Improving Tuberculosis Preventive Therapy Uptake: A Cluster-randomized Trial of Symptom-based Versus Tuberculin Skin Test-based Screening of Household Tuberculosis Contacts Less Than 5 Years of Age

Abstract

Background: Tuberculosis preventive therapy (TPT) is highly effective at preventing tuberculosis disease in household child contacts (<5 years), but is poorly implemented worldwide. In 2006, the World Health Organization recommended symptom-based screening as a replacement for tuberculin skin testing (TST) to simplify contact evaluation and improve implementation. We aimed to determine the effectiveness of this recommendation.

Methods: We conducted a pragmatic, cluster-randomized trial to determine whether contact evaluation using symptom screening improved the proportion of identified child contacts who initiated TPT, compared to TST-based screening, in Matlosana, South Africa. We randomized 16 clinics to either symptom-based or TST-based contact evaluations. Outcome data were abstracted from customized child contact management files.

Results: Contact tracing identified 550 and 467 child contacts in the symptom and TST arms, respectively (0.39 vs 0.32 per case, respectively; P = .27). There was no significant difference by arm in the adjusted proportion of identified child contacts who were screened (52% in symptom arm vs 60% in TST arm; P = .39). The adjusted proportion of identified child contacts who initiated TPT or tuberculosis treatment was 51.5% in the symptom clinics and 57.1% in the TST clinics (difference -5.6%, 95% confidence interval -23.7 to 12.6; P = .52). Based on the district's historic average of 0.7 child contacts per index case, 14% and 15% of child contacts completed 6 months of TPT in the symptom and TST arms, respectively (P = .89).

Conclusions: Symptom-based screening did not improve the proportion of identified child contacts evaluated or initiated on TPT, compared to TST-based screening. Further research is needed to identify bottlenecks and evaluate interventions to ensure all child contacts receive TPT.

Clinical trials registration: NCT03074799.

Keywords: pediatric; symptom-screening; tuberculin skin test; tuberculosis; tuberculosis preventive therapy.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Study population. Abbreviation: TST, tuberculin skin test.

Figure 2.

Number of child contacts progressing through each step of the cascade. All proportions are cluster adjusted and represent the proportion of estimated child contacts who progressed through that stage of the pediatric TB prevention care continuum. Child contacts were estimated by multiplying 0.7 by all adult index cases with pulmonary TB who did not report living alone. TPT in this study was 6 months of daily isoniazid. Numbers given in brackets indicate the interquartile ranges. Abbreviations: TB, tuberculosis; TPT, tuberculosis preventive therapy; TST, tuberculin skin test; Tx, treatment.

Figure 3.

Pediatric TB prevention continuum of care by arm from a cohort of child contacts associated with index cases admitted to TB clinics in Matlosana, South Africa from October 2015–February 2017. Adjusted proportions for each arm are displayed above each bar and represent the proportion of estimated child contacts progressing to that stage of TB preventive care. Child contacts were estimated by multiplying 0.7 by all adult TB index cases who did not report living alone. Abbreviations: TB, tuberculosis; TST, tuberculin skin test.