Waking up to the realities of drug-resistant tuberculosis in children


In my more than 13 years as a tuberculosis (TB) researcher and pediatrician, there is one prevailing trend that has increasingly troubled me: people, especially individuals in the U.S., like to believe that TB is no longer an important issue. This misperception is dangerous, especially when one accounts for its growing resistance to drugs and the difficulties of diagnosing and treating TB, especially in children.

TB causes almost 10 million new cases worldwide annually, with strains impervious to drug treatments rapidly spreading. Recent estimates suggest that a million of these new cases occur in children, but the real number may be higher. Research has not kept up, and there is a lack of reliable diagnostics for young children and treatments for drug-resistant TB.

{mosads}My colleagues and I recently treated a child with a highly drug-resistant form of TB known as extensively drug-resistant, or XDR TB. It was the first detailed account of a young child from the U.S. diagnosed and treated for XDR TB and is a sharp rebuke to anybody who thinks TB is a disease we have already conquered.

The child was brought to The Johns Hopkins Hospital with unrelenting fever after returning from a trip to India. An initial battery of tests showed no clear cause, but a chest X-ray revealed suspicious lung and lymph node spots — a telling clue for TB. Even though initial tests remained negative, preemptive treatment for TB was administered, largely because preliminary test results are notoriously unreliable. The child’s symptoms improved with standard treatment, but a repeat X-ray revealed signs of persistent lung infection. Lab tests ultimately showed that the child harbored XDR TB. In all, conclusive identification of drug-resistant TB took 12 weeks.

Around that time, the child’s fevers came back. We needed to move quickly and initiated a combination treatment cocktail with five new drugs. But, we faced yet another hurdle: We had no fast, reliable way to monitor how her TB would respond to the drug cocktail. Confirmatory lab tests could take weeks.

In the absence of reliable clinical markers, the need for rapid readouts and the dangers of treatment failure, we felt a CT scan was our best option. The scans suggested successful response to the revised drug cocktail 10 weeks before reliable improvements in any physical symptoms (consistent weight gain) were noted in this child. CT scanning proved useful for monitoring treatment in this patient, and we need additional studies to confirm this finding. Other imaging approaches under development have the potential to provide even more precise information than CT.

Given the child’s good overall health and the fact that her disease is in remission, we believe that relapse of the disease is less likely. However, we will continue to follow the child for another two years or so.

The difficulties of treating this young child — delays in diagnosis, the 12 weeks it took to identify a drug-resistant disease and limited drug treatment and monitoring options for a child of this age — illustrate the ways in which U.S. medical and public health infrastructure is inadequately prepared for drug-resistant bacteria.

In the last 40 years or so, only two new TB drugs have been brought to market. And only a few TB drugs are available in “child-friendly” forms — healthcare workers or parents routinely chop or crush pills to administer them to young children. While progress has also been made in developing better TB diagnostics for adults, these technologies have not performed well in children.

We need to think outside the box and invest in research to develop novel diagnostics and treatment options. This is necessary and pressing in the context of rapid diagnosis of drug-resistant bacteria, hiding in inaccessible sites deep inside the body, and monitoring responses to TB treatments.

While we are thrilled that our patient is doing well, the case underscores the need for ongoing investment in research on TB. Right now in Congress, that is a tough case to make, but it is one that our representatives need to hear. For most young children, XDR TB represents a death sentence, as do many other increasingly resistant diseases. As the world has become more and more interconnected, diseases some of us once thought as belonging to other worlds need to be recognized as domestic issues.

Jain is associate professor of pediatrics and assistant professor of radiology and radiological science at The Johns Hopkins University School of Medicine and international health director at The Johns Hopkins University Center for Infection and Inflammation Imaging Research.

See all Hill.TV See all Video