Reducing Household Tuberculosis Transmission [TBN 086]

A pilot cluster-randomized controlled trial used a hybrid type 1 effectiveness-implementation design to evaluate whether a targeted respiratory bundle could reduce acquisition of Mycobacterium tuberculosis (Mtb) infection among household contacts (HHCs) of patients with pulmonary tuberculosis. The study was conducted in Santiago, Chile, between October 2021 and April 2024 across three healthcare districts comprising 44 primary healthcare clinics. Healthcare districts were randomized at the cluster level to either the intervention arm (2 districts, 25 clinics) or control arm (1 district, 19 clinics) to minimize contamination and facilitate real-world implementation.

Eligible index patients had newly diagnosed pulmonary tuberculosis confirmed by culture, acid-fast bacillus smear, or Xpert MTB/RIF Ultra PCR and had received no more than three daily doses of anti-tuberculosis therapy. Household contacts aged >5 years were invited to participate. The intervention consisted of a two-week respiratory bundle: KN95/FFP2 mask use by both patients and household contacts when sharing indoor spaces, sleeping separately for the index patient, improved ventilation through open windows, and educational materials. Controls received routine tuberculosis care. Household contacts underwent symptom screening, chest radiography, and QuantiFERON-TB Gold Plus (QFT) testing at baseline and, if initially QFT-negative, again after 12 weeks. The primary outcome was incident tuberculosis infection, defined by QFT conversion.

A total of 157 index patients and 384 household contacts were included in the analysis. Among household contacts, 32.3% had positive baseline QFT results and 67.7% were QFT-negative. Of the 216 QFT-negative contacts assigned to intervention or control groups, 179 (82.9%) completed 12-week follow-up. QFT conversion occurred in 10.8% (10/93) of controls and 12.8% (11/86) of intervention participants, yielding a risk ratio (RR) of 1.10 (95% CI, 0.71-1.71; P = .68), indicating no significant reduction in new tuberculosis infection with the intervention. In the per-protocol analysis, participants with good adherence to the respiratory bundle at both day 7 and day 14 had a QFT conversion rate of 6.7%, compared with 10.8% in controls (RR 0.69, 95% CI 0.25-1.91; P = .47), although this difference was not statistically significant. Factors independently associated with increased risk of QFT conversion included high sputum bacillary burden in index patients (adjusted RR [adjRR] 12.10, 95% CI 2.52-55.81), drug use by the index patient (adjRR 10.02, 95% CI 2.70-36.33), suboptimal treatment adherence (adjRR 3.56, 95% CI 1.17-10.74), and household contact age below 45 years (adjRR 7.56, 95% CI 1.57-35.37). The intraclass correlation coefficient for QFT conversion within households was 0.085 (95% CI 0.005-0.360).

In this pilot cluster-randomized trial, the respiratory bundle did not significantly reduce incident Mtb infection among household contacts in the intention-to-treat analysis. However, lower infection rates among participants with good adherence suggest that adherence may influence effectiveness and warrants further investigation in larger trials. Important implementation barriers included household overcrowding, limited ability to isolate index patients, family social dynamics around meals, and stigma related to tuberculosis disclosure. As a pilot study, statistical power was limited, and confidence intervals were wide. The study provides moderate-level evidence from a randomized design regarding feasibility and implementation challenges in real-world household tuberculosis prevention.

Source: Ruiz-Tagle C, Seguel R, Villarroel L, Bernales M, Vargas-García S, Pizarro A, Peña C, Neira V, García P, Allel K, Nathavitharana RR. Reducing Household Tuberculosis Transmission: A Pilot Cluster-Randomized Controlled Trial. Clinical Infectious Diseases. 2026 Feb 15;82(2):291-8.