How do we get to zero TB?

By Salmaan Keshavjee MD, PhD, ScM
Department of Global Health and Social Medicine
Harvard Medical School

 

Tuberculosis (TB) has surpassed HIV/AIDS as the biggest infectious killer of adults worldwide.  In 2015, an estimated 10.4 million people became sick with the disease—one million of whom were children—and 1.8 million people died.  That’s one person dying every 18 seconds from a disease that has been largely treatable since 1948.

Why do so many people die from this treatable disease?  Mostly because they are not diagnosed in time or do not receive the correct care.  In 2015, more than 40 percent of the estimated number of people with TB were not diagnosed and received no treatment.  An estimated 580 thousand people became sick with multidrug-resistant TB (MDR-TB), disease caused by Mycobacterium tuberculosis resistant to the two main drugs of the first-line anti-TB treatment regimen; only 22 percent of those individuals received treatment and less than half were cured.  Because the disease is airborne, those who are not diagnosed or do not receive the correct treatment continue to spread the disease in their families, communities and places of work.

Until recently, many countries faithfully adhered to the World Health Organization’s (WHO) DOTS strategy to tackle TB.  Introduced in 1993, the DOTS strategy proposed a limited set of interventions for low- and middle-income settings, aimed at “controlling” the epidemic. For the most part, the approach ignored some of the pillars of TB epidemic control that had nearly eliminated TB in rich countries: active case finding (including the screening of close contacts); rapid treatment of people sick with any form of the disease, including drug-resistant strains; and prophylaxis for individuals with TB infection that has not yet progressed to disease (e.g. isoniazid prophylaxis therapy, or IPT).

Why was this the case?  Sadly, the reasons had little to do with science.  For example, as early as 1964, the WHO’s Expert Committee on Tuberculosis discouraged the use of IPT outside of rich countries, “arguing that cost, logistical difficulties, the likelihood of defaulting, and other concerns all made it unfeasible.” (Macmillan 2015: 195).  This decision was reaffirmed in 1974 by another WHO expert committee, which, despite overwhelming data showing the benefits of IPT from the work of George Comstock and others in the United States, deemed the use of IPT “irrational”.  It was again reaffirmed in 1982 because of fears that treating TB infection would divert resources away from tackling active disease.  The WHO and its partner, the International Union Against Tuberculosis and Lung Disease (IUATLD), argued then that “in practice [IPT] has virtually no role in developing countries.” (Ibid).  Similar arguments—based primarily on dogma about cost and the belief that countries outside the “global north” would not be able to deliver more than a rudimentary level of care to their populations—were made about active case-finding and about the treatment of MDR-TB.  Instead, the DOTS strategy relied on passive case-finding—waiting for the sick to make it to a clinic—as well as diagnosis with sputum smear microscopy, a low-sensitivity test ill-suited for the diagnosis of children, people co-infected with HIV, people with extra-pulmonary TB, and those with disease caused by drug-resistant bacteria.  While the policies of the WHO have changed in some of these areas, systems built around delivering the DOTS strategy have not.

The result of ignoring these important facets of TB epidemic control—both a moral and scientific failure—has been the death of millions and a largely unabated epidemic.  Over the last decade, the decline in TB has been paltry: roughly 1.5% per year. If this trend continues, this means that it will take approximately 200 years for the global TB rate to reach the level seen today in North America and Europe.  It does not have to take this long.  In order to change this trajectory, countries like South Africa, India, China, Russia, Brazil, Indonesia, Kenya, Peru, Pakistan and many others, must take the bold step of instituting a comprehensive package of tried and tested approaches to stopping the TB epidemic.

So what should be done?  This comprehensive approach, which has been outlined by scholars and practitioners from 11 countries in a series in The Lancet called How to Eliminate Tuberculosis, is conceptually simple, but requires that we rethink the way we are struggling against TB.  The series outlines how we should clearly know the TB epidemic, using data and deploying epidemic control strategies as needed to different hotspots.  It also outlines a strategy of three interlinked components: SEARCH, TREAT, and PREVENT.

SEARCH means to actively find people sick with TB, as well as those infected with TB but who are at high risk of becoming sick.  Finding those people who are already sick with TB is critical because they are infectious and continue to spread the disease in their families and communities.  Finding out who has been infected or exposed to TB—and who may later become sick—is also a critical part of searching.  Data have clearly shown that people infected with TB have at least a five percent chance of becoming sick with active disease within the first two years after infection.  That’s one in twenty people that will get the disease and continue to transmit the disease in families and communities, even after the original index patient has been treated.  Thus, stopping the epidemic means finding these people and offering them post-exposure treatment. Where does one find individuals at most risk of developing TB?  Again, the data are quite clear: people living in the household of a TB patient have a one to five percent chance of having active TB; those seeking care in general health care facilities have a five to ten percent chance of having active TB; and individuals receiving HIV-associated care have a one to 25 percent chance of having active TB.  There are other high-risk groups—such as people working in mines, garment factories, or spending considerable time in other over-crowded areas—but households and health care facilities are certainly an important place to start looking.

TREAT means ensuring that people sick with TB get the quickest correct treatment for their TB, regardless of whether they have a drug-sensitive or drug-resistant strain.  The correct treatment of the disease stops people from dying, from having long-term sequelae from the disease, and stops transmission.  Studies from the 1950s, 1960s, and even recently, have shown that if a sick person is started on the correct therapy—a therapy capable of killing the strain of TB with which he or she is infected—he or she is no longer infectious.  Part and parcel of this is ensuring rapid and ready access to new anti-TB drugs and fast-tracking research on shorter and more efficacious regimens.  One can never forget that TB leads to an almost certain death—like many cancers—so the risk of initiating treatment with new drugs or drugs with adverse events is far outweighed by the benefits.

PREVENT means engaging in a set of activities that will help stop the transmission of TB.  First, it is critical to ensure that infection control measures are taken in health care facilities so that TB does not spread.  Second, it means ensuring that individuals infected with the TB bacillus, but who are not yet sick with TB disease, receive post-exposure treatment that will prevent their infection from progressing.  Pathbreaking studies from the 1960s showed that prophylaxis after infection—coupled, of course, with active case finding and treatment of people sick with TB—not only helped bring down the rates of TB dramatically, but reduced TB deaths for at least 20 years after the intervention.

As we know, TB is a disease that moves preferentially among the poor, the malnourished, and the immunocompromised.  People with HIV coinfected with TB have a 5 to 10 percent chance each year of becoming sick with TB; malnourished people with a low body mass index (BMI) have a ten-fold risk of getting TB.  This means that treatment and prevention will require ensuring that people sick with TB and those receiving post-exposure treatment have enough food to eat, that they have access to appropriate housing, and that their co-morbid conditions (e.g. HIV, diabetes, malnutrition) are cared for.  Because TB is itself a driver of poverty, prevention also requires health systems to engage in a multi-sectoral approach, including linking people and families sick with TB to innovative poverty-alleviation mechanisms.

The interventions that are part of the SEARCH, TREAT, and PREVENT (S-T-P) strategy will take a major push, and many will be tempted to implement them piecemeal.  This would be a mistake.  Both global experience and mathematical models suggest that deploying these interventions in combination will rapidly lower both TB cases and deaths.  Creating systems capable of implementing the S-T-P strategy will require resources, and in many cases, reorganization and integration of activities with other programs.  If done properly this will not only move us rapidly towards eliminating the scourge of TB, but the systems developed can be used to give care to people with asthma, diabetes, hepatitis C, and a number of other diseases.  Taking the correct steps to end the TB epidemic is vital to building our collective capacity to provide high quality universal health care.

References:

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Dye C, Glaziou P, Floyd K, Raviglione M. Prospects for tuberculosis elimination.  Annual Review of Public Health 2013; 34: 271–86.

McMillen, CW.  Discovering Tuberculosis: A global history 1900 to the present.  New Haven: Yale University Press, 2015.

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