Overall, as many as 1 million children become sick with TB each year, about twice the number previously thought, and of these, only a third of the cases are ever diagnosed, the study found.
"A huge proportion (of children) are suffering and dying from TB unnecessarily," said Helen Jenkins of Brigham and Women's Hospital's Division of Global Health Equity, the lead statistician on the study published on Sunday in the Lancet.
The findings, published as part of a special theme issue of Lancet to commemorate World TB Day on March 24, offer the clearest picture yet of the global burden of tuberculosis among its youngest victims, and for the first time estimate the burden of multidrug-resistant tuberculosis or MDR-TB.
"Despite children comprising approximately one quarter of the world's population, there have been no previous estimates of how many suffer from MDR-TB disease," said Dr Ted Cohen, also of the Harvard-affiliated Brigham and Women's Hospital, and a co-author on the paper.
For decades, researchers had largely ignored tuberculosis infections in young children, in part because children are less likely to transmit the disease than adults.
TB infections are especially hard to diagnose in children because the infection looks different in children than adults.
The disease is caused by bacteria that typically attacks the lungs and is often spread through the air when people who have an active infection cough.
Tuberculosis typically attacks the lungs and is spread through the air when people who have an active infection cough.
"In kids, you are much more likely to have TB disease in other parts of the body, not necessarily in the lungs," Jenkins said. Even when children do have TB in their lungs, there are fewer TB pathogens present, "making kids with TB invisible" to current diagnostic methods, she said.
To arrive at their estimates, Jenkins and colleagues scoured publicly available databases and devised a way to correct for chronic underreporting of TB in children.
"What we found was that whereas previous estimates for the total number of TB cases in kids were about half a million, when you account for (underreporting) in your estimates, it's more like 1 million children develop active TB disease every year," she said.
The World Health Organization estimates that 8.6 million people developed TB in 2012 and 1.3 million died from the disease. According to the WHO, half a million people became sick with dangerous superbug strains of tuberculosis in 2012, it estimates that up to 2 million people worldwide may be infected with drug-resistant TB by 2015.
Keeping track of TB rates in children is important for two reasons, Jenkins said. First, children with drug-sensitive forms of TB generally respond very well to treatment.
Second, because TB disease develops very quickly in children, often within weeks of exposure, finding an infected child can offer key clues about TB transmission within a community.
"That's telling you you've got some kind of system failure going on there," Jenkins said.
She said the findings illustrate the need for better methods of collecting data on childhood TB, including better diagnostics and more systematic data collection.