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For those responsible for TB programmes

The world is not on track to reach tuberculosis (TB) control goals

TB is the leading cause of death globally from a single infectious disease, killing more people than HIV

95%
of deaths are in low-income and middle-income countries*1

The END TB strategy aimed to reduce tuberculosis deaths by 35% by 2020 (and by 95% by 2053);
from 2015-2019, tuberculosis deaths were reduced by only 14% >> far from WHO goals1.

In 2019 alone, 10 million people developed TB disease1

2019 TB cases

  • 5.6 million men

  • 3.2 million women

  • 1.2 million children

Resulting in an estimated:
1,4 million deaths including
208,000 deaths in people living with HIV.1

*In 119 low- and middle-income countries that reported data in 2019 and accounted for 97% of TB cases globally.

Additional impact of COVID-19

Disruptions because of COVID-19 may result in additional TB cases and deaths:

The WHO estimates that there is a 50% reduction in TB cases detected and that TB deaths in 2020 will be ~1.85 million worldwide.

A modeling analysis by the Stop TB Partnership estimates that the disruption of TB control programs under a 3-month lockdown and a protracted 10-month restoration of services, the world could see an additional 6.3 million cases of TB between 2020 and 2025 and an additional 1.4 million TB deaths during that same period.

TB prevention needs more attention

Treatment of latent TB infection (LTBI) is the main intervention available to prevent development of active TB disease in those already infected with Mycobacterium tuberculosis, but current coverage rates are not optimal.1

We need do to more for TB prevention

Current coverage rates of latent TB treatment, the main intervention available to prevent development of active TB disease, are not optimal.1

Coverage rates of TB preventive treatment in people living with HIV1

Malawi:
26%

Indonesia:
12%

Gaps in TB prevention and TB detection for people who were newly enrolled in HIV care in 2019, selected countries1

100 75 50 25 0 Percentage (%) UR Tanzania Indonesia Papua New Guinea Malawi Myanmar Percentage (%) 100 75 50 25 0 UR Tanzania Indonesia Papua New Guinea Malawi Myanmar
  • Gap in TB detection and TB prevention

  • Detected and notified with active TB disease

  • Started on preventive treatment

What are the real costs of not accelerating efforts?

At the current rate, by 2030 failing to stop TB could cost nearly 1 TRILLION USD.
An estimated 28 million people will die from TB between 2015-2030, at a global cost 983 billion USD.2
It’s more than the annual GDPs of Nigeria, South Africa and Egypt combined!

Economic burden of TB infection among the top 10 countries (2015-2030, in USD)1
India 253 billion
South Africa 132 billion
Indonesia 124 billion
Nigeria 79 billion
China 60 billion
Russia 32 billion
Bengladesh 22 billion
Japan 20 billion
Thailand 18 billion
Pakistan 14 billion
Worldwide 956 billion

Across healthcare settings, drug costs represent up to 12% of the overall cost for treating drug-sensitive TB.
Hospitalisation cost is the major driver of costs to healthcare systems, and represents more than twice the cost of drugs.4

48% 19% 12% 9% 11%
Spending on the treatment of TB in low and lower-middle income countries 4
  • Hospitalisation

  • Outpatient*

  • Drugs

  • Diagnostic and monitoring

  • Other

*Cost for the care that patients receive without being admitted or for a stay of less than 24 hours.

Preventing tb can offset direct and indirect societal costs

Both the direct and indirect costs of TB should be considered when measuring the impact on society and our healthcare systems.

Direct costs

  • Out of pocket expenditure for patients due to their illness
  • Costs of transportation to health facilities
  • Expenditure for medication not covered by insurance or over the counter medications

Indirect costs

Cost of time lost due to illness, including:

  • Scheduled visits to health facilities and unscheduled hospitalisation
  • Time lost due to inability to work due to illness

How can we stop TB by treating LTBI?

People with latent TB infection represent a significant pool of individuals who could develop active TB disease at some point in the future.
26% of the world’s population has latent TB infection (LTBI). The World Health Organization’s END TB strategy aims to eliminate TB by 2050. The only way to achieve this objective is to treat both TB and LTBI.7

Eliminating tuberculosis requires the simultaneous attack on the two components of the M. tuberculosis lifecycle - latent TB infection and active TB cases.7,8

High-risk LTBI populations are critically more vulnerable to disease progression:1

  • Close contact with TB case
  • Children
  • People living with HIV
  • Weakened immune system

Cost of treating each case of LTBI is significantly lower than active and MDR TB

Treating LTBI is essential to decrease the reservoir of latent TB infection, and the cost of its treatment is significantly lower compared to the cost of a treatment for active and multidrug resistant (MDR) TB.12,13

LTBI

≈ USD 422

Active TB

USD 8,241 - 9,214

MDR-TB

(including extensively drug resistant TB) USD 64,314 - or more 184, 349

Australian & EU-15 Health system 12,13

EU-15 - member countries of the EU prior to May 1, 2004.
Adapted from Diel R, et al (2014) and Chan EC, et al (2017)

TB is the leading cause of death among people living with HIV, causing more than one third of all AIDS-related deaths.4
Adults and adolescents living with HIV should receive TB preventive treatment as part of a comprehensive package of HIV care.5
People with HIV should ask their practitioner about TB preventative therapy as part of a comprehensive package for HIV care.

Treat HIV. Treat LTBI

For your information:
• HIV (human immunodeficiency virus) is a virus that damages the cells in your immune system and weakens your ability to fight everyday infections and disease.
• AIDS (acquired immune deficiency syndrome) is the name used to describe a number of potentially life-threatening infections and illnesses that happen when your immune system has been severely damaged by the HIV virus.

1 Insufficient coverage rates

Coverage rates of LTBI treatment are insufficient. Coverage is low among one of the most vulnerable patient groups - children aged under 5 years, reaching only 33%. 1

Among the 23 high TB/HIV burden countries with reported data, coverage of TB preventive treatment to people newly enrolled in HIV care ranged from ranged from less than 1% in Thailand to 89% in Zimbabwe, and there are still countries where the coverage cannot be calculated.1

The United Nation General Assembly Declaration Political declaration has for the first time in history specified a target for people to be put on LTBI treatment with focus on high burden countries - 30 million individuals over 2018-2022.14

2 Adherence and completion rates

Low adherence & completion rates lead to high lifelong risk of active TB.15,16

Completion of LTBI treatment is more likely with regimens of 3-4 months compared to those that require longer treatment duration (meta-analysis). 15

Overall completion rates worsen depending on treatment course duration. 16
Adapted from Goswami ND, et al (2012).

Shorter and cost effective LTBI treatments could be beneficial to tackle LTBI1

Why is cost-effectiveness important?

It indicates which interventions provide the highest "value for money" and helps in the choice of the interventions and programmes that maximise health for the available resources.

In this fight, we need to arm ourselves with the best tools available!

Over a 20-year period, treatment of LTBI with 3HP is predicted to result in 25 fewer lost QALYs and in 5.2 fewer cases of TB per 1000 individuals treated than with 9H.17

The quality-adjusted life year (QALY) is an outcome measure that expresses the duration and quality of life.

TB cases prevented per 1,000 patients treated, 20 year horizon
10 5 0 3HP 9H
QALYs lost per 1,000 patients treated, 20 year horizon
60 40 20 0 3HP 9H

Adapted from Shepardson D, et al (2013).

Research done in 2020 showcases that the combination of:

• upscaling contact tracing for children
• treating both active TB and LTBI with short regimen

is modelled as cost effective among children in the 12 countries for which the strategy was modelled.20

  • Shorter regimens could reduce the refusal rates and are associated with higher adherence but these were less known by HCPs than longer regimens.11
  • Only 1 out of 5 HCPs in South Africa and only 1 out of 2 HCPs in the US, where it is included in national guidelines, knew of 3HP.11

Available LTBI treatments: Average pricing and number of intakes for WHO recommended regimens

Regimen description Price, US$* Number of day dosing** Treatment duration Schedule
6H 300mg of isoniazid 3.18 180 6 months daily
9H 300mg of isoniazid 4.77 270 9 months daily
3HP 900mg of isoniazid +
900mg of rifapentine
16.39 12 3 months weekly
3R 600 mg of rifampicin 24.79 90 3 months daily
3HR 600 mg of rifampicin
+ 300 mg of isoniazid
26.37 90 3 months daily
1HP 600 mg of rifapentine
+ 300 mg of isoniazid
26.78 30 1 month daily
4R 600 mg of rifampicin 33.05 120 4 months daily
4HR 600 mg of rifampicin
+ 300 mg of isoniazid
35.17 120 4 months daily
Lowest cost of an adult regimen based on January 2020 GDF catalog prices; pyridoxine for isoniazid-containing regimens is not included in this calculation
**1 month = 30days

Let’s make every dollar and cent count in the fight against TB!

Meet Mokgadi Letsatsi, Senior Nurse, RSA
00:00
Chapter 1: Meet Mokgadi Letsatsi, Senior Nurse, RSA
TB & LTBI. Personal experience
00:22
Chapter 2: TB & LTBI. Personal experience
Why TB prevention is important?
00:53
Chapter 3: Why TB prevention is important?
Advice to implementers
01:47
Chapter 4: Advice to implementers
What LTBI treatment brings in 3 words
02:42
Chapter 5: What LTBI treatment brings in 3 words
 Story from  South Africa

Prevent Tuberculosis
Management of TB infection Continuing Medical Education (CME) opportunity available at:

  • Module 1. Introduction to TB
  • Module 2. Pathogenesis of TB
  • Module 3. At risk populations
  • Module 4. Identifying TB infection
  • Module 5. TB Prevention Treatment (TPT)
  • Module 6. Implementation of TB prevention

This eCME material has been developed with finacial support from Sanofi.

References:

  1. World Health Organization. Global tuberculosis report and fact sheet, 2020, available at https://www.who.int/tb/publications/global_report/en, last accessed October 2020.
  2. Global TB Caucus. The price of a pandemic, 2017; available at https://www.globaltbcaucus.org/research, last accessed January 2020.
  3. Stop TB Partnership in collaboration with Imperial College, Avenir Health, Johns Hopkins University and USAIDon T. Modeling Report of the impact of COVID-19 B, 1 May 2020.
  4. Laurence YV, et al. Pharmacoeconomics. 2015;33:939-55.
  5. Kik S, et al. BMC Public Health. 2009;9:283-90.
  6. Castro KG, et al. Int J Tuberc Lung Dis. 2016;20:926-33.
  7. Dye C, et al. Annu Rev Public Health. 2013;34:271-86.
  8. UNAIDS Global HIV & AIDS statistics — 2020 fact sheet
  9. Fox GJ et al. Preventive therapy for latent tuberculosis infection — the promise and the challenges. Int. Journal of Infectious Dis. 2017 Mar;56:68–76
  10. WHO consolidated guidelines on tuberculosis. Module 1: prevention. Tuberculosis preventive treatment, 24.03.2020
  11. World Health Organization. The END TB STRATEGY, 2015 // WHO - world health organization, UNGA- United Nations General Assembly.
  12. Diel R, et al. Eur Respir J. 2014;43:554-65.
  13. Chan EC, et al. Communicable Dis Intel. 2017;41:E191-4.
  14. United Nations 73rd session of the General Assembly; resolution on the fight against tuberculosis (adopted 10 October 2018).
  15. Pease C, et al. BMC Infectious Diseases. 2017;17:265.
  16. Goswami ND, et al. BMC Public Health. 2012;12:468.
  17. Shepardson D, et al. Int J Tuberc Lung Dis. 2013;17:1531-7.
  18. January 2021 medicines catalog, GDF.
  19. Research conducted in 5 countries by the agency Axess Research for sanofi, August and September 2019.
  20. Y. Jo et al., Cost-effectiveness of scaling up short course preventive therapy for tuberculosis among children across 12 countries, EClinicalMedicine (2020) https://doi.org/10.1016/j.eclinm.2020.100707
  21. Research conducted in 5 countries by the agency Axess Research for sanofi, August and September 2019.
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MAT-GLB-2100137 March-2021