End TB strategy target setting Philippe Glaziou Manila, December 2014

Outline Rationale for global projections post-2015 TB burden assessment Country targets Short-term (3-5 years) Long-term (≥10 years)

Decline in TB burden in England and Wales TB mortality TB incidence -3%/year

CFR in England and Wales Global CFR : 1 CFR in England and Wales Global CFR : 1.5 million deaths / 9 million incident Chemotherapy introduced Global CFR in 2013

Slow decline in global incidence, faster decline in mortality Mortality (including HIV) Falling 2% per year (2007-2013) Falling 4.7% per year (2007-2013)

Why is global TB incidence declining so slowly?

Average lifetime risk of disease 5- 15%* World 7 billion Disease ≈9 million/yr Infected ≈2.3 billion *Am J Epidemiol Vol. 152, No. 3, 2000

Tools required for mitigating infection Mass Screening and Treatment may stop transmission but not TB reactivation Mass Prophylactic Treatment IPT prevents 70% of reactivation in HIV-neg Safety on a mass scale? (4-7/100,000 fatal hepatitis) Millard PS et al. West J Med. 1996 Jun;164(6):486-91. Mass Post-Exposure Vaccination

Business as usual -2%/year Global TB incidence rate

Optimize use of current tools, universal access, social protection -2%/year Business as usual -10%/year -5%/year

R&D pipelines No point of care test yet 2 new drugs, little epi impact anticipated 15 vaccines in development New vaccine not likely until 2024 (AERAS)

Beyond 2025 Potential impact of vaccine Introduced in 2025 60% post-exposure efficacy 95% coverage reached after 10 years Assess year by which epidemic of TB could be "ended" TB disease ~2 7+ billion

Technological breakthrough by 2025 addresses the pool of infection -2%/yr Business as usual -10%/yr Optimize current tools -5%/yr Post-exposure vaccine ± safe PT -17%/yr "End the global TB epidemic"

Goal: End the global TB epidemic 2025 and 2035 TB targets Goal: End the global TB epidemic TB deaths TB incidence Rate per 100,000 population Millions -75% vs. 2015 -95% vs. 2015 10 per 100,000

Estimating TB incidence National incidence surveys impractical Best documented through state-of-the art TB surveillance. Estimates are uncertain due to Under-reporting Under-diagnosis Estimation from tuberculin surveys not satisfactory Prevalence surveys

Capture-recapture in Iraq 1980 detected, under-reporting = 16% 473 additional cases estimated (394–565)

How else can we estimate incidence? From results of prevalence surveys

Method 1 – deterministic model Untreated Treated mortality cure

Method 1 π ~ U (0, 0.1) 300 79 6.1 (5-7.5) 1.8 (1.1-1.6) 3.3 (2-4.8) Prevalence (per 1000) Duration (year) Incidence (per 1000/yr) Myanmar 2009 300 79 6.1 (5-7.5) 1.8 (1.1-1.6) 3.3 (2-4.8) Thailand 2012 136 60 2.5 (1.9-3.5) 1.1 (0.5-1.6) 2.3 (1-3.5) Indonesia 2013 407 122 6.6 (5.2 – 8.1) 1.6 (1 – 2.2) 4.1 (2.4 – 5.8)

Method 2 Reverse WHO method to estimate prevalence from incidence based on standard assumptions about disease duration (4 case categories) Notified HIV- ~U (0.2 - 2) year Not notified HIV- ~U (1 - 4) year Notified HIV+ ~U (0.01 – 1) year Not notified HIV+ ~U (0.01 – 0.2) year

Incidence in Indonesia (2013), ensemble model Ensemble 402 (276 - 552) per 100,000/year Method 1 (dynamic) Method 2 (duration)

Data on TB deaths (HIV-) from vital registration 74 countries with no reliable data on causes of deaths 38 other countries with low-quality data

Sources of data Best sources of data on TB burden are TB notifications when data meet quality criteria and under-reporting low and documented TB mortality from Vital Registration with COD Prevalence from national prevalence surveys Impact assessment methods tailored to the existing data 2015: meeting the WHO task force on TB impact measurement to review methods to evaluate the 2015 targets achievement

Short-term targetting (3-5 years) Monitor progress towards set target Use a directly measured indicator Not incidence, not CDR, because in most cases it will not be possible to state whether the country is on track Mortality if Vital Registrations or sample VR Prevalence if repeat survey within the programme cycle Case notifications Treatment success

Adaptation at country level Short-term targets (2016-2020) Based on a thorough epi analysis, standards and benchmarks for surveillance Assessment of planned actions Long-term targets (2025, 2035) Project incidence and CFR over time Target for catastrophic cost achieved if universal access is achieved

In conclusion Ambitious post-2015 global targets Country adoption of targets: Evaluate surveillance system Projections Short-term, programme planning based on measurable indicators Long-term, based on indicators that will become measurable Acceleration of the decline in incidence Improvements over the case fatality ratio (% of incident cases who die from TB)  faster decline of TB mortality