Healthcare professionals

It's time to stop

Latent TB infection, for good

It's time to stop

Latent TB infection, for good

Information about latent TB infection (LTBI)

Latent tuberculosis infection (LTBI) is dormant but can progress to life-threatening disease. Exposure to M. tuberculosis results in a dynamic continuum with two common outcomes:¹

those who eliminate the infection
those in whom the bacteria infects the lungs. This can initially be a latent (asymptomatic) infection, but can progress to active, potentially life threatening disease, which can sometimes progress to active, potentially life threating disease. This may happen years after the initial latent infection occurs.

Healthy

Infection eliminated by innate immune response or adaptive immune response

Exposure to airborne bacteria

LTBI

Asymptomatic Not Contagious TST + / IGRA +

Active TB

+/- Symptomatic Contagious Usually abnormal CXR

Risk of progression after infection by air-borne bacteria

CXR: Chest x-ray; IGRA: Interferon-gamma release assay; TST: Tuberculin skin test.

LTBI is fueling TB worldwide

LTBI affects 26% of the world’s population and represents a significant pool of individuals who could develop active TB disease in the future. Certain populations have a high-risk of LTBI progressing to active TB, and these patients need to be identified and treated. Because active TB is still in the top 10 causes of death worldwide, this large LTBI reservoir also represents a risk of future deaths.²

In 2019

2 billion

infected with the bacteria worlwide ²

LTBI

10 million

new cases each year worlwide ²

1.4 million

deaths each year worlwide ²

Death

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.

Populations at high risk are those patients with LTBI that are critically more vulnerable to disease progression. In the general population, LTBI will progress to active TB for approximately 1 in 10 people over their lifetimes.
However, people that fit into the population groups below have been shown to be at higher risk and their likelihood of disease progression is significantly increased.⁴

These populations should be identified and treated:

Close contact

From 16 to 46 times ^*

People living with HIV

From 16 to 46 times ^*

Immuno-suppressed patients

TNF-a inhibitors: 10 times ^*
Advanced kidney disease: 8 times ^*
Organ transplant: from 70 to 300 times ^*
Stem cell transplant: 20 times ^*

Children

Age <2-3 years: >10 times ^*
age 3-4 years: >3 times ^*

*For individuals with LTBI: Lifetime risk of developing TB disease compared to those without the risk factor. ⁴

It is recommended to treat specific high risk subgroups directly (testing for LTBI is not mandatory), including HIV-positive patients and children < 5 years old in close contact with TB infected patients. Those without HIV-infection in other age groups who are in close contact with a person with active TB infection may be treated directly, based on a clinical judgement of TB exposure and risk balanced against the availability of LTBI testing.

Ending TB requires treatment of both LTBI and active TB

Treating LTBI is not an option.
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 active TB and LTBI.

Treat LTBI to neutralise the reservoir of latent TB infection, which is a main source of future active TB disease.⁵

Develop a strategy to protect your patients

Treat LTBI the right way and lower your patients’ risk of becoming sick from active TB.⁶

Identify

Identify your patients who are most at risk of having LTBI

Test^*

for LTBI and rule out active TB

Treat

Rather than waiting for LTBI to progress to active disease, it is best to identify and treat it at the latent stage.

WHO recommended regimens:

Regimen description	Number of day dosing^*	Treatment duration	Schedule
6H 300mg of isoniazid	180	6 months	daily
9H 300mg of isoniazid	270	9 months	daily
3HP 900mg of isoniazid + 900mg of rifapentine	12	3 months	weekly
3R 600 mg of rifampicin	90	3 months	daily
3HR 600 mg of rifampicin + 300 mg of isoniazid	90	3 months	daily
1HP 600 mg of rifapentine + 300 mg of isoniazid	30	1 month	daily
4R 600 mg of rifampicin	120	4 months	daily
4HR 600 mg of rifampicin + 300 mg of isoniazid	120	4 months	daily

*1 month = 30days

Patients could benefit from shorter treatments with minimal side-effects.⁷

The most-common LTBI treatments are long-course regimens (6-9 months), for which most patients don’t finish treatment. This discourages both you and the patient, and it increases the burden of active disease within the community. Treating LTBI lowers the number of drug susceptible-TB patients requiring treatment and also prevents drug resistant-TB by shrinking the reservoir from which acquired resistance can develop.

Did you know that

- 1 out of 3 patients in South Africa and 1 out of 4 patients in the US refused preventative treatment ¹¹
- From those who refused the treatment:

• 62% out of 100% considered the treatment was too long
• 60% out of 100% didn’t think LTBI was a serious problem

Methodology	Completion rate	Regimen length
Isoniazid⁸ (6H) Local observation methods to determine asherence^*	44.5%	6 months 180 doses
Isoniazid⁹ (9H) Self-administered treatment. Completion rate based on prescriptions filled each month	31%	9 months 270 doses

*Study covering 29 jurisdictions in the US and Puerto Rico with 67,585 contacts; ‘completed treatment’ means taking at least 80% of the doses in a prescribed regimen within 150% of the intended treatment duration, as observed by local methods for monitoring adherence.

To ensure that the enormous reservoir of LTBI is eliminated, any treatment has to have:

Effectiveness

The regimen must have clinically proven effectiveness for the elimination of LTBI
Adherence

The patient must complete their regimen as prescribed to ensure the proper elimination of LTBI
Well-documented safety profile

The treatment must minimize health risks so as not to deter the patient from starting and completing the regimen

A shorter LTBI treatment duration than standard 6 or 9 month treatment can lead to improved completion rates and better effectiveness for the prevention of active TB cases.

As effective as daily INH

12 doses of 3HP is as clinically effective as 270 doses of daily INH¹²
Improved adherence

3HP is just 12 doses in only 3 months, a shorter regimen than 6 to 9 months INH¹³
Well-documented safety profile

The safety profile of 3 HP is one that LTBI patients can trust¹²

Less time

Fewer doses

Better completion rates than longer regimen

The 3HP treatment regimen is non-inferior to the INH-only regimen(upper limit of the 95% CI of the difference, <0.75%)

Rate difference of progression to TB (intention-to-treat-population)

PREVENT-TB: a randomised, open-label, non-inferiority trial of 3HP given as directly observed therapy compared to 9 months daily INH self administered therapy, in adults and children 12 years and above with LTBI.

3HP treatment for LTBI has demonstrated clinical effectiveness in line with isioniazid (INH):12 doses of 3HP is as effective as 270 doses of dailly INH¹²

Improved adherence with short LTBI treatment:

3HP is just 12 doses in only 3 months, a shorter regimen than 6 to 9 months INH. Studies have shown improved adherence, including in some subgroups that may be difficult to follow^12.13

Rates of treatment completion in subgroups in PREVENT-TB ¹³

Subgroup	3HP	9H	P-values
	Completion rates(Directly observed therapy)		P-values
Subgroup	3HP	9H	P-values
PLHIV	88.8%	63.7%	<0.001
Children(aged 2 to 17)	88.1%	80.9%	0.003

Overall Treatment completion in PREVENT-TB ¹²

Well-documented safety profile:

The safety profile of 3HP is one that LTBI patients can trust.
In PREVENT-TB, the safety, the 3HP treatment regimen had a toxicity profile similar to that of the INH-only group, with lower rates of adverse events, serious adverse events, and hepatotoxicity although a higher rate of possible hypersensitivity reactions was seen.¹²

reasons	N = 4040 3 months 3HP regimen	N = 3759 9 months INH monotherapy	P-values
Discontinuation for any reason	17.9%	31%	p<0.001
Discontinuation for adverse event	4.9%	3.7%	p = 0.009
Any serious adverse event	1.6%	2.9%	p<0.001
Drug related adverse events	8.2%	5.5%	p<0.001
Possible hypersensitivity	3.8%	0.5%	p<0.001
Other drug reactions	3.2%	1.7%	p<0.001
Hepatotoxicity	0.4%	2.7%	p<0.001

A wider adoption of 3HP is possible and should be implemented to increase coverage and completion of LTBI treatment¹¹

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

Patient perspective on LTBI

35 years old, India

Meet Danvir

Like many people in high-risk populations, he knew about TB but did not worry about it. And despite being in contact with people who have TB, like most people, he figured those things only happen to others…

...Untill he became sick after his LTBI progressed to active TB

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

Union e-learning

Go to e-learning website

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.

Check out this video from South Africa showing how TB prevention can make a difference.