Epidemiology of smear-negative pulmonary tuberculosis in the United States, 1993-2008

Smear-negative tuberculosis (TB) is difficult to diagnose and has been associated with poor treatment outcomes and excessive mortality, particularly in high human immunodeficiency virus (HIV) prevalent settings. However, few studies have used mycobacterial culture to rigorously confirm all smear-negative TB cases in a population-based cohort.

We included all culture-confirmed, pulmonary TB cases reported to the US National TB Surveillance System from 1993 to 2008. We analyzed smear-negative TB risk factors and survival, as compared to smear-positive TB. We calculated prevalence ratios (PRs) and adjusted for confounders (aPR).

From 1993 to 2008, 159,121 cases of culture-confirmed pulmonary TB were reported in the United States, of which 58,786 (37%) were sputum smear-negative. Smear-negative TB cases were more likely to be foreign-born (aPR 1.10, 95%CI 1.08-1.12), incarcerated (aPR 1.52, 95%CI 1.48-1.56) or HIV-infected (aPR 1.27, 95%CI 1.24-1.30). Hispanics and non-Hispanic Blacks were less likely to have smear-negative TB (respectively aPR 0.87, 95%CI 0.85-0.89 and aPR 0.90, 95%CI 0.89-0.92). Smear-negative TB cases had lower mortality (aRR 0.78, 95%CI 0.74-0.81), independent of HIV status.

Smear-negative TB represents a large proportion of TB cases in the United States, and occurs more often among persons in groups more likely to undergo TB screening. The lower mortality may indicate earlier TB detection, and underscores the need for continued vigilance in screening of high-risk persons.