Duration of Exposure Among Close Contacts of Patients With Infectious Tuberculosis and Risk of Latent Tuberculosis Infection

Abstract

Background: Predictors of latent tuberculosis infection (LTBI) among close contacts of persons with infectious tuberculosis (TB) are incompletely understood, particularly the number of exposure hours.

Methods: We prospectively enrolled adult patients with culture-confirmed pulmonary TB and their close contacts at 9 health departments in the United States and Canada. Patients with TB were interviewed and close contacts were interviewed and screened for TB and LTBI during contact investigations.

Results: LTBI was diagnosed in 1390 (46%) of 3040 contacts, including 624 (31%) of 2027 US/Canadian-born and 766 (76%) of 1013 non-US/Canadian-born contacts. In multivariable analysis, age ≥5 years, male sex, non-US/Canadian birth, smear-positive index patient, and shared bedroom with an index patient (P < .001 for each), as well as exposure to >1 index patient (P < .05), were associated with LTBI diagnosis. LTBI prevalence increased with increasing exposure duration, with an incremental prevalence increase of 8.2% per 250 exposure hours (P < .0001). For contacts with <250 exposure hours, no difference in prevalence was observed per 50 exposure hours (P = .63).

Conclusions: Hours of exposure to a patient with infectious TB is an important LTBI predictor, with a possible risk threshold of 250 hours. More exposures, closer exposure proximity, and more extensive index patient disease were additional LTBI predictors.

Keywords: close contacts; epidemiology; exposure; exposure hours; latent tuberculosis infection.

Figure 1.

A, Probability of contacts with an LTBI diagnosis by total hours of exposure to an index patient with TB. Observed values are indicated as circles representing the proportion of contacts with LTBI in 250-hour increments (<250 hours, 251–500 hours, 501–750 hours, 751–1000 hours, etc). Denominators for 250-hour increments <2000 hours range from 132 to 899, and denominators for 250-hour increments >2000 hours range from 0 to 64 (denominators for <250, 250–499, 500–749, 750–999, 1000–1249, 1250–1499, 1500–1749, 1750–1999, 2000–2249, 2250–2499, 2500-1749, 2750–2999, 3000–3249, 3250–3499, 3500–3749, 3750–3999, 4000–4249, and 4250–4499 hours are 899, 760, 443, 205, 194, 149, 132, 57, 64, 30, 20, 30, 20, 8, 4, 0, 3, and 6, respectively; exposure hours were missing for 16 contacts). B, Probability of contacts with an LTBI diagnosis by total hours of exposure to an index patient with TB and smear status of the index patient (smear-status positive indicated in red and smear-status negative in blue). C, Probability of contacts with an LTBI diagnosis by total hours of exposure to an index patient with TB for exposure durations <250 hours. Observed values are indicated as circles representing the proportion of contacts with LTBI in 50-hour increments (<50, 51–100, 101–150, 151–200, and 201–250 hours). D, Probability of contacts with LTBI diagnosis by total hours of exposure to an index patient with TB and contact birthplace (US/Canadian birth indicated in blue and non-US/Canadian birth indicated in red). E, Probability of contacts with LTBI diagnosis by total hours of exposure to an index patient with TB and exposure location (nonhousehold in green, shared bedroom in household in red, no shared bedroom in household in blue). Predicted values based on logistic regression modeling of all data points are indicated by the solid lines; the shaded areas represent the 95% confidence intervals. Color figure present online. Abbreviations: BIRTHCONT, contact birthplace; expoEnvir, exposure environment; LTBI, latent tuberculosis infection; TB, tuberculosis.