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Boy's Mysterious Infection Cured After DNA Sequencing

Research technicians prepare DNA samples to be sequenced in the production lab of the New York Genome Center on Sept. 19, 2013 in New York City. The Center, which is already operating with a staff of 51 people, aims to sequence and analyze DNA for academic and commercial purposes. Andrew Burton / Getty Images file

Modern genetic sequencing helped doctors diagnose and cure a teen boy’s mysterious infection, offering a glimpse into hospital techniques of the future.

A report in the New England Journal of Medicine describes how the youngster's case was baffling doctors, who tried treatment after treatment as his brain swelled. Current tests gave no clue as to what was causing it.

Finally, a new sequencing technique that looks at all the genetic material circulating in the boy's spinal fluid gave up the culprit — leptospirosis, a bacterial disease, probably contracted when he went swimming on a trip to Puerto Rico.

While such tests are still beyond the reach of the average doctors, they won’t be for long, experts predict.

“This is the wave of the future."

“We are hoping we can apply this to any patient who comes into the hospital with any infection,” said Dr. Charles Chiu of the University of California, San Francisco, who led the research team.

“This is the wave of the future, although it will take a little bit of time to iron out the wrinkles,” agreed Dr. William Schaffner, an infectious diseases expert at Vanderbilt University, who was not involved in the research.

The 14-year-old boy, who isn’t identified in the report, had severe combined immunodeficiency or SCID, sometimes known as bubble-boy disease. In this case, his immune system was strong enough for him to live normally and even travel.

“He had gone on a missionary trip to Puerto Rico during the first two weeks of August 2012 where he swam in a river and the ocean,” Chiu’s team wrote.

The boy visited the hospital three times over four months with fever and headache. Eventually his brain swelled up and he had to be put into a medically induced coma.

Frantic doctors ran a battery of tests, but didn’t suspect bacterial meningitis. They thought it might be something a cat gave him — the boy’s family had pets, and the boy’s group had interacted with feral cats in Puerto Rico.

They gave him immune globulin treatment, Rituxan to counter a possible autoimmune reaction and even took a brain biopsy. He got even more immune-boosting treatments — but did not get better.

The boy’s family agreed to enroll him in a clinical trial using next-generation sequencing. This approach uses modern, fast genetic sequencing to look at all the DNA in a sample. It found evidence of leptospirosis infection in his spinal fluid and doctors decided to treat him with penicillin — the cheap, basic antibiotic that best attacks the infection. That did the trick.

The boy got well enough to go home a month later.

Later on, specific testing using polymerase chain reaction (PCR) confirmed it was leptospirosis. “We suspect that the patient most likely contracted leptospirosis during his trip to Puerto Rico,” the researchers wrote. Another teen on the trip was hospitalized with fever and blood in the urine and may have had the same infection.

Infections such a meningitis and pneumonia often stump doctors. The standard way to test is to take some blood or perhaps coughed-up sputum and try to culture, or grow, bacteria. But more than 100 different agents, including bacteria, viruses, mold and fungi, can cause meningitis.

“More than half the cases of meningoencephalitis remain undiagnosed, despite extensive clinical laboratory testing,” Chiu’s team wrote. Leptospires, the bacteria that cause leptospirosis, are hard to detect and they don’t grow well in standard tests that culture bacteria.

“We spend a huge amount of money to work up these cases, and despite the latest generation of tests, we’re still unable to diagnose up to 30 percent of cases of pneumonia in hospitalized patients,” Chiu told NBC News.

“We estimate that the cost of hospitalization for this boy was well over $250,000."

“We’re unable to make a diagnosis, using older methods, like growing out cultures. More recently, other types of tests have become available, such as PCR, which looks for specific sequences — but for only one organism at a time, and you have to have a prior target,” he added.

“Current diagnostic techniques, especially to find viruses, often don’t work well.”

The downside is the gene-sequencing machine — this one’s made by a company called Illumina — costs $100,000 or more. That’s a lot for a hospital to invest in. Chiu estimates a test would cost $2,000 a pop.

But Chiu argues that next-generation sequencing will save money. “We estimate that the cost of hospitalization for this boy was well over $250,000,” he said. “There was probably $30,000 spent on diagnostic tests that turned out negative.”

And that doesn’t include the distress to his family. “If we could have done it on the very first day he came to the hospital, we would have potentially spared him three hospitalizations , an invasive brain biopsy and a stay in the ICU,” Chiu said.

Other experts agreed the case could illustrate what’s coming in a few years.

"This article is about a single case, but I believe it represents a turning point in the use of sequencing to diagnose infections,” said genetics expert Dr. Robert Green of Brigham and Women’s Hospital and Harvard Medical School, who was not involved in the study.

“While I would not expect this to become integrated into care immediately, I would not be surprised if this is sort of genomic characterization of infectious agents is deeply integrated into clinical care within the next five years."

NBC News senior researcher Judy Silverman and producer Stacey Naggiar contributed to this story.