Specialists at the Johns Hopkins Children’s Center claim to have successfully treated a then two-year-old patient with extensively drug-resistant tuberculosis.

Now five years old, the patient was afflicted with XDR TB, a highly virulent, drug-resistant form of tuberculosis. It was deemed the first detailed case of XDR TB diagnosed in the United States, and among only a handful documented in children below age five around the world.

TB expert and pediatrician Dr. Sanjay Jain of Johns Hopkins said that despite the good news, this is “a wake-up call to the realities of TB,” which involves the Mycobacterium tuberculosis, estimated to cause nearly 10 million new TB cases worldwide every year and with strains increasingly becoming resistant to drugs.

Hurdles in Diagnosis

In the Nov. 16 issue of the journal Lancet Infectious Diseases, the team recounted the challenges in treating the unidentified child, including the lack of fast and reliable diagnostics, reliable markers for drug response monitoring, and child-friendly medications.

TB child patients, for instance, have fewer bacteria in their bodies than adults, making initial tests potentially inconclusive. Lab methods may also be unreliable and cause delays in finding results.

The successfully treated child was brought to the hospital out of unrelenting fever and malaise after a three-month stay in India. No evidence of TB infection showed during initial testing, but a lung spot manifested in the chest X-ray.

"Preliminary test results are notoriously unreliable and this case provides a perfect illustration of the need for swifter and more reliable techniques," said Jain, recalling that after four weeks from initial sampling, they confirmed TB.

Conclusively identifying drug-resistant TB in the child took 12 weeks in total, the researchers added.

Treatment and CT Scanning

The child had worsened around the time of conclusive diagnosis, with CT scan revealing lung inflammation and spots indicative of dying lung tissue.

The Johns Hopkins team treated the child using a new combination of five drugs with vitamin B6, albeit with no reliable way to track bacterial response to the medication.

They turned to CT imaging, as inspired by Jain’s team’s ongoing work on TB, for rapid feedback on the disease’s progress. Each child-appropriate, low-radiation CT scan – deemed Jain their best option given surrounding treatment failure risks – provided a dose comparable to two to three months of natural background radiation coming from the environment, wrote the team.

Scan results then began to show diminishing lung inflammation as well as reduced bacterial counts.

Dr. Antonio Sastre, National Institute of Biomedical Imaging and Bioengineering program director, confirmed that CT monitoring, first demonstrated in lab mice, was a “readily translatable solution for this case.”

The child’s TB is now in full remission, with no sibling or family member infected. The team saw a reactivation as unlikely, but out of caution it will continue monitoring the child for another two years.

A million children are estimated to develop TB every year, although the real rate may be higher due to difficulties in diagnosing kids.

Drug-resistant strains are on the rise, particularly in countries like China, India, and Africa. In the U.S., the rare XDR form – 74 cases since 1993, including two in children below age five – is treated while patients are isolated from the public and the strain’s spread is prevented.

Research on new options for multidrug-resistant tuberculosis has only started.

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