TB prevention is no longer a choice, but essential part of end TB strategy

Shobha Shukla *

"TB prevention is no longer a choice but an essential intervention to end TB...TB is one of the few infections that we ignore and do not treat till it manifests as late stage disease that has already [been] transmitted to several others. The strategy needs to expand to include preventing full blown TB disease" tweeted Dr Suvanand Sahu, Deputy Executive Director of Stop TB Partnership. "If you are not doing TB prevention, you are in the old era of controlling TB - not ending it."

World Health Organization (WHO) estimates that about one-third of the global population has latent TB infection (LTBI). This means that there is TB infection in the body of these otherwise healthy individuals who neither have the active TB disease, nor any symptoms of it. But 10% of them may progress to active TB disease in later life.

If we want to end TB we will have to not only treat and cure all patients with active TB disease but also manage LTBI and prevent its progression to active TB. While this is doable, it is by no means easy.

"The first big scientific challenge is that we do not know which of the 1.7 billion people with LTBI globally will actually develop active TB disease. But the risk is highest in recently infected people. There is an urgent need for more research to get some diagnostic test that can identify which of these people are at higher risk so that we can target that group for TB preventive treatment (TPT)," said Dr Soumya Swaminathan, Chief Scientist at the World Health Organization (WHO) to CNS (Citizen News Service, www.citizen-news.org).

Diagnostic Limitations:

Currently, there are two WHO recommended tests for LTBI - the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA) blood test. TST is not very sensitive and specific, especially in those who have had the BCG vaccine. The IGRA test is much more specific and is much easier to perform. But it does involve a blood draw and we also need a laboratory to do the testing. It is also more costly and that limits its accessibility in low resource settings.

“There are new skin tests in development that are based on the same antigen used in the in-vitro IGRA test. Ideally what is needed is a biomarker- blood or saliva or urine that can really identify the people who are at risk of progression from latent TB to active TB disease. It is not enough to know whether one has LTBI but also if the person is going to progress to active disease or not”, said Swaminathan.

We need to develop an affordable, sensitive and specific test for latent TB infection which could be used more broadly than what we have now, she added.

Dr Mario Raviglione, former Director of the Global TB Programme at the WHO, dittos these concerns. In his opinion, “If there was a test that could absolutely tell that a person is not just latently infected because of exposure to the TB bacteria but that the person is still harbouring TB bacilli and is therefore at risk of progressive slow development of TB especially when some other risk factor comes in like HIV, malnourishment, diabetes, tobacco or alcohol use, etc, then it would be worthwhile to screen the entire human population as we would know exactly who amongst the LTBI would progress into active TB disease. We really need such a point of care test for LTBI”.

Drug-resistant strain of latent TB

If the index case has drug resistant TB then the infection transmitted to the other person would also be of drug-resistant latent TB. “Studies done in South Africa have shown that in settings where there is high drug-resistant TB, there is a 50% chance that one might get infected with drug-resistant latent TB infection from own family person with drug-resistant TB, and 50% chance to pick up the infection from someone else outside the house. As the same tests are used to detect both forms of latent TB, it is a challenge to find out if a contact is infected with drug-resistant or drug-sensitive latent TB. So it is only through wait and watch to guess if the person possibly has drug-resistant latent TB infection”, said Dr Swaminathan.

TB preventive treatment (TPT)

Some WHO recommended treatment options for TPT in high TB incidence countries are:

o 6H- Daily INH (Isoniazid ) for 6 months for adult and child contacts of bacteriologically confirmed cases of TB.
o 3HP – Once-weekly isoniazid–rifapentine for 3 months for adult and child contacts of bacteriologically confirmed cases of TB
o 3HR- Daily rifampicin- isoniazid for 3 months for children and adolescents aged < 15 years
o 36H - Daily INH for 36 months for adults and adolescents living with HIV who have an unknown or a positive TST and are unlikely to have active TB disease, regardless of whether they are receiving ART

Challenges in roll out of TPT:

The currently available TPT regimen in India is isoniazid preventive therapy. Says Dr Randeep Guleria, Director, All India Institute of Medical Sciences (AIIMS), and Chairman of government of India's Technical Working Group on latent TB infection (LTBI): “It is not easy to ask people with LTBI to take medicines on the premise that they might develop TB in future despite being healthy at the moment, especially as the current treatment regimen is of 6 months duration. It will be difficult to convince healthy and asymptomatic contacts of TB patients to take a tablet everyday for 6 months, (more so if these contacts are children) to prevent them from getting TB in future. The acceptability in the community and among parents of contacts is less and the compliance of taking medication regularly for 6 months is low."

To overcome these problems, Dr Guleria proposes two strategies:
o Use of the new shorter treatment regimens that are now available - the 3HP regimen for HIV negative adult and child contacts, or a one month long daily regimen of rifapentine and isoniazid for people living with HIV
o Increasing awareness in the general public that TPT will protect adults and children with LTBI from developing TB and also that the treatment is safe and has no side effects.

So improved awareness and roll out of simpler regimens for TPT need to be looked into, he emphasises.

Test and treat

Experts believe that, scientifically speaking, we should test people before we give them TPT because infection precedes the disease. Practically speaking there are hardly any affordable and reliable tests available currently that can be used in low-income and high TB burden countries to test millions of people for LTBI. For high TB burden countries like India, Dr Guleria makes an argument to treat without testing in certain groups where the risk is very high, and to test and treat in other groups where the risk is moderate, for latent TB to progress into active TB disease.

Holistic approach to #endTB

“To defeat TB we will have to think of newer strategies which may not only be related to medication but also look at improving the host’s immune response. TB in the western world came down not just because of medication but also because of improvements in hygiene and socio economic status. If overall nutrition, health and hygiene of the population is improved and if there is better awareness of preventive measures, the fight against TB will be easier. We need to have a more holistic approach and focus also on tackling under nourishment, overcrowding, poverty, and not on merely giving medication to treat TB”, said Dr Guleria.

Agrees Dr Raviglione that, “We need a multi-sectoral and multi-disciplinary approach to eliminate TB. In the case of latent TB the role of non-health sectors becomes even more important because we are aiming to reach out to a seemingly healthy population to empty the pool of latent TB. We have to think more about conditions that determine the exposure to TB and the passage for latent infection for those exposed to the disease. If there is overall development aimed at good education, good nutrition, cleaner energy, especially to reduce indoor air pollution, and good living conditions, TB rates will go down”.

Growing political commitment to prevent TB to end TB

The political declaration at the first ever UN high-level meeting on TB in September 2018 included a target to provide TB preventive treatment to at least 30 million people during 2018–2022: 6 million people living with HIV, 4 million children below 5 years of age who are household contacts of people with active TB, and 20 million other household contacts, with a view to empty this pool of latent TB.

At the 10th International AIDS Society Conference on HIV Science (IAS 2019), a strong Call To Action was launched for a coordinated HIV and TB response to reach 6 million people living with HIV with tuberculosis preventive treatment.