Treatment of Latent TB: A High Priority

By Carol A. Kemper, MD, FACP

Source: Horsburgh CR Jr. N Engl J Med. 2004;350: 2060-2067.

Reduction in the number of cases of tb in the United States is one of the United States Public Health Department’s highest priorities. In order to achieve this goal, the numbers of patients who undergo testing and treatment for latent TB must be increased. Dr. Horsburgh says he’s always encouraged patients to accept treatment by providing a rough estimate of their lifetime risk of reactivation (~5-10%), but specifically encourages 3 groups of patients, irrespective of age, to accept treatment: those with 1) recent skin test conversion, 2) evidence of old healed disease on chest radiograph, or 3) those with immunosuppression, corticosteroid use, or HIV. Of course, any infant or child < 5 years of age with household exposure should be presumptively treated with INH; such patients are at high risk for primary progressive disease, and it is too late to wait for skin test conversion.

It has always been assumed that the risk of reactivation is generally greatest in the 2-3 years following conversion, then begins to decrease over the next decade, and remains fairly stable at low levels thereafter. Recent data suggests that ~10% of patients lose their tuberculin reactivity each decade; these individuals do not contribute to the overall risk of reactivation TB. Therefore, estimates of the risk of reactivation may actually be lower than previously assumed especially in younger persons, but the effect of this statistical finding on risk diminishes as patients age.

Believing that more precise information on the risk of reactivation can allow clinicians to target groups at highest risk, Dr. Horsburgh constructed a risk model based on age, degree of induration on tuberculin skin test, and whether there was recent conversion, evidence of old healed TB, immunosuppressive therapy, or HIV. Five groups at significant lifetime risk for reactivation TB were identified: 1) children < 5 years of age with > 10 mm of induration have a 10-20% risk; 2) younger persons < 35 years of age with > 15 mm of induration and recent conversion have a 10-20% risk; 3) younger persons < 35 years of age with > 15 mm of induration receiving immunosuppressive therapy have a 10-20% risk; 4) persons with > 10 mm of induration and evidence of old healed TB have > 20% risk.

Interestingly, in Horsburgh’s model, persons > 66 years of age have < 10% risk of reactivation under any circumstance (except HIV infection); this suggests that it may be reasonable to defer treatment in persons over the age of 65.

Dr. Horsburgh suspects the reason that too few patients are treated for latent TB is because clinicians still have 3 bad rules stuck in their heads: these include patients with a history of a positive test for many years do not need treatment, a history of BCG means you don’t need treatment, you have a false-positive PPD, and anyone older than 35 is at higher risk for side effects and should not be treated. This backwards approach ensures that immigrants from a country endemic for TB (especially one where BCG is common), and anyone over the age of 35, is less likely to receive treatment for latent TB, even if they have risk factors. Confronting these fallacies, convincing clinicians that the benefits of INH prophylaxis outweigh the risks, disregarding a history of BCG, and keeping the rules of who should be treated as simple as possible may ensure that more patients receive treatment for latent TB.

This article was published in the October 2004 issue of Infectious Disease Alert.

Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates, Section Editor, HIV.