Managing Pediatric Tuberculosis

In 2013, 485 cases of pediatric tuberculosis (TB) were reported, according to estimates from the Centers for Disease Control and Prevention. Although treatment has made significant strides in recent years, the United States has a long road ahead before TB is eradicated in the United States.

To answer our questions about managing TB infection in children, Consultant360 spoke with Jeffrey R. Starke, MD, FAAP, who is a professor of Pediatrics-Infectious Disease at the Baylor College of Medicine in Houston, Texas. He recently spoke about “TB or Not TB: What’s New in the Management of Childhood Tuberculosis” at the Celebration of Pediatric Pulmonology and Sleep 2019.

CONSULTANT360: What’s new in the management of TB in children?

Jeffrey Starke: The major changes are in diagnosis and treatment of TB infection. The interferon-gamma release assay (IGRA) blood tests are slowly replacing the tuberculin skin test (TST) as the test of choice for TB infection—also called latent TB infection, although the infection is hardly latent in children. We have always known that the IGRAs are more specific than the TST, because they do not cross-react with most nontuberculous mycobacteria and the BCG vaccines. The issue has been the relative sensitivities of the two test types in young children, who have a higher risk for developing TB if their infection goes untreated. However, there has been much more experience with the IGRAs, and the American Academy of Pediatrics (AAP) now recommends their routine use in children aged 2 years or older, with some experts (like in my clinic) using the IGRAs in younger children.

Using 9 months (270 doses) of daily isoniazid as the traditional treatment of TB infection in children, the completion rate averages only 50% because of the long duration of therapy. There are now two additional and much shorter regimens that are recommended by the AAP for children. Rifampin can be given daily (120 doses) for 4 months with equal effectiveness and safety. Even better, for children aged 2 years or older, a 12-dose regimen of once weekly isoniazid and rifapentine—a long-acting rifamycin, a “cousin” to rifampin—is at least as effective as and safer than 9 months of isoniazid. It is available through most health departments in the United states.

C360: How has this treatment changed over the years?

JS: Treatment of TB infection has become shorter and safer by the use of the two new regimens, leading to higher acceptance by families and better rates of adherence and completion of therapy. The treatment of TB has not changed as much, with the initial 4-drug combination of rifampin, isoniazid, pyrazinamide, and ethambutol—so-called “RIPE” therapy—remaining the backbone of treatment. The major changes have been in the management of drug-resistant TB, which thankfully is rare in children in the United States. The World Health Organization (WHO) now recommends an all-oral regimen for the treatment of certain cases of multidrug-resistant (MDR) TB, avoiding the use of injectable drugs that are painful and have significant rates of adverse reactions. Two new drugs, bedaquiline and delamanid, are now available for the treatment of MDR TB, and repurposed drugs such as levofloxacin and linezolid have also proven effective against most strains of Mycobacterium tuberculosis. In short, with the increased number of drugs, the rates of successful treatment of MDR TB have risen tremendously.

An important change is the recent development and distribution of child-friendly dispersible formulations of individual and combination TB medications. Previously, and still in many countries, children have been treated with formulations that were designed for adults—pills and capsules—making treatment of small children quite challenging. These new dispersible formulations are being distributed in many high-burden countries; unfortunately, because of licensing issues, they are not available in the United States.

C360: What are the current controversies around treating TB in children?

JS: There are not very many controversies at present. Because of the relative paucity of studies of the management of MDR TB in children, much of the treatment remains individualized. As new drugs are developed, the child care community has determined that if a drug or drug regimen is effective for adults, it very likely will be effective for children, and the major areas for pediatric study are pharmacokinetics, safety, and tolerability. The rapid development of child-friendly formulations is and will remain a difficult area as there are few economic incentives for industry to make and test these formulations.

C360: What is the key takeaway from your session for pulmonologists and infectious disease specialists?

JS: There are three key takeaways. The first is that the management of childhood TB infection and disease is rapidly changing. We already have seen this change in the diagnosis and treatment of TB infection. There are several new TB drugs and drug regimens that are being tested in adults, and if these new regimens are successful, the recommendations for treatment of TB in adults will change profoundly. The challenge for pediatricians will be to determine how and when to use these new drugs and regimens in children and adolescents. Some experts have predicted that if these new drug regimens are proven successful, drugs like isoniazid and rifampin will be used rarely in the future.

The second key takeaway is that the “Holy Grail” of childhood TB research is the development of a new and accurate diagnostic test for TB. While 90% of adult TB cases can be confirmed with microbiology, only 30% to 40% of childhood cases can be confirmed; for children, the diagnosis depends on symptoms, radiographic and physical examination findings, tests of infection, and epidemiology—linking the child to the person who transmitted the organism. WHO has estimated that 75% of the childhood TB cases are never reported, and most are not even discovered or treated. A major reason for this is the lack of a simple, rapid, and accurate test for diagnosis in children.

The third takeaway is that while the BCG vaccines have saved many children’s lives by their protection against tuberculous meningitis and disseminated disease, they are not capable of eradicating the disease. We need a new and effective vaccine! Increasing case detection, improving treatment of TB disease, and preventing TB infection from progressing disease will greatly lower the burden of TB. Truly controlling and eliminating the disease will require a truly effective vaccine. Developing such a vaccine will be difficult and expensive but well worth the effort in terms of saving lives and avoiding suffering throughout the world.

To read more about Dr Starke's research, click here