58

59. The curable disease that continues to kill • Leading cause of morbidity and mortality in developing countries: 86% of all cases in Africa and Asia. • Declining trend was observed in most developed countries, this was not evident in many developing countries. • In developing countries, about 7% of all deaths are attributed to TB which is the most common cause of death from a single source of infection among adults. It is the first infectious disease declared by the World Health Organization (WHO) as a global health emergency. • 10.4 million new TB cases worldwide in 2015. • 60% of these cases in: India, Africa, Nigeria, Pakistan. • 1.8 million people died in 2015 • Global tb death fallen by 22% since 2000. • However, TB is still in top 10 causes of death globally in 2015. (WHO) “Countries are failing to diagnose and treat millions of people with TB. Governments need to get their heads out of the sand and realize that TB is not a disease consigned to the 1800s; we see and treat TB in our clinics every day, and it's a deadly threat to all of us.” The governments are mainly failing because of shortage of funding. - WHO TB control leader 59

60. Fig: Estimated new tuberculosis cases (all forms) per 100,000 population per year. (WHO Global tuberculosis Report., 2014) Global Tuberculosis Report 2014. Geneva, World Health Organization, 2014. Copyright © 2014 World Health Organization. Available at: http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf?ua=1. (Accessed on January 12, 2015). 60

61. 95 percent of TB cases occur in developing countries. 1 in 14 new TB cases occur in individuals who are infected with HIV (6% of all TB cases); 78 percent of these cases occur in Africa. 480,000 cases of multidrug-resistant (MDR)-TB also occur annually. Socioeconomic development and access and quality of health services appear to be important TB control measure. Risk factors for TB: host immunity (eg: immunologic defects that lead to increased susceptibility to infection), environmental exposure to infection (eg: risk of exposure to a case of infectious TB) Fig: Countries with high burden of tuberculosis (WHO., 2015) REF: World Health Organization. Use of high burden country lists for TB by WHO in the post-2015 era: Summary. Available at: http://www.who.int/tb/publications/global_report/high_tb_burdencountrylists2016-2020summary.pdf?ua=1 (Accessed on September 13, 2016). 61

62. TB in men, women and age groups. Case study of Hoa, Nguyen Binh et al. "National Survey Of Tuberculosis Prevalence In Viet Nam". Bulletin of the World Health Organization 88.4 (2010): 273-280. Web Table: Worldwide results of smear positive test in men and women in 2004 (WHO., 2015) Ratio of female to male TB cases notified globally is 0.47:0.67 (WHO., 2015) 62

63. Political Commitment Provision of adequate resources (financial, human and infrastructure) Political authorities participation in advocacy of TB laws and policies promulgations and social protection interventions. 63

64. National notification and vital registration systems (with standard coding of causes of death) of high coverage and quality are needed in all countries. BCG vaccination should be provided as part of national childhood immunization programs according to a country’s TB epidemiology. Funding to accelerate the production of new Vaccines for prevention in adults needed! Rapid molecular tests should be funded for diagnosis in all countries, since more accurate than the standard sputum smears, and more rapid culture. 64

65. Case Detection Active case findings Training pharmacists and traditional healers Training, deployment and supervision of 2 sputum fixers 65

66. Standardized Treatment First and second line of anti-TB drugs Supervised treatment (direct observation of therapy) Improving access to treatment Preventive therapy in people with HIV infection Preventive therapy of people in contact with TB patients 66

67. Effective Drug Supply Proper distribution of drugs among patients Free of charge BCG Immunization 67

68. Tuberculosis: scope/extent Widespread emergence of extensively drug-resistant (XDR) TB and resistance beyond XDR tuberculosis; Global diagnostic capacity is low, and the case detection rate is suboptimum (64% in 2013); Underdiagnoses is another issue. Access to TB preventive treatment needs to be expanded. Increasing age, more extensive disease, and HIV co-infection are associated with increased mortality; Preventive therapy for people at high risk is an important component of the strategies to eliminate TB outlined by WHO in their post-2015 strategy. Communitybased, low-cost, sensitive, user-friendly, high-throughput, and same-day point-of-care screening test for TB is clearly needed; 68

69. CONCLUSION “Countries are failing to diagnose and treat millions of people with TB. Governments need to get their heads out of the sand and realize that TB is not a disease consigned to the 1800s; we see and treat TB in our clinics every day, and it's a deadly threat to all of us.” The governments are mainly failing because of shortage of funding. - WHO TB control leader 69

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96. 96

97. 97 ABUBAKAR, I., PIMPIN, L., ARITI, C., BEYNON, R., MANGTANI, P., STERNE, J.A., FINE, P.E., SMITH, P.G., LIPMAN, M., ELLIMAN, D., WATSON, J.M., DRUMRIGHT, L.N., WHITING, P.F., VYNNYCKY, E. and RODRIGUES, L.C., 2013. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guerin vaccination against tuberculosis. Health technology assessment (Winchester, England), 17 (37), pp. 1-372, v-vi. AMO-ADJEI, J., KUMI-KYEREME, A., AMO, H.F. and AWUSABO-ASARE, K., 2014. The politics of tuberculosis and HIV service integration in Ghana. Social science & medicine, 117 , pp. 42-49. ARNOLD, A., WITNEY, A.A., VERGNANO, S., ROCHE, A., COSGROVE, C.A., HOUSTON, A., GOULD, K.A., HINDS, J., RILEY, P. and MACALLAN, D., 2016. XDR-TB transmission in London: Case management and contact tracing investigation assisted by early whole genome sequencing. Journal of Infection, 73 (3), pp. 210-218. ASSEMBLY, U.G., 2015. Transforming our world: the 2030 Agenda for Sustainable Development. New York: United Nations. BALTUSSEN, R., FLOYD, K. and DYE, C., 2005. Cost effectiveness analysis of strategies for tuberculosis control in developing countries. BMJ (Clinical research ed.), 331 (7529), pp. 1364. BELL, C.A., DUNCAN, G.J., EANG, R. and SAINI, B., 2015. Stakeholder perceptions of a pharmacy-initiated tuberculosis referral program in Cambodia, 2005-2012. Asia-Pacific journal of public health, 27 (2), pp. NP2570-7. BERZKALNS, A., BATES, J., YE, W., MUKASA, L., FRANCE, A.M., PATIL, N. and YANG, Z., 2014. The road to tuberculosis (Mycobacterium tuberculosis) elimination in Arkansas; a re-examination of risk groups. PloS one, 9 (3), pp. e90664. BRIMNES, N., 2008. BCG vaccination and WHO's global strategy for tuberculosis control 1948–1983. Social science & medicine, 67 (5), pp. 863-873. CHIANG, C., VAN WEEZENBEEK, C., MORI, T. and ENARSON, D.A., 2013. Challenges to the global control of tuberculosis. Respirology , 18 (4), pp. 596-604.

98. 98 COLEMAN, C.H., JARAMILLO, E., REIS, A. and SELGELID, M., 2010. Guidance on ethics of tuberculosis prevention, care and control. Guidance on ethics of tuberculosis prevention, care and control, . COMMISSION ON SOCIAL DETERMINANTS OF HEALTH, 2008. Closing the gap in a generation: health equity through action on the social determinants of health: final report of the commission on social determinants of health. COURTWRIGHT, A. and TURNER, A.N., 2010. Tuberculosis and stigmatization: pathways and interventions. Public health reports, , pp. 34-42. D'AMBROSIO, L., CENTIS, R., SOTGIU, G., PONTALI, E., SPANEVELLO, A. and MIGLIORI, G.B., 2015. New anti-tuberculosis drugs and regimens: 2015 update. ERJ Open Research, 1 (1), pp. 00010-2015. DHEDA, K., BARRY III, C. and MAARTENS, G., 2016. Tuberculosis ( vol 387, pg 1211, 2016). Lancet, 387 (10024), pp. 1162-1162. DIWAN, V.K. and THORSON, A., 1999. Sex, gender, and tuberculosis. The Lancet, 353 (9157), pp. 1000- 1001. DYE, C., LÖNNROTH, K., JARAMILLO, E., WILLIAMS, B. and RAVIGLIONE, M., 2009. Trends in tuberculosis incidence and their determinants in 134 countries. Bulletin of the World Health Organization, 87 (9), pp. 683-691. DYE, C., 2006. Global epidemiology of tuberculosis. The Lancet, 367 (9514), pp. 938-940. ELMI, O.S., HASAN, H., ABDULLAH, S., JEAB, M.Z.M., ALWI, Z.B. and NAING, N.N., 2015. Multidrug- resistant tuberculosis and risk factors associated with its development: a retrospective study. The Journal of Infection in Developing Countries, 9 (10), pp. 1076-1085. FOCHSEN, G., DESHPANDE, K., RINGSBERG, K.C. and THORSON, A., 2009. Conflicting accountabilities: Doctor's dilemma in TB control in rural India. Health policy, 89 (2), pp. 160-167. FRICK, M.W., 2015. Ethical Considerations in TB. San Antonio, TX: Heartland National TB Center . FRIEDEN, T.R., 2002. Can tuberculosis be controlled? International journal of epidemiology, 31 (5), pp. 894-899. GYAWALI, S., RATHORE, D.S., SHANKAR, P.R. and KUMAR, K.V., 2013. Strategies and challenges for safe injection practice in developing countries. Journal of pharmacology & pharmacotherapeutics, 4 (1), pp. 8- 12.

99. 99 HOA, N.B., SY, D.N., NHUNG, N.V., TIEMERSMA, E.W., BORGDORFF, M.W. and COBELENS, F.G., 2010. National survey of tuberculosis prevalence in Viet Nam. Bulletin of the World Health Organization, 88 (4), pp. 273-280. HOLLOWAY, K., STAUB, K., RÜHLI, F. and HENNEBERG, M., 2014. Lessons from history of socioeconomic improvements: a new approach to treating multi-drug-resistant tuberculosis. Journal of Biosocial Science, 46 (05), pp. 600-620. HORSBURGH, R.C., Sep 29, 2016, 2016-last update, Epidemiology of tuberculosis [Homepage of UpToDate], [Online]. INTERRANTE, J.D., HADDAD, M.B., KIM, L. and GANDHI, N.R., 2015. Exogenous Reinfection as a Cause of Late Recurrent Tuberculosis in the United States. Annals of the American Thoracic Society, 12 (11), pp. 1619-1626. JAMISON, D.T., BREMAN, J.G., MEASHAM, A.R., ALLEYNE, G., CLAESON, M., EVANS, D.B., JHA, P., MILLS, A. and MUSGROVE, P., 2006. Disease control priorities in developing countries. World Bank Publications. LAWN, S.D. and ZUMLA, A.I., 2011. Tuberculosis. Lancet (London, England), 378 (9785), pp. 57. LIENHARDT12, C., 2001. From exposure to disease: the role of environmental factors in susceptibility to and development of tuberculosis. Epidemiol Rev, 23 (2),. LOBATO, M.N., SUN, S.J., MOONAN, P.K., WEIS, S.E., SAIMAN, L., REICHARD, A.A. and FEJA, K., 2008. Underuse of effective measures to prevent and manage pediatric tuberculosis in the United States. Archives of Pediatrics & Adolescent Medicine, 162 (5), pp. 426-431. LÖNNROTH, K., JARAMILLO, E., WILLIAMS, B., DYE, C. and RAVIGLIONE, M., 2010. Tuberculosis: the role of risk factors and social determinants. Equity, social determinants and public health programmes, 219 . MANGTANI, P., ABUBAKAR, I., ARITI, C., BEYNON, R., PIMPIN, L., FINE, P.E., RODRIGUES, L.C., SMITH, P.G., LIPMAN, M., WHITING, P.F. and STERNE, J.A., 2014. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 58 (4), pp. 470-480. MARAIS, B.J. and ZUMLA, A., 2013. History of tuberculosis and drug resistance. N Engl J Med, 368 (1), pp. 88.

100. 100 MEARS, J., ABUBAKAR, I., CRISP, D., MAGUIRE, H., INNES, J.A., LILLEY, M., LORD, J., COHEN, T., BORGDORFF, M.W. and VYNNYCKY, E., 2014. Prospective evaluation of a complex public health intervention: lessons from an initial and follow-up cross-sectional survey of the tuberculosis strain typing service in England. BMC public health, 14 (1), pp. 1. MURRAY, E.J., BOND, V.A., MARAIS, B.J., GODFREY-FAUSSETT, P., AYLES, H.M. and BEYERS, N., 2013. High levels of vulnerability and anticipated stigma reduce the impetus for tuberculosis diagnosis in Cape Town, South Africa. Health policy and planning, 28 (4), pp. 410-418. OLFATIFAR, M., KARAMI, M., HOSSEINI, S.M. and PARVIN, M., 2016. Clustering of Pulmonary Tuberculosis in Hamadan Province, western Iran: A Population Based Cross Sectional Study (2005-2013). Journal of Research in Health Sciences, 16 (3), pp. 166-169. ONOZUKA, D. and HAGIHARA, A., 2015. The association of extreme temperatures and the incidence of tuberculosis in Japan. International journal of biometeorology, 59 (8), pp. 1107-1114. OTU, A.A., 2013. Is the directly observed therapy short course (DOTS) an effective strategy for tuberculosis control in a developing country? Asian Pacific Journal of Tropical Disease, 3 (3), pp. 227-231. REID, S.E., TOPP, S.M., TURNBULL, E.R., HATWIINDA, S., HARRIS, J.B., MAGGARD, K.R., ROBERTS, S.T., KRÜÜNER, A., MORSE, J.C., KAPATA, N. AND CHISELA, C., 2012. Tuberculosis and HIV control in sub- Saharan African prisons: “thinking outside the prison cell”. Journal of Infectious Diseases , 205 ( suppl 2), pp. S265-S273. RODRIGUES, L.C., DIWAN, V.K. and WHEELER, J.G., 1993. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. International journal of epidemiology, 22 (6), pp. 1154-1158. ROY, A., EISENHUT, M., HARRIS, R.J., RODRIGUES, L.C., SRIDHAR, S., HABERMANN, S., SNELL, L., MANGTANI, P., ADETIFA, I., LALVANI, A. and ABUBAKAR, I., 2014. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ (Clinical research ed.), 349 , pp. g4643. SELGELID, M. and REICHMAN, L., 2011. Ethical issues in tuberculosis diagnosis and treatment. The International Journal of Tuberculosis and Lung Disease, 15 (Supplement 2), pp. S9-S13.

101. 101 SIMON, G.G., 2016. Impacts of neglected tropical disease on incidence and progression of HIV/AIDS, tuberculosis, and malaria: scientific links. International Journal of Infectious Diseases, 42 , pp. 54-57. SMITH, C.B., BATTIN, M.P., JACOBSON, J.A., FRANCIS, L.P., BOTKIN, J.R., ASPLUND, E.P., DOMEK, G.J. and HAWKINS, B., 2004. Are there Characteristics of Infectious Diseases that Raise Special Ethical Issues? Developing World Bioethics, 4 (1), pp. 1-16. STOP TB PARTNERSHIP, November 4, 2015, 2015-last update, TB language guide: ‘United to End TB: Every Word Counts’ [Homepage of TB Online, Global Tuberculosis Community Advisory Board], [Online]. Available: http:// www.tbonline.info /posts/2015/11/4/ tb -language-guide-united-end- tb -every- word-counts/ [11/06, 2016]. TRUNZ, B.B., FINE, P. and DYE, C., 2006. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. The Lancet, 367 (9517), pp. 1173-1180. UPLEKAR, M., WEIL, D., LONNROTH, K., JARAMILLO, E., LIENHARDT, C., DIAS, H.M., FALZON, D., FLOYD, K., GARGIONI, G., GETAHUN, H., GILPIN, C., GLAZIOU, P., GRZEMSKA, M., MIRZAYEV, F., NAKATANI, H., RAVIGLIONE, M. and WHO'S GLOBAL TB PROGRAMME, 2015. WHO's new end TB strategy. Lancet (London, England), 385 (9979), pp. 1799-1801. WHITE, P.J. and ABUBAKAR, I., 2016. Improving control of tuberculosis in low-burden countries: insights from mathematical modeling . Frontiers in microbiology, 7 . WHITE, V.L., PALIWALLA, M., STEVES, C.J., JADHAV, D. and MOORE-GILLON, J., 2002. Management of tuberculosis in a British inner-city population. Journal of public health medicine, 24 (1), pp. 49-52. WHO, 2016-last update, Global Tuberculosis Report 2016 [Homepage of WHO], [Online]. Available: http:// www.who.int / tb /publications/ global_report / en / 2016]. WHO, 2016-last update, Trade, foreign policy, diplomacy and health: Tuberculosis control [Homepage of WHO], [Online]. Available: http:// www.who.int /trade/ distance_learning / gpgh /gpgh3/ en /index7.html [11/11, 2016]. WHO, 2016-last update, Tuberculosis (TB): Addressing the needs of vulnerable populations [Homepage of WHO], [Online]. Available: http:// www.who.int / tb /areas-of-work/population-groups/ en / [11/06, 2016].

102. 102 WHO, 2016-last update, Tuberculosis (TB): Childhood TB [Homepage of WHO], [Online]. Available: http:// www.who.int / tb /areas-of-work/children/ en / [11/06, 2016]. WHO, March 22, 2016, 2016-last update, WHO calls on countries and partners to "Unite to End Tuberculosis" [Homepage of WHO], [Online]. Available: http:// who.int / mediacentre /news/statements/2016/ tb -day/ en / [11/06, 2016]. WHO, 2015-last update, Use of high burden country lists for TB by WHO in the post-2015 era [Homepage of World Health Organisation], [Online]. Available: http:// who.int / tb /publications/ global_report /high_tb_burdencountrylists2016-2020summary.pdf?ua=1 [11/13, 2016]. WHO, 2014-last update, Ethical issues in Tuberculosis prevention, care and control [Homepage of World Health Organisation], [Online]. Available: http:// www.who.int / tb /publications/ethics_in_tb_factsheet_28jan11rev.pdf [11/6, 2016]. WORLD HEALTH ORGANIZATION, 2015. The End TB Strategy.Geneva , Switzerland: WHO, 2015, . WORLD HEALTH ORGANIZATION, 2006. Global tuberculosis control: surveillance, planning, financing: WHO report 2006. WORLD HEALTH ORGANIZATION, 2004. BCG vaccine. WHO position paper. Releve epidemiologique hebdomadaire , 79 (4), pp. 27-38. YASIN, Y., BIEHL, K. and EROL, M., 2015. Infection of the Invisible: Impressions of a Tuberculosis Intervention Program for Migrants in Istanbul. Journal of Immigrant and Minority Health, 17 (5), pp. 1481-1486. ZAMAN, K., 2010. Tuberculosis: a global health problem. Journal of health, population and nutrition, , pp. 111-113.