Open Access Highly Accessed Research article

Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda

Ningning Ma1, Sarah Zalwango3, LaShaunda L Malone13, Mary Nsereko3, Eddie M Wampande4, Bonnie A Thiel13, Brenda Okware3, Robert P Igo2, Moses L Joloba34, Ezekiel Mupere234, Harriet Mayanja-Kizza34, W Henry Boom13, Catherine M Stein23* and for the Tuberculosis Research Unit (TBRU)

Author Affiliations

1 Department of Medicine, Case Western Reserve University, 2103 Cornell Rd, Wolstein Research Building room 1316, Cleveland, OH 44106, USA

2 Department of Epidemiology & Biostatistics, Case Western Reserve University, 2103 Cornell Rd, Wolstein Research Building room 1316, Cleveland, OH 44106, USA

3 Uganda – CWRU Research Collaboration, Makerere University and Mulago Hospital, Kampala, Uganda

4 College of Health Sciences, Makerere University and Mulago Hospital, Kampala, Uganda

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BMC Infectious Diseases 2014, 14:352  doi:10.1186/1471-2334-14-352

Published: 27 June 2014

Abstract

Background

Despite 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.

Methods

During 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.

Results

When 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).

Conclusions

Though 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.

Keywords:
Transmission risk factors; Latent Mtb infection; Exposure; Household characteristics; PPD test