DNA Sequencing May Help ID Tuberculosis Versus Sarcoidosis

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by Margarida Maia |

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A DNA sequencing technology called next-generation sequencing (NGS) may be used to detect tuberculosis (TB) rapidly and accurately — which could help in distinguishing it from sarcoidosis, a study suggests.

While tuberculosis and sarcoidosis share many symptoms, the therapies for the two diseases differ greatly, according to researchers.

“If TB is misdiagnosed as [sarcoidosis], the misuse of high-dose corticosteroids will promote the spread of … infection, leading to serious consequences for the patient,” they wrote. “Thus, a rapid and accurate differential diagnosis of these two diseases is critical for the patient prognosis.”

The results of this study suggest that next-generation sequencing may aid clinicians in diagnosing tuberculosis versus sarcoidosis, the researchers said.

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The study, “Rapid discrimination between tuberculosis and sarcoidosis using next-generation sequencing,” was published in the International Journal of Infectious Diseases.

Tuberculosis is caused by infection with a bacterium called Mycobacterium tuberculosis, and one hallmark symptom is cough. In areas where cases of tuberculosis are frequent, the similarity in symptoms between the two diseases can make it challenging for healthcare providers to properly diagnose sarcoidosis.

Therefore, improved diagnostic tests are needed to help distinguish between the two diseases, the researchers said.

Now, researchers in China investigated whether NGS, an approach that rapidly sequences entire genomes, could provide a good strategy to detect M. tuberculosis. Its small genome, comprising about 4,000 genes, “is well suited to NGS,” the investigators wrote.

A total of 91 patients were enrolled; they had been diagnosed at a mean age of 52. Based on traditional diagnostic methods, 44 patients had tuberculosis and 47 had sarcoidosis. All of the individuals had granulomas, or clumps of immune cells — a shared feature of TB and sarcoidosis.

Patients with TB were treated with anti-tuberculosis medications while patients with sarcoidosis received prednisone, a corticosteroid.

Samples for NGS were pieces of tissue obtained from patients during surgery or biopsy, rather than sputum — a mixture of saliva and mucus coughed up from the airways that is traditionally used for the diagnosis of tuberculosis. Using the tissue allowed researchers to provide a faster diagnosis.

In a first analysis, the M. tuberculosis genome was detected in 51 patients (56%). Of these, 38 individuals (74%) had been clinically diagnosed with tuberculosis. Of the 40 patients in whom the M. tuberculosis genome was not detected, six (15%) had been clinically diagnosed with TB.

The amount of data generated by NGS should cover more than 80% of the genome as per generally accepted standards. However, among the 51 patients in whom the M. tuberculosis genome was detected, only 18 (35%) reached this standard.

While all had received a clinical diagnosis of tuberculosis, the current approach had a sensitivity of 0f 40%, meaning it was providing a large proportion of false negatives, diagnosing tuberculosis patients as not having the condition.

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Therefore, the researchers progressively reduced the coverage threshold to 15%, which balanced the accurate detection of tuberculosis and non-TB cases. Using this approach, the proportion of sarcoidosis patients who were accurately diagnosed with the condition dropped slightly from 100% to 81.8%, but the proportion of tuberculosis patients accurately diagnosed as such increased to 95.7%.

“NGS is efficient with regard to time and could be a potentially powerful and useful novel diagnostic method for TB,” the team wrote.

The researchers also described the cases of two patients in more detail.

The first was a 56-year-old man who would be excluded from a diagnosis of tuberculosis based on sequencing data covering more than 80% of the genome. With the threshold of 15%, the patient was diagnosed with TB and was cured after receiving anti-tuberculosis treatment.

The second patient was a 73-year-old woman who was diagnosed with tuberculosis based on close examination of a piece of the patient’s tissue. However, based on the results of NGS, the patient was finally diagnosed with sarcoidosis, for which she received prednisone. Her symptoms improved after one year of treatment.

The misuse of corticosteroids may promote the spread of M. tuberculosis infection, which could have serious consequences for the patient, the researchers noted. These cases illustrated how the right diagnosis is key to ensure proper treatment.

“This study established an improved NGS strategy for rapidly distinguishing patients with TB from those with [sarcoidosis] and has potential clinical benefits,” they concluded.