The Union wanted to share facts about tuberculosis (TB) to dispel some myths, misconceptions, and half-truths getting in the way of ending TB.
- Tuberculosis is already ended. It is only of historical interest.
There are approximately 10 million new cases of TB and 1.6 million deaths due to TB every year. Prior to COVID-19, there were more deaths due to TB than any other infectious disease. TB is not already ended.
There are at least three probable bases for this myth. First, TB has been virtually eliminated since the 1970s in many countries in Northern and Western Europe, North America, and high-income parts of East Asia and Oceania. Hence, many living in these countries have no lived experience of TB and cannot perceive it as a problem. Second, we have had effective treatment to cure people with TB for 70 years; many people know this and assume the problem must be over. Third, even in countries where TB is not ended, many of the cases are hidden, either because people with TB are not diagnosed or, if they are diagnosed, they are subject to stigma and tend to hide their diagnosis.
- I have had the TB vaccine (BCG). I have nothing to fear from TB.
The Bacillus Calmette–Guérin (BCG) vaccine was developed during the 1910s in Lille, France, first administered to humans at the Charité Hospital in Paris in 1921, and has been in widespread use since a series of trials conducted in the 1950s. The vaccine forms part of the Expanded Program on Immunization.
The main benefits of BCG vaccination are in offering some protection against infant and early childhood deaths and disability due to severe TB disease, to which they are particularly susceptible. It may have some benefits in preventing this disseminated form of TB disease in older children and adults. However, it seems to have very little, if any, effect in reducing the incidence of TB affecting the lungs. This is the most common adult manifestation of TB and is the only infectious form of TB. Hence, BCG vaccination essentially has no role in preventing transmission of TB and, although it is important in reducing child deaths due to TB in settings where TB infection is common, its role in ending TB is very limited. TB was essentially eliminated in USA without any systematic use of BCG vaccination. Indeed, we need a more effective vaccine that protects against the most infectious forms of TB to reduce transmission. There is encouraging work on this, but we are not there yet.
- I have recovered from TB. I have nothing to fear from TB any more.
For some diseases, like measles and chickenpox, one episode of disease confers life-long protection. It was widely believed that people who had recovered from TB were, at least partially, immune from subsequent infection and disease. In fact, we now know that people who have recovered from TB are not well protected from subsequent infection and disease. This is the case even when we exclude those cases that are due to relapse of inadequately treated disease.
- We have vaccines for many diseases, if we try harder and spend more money, we must be able to produce a vaccine against TB and this should solve the problem.
The general principle of vaccines is that they induce the immunity arising from natural infection without causing the illness. However, as noted above, TB disease does not, in fact, induce long-lasting protective immunity against TB. Hence, any effective TB vaccine needs to do better than natural immunity. This is not impossible and there are several promising leads (e.g. Advax and M72/AS01E). However, we are not there yet, and we should not assume that it will be achieved. It is noteworthy that feasible and effective vaccines for other high-burden diseases, such as HIV and malaria, have proved elusive.
- We need to focus on high-risk groups to end TB in high burden settings.
Most people who develop TB in countries with a high burden of TB are not members of any high-risk groups. “High-risk” group refers to a group of people (e.g. household contacts, people living with HIV, people with diabetes, homeless people and people in prison) who have a higher risk of having TB than people who are not members of that group. However, in most settings, these groups represent a small minority of the population (except for people living with HIV in some sub-Saharan African settings). Even if the members of these groups individually have a higher risk of having TB than others, the number of high-risk people detected with TB will almost always represent a small proportion of all the people with TB. Furthermore, some people who are at high risk of having TB (e.g. young child contacts and people living with HIV) are less likely than other people with TB to transmit the disease to others.
Hence, while focusing on high-risk groups is beneficial for the members of those groups who have TB (at least until they are re-infected with TB due to subsequent exposure), it will not be sufficient to end TB in high-burden settings.
This argument does not apply in settings with a low burden of TB. In those settings, most people who develop TB are, indeed, members of high-risk groups (in particular, the group of immigrants who were born, or lived in, a country with a high burden of TB). In those settings, further progress in ending TB is best achieved by focusing on these high-risk groups. The problem has been the transfer of the logic from low-burden to high-burden settings, where the epidemiology is fundamentally different.
- TB is caused by poverty; we can’t end TB until we end poverty.
There is only one “cause” of TB: infection with Mycobacterium tuberculosis. It is true that many correlates of poverty increase the risk of acquiring TB infection and of progressing to active TB disease. It also true that TB disease causes poverty in many individuals, and the families of many individuals, who suffer from it due to loss of income and the catastrophic costs that are incurred.
It is not true that progress towards ending TB cannot be achieved unless we end poverty. Cuba was, and is, a poor country but achieved substantial progress towards ending TB by prioritising effective interventions. In Ca Mau, Vietnam, active case-finding implemented annually over just three years resulted in a reduction in incidence of 57%, without any action on the socioeconomic determinants of health (additional reference).
At least one of the major causes for the association between poverty and a high burden of TB is the inability of poor countries to pay for the interventions required to end TB. Fortunately, some new tools are making this more feasible, but it is likely that support from the Global North will be required to fully enable the ending of TB in the Global South. Of course, it remains important to support coordinated global action to end poverty. However, we do not need to wait for the end of poverty to achieve the end of TB. People living in poverty should not be condemned to live and die with TB.
- TB is a private problem: it is up to individuals to seek care and to decide what treatment they want.
Cancer, diabetes, high blood pressure, asthma and all non-communicable diseases are “private” problems. The main person affected is the person who suffers the illness. That person’s carers and dependants, their work colleagues and the entity that is required to provide health care and social support for them may also be affected, but to a lesser extent. Finally, the individual with the illness is the major stakeholder in their illness. All decisions about diagnosis and treatment rightly rest with that individual.
In contrast, communicable diseases are public problems; the more transmissible the infection, the more public is the problem. TB is communicable by the airborne route and, if undiagnosed and untreated for a prolonged period, is likely to result in the infection of many others in the community. Furthermore, if treated with the wrong medicines, intermittently or for an inadequate duration, there is a risk of development of drug-resistant strains that can also be transmitted to others. Those who are at risk of being infected by a person with TB are stakeholders in that person’s illness; they have a legitimate interest in ensuring that the individual is diagnosed with, and effectively treated for, TB to prevent the risk of transmission to others. To put this in its most extreme form, we must recognise that people with TB do not have the right to harm others by knowingly and wilfully exposing them to the risk of infection with TB. It is in this sense that TB is a public problem.
It is possible to respect the autonomy and rights of the individual affected by TB while, at the same time, respecting the right of their community to be protected from infection. In fact, their interests are mostly aligned: ensuring the person is rapidly diagnosed and safely and effectively treated. However, it is important to recognise the mutual rights and responsibilities of the individual and the community in dealing with the problem of TB.
- We would have ended TB long ago if not for HIV.
There is no doubt that people living with HIV are a far greater risk than people without HIV infection of progressing to active TB (and hence being infectious to others). There is also no doubt that, in sub-Saharan Africa, the HIV epidemic was associated with an acceleration of the TB epidemic, particularly before the advent of effective anti-retroviral therapy. However, people living with HIV only develop TB if they are, or have been, exposed to another person with active pulmonary TB disease, from whom they acquire the infection. In countries where TB is not endemic, people living with HIV rarely develop TB. Hence, it remains possible to end TB, even in the presence of HIV. Furthermore, much of the world did not suffer the extensive HIV pandemic that was seen in sub-Saharan Africa. These countries (e.g. India, Indonesia, China, Vietnam, Bangladesh and Philippines) have uncontrolled TB epidemics that are unrelated to HIV.
- Even if we find all currently infectious cases and prevent all new infections, we can never end TB while there are nearly two billion people with latent TB infection.
It is true that there are many people with latent TB infection, that is people who have TB infection but do not currently manifest any evidence of disease. Although it cannot be directly measured, immunological tests are able to detect probable latent TB infection in 30-50% of adults in high burden settings. Most of these people have never been treated for TB infection and we know from observations in people living with HIV and in people treated with potent immunosuppressive drugs that the infection is highly likely to reactivate if the immune system is disrupted in a specific manner (that is, the person will develop active TB disease).
However, we also know from studies in low-burden TB settings that, in the absence of these specific triggers, the rate of reactivation of latent TB infection that was acquired in the remote past (more than 2 -3 years) is very low. In these settings, this low rate of reactivation has not led a resurgence of TB transmission, even in the absence of widespread treatment of latent TB infection.
In high-burden settings, reactivation of remote past latent TB infection represents a small (and possibly very small) proportion of all incidence of active TB. Therefore, it does not prevent action to transform high-burden to low-burden settings and, with some management, can be prevented from causing a resurgence of community transmission of TB in low-burden settings.
- Finding some more people with TB goes some way to ending TB.
TB is an infectious disease, spread by the aerosol route, mainly in indoor settings including homes, workplaces and public spaces. One infectious person with TB can infect many others, particularly, if they remain infectious for many weeks, months or even years (additional reference). There is evidence that this infectiousness is not limited to the household and close contacts (additional references from Buu and Glynn). Hence, leaving any undetected, and hence untreated, people with TB behind poses a risk to the entire community, not just the household. Finding just a few more people with TB and leaving many behind is unlikely to have any impact on the rate of transmission of TB infection, and hence on ending TB. It seems clear we need to aim to find all, or nearly all, people with TB in the community to break the chain of transmission.
- Active case-finding (screening) for TB is mainly for the benefit of the people who are detected.
People with undiagnosed TB are at risk of death or severe long-term disability due to the disease. Hence, finding and treating people with undiagnosed TB is beneficial for them. There are similar benefits for finding, diagnosing and treating people with non-communicable diseases (e.g. breast cancer, hypertension and metabolic diseases), when drug treatment or surgery is likely to prevent severe adverse outcomes.
However, unlike non-communicable diseases, the benefit doesn’t end with the person who is found and treated. Indeed, the main rationale for active case finding for TB (and other communicable diseases) is to prevent infection of others by finding and treating people with infectious disease, so they are no longer infectious to others.
- Active case-finding is active case-finding; it doesn’t matter how you do it, it all helps end TB.
The role of active case-finding in ending TB is to find and treat all, or nearly all, people with active pulmonary TB disease in a geographically defined community so that people living in that community will be prevented from acquiring TB infection. This is how we break the chain of the TB epidemic.
- All people (older children and adults) in the geographically defined locality are screened (not just those in high risk groups, those who volunteer, or those with symptoms)
- The first stage screening test has high sensitivity for TB, that is, it does not miss many people with TB
- All confirmed people with TB should receive, and complete, appropriate and effective TB drug therapy
- The active case-finding intervention must be repeated regularly (say, annually) until the number of people is very low and the cycle of ongoing infection and disease is broken. This may take five to 15 years, depending how many people have TB when you start and how effective the active case-finding program is.
Unfortunately, ~50% of people with TB in the general community do not have symptoms, such as cough, fever or weight loss (additional reference). Therefore, screening people using symptoms as the first stage of screening is not useful, as it will be miss half of the cases in the community. Also, sputum smear microscopy, the traditional test performed on sputum in TB labs, has a sensitivity of only ~50% and, therefore, is not a useful test in active case-finding.
The only two screening tests currently available that have sufficient sensitivity to be useful as a first stage screening test, are chest radiography with AI-reading of images and expectorated sputum tested using nucleic acid amplification tests specific for TB. In the future, new tools will be available that will need to simpler, more effective and more efficient screening algorithms.
- The cost per case detected in community-wide active case finding is high. Therefore, the intervention cannot be considered cost-effective compared with other interventions.
This would be correct if TB was a non-communicable disease, in which the only beneficiaries are the people with disease who are detected. However, calculating the number of people needed to be screened to detect a single person with TB – the yield – is the wrong measure to gauge the value of active case-finding for TB. This measure completely discounts (ignores) the prevention benefits due to finding and treating people with infectious TB.
The goal is to end TB by breaking the chain of transmission. The relevant endpoint is the impact on the incidence of TB. The number of people with TB who remain undetected, rather than the number of people detected with TB, is a more relevant intermediate endpoint.