1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis

Abstract

Background: Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups.

Methods: We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year. Incidence was estimated across age and risk groups (<5 years; ≥5 years, diagnosed with human immunodeficiency virus [HIV]; ≥5 years, not diagnosed with HIV/unknown, baseline TBI-positive) by logistic or log-binomial regression fitted using generalized estimating equations.

Results: Of 1016 HHCs, 850 (83.7%) from 247 households were assessed (median, 51.4 weeks). Among 242 HHCs, 52 tested interferon-gamma release assay-positive, yielding a 1-year 21.6% (95% confidence interval [CI], 16.7-27.4) TBI cumulative incidence. Sixteen of 742 HHCs developed confirmed (n = 5), probable (n = 3), or possible (n = 8) TBD, yielding a 2.3% (95% CI, 1.4-3.8) 1-year cumulative incidence (1.1%; 95% CI, .5-2.2 for confirmed/probable TBD). TBD relative risk was 11.5-fold (95% CI, 1.7-78.7), 10.4-fold (95% CI, 2.4-45.6), and 2.9-fold (95% CI, .5-17.8) higher in age <5 years, diagnosed with HIV, and baseline TBI high-risk groups, respectively, vs the not high-risk group (P = .0015). By 1 year, 4% (21 of 553) of high-risk HHCs had received TPT.

Conclusions: TBI and TBD incidence continued through 1 year in rifampin-/multidrug-resistant TB HHCs. Low TPT coverage emphasizes the need for evidence-based prevention and scale-up, particularly among high-risk groups.

Keywords: household contacts; multidrug-resistant tuberculosis; tuberculosis disease; tuberculosis infection; tuberculosis preventive treatment.

Figure 1.

Flow from baseline enrollment of the index MDR TB cases and HHCs to HHCs reassessed at 1 year (from 247 households) who were either at risk of TBD or TBI. TBD and TBI analyses were completed separately, as all HHCs at risk of incident TBD were not necessarily at risk of incident TBI. Abbreviations: HHC, household contact; IGRA, interferon-gamma release assay; MDR, multidrug-resistant; RR, rifampin-resistant; TB, tuberculosis; TBD, tuberculosis disease; TBI, tuberculosis infection.

Figure 2.

One-year cumulative incidence of TB infection (TBI) and TB disease (TBD) in household contacts of rifampin- or multidrug-resistant TB index cases. One-year cumulative incidence of TBI defined by IGRA conversion with comparisons made between age groups (A) and HIV status (B). One-year cumulative incidence of TBD stratified by confirmed/probable TB and possible disease with comparisons made between age groups (C) and risk group (D). High-risk group includes age <5 (regardless of HIV and TBI status); age ≥5 years diagnosed with HIV (regardless of TBI status); and age ≥5, and not diagnosed with HIV, baseline TST/IGRA positive. Cumulative incidence estimated using generalized estimated equations to account for household clustering. Longitudinal bars represent 95% confidence intervals. Abbreviations: HIV, human immunodeficiency virus; IGRA, interferon-gamma release assay; TB, tuberculosis; TST, tuberculin skin test.