TB "Active" kills about 1.5 million people a year, but the World Health Organization (WHO) estimates that a third of the world's population has latent TB, meaning that Mycobacterium tuberculosis can be grown from their sputum, but their immune cells release interferon gamma even if mixed with pieces of the microbe. A skin test called "delayed hypersensitivity" is also widely used to determine latency. Only about 10% of these people will develop TB at some point in their lives, and one of the major challenges in the fight against tuberculosis is that there is no way of knowing who is at risk. X-rays of the lungs latent patients show nothing abnormal. WHO recommendations call for treating people infected with HIV who have latent TB with a drug, isoniazid, as prophylaxis, but often not.
In the new study, the scientists used more sophisticated techniques to look at the lungs of 35 people infected with HIV in South Africa that have latent TB, according to standard tests. A scan using computed tomography (CT), which shows the anatomy of a much more detailed lung radiography; the other is a positron emission scanner (PET) using a radioactive glucose injection, which is absorbed by metabolically active cells and indicates the presence of M . tuberculosis.
Ten people had clear nodules "hot" in their lungs. "We saw quite magnificent manifestations of the disease," says Clifton Barry, who directs tuberculosis research at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and also has a laboratory at the University of Cape Town (UCT) in South Africa. (the Barry team conducted the work with Rob Wilkinson group at UCT.) the team saw no hot spots in the other 25 patients lungs.
the researchers planned to everyone in the study of isoniazid. But in the few weeks between scans and when treatment began, four of the 10 patients with abnormal CT hotspots or developed TB symptoms, and M . TB found in the sputum of the others. in essence, analyzes had shown the people who were about to get ill and had a urgent need for TB treatment drugs-fledged three different doses for 6 months. "The data are very compelling," said David Russell, a researcher of tuberculosis at Cornell University. "There's nothing out there with this resolution."
The researchers continued to do lung tests during the treatment period, and they showed lung abnormalities dissolution, meaning they could use the technique to analyze the effectiveness of the treatment. "for many of us it opened a new door to think about whether we really need to be treated for six months, "says Jens Lundgren, an infectious disease specialist at the University of Copenhagen. "This is a really exciting place for personalized medicine so we can separate those who may have a shorter treatment period." That would be welcome, because the standard treatment is a challenge for many patients.
Although TB in these 10 people was far from "latent" Barry said he is convinced that many, if not most, of the other 25 people, did not have all TB. He suspected they had only interferon gamma responses M . TB because their immune systems had cleared the germ at some point in the past. "It is wrong to say that a third of the world has latent TB," Barry said. "This figure made great starts for the scientific articles, but it is quite misleading."
Lucica Ditiu who heads the Stop TB Partnership, a nonprofit in Geneva, Switzerland, recognizes that "latent" is not an accurate term. "These data are extremely interesting and something that we should move forward" Ditiu said.
Unfortunately, CT and PET are very expensive, Barry acknowledges, and it would be impossible to track more than 2 billion people, most of them in poor countries, which meet the definition of tuberculosis the tent. But the analyzes could be very useful in research, he says, for example, in the first tests of new TB drugs to see which ones deserve large-scale efficacy studies. Wilkinson also found another possible way to identify people with an active infection. He made a so-called transcriptome analysis that compared the immune genes that were activated in 10 people who had the hot spots and the 25 who did not. Six "biomarkers" surfaced that theoretically could identify people who are most likely to develop symptomatic disease and infectious. (Other laboratories have recently identified biomarker transcription, too.)
Barry notes that on average, each person has an active M . TB infection transmits the pathogen to 10 others. "If we can identify people with subclinical disease before transmitting, it is potentially a game changer in terms of eradication of tuberculosis," he said.
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