When a 2-year-old returned sick from a visit to India, U.S. doctors suspected tuberculosis even though standard tests said no.

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It would take three months to confirm she had an extreme form of the disease -- a saga that highlights the desperate need for better ways to fight TB in youngsters in countries that can't afford such creative care.

Drug-resistant tuberculosis is a global health threat, and it's particularly challenging for young children who are harder even to diagnose, much less treat.

Doctors at Johns Hopkins Children's Center are reporting how they successfully treated one of the few tots ever diagnosed in the U.S. with the worst kind -- extensively drug-resistant TB, or XDR-TB, that's impervious to a list of medicines.

"This was so difficult, even when we had all these resources," said Hopkins pediatric TB specialist Dr. Sanjay Jain, who co-authored the report being published Monday in The Lancet Infectious Diseases. The child now is 5 and healthy, but Jain calls the case "a wake-up call to the realities of TB."

Tuberculosis is a bacterial infection that usually strikes the lungs, spreading through coughs and sneezes. A recent World Health Organization report says TB sickened nearly 10 million people worldwide in 2014, including 1 million children. That's double earlier child estimates, reflecting some countries' better counts. Many experts suspect the toll is still higher because children in hard-hit countries can die undiagnosed.

In much of the world, doctors "don't have anything like a CT scan to use to help them with this. They just have to use a stethoscope and a scale and their clinical judgment," said Dr. Anna Mandalakas, director of the global tuberculosis program at Texas Children's Hospital and Baylor College of Medicine.

The Hopkins patient, who wasn't identified, returned from a three-month family trip to India with a high fever. A battery of tests yielded no diagnosis, and no relatives were sick. But X-rays and CT scans found clues, a spot on her lung and some enlarged lymph nodes.

To diagnose adults, doctors check their sputum for TB germs. Children, especially younger than 5, don't harbor nearly as much bacteria -- and tots tend to swallow rather than cough out the mucus, Jain explained. Suspicious doctors threaded a tube into the girl's stomach for samples, so a lab could try to grow and identify any bacteria lurking in them.

Meanwhile, the child was prescribed four standard TB drugs. Her fever broke, and she gained weight -- changes that in many TB-stricken countries would signal successful treatment. But X-rays showed persistent lung inflammation. And after a month, workers finally detected slow-growing TB germs in one of those lab samples, something to use for more complex testing.

Confirmation that she had the scary XDR-TB came 12 weeks after the girl's initial exam, Jain said. Three of the four drugs she was taking didn't work. Her fever roared back, lung tissue began dying. Doctors switched her to five different, riskier, medications -- but had no fast way to monitor if they were working.

So Jain tried something experimental, stemming from his research on using special low-radiation CT scans to track infections. A scan showed her lungs were starting to clear weeks into the new therapy. She was declared in remission after 18 months of treatment, and continues to be healthy.

Drug-resistant strains of TB are on the rise, especially in India, China and Africa. The hardest-to-treat XDR form is very rare in the U.S., where patients are isolated from the public while being treated to prevent the strain's spread. The Centers for Disease Control and Prevention counts 74 XDR-TB cases since 1993, two in children under 5.

The Hopkins case offers a lesson for hard-hit countries, that children may harbor resistant TB even if they seem to improve shortly after beginning standard treatment, Mandalakas said.

Beyond the challenge of diagnosis in children, few TB medications come in pediatric doses, forcing health workers or parents to chop or crush pills. The nonprofit TB Alliance, the Global Alliance for TB Drug Development, is developing a child-friendly formulation of standard tuberculosis treatment -- combining proper doses in easy-to-take tablets -- expected to become available next year.

Research is only beginning on possible new options for multidrug-resistant TB.

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