Abstract
BackgroundDespite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment.MethodsDuring a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed.ResultsWhen analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5–15 age group (p = 0.009).ConclusionsThough many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.
Highlights
Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST)
This study examines well-characterized risk factors for Mtb infection to determine if specific epidemiologic factors explain the Persistently tuberculin skin test negative (PTST)- phenotype, and to assess whether they are less likely to acquire Mtb infection
Comparison of epidemiologic risk factors for PTST, TST converters (TSTC) and TST + contacts We found that there were no significant differences in the distributions of sex, Human immunodeficiency virus (HIV) status, or presence of Bacillus CalmetteGuerin (BCG) scar across the 3 clinical groups (Table 1)
Summary
Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Uganda is one of the world’s 22 highest burden countries with TB, with an annual risk of infection of 3% and annual incidence of new smear positive TB cases of 9.2 per 1000 in an urban setting [1]. It is not surprising that markers of close contact, such as crowded quarters, urban living, and lower socio-economic status, are associated with acquisition of Mtb [2,3]. Clinical characteristics of the person with pulmonary TB that increase the risk of contacts becoming infected include cavitary disease, sputum smear grade, and extent of disease based on x-ray [4,5,6,7,8]
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