Isoniazid or rifampicin preventive therapy with and without screening for subclinical TB: a modeling analysis

BMC Medicine

Rachel W. Kubiak¹  Paul K. Drain²  Emily A. Kendall³  Amber Kunkel⁴  Anete Trajman⁵  Hamidah Hussain⁶  Richard Menzies⁷ 

[1]Department of Epidemiology, University of Washington, 3980 15th Ave NE, 98195, Seattle, Washington, USA

[2]Departments of Global Health, Medicine, and Epidemiology, University of Washington, Box 359927, 325 Ninth Ave, 98104, Seattle, Washington, USA

[3]Division of Infectious Diseases and Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 1550 Orleans Street, 21287, Baltimore, Maryland, USA

[4]Emerging Diseases Epidemiology Unit, Institut Pasteur, 25-28 Rue du Dr Roux, 75015, Paris, France

[5]Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro, R. São Francisco Xavier, 20550-900, Rio de Janeiro, Brazil

[6]Interactive Research and Development (IRD) Global, 583 Orchard Road #06-01 Forum, Singapore, Singapore

[7]Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute & McGill International TB Centre, 3650 St-Urbain Street, H2X 2P, Montreal, Quebec, Canada

关键词: Tuberculosis infection;    Subclinical tuberculosis;    Preventive therapy;    Screening;    Chest radiography;    Global health;    Antimicrobial resistance;   

DOI  :  10.1186/s12916-021-02189-w

来源: Springer

【 摘 要 】

BackgroundShort-course, rifamycin-based regimens could facilitate scale-up of tuberculosis preventive therapy (TPT), but it is unclear how stringently tuberculosis (TB) disease should be ruled out before TPT use.MethodsWe developed a state-transition model of a TPT intervention among two TPT-eligible cohorts: adults newly diagnosed with HIV in South Africa (PWH) and TB household contacts in Pakistan (HHCs). We modeled two TPT regimens—4 months of rifampicin [4R] or 6 months of isoniazid [6H]—comparing each to a reference of no intervention. Before initiating TPT, TB disease was excluded either through symptom-only screening or with additional radiographic screening that could detect subclinical TB but might limit access to the TPT intervention. TPT’s potential curative effects on both latent and subclinical TB were modeled, as were both acquisitions of resistance and prevention of drug-resistant disease. Although all eligible individuals received the screening and/or TPT interventions, the modeled TB outcomes comprised only those with latent or subclinical TB that would have progressed to symptomatic disease if untreated.ResultsWhen prescribed after only symptom-based TB screening (such that individuals with subclinical TB were included among TPT recipients), 4R averted 45 active (i.e., symptomatic) TB cases (95% uncertainty range 24–79 cases or 40–89% of progressions to active TB) per 1000 PWH [17 (9–29, 43–94%) per 1000 HHCs]; 6H averted 37 (19–66, 52–73%) active TB cases among PWH [13 (7–23, 53–75%) among HHCs]. With this symptom-only screening, for each net rifampicin resistance case added by 4R, 12 (3–102) active TB cases were averted among PWH (37 [9–580] among HHCs); isoniazid-resistant TB was also reduced. Similarly, 6H after symptom-only screening increased isoniazid resistance while reducing overall and rifampicin-resistant active TB. Screening for subclinical TB before TPT eliminated this net increase in resistance to the TPT drug; however, if the screening requirement reduced TPT access by more than 10% (the estimated threshold for 4R among HHCs) to 30% (for 6H among PWH), it was likely to reduce the intervention’s overall TB prevention impact.ConclusionsAll modeled TPT strategies prevent TB relative to no intervention, and differences between TPT regimens or between screening approaches are small relative to uncertainty in the outcomes of any given strategy. If most TPT-eligible individuals can be screened for subclinical TB, then pairing such screening with rifamycin-based TPT maximizes active TB prevention and does not increase rifampicin resistance. Where subclinical TB cannot be routinely excluded without substantially reducing TPT access, the choice of TPT regimen requires weighing 4R’s efficacy advantages (as well as its greater safety and shorter duration that we did not directly model) against the consequences of rifampicin resistance in a small fraction of recipients.

【 授权许可】

CC BY