One in Eight TB Cases in Children Is Isoniazid-Resistant

Ricki Lewis, PhD

June 01, 2015

Isoniazid-resistant tuberculosis (TB) is more common than had been thought among children, particularly in Europe, according to the results of a study published online June 1 in Pediatrics.

About 15% of tuberculosis cases are resistant to isoniazid, but little is known about the percentage of children who are resistant, nor about where they live. Resistance is difficult to identify in children because specimens typically do not harbor enough bacteria to test drug susceptibility.

Undiagnosed resistance can result in ineffective treatment and increases the risk for treatment failure and death. Cases of isoniazid-resistant TB in children have been reported from all over the world, but the proportion and number of cases have not been evaluated. These measures could inform public health policy.

Courtney M. Yuen, PhD, from the Division of Global Health Equity, Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues conducted a systematic literature review (43 reports) that used World Health Organization data to estimate the proportion and number of children aged 0 to 14 years with TB and isoniazid resistance by region.

For 2010, 12.1% (95% confidence interval [CI], 9.8% - 14.8%) of all children with TB had isoniazid-resistant disease, which corresponds to 120,872 (95% CI, 96,628 - 149,059) cases. Although most of the cases were in the Western Pacific and Southeast Asia, the greatest proportion (26.1%; 95% CI, 20.0% - 33.6%) of child TB cases that were isoniazid-resistant was in Europe.

"The finding that 1 in 8 children with TB globally have isoniazid-resistant disease has enormous implications for the effectiveness of treatment," the researchers write. Extrapolating from the 7.6 million new latent TB infections in the 22 nations with the highest TB burdens to a global level, the researchers estimate that more than a million children contract isoniazid-resistant infections annually. Many cases trace to adults with isoniazid-resistant tuberculosis, they hypothesize.

The investigators caution that other resistances may be present too, and advise that in areas in which isoniazid resistance status is not known, and specimens from children are not obtained, a minimum of four drugs should be deployed for the initiation stage of treatment. They add that if resistance to isoniazid alone is known or the child has been exposed to such a case, the child should receive at least three drugs (rifampicin, pyrazinamide, and ethambutol) for 6 months.

Limitations of the study include reliance on previously published data collected from 1995 to 2013 and the assumption that the data were applicable to 2010, spotty coverage of countries in the World Health Organization data, and the assumption that proportions of resistance in adults are parallel among children.

Janssen Pharmaceuticals provided funding for this study. Dr Yuen and three coauthors report salary support through a grant from Janssen to Harvard Medical School. One coauthor also reports salary support from the Eli Lilly MDR-TB Partnership. The remaining author has disclosed no relevant financial relationships.

Pediatrics. Published online June 1, 2015.

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