Date Published: April 30, 2019
Publisher: Public Library of Science
Author(s): Colleen F. Hanrahan, Bareng A. S. Nonyane, Lesego Mmolawa, Nora S. West, Tsundzukani Siwelana, Limakatso Lebina, Neil Martinson, David W. Dowdy, Mark Hatherill
Abstract: BackgroundThere is a dearth of comparative effectiveness research examining the implementation of different strategies for active tuberculosis (TB) case finding, particularly in rural settings, which represent 60% of the population of sub-Saharan Africa.Methods and findingsWe conducted a pragmatic, cluster-randomized comparative effectiveness trial of two TB case finding strategies (facility-based screening and contact tracing) in 56 public primary care clinics in two largely rural districts of Limpopo Province, South Africa. In the facility-based screening arm, sputum Xpert MTB/RIF was performed on all patients presenting (for any reason) with TB symptoms to 28 study clinics, and no contact tracing was performed. In the contact-tracing arm, contacts of patients with active TB were identified (via household tracing in 14 clinics and using small monetary incentives in the other 14 clinics), screened for TB symptoms, and offered Xpert MTB/RIF testing. The primary outcome was the number of newly identified patients with TB started on treatment. The analysis used multivariable Poisson regression adjusted for historical clinic-level TB case volumes and district. The trial was registered with ClinicalTrials.gov (NCT02808507). From July 18, 2017, to January 17, 2019, a total of 3,755 individuals started TB treatment across 56 study clinics in the 18-month period. Clinic characteristics and clinic-level averages of patient characteristics were similar across the two arms: 40/56 (71%) clinics were in a rural location, 2,136/3,655 (58%) patients were male, and 2,243 (61%) were HIV positive. The treatment initiation ratio comparing the yield of TB patients started on treatment in the facility-based arm compared to that from the contact-tracing arm was 1.04 (95% confidence interval [CI] 0.83–1.30, p = 0. 73). In the contact-tracing arm, 1,677 contacts of 788 new TB index patients were screened, yielding 12 new patients with TB. Prespecified subgroup analyses resulted in similar results, with estimated treatment initiation ratios of 0.96 (95% CI 0.64–1.27; p = 0.78) and 1.23 (95% CI 0.87–1.59; p = 0.29) among historically smaller and historically larger clinics, respectively. This ratio was 1.02 (95% CI 0.66–1.37; p = 0.93) and 1.08 (95% CI 0.74–1.42; p = 0.68) in the Vhembe and Waterberg districts, respectively. The estimated treatment initiation ratio was unchanged in sensitivity analyses excluding 24 records whose TB registration numbers could not be verified (1.03, 95% CI 0.82–1.29; p = 0.78) and excluding transfers-in (1.02, 95% CI 0.80–1.29; p = 0.71). Study limitations include the possibility of imbalance on cluster size owing to changes in catchment population over time and the inability to distinguish the independent effects of the two contact investigation strategies.ConclusionsContact tracing based on symptom screening and Xpert MTB/RIF testing did not increase the rate of treatment initiation for TB relative to the less resource-intensive approach of facility-based screening in this rural sub-Saharan setting.Trial registrationClinicalTrials.gov NCT02808507.
Partial Text: Tuberculosis (TB) is the world’s leading infectious disease killer, causing 10 million new cases and 1.3 million deaths in 2017 . TB case detection has languished at near two-thirds for over a decade—in 2017, an estimated 3.6 million cases went unreported or undetected . Evidence from large-scale studies of intensive active case finding strategies in high-burden settings have shown that approaches such as community-wide case finding campaigns, household visits, and contact tracing identify more new patients with TB compared to traditional passive case finding and have a population-level impact, lowering TB prevalence [2, 3]. Investigation of household and other close contacts has been a pillar of TB control activities in high-income, low-prevalence settings for decades [4, 5] but, despite global guidelines in place since 2012 , has been poorly implemented in low- and middle-income, high-burden settings. In order to meet ambitious global targets of reducing TB incidence and mortality by 90% by 2035, WHO recommends that ≥90% of contacts of new patients with TB should be investigated for TB .
This pragmatic cluster-randomized trial of 3,755 individuals initiating TB treatment in 56 predominantly rural South African clinics found no difference in treatment initiation rate at the clinic level, comparing the current standard of care (facility-based screening) against feasibly delivered contact tracing based on symptom screening and Xpert MTB/RIF testing. This finding was primarily driven by a lower-than-expected yield of contact tracing, which found only 12 patients across 28 clinics during an 18-month time period. These findings suggest that although close contacts are a high-risk group (estimated TB prevalence 720 per 100,000) and should continue to be prioritized for case finding, the prevalence of TB among contacts may not be higher than that of individuals presenting to healthcare facilities. Diagnostic algorithms with greater sensitivity than symptom-driven Xpert MTB/RIF testing may be necessary for contact tracing to increase TB treatment initiation rates at the clinic level.