Isoniazid or rifampicin preventive therapy with and without screening for subclinical TB: a modeling analysis
Isoniazid or rifampicin preventive therapy with and without screening for subclinical TB: a modeling analysis
Data
2021
Autores
Kendall, Emily A.
Hussain, Hamidah
Kunkel, Amber
Kubiak, Rachel W.
Trajman, Anete
Menzies, Richard
Drain, Paul K.
Journal Title
Journal ISSN
Volume Title
Publisher
BMC Medicine
Resumo
Background: Short-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.
Methods: We 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.
Results: When 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.
Conclusions: All 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.
Description
Palavras-chave
Tuberculosis infection, Subclinical tuberculosis, Preventive therapy, Screening, Chest radiography, Global health, Antimicrobial resistance.
Citação
Kendall EA, Hussain H, Kunkel A, Kubiak RW, Trajman A, Menzies R, Drain PK. Isoniazid or rifampicin preventive therapy with and without screening for subclinical TB: a modeling analysis. BMC Med. 2021 Dec 14;19(1):315. doi: 10.1186/s12916-021-02189-w.