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American Journal of Respiratory and Critical Care Medicine Vol 165. pp. 1452, (2002)
© 2002 American Thoracic Society


Correspondence

Improving tuberculin skin testing in hiv-infected individuals

To the Editor :

We read with interest the article by Lalvani and colleagues (1) and the editorial by Barnes (2) concerning rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. This method of testing for latent tuberculosis infection (LTBI) is more sensitive, more specific, and more convenient than the tuberculin skin test (2). This scientific advance in diagnosing LTBI is especially useful for HIV-infected individuals, who are more at risk of acquiring M. tuberculosis infection (3). Certain subgroups of HIV-infected individuals are also more at risk of not returning a second time for interpretation of the tuberculin skin test (4).

In our retrospective study, we examined a population-based cohort of individuals in New Orleans (>= 13 years) diagnosed with HIV infection from June 1995 through June 1997. The purpose of the Centers for Disease Control and Prevention study was to assess whether the U.S. Public Health Service guidelines to prevent M. tuberculosis in HIV-infected persons were completed. Data were extracted from medical records for care provided from first HIV positive test through December 1998 or death.

The sample included 370 people. Most patients were male (71.5%) and African American (71.7%). The mean age was 35.8 years (SD, 10.52 years). More than one-third of the patients (36.2%) did not have any tuberculin skin tests recorded in their charts. After adjustment for CD4 cell count, multivariate analysis showed that male, African American, and subjects with no history of preventive or antiretroviral care were significantly associated with no tuberculin skin tests recorded in the medical charts. Receiving care at a public HIV outpatient clinic, as opposed to private care, inpatient care, or hospital outpatient care, was protective. The odds ratio for no tuberculin skin testing among those receiving care at a public HIV clinic compared with others was 0.22 (95% confidence interval [CI], 0.07–0.72].

HIV-infected patients receiving care in New Orleans' private facilities and hospitals need improved access to tuberculin skin testing. Providers also need to provide more tuberculin skin testing and care to males and African Americans. A more convenient test, such as the one described by Lalvani and colleagues may improve testing for LTBI in New Orleans. In our study, approximately a third of the patients who did receive a tuberculin skin test (31.9%) did not return for interpretation of the test. We recommend better tests to diagnose LTBI in HIV-infected individuals, such as the one described by Lalvani and colleagues.

Kathleen J. Welch and Anne Morse

HIV/AIDS Program Office, Louisiana Office of Public Health New Orleans, Louisiana

REFERENCES

  1. Lalvani A, Pathan AA, McShane H, Wilkinson RJ, Latif M, Conlon CP, Pasvol G, Hill AVS. Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Am J Respir Crit Care Med 2001;163:824–828.[Abstract/Free Full Text]
  2. Barnes PF. Diagnosing latent tuberculosis infection. The 100-year upgrade. Am J Respir Crit Care Med 2001;163:807–808.[Free Full Text]
  3. Markowitz N, Hansen NI, Hopewell PC, Glassroth J, Kvale PA, Mangura BT, Wilcosky TC, Wallace JM, Rosen MJ, Reichman LB. Incidence of tuberculosis in the United States among HIV-infected persons. The Pulmonary Complications of HIV Infection Study Group. Ann Intern Med 1997;126:123–132.[Abstract/Free Full Text]
  4. Fitzgerald JM, Patrick DM, Strathdee S, Rekart M, Elwood RK, Schecter MT, Montaner J, O'Shaughnessy M. Use of incentives to increase compliance for TB screening in a population of intravenous drug users. Vancouver Injection Drug Use Study Group. Int J Tuberc Lung Dis 1999;3:153–155.[Medline]

 
From the authors:

Welch and More highlight the operational difficulties of the century-old tuberculin skin test (TST). Many people who should be tested are not, and many who are tested fail to return to have the test read. Welch and More have identified important risk groups in the United States who are not being offered TST, despite the fact that the U.S. has a more vigorous and comprehensive approach to identifying and treating latent tuberculosis infection (LTBI) than almost any other country (1).

As Welch and More point out, the world awaits an improved diagnostic test for LTBI. Such a test should not only be more convenient, but also more accurate than the TST. The rapid enzyme-linked immunospot (ELISPOT) test that we have developed is more convenient, as it is a blood test that generates results by the next day and requires no return visit (2, 3). We have recently further simplified the format and procedure of the ELISPOT assay along the lines suggested by Barnes (4). The new streamlined assay could soon be suitable for deployment in routine hospital laboratories.

Proving that a new test for LTBI is more accurate than the TST is difficult, as there is no gold standard against which to measure the accuracy of a new test. Given that time spent sharing room air with an infectious source case is a key determinant of M. tuberculosis transmission, an improved test for LTBI should correlate better with intensity of exposure to M. tuberculosis than the TST. We recently reported a study of 50 tuberculosis contacts in London that showed that our ELISPOT assay did indeed correlate more closely with the level of M. tuberculosis exposure than the TST, and unlike the TST, was independent of BCG vaccination status (5). However, before clinical decisions could be based on ELISPOT assay results, its relationship to M. tuberculosis exposure would need to be precisely defined in a larger study with sufficient power to generate statistically significant results with narrow confidence intervals. We have recently undertaken such a study in a major tuberculosis outbreak due to a single source case in a school in the United Kingdom, together with the local health authority. This large (n = 545), prospective, blinded trial compares the relationship of the ELISPOT assay and TST with M. tuberculosis exposure, as quantified precisely from school timetables. This should provide a definitive answer as to whether the ELISPOT assay could replace the TST for diagnosing LTBI in the 21st century.

Ajit Lalvani

University of Oxford, John Radcliffe Hospital Oxford, United Kingdom

REFERENCES

  1. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221–S247.[Free Full Text]
  2. Lalvani A, Pathan AA, McShane H, Wilkinson RJ, Latif M, Conlon CP, Pasvol G, Hill AVS. Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Am J Respir Crit Care Med 2001;163:824–828.
  3. Lalvani A, Nagvenkar P, Udwadia Z, Pathan AA, Wilkinson KA, Shastri JS, Ewer K, Hill AV, Mehta A, Rodrigues C. Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. J Infect Dis 2001;183:469–477.[CrossRef][Medline]
  4. Barnes PF. Diagnosing latent tuberculosis infection. The 100-year upgrade. Am J Respir Crit Care Med 2001;163:807–808.
  5. Lalvani A, Pathan AA, Durkan H, Wilkinson KA, Whelan A, Deeks JJ, Reece WH, Latif M, Pasvol G, Hill AV. Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001;357:2017–2021.[CrossRef][Medline]




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Copyright © 2002 American Thoracic Society