New Study Addresses Prevalence of Multidrug-resistant Tuberculosis in Children

Tuberculosis (TB), an infection caused by the bacterium Mycobacterium tuberculosis, is listed by the World Health Organization (WHO) as one of the top 10 leading causes of death worldwide. It was estimated in 2015 that 10.4 million individuals were infected with M. tuberculosis, leading to 1.8 million associated deaths. There were 1 million children estimated to have fallen ill with TB in 2015; 170,000 died from the disease.

On a larger scale, multi-drug resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid and rifampicin, is a global problem, affecting approximately 500,000 individuals worldwide. The MDR-TB burden in children has been difficult to estimate, thus, making it difficult to develop better plans to effectively treat children with second-line drugs.

In a new study published by the Oxford University Press, principal investigator Sarita Shah, MD, MPH, and her colleagues seek to describe the epidemiology of MDR-TB in children in the past 20 years—a question that was previously unaddressed. The authors note that previous estimates of the MDR-TB burden in children were significantly underestimated due to the difficulty in confirming TB in children through microbiological techniques. Confirmation of TB via these techniques is one of the verification criteria for TB cases to be counted in the US national TB surveillance system (NTSS), a program where each of the 50 states, as well as the district of Columbia, report TB cases. Instead, diagnosis of TB in children has been traditionally based on chest x-rays and symptoms.

In the study, the authors compiled all newly-diagnosed cases of TB from children aged 15 years and younger that were reported to the NTSS from 1993 through 2014. In order to determine the possible underestimation of pediatric MDR-TB in NTSS, the authors contacted the 6 top states that had the highest number of laboratory-confirmed MDR-TB cases in children during the years of the study. They asked each state to report all cases of TB patients who received MDR-TB treatment, and to provide justification for the decision when possible.

There were 20,789 cases of pediatric TB reported from 1993 to 2014, of which approximately 25% had culture-confirmed TB. The authors found that 1.7% of the pediatric TB cases reported were MDR-TB, with 81% being resistant to at least one other first-line drug and one-third being resistant to at least one second-line drug. In the pediatric MDR-TB cases reported, 96% of patients were initially treated with first-line drugs only for an average duration of treatment of 20 months. For those that started treatment before 2013, the majority of patients (86%) completed treatment while the remaining 14% either died, refused treatment, or had no treatment history recorder.

Overall, Dr. Shah and her colleagues found that the prevalence of MDR-TB in children in the US from 1993 to 2014 was lower than the overall prevalence of MDR-TB globally (1.7% vs 3.2%) and was similar to the overall prevalence of MDR-TB in the United States (1.7% vs 1.5%). Interestingly, the authors note that two-thirds of the MDR-TB cases reported in children were from US-born patients, which suggests that MDR-TB is being transmitted in the United States.

This study represents the first time the epidemiology of MDR-TB in children was examined in the United States, and highlights the need for new molecular diagnostics to overcome the hurdle of efficiently diagnosing TB in children.

Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing her PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.