Childhood tuberculosis: Are we at the tipping point?
In 2012, tuberculosis remains one of the major global diseases, with almost 10 million annual cases and 1.7 million deaths caused by the disease.
Drug-susceptible TB can be cured with less than $100 of medications; a course of isoniazid to prevent TB infection from becoming TB disease costs only a few dollars; and bacille Calmette-Guérin (BCG) vaccines have been given to billions of patients. Yet, the disease persists, and now more than 500,000 people annually develop drug-resistant TB, which is purely a manmade problem caused by poor TB control.
Our failure to control TB remains the biggest public health failure in history. In the 1950s, René Dubos famously called TB “a social disease” and predicted that we would fail to control it unless the societal issues of how we confront it were addressed in a more meaningful way. Unfortunately, these words ring true 60 years later.
No group has been more affected by our inadequate approach than children. We really do not know how many children develop TB every year because children often receive few TB-related services in the highest TB-burden countries. WHO estimates that there are nearly 1 million annual TB cases among children, resulting in several hundred thousand annual deaths from this curable disease. However, many of these cases are not found and the children never treated, or treated only after the disease has become far advanced.
Diagnosis and treatment
TB has been found to be one of the leading causes of death in children with HIV infection in Africa. Children are rarely contagious, so they receive little priority in high-burden settings, where the only available diagnostic test for pulmonary TB is commonly an acid-fast sputum smear, which is positive in fewer than 10% of children with TB. Even the culture is positive in fewer than 40% of children with TB. Diagnosis of TB in children requires specific expertise, simple tools such as a chest X-ray and a health care system that provides care for entire families, not just the adult with TB.
Although WHO has recommended for more than 30 years that asymptomatic children living with an adult with pulmonary TB should be given isoniazid to prevent them from developing TB disease — standard practice in low-burden countries — this low-cost intervention is rarely carried out in the high-burden countries, where it would have the greatest impact.
Even in wealthy countries, most childhood TB cases are diagnosed using a combination of history and physical examination (dating to about 400 B.C.), smear and culture (1882), chest X-ray (1895) and the tuberculin skin test (1907). No “game-changing” diagnostic tool has been developed in more than 100 years!
The last TB drug to be approved was rifampin (1967), and the BCG vaccine dates to the 1930s. Would we tolerate such lack of progress for any other infectious disease that affects so many children? We must be honest and state that complacency among pediatricians and those who advocate for children has played a part in this lack of progress.
Every year, March 24th is World TB Day, and this year, for the first time, childhood TB will be the major theme. The good news is that there has been a convergence of events and efforts that have the potential to change things for children. In his 2000 book, The Tipping Point, Malcolm Gladwell described the three basic elements of social “epidemics” that lead to fundamental change — the “tipping point.” First was how trends are often driven by a handful of exceptional people (The Law of the Few). Second was the central importance of environment in changing behaviors (The Power of Context). And third was how to make a “contagious” message memorable (The Stickiness Factor). The question is: Are we at the tipping point for childhood TB? I think we have the potential now to excel in all three elements.
Times are changing
There is a small but highly committed group of childhood TB researchers (The Few) who, in the past year, have improved collaboration in a very meaningful way. At two international meetings, these exceptional people have standardized definitions of childhood TB for research, begun developing standard operating procedures for virtually all diagnostic techniques, and developed a fundable research agenda. Several networks of researchers from five continents have formed to develop research protocols and operational improvements. Through WHO, a “roadmap” for investigating and controlling childhood TB is being developed. One challenge will be to develop both research protocols and improvements in public health and patient care that can be adapted for local conditions in low- and high-burden settings (The Context).
Although we generally excel at developing science, followed by writing clinical guidelines, we often fail in developing effective local policies and practice to put new developments into action. What is desperately needed is a marketing plan (The Stickiness) for childhood TB. We need to impress upon funders, industry, health officials and governments that children can no longer be excluded from research protocols, new drug development and public health services. There must be advocacy to change the behaviors of decision-makers in science, industry and public policy. The pediatric infectious disease community needs to take a leadership role in this effort so that this ancient disease will no longer needlessly kill children all over the world.
Disclosure: Dr. Starke reports no relevant financial disclosures.