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Immunological testing alone missed TB cases in HIV population

SAN DIEGO – Mycobacterium tuberculosis can still be grown in the sputum of people living with HIV who have negative TB immunological testing, and in people who have been treated with TB previously, results from a study of nearly 200 patients demonstrated.

"Previous studies in low TB incidence areas have tested people with positive tuberculin skin tests or interferon release assays for active TB, but we have tested people for TB irrespective of this – and found a case of active tuberculosis and someone with TB in their sputum who would otherwise not have been tested using previous guidelines," lead author Dr. Santino Capocci, a research registrar in respiratory medicine at Royal Free Hospital, London, said in an interview in advance of an international conference of the American Thoracic Society, where the research was presented.

Dr. Santino Capocci

Guidelines from the United Kingdom recommend using blood interferon-gamma release assay with or without tuberculin skin testing for latent TB diagnosis, but it does not cover screening for active TB. "Implementation is patchy with little robust evidence for effectiveness," the researchers wrote in their abstract.

In an effort to determine the impact of comprehensive assessment for TB disease and infection in an ambulatory HIV clinic population with high antiretroviral usage, Dr. Capocci and his associates tested 194 patients, mean age 46 years, who had no clinical suspicion of active tuberculosis. Testing consisted of tuberculin skin testing (TST), interferon-gamma release assay (IGRA), frontal chest radiograph (CXR), and sputum induction for TB culture. Latent TB was defined as a positive IGRA and/or TST of 5 mm or greater in the absence of previously active TB disease.

Nearly one-quarter of patients (24%) were black African, 81% had received a previous Bacillus Calmette-Guerin vaccination, 94% were on antiretroviral medication, and 8% had previous TB disease. Dr. Capocci reported that latent TB infection was detected in 12 (6%) of the 194 patients. Of these, four were diagnosed by positive IGRA and TST of 5 mm or greater; one was diagnosed by positive IGRA and negative TST; five were diagnosed by TST of 10 mm or greater (with negative or borderline IGRA), and two were diagnosed by TST 5-9 mm (with negative IGRA). Two subjects had a positive sputum culture.

"One subject had evidence of tuberculosis in his sputum but no symptoms, normal blood tests and x-rays, and negative immunological testing (tuberculin skin test and IGRA)," Dr. Capocci said. "This has been seen in Africa in people living with HIV, but is not reported as far as we know in low TB incidence areas such as the UK. The case of active TB that we saw was in someone who has had tuberculosis previously, but without persistent symptoms. He may not have been tested using national testing guidelines."

Dr. Capocci acknowledged certain limitations of the study, including the fact that the sample size is "fairly small compared to studies that have used IGRAs or tuberculin skin testing. "It is also important to evaluate the cost effectiveness of this approach [for] future health care policy."

Dr. Capocci said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

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SAN DIEGO – Mycobacterium tuberculosis can still be grown in the sputum of people living with HIV who have negative TB immunological testing, and in people who have been treated with TB previously, results from a study of nearly 200 patients demonstrated.

"Previous studies in low TB incidence areas have tested people with positive tuberculin skin tests or interferon release assays for active TB, but we have tested people for TB irrespective of this – and found a case of active tuberculosis and someone with TB in their sputum who would otherwise not have been tested using previous guidelines," lead author Dr. Santino Capocci, a research registrar in respiratory medicine at Royal Free Hospital, London, said in an interview in advance of an international conference of the American Thoracic Society, where the research was presented.

Dr. Santino Capocci

Guidelines from the United Kingdom recommend using blood interferon-gamma release assay with or without tuberculin skin testing for latent TB diagnosis, but it does not cover screening for active TB. "Implementation is patchy with little robust evidence for effectiveness," the researchers wrote in their abstract.

In an effort to determine the impact of comprehensive assessment for TB disease and infection in an ambulatory HIV clinic population with high antiretroviral usage, Dr. Capocci and his associates tested 194 patients, mean age 46 years, who had no clinical suspicion of active tuberculosis. Testing consisted of tuberculin skin testing (TST), interferon-gamma release assay (IGRA), frontal chest radiograph (CXR), and sputum induction for TB culture. Latent TB was defined as a positive IGRA and/or TST of 5 mm or greater in the absence of previously active TB disease.

Nearly one-quarter of patients (24%) were black African, 81% had received a previous Bacillus Calmette-Guerin vaccination, 94% were on antiretroviral medication, and 8% had previous TB disease. Dr. Capocci reported that latent TB infection was detected in 12 (6%) of the 194 patients. Of these, four were diagnosed by positive IGRA and TST of 5 mm or greater; one was diagnosed by positive IGRA and negative TST; five were diagnosed by TST of 10 mm or greater (with negative or borderline IGRA), and two were diagnosed by TST 5-9 mm (with negative IGRA). Two subjects had a positive sputum culture.

"One subject had evidence of tuberculosis in his sputum but no symptoms, normal blood tests and x-rays, and negative immunological testing (tuberculin skin test and IGRA)," Dr. Capocci said. "This has been seen in Africa in people living with HIV, but is not reported as far as we know in low TB incidence areas such as the UK. The case of active TB that we saw was in someone who has had tuberculosis previously, but without persistent symptoms. He may not have been tested using national testing guidelines."

Dr. Capocci acknowledged certain limitations of the study, including the fact that the sample size is "fairly small compared to studies that have used IGRAs or tuberculin skin testing. "It is also important to evaluate the cost effectiveness of this approach [for] future health care policy."

Dr. Capocci said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Mycobacterium tuberculosis can still be grown in the sputum of people living with HIV who have negative TB immunological testing, and in people who have been treated with TB previously, results from a study of nearly 200 patients demonstrated.

"Previous studies in low TB incidence areas have tested people with positive tuberculin skin tests or interferon release assays for active TB, but we have tested people for TB irrespective of this – and found a case of active tuberculosis and someone with TB in their sputum who would otherwise not have been tested using previous guidelines," lead author Dr. Santino Capocci, a research registrar in respiratory medicine at Royal Free Hospital, London, said in an interview in advance of an international conference of the American Thoracic Society, where the research was presented.

Dr. Santino Capocci

Guidelines from the United Kingdom recommend using blood interferon-gamma release assay with or without tuberculin skin testing for latent TB diagnosis, but it does not cover screening for active TB. "Implementation is patchy with little robust evidence for effectiveness," the researchers wrote in their abstract.

In an effort to determine the impact of comprehensive assessment for TB disease and infection in an ambulatory HIV clinic population with high antiretroviral usage, Dr. Capocci and his associates tested 194 patients, mean age 46 years, who had no clinical suspicion of active tuberculosis. Testing consisted of tuberculin skin testing (TST), interferon-gamma release assay (IGRA), frontal chest radiograph (CXR), and sputum induction for TB culture. Latent TB was defined as a positive IGRA and/or TST of 5 mm or greater in the absence of previously active TB disease.

Nearly one-quarter of patients (24%) were black African, 81% had received a previous Bacillus Calmette-Guerin vaccination, 94% were on antiretroviral medication, and 8% had previous TB disease. Dr. Capocci reported that latent TB infection was detected in 12 (6%) of the 194 patients. Of these, four were diagnosed by positive IGRA and TST of 5 mm or greater; one was diagnosed by positive IGRA and negative TST; five were diagnosed by TST of 10 mm or greater (with negative or borderline IGRA), and two were diagnosed by TST 5-9 mm (with negative IGRA). Two subjects had a positive sputum culture.

"One subject had evidence of tuberculosis in his sputum but no symptoms, normal blood tests and x-rays, and negative immunological testing (tuberculin skin test and IGRA)," Dr. Capocci said. "This has been seen in Africa in people living with HIV, but is not reported as far as we know in low TB incidence areas such as the UK. The case of active TB that we saw was in someone who has had tuberculosis previously, but without persistent symptoms. He may not have been tested using national testing guidelines."

Dr. Capocci acknowledged certain limitations of the study, including the fact that the sample size is "fairly small compared to studies that have used IGRAs or tuberculin skin testing. "It is also important to evaluate the cost effectiveness of this approach [for] future health care policy."

Dr. Capocci said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

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Immunological testing alone missed TB cases in HIV population
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Key clinical point: Use of immunological testing alone to detect TB in people with HIV missed cases of subclinical disease.

Major finding: Despite the convenience of immunological tests to screen for TB in people with HIV, the use of comprehensive assessments detected 12 cases of latent TB in 194 patients with HIV, even in those with good CD4 and no symptoms.

Data source: A study of 194 HIV patients, mean age 46 years, who had no clinical suspicion of active tuberculosis.

Disclosures: Dr. Capocci had financial conflicts.