Last year, the World Health Organization released updated procedures on how best to tackle the global scourge of tuberculosis. The fourth edition of the “Treatment of tuberculosis: Guidelines” recommended, among other changes, increasing the dosage of tuberculosis medication required to treat children. But, in a sense, the new guidance provided a destination without a map: it failed to address the larger problem of how to improve the accuracy of pediatric dosing.

In recent months, researchers have pointed to a host of problems plaguing the diagnosis and treatment of tuberculosis in children, especially those younger than age 5. For example, at a June workshop held by a taskforce of the US Centers for Disease Control and Prevention, Steve Graham of the Royal Children's Hospital in Melbourne, Australia called for new and better means of pediatric tuberculosis diagnosis, which can be complicated by concurrent ailments such as malnourishment, HIV infection and pneumonia. And, in September, scientists noted that a negative result from the new interferon-gamma release assays cannot definitively rule out tuberculosis in children (Pediatr. Infect. Dis. J. 30, 817–818, 2011). Also in September, another group urged that animal models for tuberculosis “must be designed and utilized in a manner that is also pertinent to the pediatric population” by addressing age-related variance in drug metabolism (Pharmacol Res. 64, 176–179, 2011).

If pediatric tuberculosis is overlooked, it may in part have to do with the thought that children with the illness are less infectious than affected adults, so disease control programs tend to focus on older populations capable of spreading the pathogen within their communities. But, in certain regions of the world with high rates of the disease, “the average risk of [childhood infection] is about 20% per year of life in the first five years, so this is not a minor component that can be easily overlooked,” says Tobias Kollmann, a pediatric infectious disease specialist at the University of British Columbia in Vancouver, Canada. “It's a huge growing problem in areas where tuberculosis is resurgent.”

Current tuberculosis medications are comprised of a single, fixed-dose combination tablet that combines a number of drugs. As Graham cautioned in a paper published in March, the ratios of those medications should also vary according to a child's age and size, an issue that is also not addressed in the new guidelines (Paediatr. Respir. Rev. 12, 22–26, 2011). Currently, to treat small children the adult tablets are cut or crushed, which often leads to inaccurate dosing and inappropriate ratios.

To avoid these issues, experts say weight-adjusted tablets or a liquid formulation need to be developed specifically for children, so that treatments can be more easily tailored. But, despite the fact that an estimated 1 million children currently suffer from tuberculosis, pharmaceutical companies do not see huge profit margins in addressing the problem and have not made significant investments in this area. Graham suggests that a solution is to give drug developers “the assurance that they would have a market.”

In addition, clinical trials for children need to be implemented so that child-specific formulations can move forward. “Companies are doing the studies in the adults and forgetting about the kids, and meanwhile all these children die,” says Grace Aldrovandi, a pediatric infectious disease researcher at the University of Southern California–Los Angeles.

A handful of developers are bucking the trend. The German drug giant Bayer is currently testing its antibacterial drug Avelox (moxifloxacin) in a 2,400-adult phase 3 clinical trial for tuberculosis that could potentially be suitable for children. If the drug proves effective for grownups, it may be in safety trials in children by 2014, says Elizabeth Gardiner, head of market access for the New York-based TB Alliance, which is cosponsoring the international study. The US pharmaceutical company Janssen Therapeutics in is in the early stages of developing a child-specific tuberculosis treatment called TMC207 and is in discussions with The IMPAACT Network, a clinical trials group, to begin trials with children.

“We're on the verge of real change when it comes to pediatric tuberculosis,” Gardiner says, “and we hope that it really happens.”