Nazir Ismail CTB/NICD & WHO-SRL & UP The epidemiology and drivers of the TB epidemic in high burdened HIV settings Nazir Ismail CTB/NICD & WHO-SRL & UP

Overview Situational analysis TB … DR TB Ending TB Drivers Conclusion

Global Distribution of TB incidence WHO Global TB report 2015

Top 10 countries

TB is a killer

Regional TB notifcations by Age, 2014 KYE…KYR

Trends in burden and mortality in millions Source: WHO Global Report 2015

True Burden… Blue – estimates using notification data Red – measured by Survey

Population attributable fraction Among the 22 High TB Burden Countries (HBC = 80% of the estimated global TB burden) Malnutrition (27%), Smoking (23%), HIV (19%), Diabetes (6%), harmful alcohol use (13%) and Indoor air population (26%) evidence base still weak However regionalized PAF …HIV is a much more important risk factor in the Africa >50%)

HIV co-infection

HIV survival Murray, Christopher J L et al. “Global, Regional, and National Incidence and Mortality for HIV, Tuberculosis, and Malaria during 1990–2013: A Systematic Analysis for the Global Burden of Disease Study 2013.” Lancet 384.9947 (2014): 1005–1070. PMC. Web. 3 Aug. 2016.

HIV survival on ART Murray, Christopher J L et al. “Global, Regional, and National Incidence and Mortality for HIV, Tuberculosis, and Malaria during 1990–2013: A Systematic Analysis for the Global Burden of Disease Study 2013.” Lancet 384.9947 (2014): 1005–1070. PMC. Web. 3 Aug. 2016.

TB outcomes in PLHIV

mPTB trends SA 2004-12 Provincial variation Role of ART + other factors Nationwide and regional incidence of microbiologically confirmed pulmonary tuberculosis in South Africa, 2004-12: a time series analysis. Nanoo A, Izu A, Ismail NA, Ihekweazu C, Abubakar I, Mametja D, Madhi SA. Lancet Infect Dis. 2015 Sep;15(9):1066-76. doi: 10.1016/S1473-3099(15)00147-4. Epub 2015 Jun 22.

Age specific mPTB incidence Levels in 25-44 age group >2000/100 000 in EC ¼ of that in LP

2015 targets

ENDing TB 70% CDR 85% Cure rate = annual decline ~6% Observed ~1-2% Eliminate TB = incidence < 1 new case per million population per year by 2050 Lo¨nnroth, K., et al., Drivers of tuberculosis epidemics: The role of risk factors and social determinants, Social Science & Medicine (2009), doi:10.1016/j.socscimed.2009.03.041

TB in Europe Pre-antibiotic era Role of… Europe TB death rates were close to 1% per year > current high HIV prevalence areas Role of… Industrialization and improvement of socioeconomic conditions Sanatoria/Isolation Lo¨nnroth, K., et al., Drivers of tuberculosis epidemics: The role of risk factors and social determinants, Social Science & Medicine (2009), doi:10.1016/j.socscimed.2009.03.041

TB cycle (individual) Hargreeves. Am J Public Health. 2011 April ; 101(4): 654–662. doi:10.2105/AJPH.2010.199505.

Proximate vs Upstream factors Lo¨nnroth, K., et al., Drivers of tuberculosis epidemics: The role of risk factors and social determinants, Social Science & Medicine (2009), doi:10.1016/j.socscimed.2009.03.041

Risks are not uniform in space and time Time and Space Risks are not uniform in space and time

Drivers Socioeconomic gradient Poorest have the highest risk Confounded – economic development migration to urban slums Interventions – treatment is prevention? TB/ART (untreated individuals) IPT/BCG? Role of other factors age group and social network! Catalyst in space and time Targeting hotspots of transmission greatest impact

Drug Resistant TB

Global burden of DR TB

SA TB DRS 2012-14 Stable MDR rate Doubling in RMR DS Cure Rate… 2.8% overall (2012-14) 2.9% overall (2001-2) Doubling in RMR New cases: 1.8% … 3.4% ?Transmission DS Cure Rate… Vs … undetected DR TB Available at www.nicd.ac.za

Global DR – TB outcomes MDR ~ 50% success XDR ~ 20% success

Conclusion Declining burden of TB but not fast enough DR TB Role of HIV important KYE/KYR is essential Catalysts of proximal factors are low hanging fruit Upstream factors vital to accelerate decline DR TB Stable but outcomes horrific Role of DS TB Important role of transmission (catalyst)

Acknowledgments