Global tuberculosis targets and milestones set for 2016-2035: definition and rationale.

BACKGROUND: Global tuberculosis (TB) targets were set as part of the World Health Organization's End TB Strategy (2016-2035) and the Sustainable Development Goals (2016-2030).
OBJECTIVE: To define and explain the rationale for these targets.
DESIGN: Scenarios for plausible reductions in TB deaths and cases were developed using empirical evidence from best-performing countries and modelling of the scale-up of under-used interventions and hypothetical TB vaccines. Results were discussed at consultations in 2012 and 2013. A final proposal was presented to the World Health Assembly in 2014 and unanimously endorsed by all Member States.
RESULTS: The 2030 targets are a 90% reduction in TB deaths and 80% reduction in TB incidence compared with 2015 levels. The 2035 targets are for reductions of 95% and 90%, respectively. A third target-that no TB-affected households experience catastrophic costs due to the disease by 2020-was also agreed.
CONCLUSION: The global TB targets and milestones set for the period 2016-2035 are ambitious. Achieving them requires concerted action on several fronts, but two things are fundamental: 1) progress towards universal health coverage to ensure that everyone with TB can access high-quality treatment; and 2) substantial investment in research and development for new tools to prevent TB disease among the approximately 1.7 billion people infected.

AT THE TURN of the twenty-first century, the United Nations (UN) established eight Millennium Development Goals (MDGs) and associated targets for 2015. These were endorsed by all countries and became the focus of national and international development efforts (www.un.org/millenniumgoals). Within this framework, three targets for reductions in the tuberculosis (TB) disease burden were set: incidence should be falling by 2015, and prevalence and mortality rates should be halved by 2015 compared with 1990 levels. The World Health Organization's (WHO's) Stop TB Strategy 2006–2015 was designed to achieve these targets.1 The WHO published its assessment of whether the targets were achieved in its 2015 global TB report; incidence was estimated to have been falling at an average of 1.5% per year since 2000, and prevalence and mortality rates were assessed to have fallen by respectively 47% and 42% compared with the levels in 1990.2

Work on post-2015 UN goals and targets began in 2012, and 17 Sustainable Development Goals (SDGs) for 2030 were agreed in September 2015.3 One of the SDGs is to ‘Ensure healthy lives and promote well-being for all at all ages’, under which a target is to ‘End the epidemics of AIDS, TB, malaria and neglected tropical diseases, and combat hepatitis, water-borne diseases and other communicable diseases’. In this context, the WHO initiated the development of a post-2015 global TB strategy and targets in 2012.

Following 2 years of consultations, the new strategy, now known as the End TB Strategy and covering the period 2016–2035, was endorsed by the World Health Assembly in 2014.4,5 The overall goal is to ‘End the global TB epidemic’, and ambitious targets for reductions in TB deaths and cases have been set for 2030 (the SDG end date) and 2035. The present article defines and explains the rationale for these targets and associated milestones set for 2020 and 2025.

METHODS

Target setting was underpinned by seven principles (Table 1) consistent with those used for the SDGs.6 The number of TB deaths and the TB incidence rate (new cases per 100 000 population per year) were selected as the two most important indicators for which targets should be set.

Table 1

Principles underpinning post-2015 global TB targets

The number of TB deaths is directly measurable at country level via national vital registration systems, in which causes of death are recorded using standard international coding systems; 128 countries had such systems in 2015 (Figure 1), and they could be introduced elsewhere. Targets for reductions in TB deaths can be more ambitious than those for TB cases, as mortality can fall faster than disease incidence if both incidence and the proportion of TB cases who die from the disease (case fatality ratio [CFR]) decline. Reductions in TB deaths can also be linked to equity: whatever the number of cases, all countries can aim to reach the same low CFR based on universal health coverage (UHC), i.e., access for all to essential preventive and treatment health care interventions, with financial protection.7,8

Figure 1

Availability of vital registration data. Countries shown in black are those in which TB mortality could be measured directly from vital registration data in 2015. TB = tuberculosis.

TB incidence was selected as an indicator for measuring reductions in the number of cases of TB disease. Although incidence was estimated with considerable uncertainty in most countries in the MDG era,2 notifications of TB cases to national authorities provide a good proxy if there is limited under-reporting of detected cases, limited under-diagnosis and limited misdiagnosis. Underreporting, underdiagnosis and misdiagnosis can be addressed by strengthening national surveillance and health systems. The alternative indicator, TB prevalence, was considered unsuitable because it will not be measured directly in most countries after 2015. As the burden of TB disease falls, the sample size required for national prevalence surveys become prohibitively expensive and logistically challenging.9

To define plausible scenarios for the reductions in TB deaths and incidence that could be achieved between 2015 and 2035, two periods were considered: 2015–2025 and 2026–2035. The status of the pipelines for new TB diagnostics, drugs and vaccines suggested that no major breakthroughs will occur during this first period.2 A new TB vaccine or equivalent treatment for latent tuberculous infection could become available in the second period.

Reductions in TB deaths are driven by two factors: the annual rate at which TB incidence falls, and changes in the CFR. Illustrative scenarios for the reductions in TB deaths that could be achieved by 2025 were constructed for different combinations of these variables, allowing for projected growth in population.10 The assumed trajectories for changes in the incidence rate and the CFR are shown in Figure 2.

Figure 2

Assumed change in TB incidence rate (annual rate of decline) and the CFR, 2015–2025. The trajectory assumes that the effect of progress towards universal health coverage (and implementation of new diagnostics and drugs currently in the pipeline) intensifies around 2020 and achieves full potential by 2025. To achieve further improvements, new tools such as a post-exposure vaccine would be required. CFR = case-fatality ratio; TB = tuberculosis.

A ‘plausibility zone’ for targets was defined based on historic evidence about the speed at which the TB incidence rate can fall and the lowest levels of the CFR observed in settings in which the coverage and quality of anti-tuberculosis treatment was high. The limit for the decline in incidence was set at 10% per year. This is the best-ever performance historically at the national level, achieved between the 1950s and 1970s in parts of Western Europe (Figure 3) in the context of rapid socio-economic development, UHC and the introduction of chemotherapy.11 Faster declines have only been documented in the 1950s and 1960s, in subpopulations with incidence rates ten times the 2015 global average.12,13 The global CFR limit was defined as 6.5%, the 2013–2014 average in high-income countries.

Figure 3

Long-term TB incidence trends in countries with robust surveillance data. At the national level, the best historical declines in TB incidence (solid line) reached about 10%/year (England and Wales, The Netherlands), while faster declines were observed in subpopulations (in Alaska among the Eskimo population). Current best-performing countries show a more modest decline of 3–5%/year (Cambodia, China). The current global decline rate is 2%/year. The dashed line in the top panels denotes TB mortality rates. TB = tuberculosis.

The plausibility zone reflected historic performance without allowing for the possibility of a hypothetical scale-up of two interventions: mass screening for tuberculous infection and TB disease, followed by treatment for disease and isoniazid preventive therapy (IPT) (hereafter mass TB screening [MTS]). In the MDG era, such mass campaigns were very limited, but were considered to explore the potential reductions in TB burden that could be achieved. The potential impact of MTS was explored using a simple dynamic transmission model similar in structure to other published models.14,15 The negative consequences of MTS (number of false-positive individuals treated for infection or disease and deaths associated with the side effects of IPT) were also quantified (see Appendix).[*]

For 2026–2035, further modelling was undertaken to explore the impact of a technological breakthrough. For practical purposes, the analysis focused on the potential impact of a new vaccine with 60% efficacy, introduced in 2025, providing protection for at least 10 years and achievement of 90% effective coverage by 2035 (see Appendix).

Global consultations were held to inform the development of the End TB Strategy in 2012 and 2013, two of which were especially important. The first, in February 2013, considered the analyses described above to reach consensus on targets/milestones for 2025.16 The second, in June 2013, considered the recommendations of the February 2013 consultation, results of the modelling work up to 2035 and associated target proposals for 2030 and 2035 that would correspond to the goal of ending the global TB epidemic.17

No ethical approval was required for this work.

RESULTS

The combinations of reductions in TB incidence and the CFR that would be required for reductions in TB deaths ranging from 50% to 90% by 2025 (compared with 2015) are shown in Figure 4. The plausibility zone for targets that could be reached by 2025 is shown by solid black lines. If recent trends continued (bottom right corner), the number of TB deaths would fall by about 18% between 2015 and 2025. In the most optimistic scenario, in which incidence decreases at 10% per year by 2025 and the CFR falls to 6.5% (circle), a 75% reduction in the number of TB deaths would be achieved.

Figure 4

Scenarios for reductions in TB deaths that could be achieved by 2025, and the associated ‘target zone’. Contours show combinations of annual percentage declines in incidence in 2025 (y-axis) and CFR in 2025 required to produce the corresponding reductions in TB deaths. For example (dashed lines), a 90% reduction in the number of TB deaths (to 130 000 by 2025) could be achieved if TB incidence declines at 30% per year and the CFR is reduced to 7.5% by 2025. The solid black lines illustrate the plausible zone based on previously observed declines and the average CFR in high-income countries. The circle marks the most ambitious scenario within the plausible zone. CFR = case-fatality ratio; TB = tuberculosis.

The dynamic model suggested that with a background of a 2% annual decline in TB incidence and a CFR of 16% combined with the MTS intervention, the number of TB deaths could fall by 22–65% by 2025 (Figure 5). With the most optimistic background scenario (CFR 6.5%, annual incidence decline 10%/year by 2025), the incremental impact of the MTS intervention would be lower and the total number of TB deaths could fall by 77–90% by 2025 (see Appendix). MTS may also result in considerable undesirable effects and over-treatment, with 81–93% of those provided with anti-tuberculosis treatment not having TB.

Figure 5

Trends and reductions in TB incidence and mortality as a result of a theoretical expansion of screening and treatment for active TB disease and latent tuberculous infection (mass TB screening [MTS])—2% background decline scenario. Left panels show the trends in TB incidence (top) and mortality (bottom), assuming the background decline in TB incidence remains at 2% per year and the CFR at 16%. Black lines show WHO-estimated incidence, dashed lines show the median model output, and shaded areas the 95% credible intervals (all values are relative to the 2015 estimated incidence). Right panels show the percentage reduction in incidence (top) and mortality (bottom) compared with 2015. Four scenarios are considered: no MTS (baseline); 5% of population screened per year, 10% completion of IPT (high); 10% screened, 50% completion (higher); 20% screened, 90% completion (highest). TB =tuberculosis; CFR = case-fatality ratio; WHO = World Health Organization; IPT = isoniazid preventive therapy.

The median trajectories for declines in TB deaths and incidence that could be achieved by 2035, assuming a technological breakthrough (i.e., vaccine) by 2025 building on a 75% reduction in TB deaths between 2015 and 2025 are shown in Figure 6. An incidence rate of around 14/100 000 (comparable with levels found in countries considered to have a low TB burden in recent years) and a reduction in TB deaths of around 95% could be achieved by 2035.

Figure 6

Projected TB incidence and mortality curves to reach targets and milestones, 2015–2035, assuming the annual decline in incidence reaches 10%/year, CFR is reduced to 6.5% by 2025 and the availability of an efficacious vaccine after 2025. TB=tuberculosis; CFR=case-fatality ratio.

In February 2013, agreement was reached on two targets for 2025: a 75% reduction in TB deaths and a 50% reduction in TB incidence, compared with 2015 levels. Such reductions, and in particular the underlying requirement that the CFR should fall to 6.5% by 2025, implicitly require that all people with TB can access diagnosis and treatment, i.e., UHC is in place. A third high-level target linked to UHC was therefore proposed: by 2020, no TB-affected households should suffer catastrophic costs as a result of TB. In June 2013, following extension of the modelling work described above, the targets proposed for 2025 were rephrased as milestones, and 2030 and 2035 targets corresponding to the end dates of the SDGs and End TB Strategy were proposed (Table 2). The targets and milestones shown in Table 2 were endorsed by all 194 Member States at the 2014 World Health Assembly.4,5

Table 2

The End TB Strategy's three high-level global indicators and associated targets (2030 and 2035) and milestones (2020 and 2025)

DISCUSSION

The global TB targets and associated milestones set by the WHO's End TB Strategy call for a 90% reduction in TB deaths by 2030 (compared with 2015) and a 95% reduction by 2035, with corresponding reductions of respectively 80% and 90% in the TB incidence rate. By 2025, TB deaths should be reduced by 75%, and by 2020 no TB patients and their households should face catastrophic costs due to TB.

The targets are ambitious, but within the limits of plausibility, and are consistent with the 2030 SDG targets for ending the epidemics of major infectious diseases, including TB, and achieving UHC. Comparable targets have also been set in the post-2015 strategies for HIV and malaria: a 90% reduction in the malaria death rate by 2030 compared with 2015 and a 90% reduction in deaths due to the acquired immune-deficiency syndrome by 2030 compared with 2010. The TB targets are measurable and promote equity, necessitating that all people who develop TB have the same high chance of receiving appropriate care and the same low chance of dying from the disease. They are also based on consensus, having earned unanimous endorsement by UN Member States at the 2014 World Health Assembly and wide buy-in from funding agencies, technical partners and civil society.

The technical work that informed the target setting was grounded in empirical evidence about the two key variables that can drive reductions in TB burden: the annual rate at which it is possible to reduce TB incidence and the proportion of cases that die from TB if there is universal access to high-quality diagnosis and treatment. They were also based on up-to-date information about the development pipelines for new TB diagnostics, drugs and vaccines, with post-2025 projections allowing for technological breakthroughs that could occur within one decade and greater use of currently under-used interventions.

To reach these targets, progress is required on several fronts,5 but two things are fundamental. First, UHC for essential health care services, including detection and treatment of TB, must be achieved by 2025. The 2025 milestone of reducing TB deaths by 75% requires cutting the CFR to 6.5% (the level of high-income countries), which implicitly means that all those with TB disease (both drug-susceptible and drug-resistant, and both adults and children) can access high-quality treatment. There is growing momentum to promote UHC and monitor progress towards it.7,8,18,19 The 10% per year fall in incidence that is needed by 2025 has previously been achieved only in the wider context of UHC and broader socioeconomic development, including social protection: Western Europe in the 1950s and 1960s is the best example. Similar improvements in socio-economic status, poverty reduction and improvements in living conditions in low-income countries that have the greatest burden of TB will play a key part in reaching the TB targets. Social protection mechanisms are also essential to ensure that TB patients and their households do not incur catastrophic costs, for example due to lost income from time away from work. The second fundamental requirement is a technological breakthrough by 2025 that will allow an unprecedented acceleration in the rate at which TB incidence falls between 2025 and 2035. This will happen only with substantial investment in research and development, so that new tools to substantially lower the risk of developing TB among people who are already infected can be developed.

Achievement of the targets for reductions in TB deaths and incidence at the global level does not mean that all countries need to make progress at the same pace. The strategy recognises that countries will need to make adaptations to the overall targets. The WHO has issued guidance that includes 10 priority operational indicators and associated targets that should be reached by 2025 at the latest, and recommendations for how to set country-specific targets for 2020 and 2025.20 In addition, the Global Plan to End TB produced by the Stop TB Partnership provides a roadmap for countries working towards the 2020 milestones. Progress in the countries with the highest burden, such as China, India, Indonesia, Nigeria, Pakistan, the Philippines and South Africa, which collectively accounted for two thirds of estimated incident cases in 2015, will strongly influence whether global targets can be achieved.

All of the indicators for which post-2015 global TB targets have been set are measurable. However, direct measurement of TB deaths and TB incidence (as opposed to indirect estimation reliant on modelling and expert opinion) will require the strengthening of routine information systems in many countries. Guidance exists on how to assess the capacity of national notification and vital registration systems to provide direct measurements of TB cases and deaths, respectively, and to use results to close identified gaps.21 Guidance on the measurement of catastrophic costs using special surveys has been developed.22 The WHO and the World Bank plan to issue a biennial report on progress towards UHC from 2015 onwards.19 Strengthening health information systems, in particular civil and vital registration systems, is already a prominent part of the post-2015 health agenda.23

The 2035 targets set within the End TB Strategy define the end of the global TB epidemic. Following endorsement by all UN Member States at the World Health Assembly, intensified action at national and global levels to operationalise the strategy is imperative.

Table A.1

Model parameters *

Table A.2

Intervention parameters

Table A.3

Reductions in TB incidence and mortality achieved by the mass screening and treatment intervention on top of the three background decline scenarios (2%, 4% and 10%)