During his decade of work in South Africa, Stanford’s Jason Andrews, MD, has seen many young children die from tuberculosis and been frustrated by the lack of progress in the field. Children can be readily treated with antibiotics if the disease is caught early, but until recently, there has been no way to identify those at risk, he said. So many children are diagnosed too late to be saved.
Now a new study by Andrews and his colleagues finds that a commonly used TB screening test could be extremely valuable in predicting which children infected with the bacteria are likely to develop severe disease and could benefit from early intervention. The test is a kind of interferon-gamma release assay, known as QuantiFERON-TB Gold In-Tube, which is used for TB screening in the United States and abroad. The research appeared in Lancet Respiratory Medicine.
“Given the high rates of TB (in South Africa) and the difficulty of diagnosing it in kids, this test could be used routinely in kids to identify the high-risk ones,” Andrews, an assistant professor of medicine, told me. “You could imagine in a high-burden country that at a child’s 12-month visit, they could also get a QuantiFERON test, and if it’s high, they’d get aggressively investigated for TB.”
TB is the leading cause of death by an infectious disease worldwide, accounting for more than 1.4 million deaths annually. Adults are typically screened for the disease using a sputum test, but this doesn’t work in children, who swallow their sputum after coughing. So there has been no effective TB screening program for children, Andrews told me, and they suffer higher rates of disability and mortality from the disease.
Andrews and his colleagues decided to do an analysis of the 2,512 babies enrolled in previous TB vaccine trial near Cape Town. All of them had been tested using the QuantiFERON-TB assay at various intervals during the course of the trial, which was done between 2009 and 2012. The assay measures the immune system’s release of interferon gamma, a type of cell-signaling protein, when it is exposed to the TB antigen.
The researchers found that children with high test values were much more likely to get sick than those with low values. The difference was quite dramatic – a 40-fold higher risk for those with high values, compared to those with lower numbers. That’s the sign of a “very powerful marker,” Andrews said.
“What we are hoping is that this will show the international community – the WHO, the CDC and those creating guidelines – that QuantiFERON testing can be reliable in kids, and that the quantitative values may be important so we may need to look at different thresholds than we use in adolescents or adults,” he said.
Andrew and his colleagues now are looking at whether it would be cost-effective to scale up testing for the disease among South Africa’s children, he told me.