MedicalResearch.com Interview with:
Dr. Stefan Goldberg MD
Medical Officer in CDC’s Division of Tuberculosis Elimination
Clinical Research Branch
Medical Research: What is the background for this study? What are the main findings?
Dr. Goldberg: A shorter, simpler treatment regimen for children with latent TB infection can help prevent TB disease and reduce future transmission. The results from our study, a multinational, clinical trial, found that a once-weekly regimen of the anti-TB drugs rifapentine and isoniazid taken as directly observed therapy over a period of three months was safe and as effective for children (age 2-17) in preventing TB disease as the standard self-administered nine-month daily regimen of isoniazid alone. The study also showed that children are more likely to complete the shorter course of treatment, which is important given that treatment completion can be difficult. Specifically, we found that 88 percent of the trial participants on the combination regimen completed therapy while 81 percent completed the standard regimen.
The CDC’s Tuberculosis Trials Consortium (TBTC), which conducted this study, works to include children in research when their inclusion is scientifically supportable and when children also might benefit from important new tools, such as alternative treatment regimens. This study is an extension of a large, international trial among persons age 12 and older, published by TBTC in 2011, which showed the shorter, simpler regimen to be as safe and effective as standard treatment.
Medical Research: What should clinicians and patients take away from your report?
Dr. Goldberg: It is important to know that latent TB infection can be particularly dangerous for younger age groups. In comparison to adults, children are at increased risk for developing life-threatening forms of the disease (e.g., disseminated TB, TB meningitis). Young children with latent TB infection are, by definition, more likely to have been infected recently, and therefore are among the groups most likely to develop Tuberculosis disease. However, these same risks make treatment of latent infection all the more beneficial for this age group, especially when considering children are more tolerant of the treatments than adults.
While the shorter treatment regimen is already recommended for use in otherwise healthy adults who are at high risk for developing TB disease, until now, limited data were available for children. Currently, CDC recommends the standard nine months of daily isoniazid be used to treat children aged 2-11. However, the three-month regimen can also be considered for those in this age group. One situation where shorter treatment may help would be where completion of the nine-month regimen is unlikely and the likelihood of TB disease is great.
CDC is currently working with the American Academy of Pediatrics, the American Thoracic Society, and the Infectious Diseases Society of America to update full public health guidelines for treating latent TB infection in the United States, and findings from this study will be considered for inclusion as a part of this process.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Goldberg: Addressing latent TB infection is key to eliminating TB in the United States. Overall, approximately four percent of the population (or more than 11 million people) have latent TB infection, and 5-10 percent of those will develop TB disease if not treated. If infected, it is critical that those at high risk of progressing to TB disease both begin and complete treatment.
Further research is already underway for this shorter treatment regimen in other specific populations (e.g., people living with HIV) and in TB control program settings. Cost effectiveness analyses have been performed and require further consideration.
Unsupervised treatment, which might improve cost effectiveness, also needs to be evaluated for safety and for whether it can achieve sufficient completion rates. Programmatic interventions such as culturally designed case management and additional forms of direct observation (e.g., remote video monitoring of dose ingestion) also require rigorous evaluation.
Villarino M, Scott NA, Weis SE, et al. Treatment for Preventing Tuberculosis in Children and Adolescents: A Randomized Clinical Trial of a 3-Month, 12-Dose Regimen of a Combination of Rifapentine and Isoniazid. JAMA Pediatr. Published online January 12, 2015. doi:10.1001/jamapediatrics.2014.3158.