TY - JOUR
T1 - Modeling the impact of novel diagnostic tests on pediatric and extrapulmonary tuberculosis
AU - Denkinger, Claudia M.
AU - Kampmann, Beate
AU - Ahmed, Syed
AU - Dowdy, David W.
N1 - Funding Information:
Development and publication of this manuscript was made possible with financial support from the New Diagnostics Working Group of the Stop TB Partnership, grants from the Bill and Melinda Gates Foundation (OPP1061487), the Canadian Institute of Health Research (MOP 123291), the UK Medical Research Council (MR/K011944/1) as well as the US National Institutes of Health (1R21AI101152). CMD is supported by a Richard Tomlinson Fellowship at McGill University and a fellowship of the Burroughs–Wellcome Fund from the American Society of Tropical Medicine and Hygiene. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2014 Denkinger et al.; licensee BioMed Central Ltd.
PY - 2014/9/3
Y1 - 2014/9/3
N2 - Background: Extrapulmonary tuberculosis (EPTB) and most pediatric TB cannot be diagnosed using sputum-based assays. The epidemiological impact of different strategies to diagnose EPTB and pediatric TB is unclear. Methods: We developed a dynamic epidemic model of TB in a hypothetical population with epidemiological characteristics similar to India. We evaluated the impact of four alternative diagnostic test platforms on adult EPTB and pediatric TB mortality over 10 years: (1) Nucleic acid amplification test optimized for diagnosis of EPTB (“ NAAT-EPTB“ ); (2) NAAT optimized for pediatric TB (“ NAAT-Peds“ ); (3) more deployable NAAT for sputum-based diagnosis of adult pulmonary TB (“ point-of-care (POC) sputum NAAT“ ); and (4) more deployable NAAT capable of diagnosing all forms of TB using non-invasive, non-sputum specimens (“ POC non-sputum NAAT“ ). Results: NAAT-EPTB lowered adult EPTB mortality by a projected 7.6% (95% uncertainty range [UR]: 6.5-8.8%). NAAT-Peds lowered pediatric TB mortality by 6.8% (UR: 4.9-8.4%). POC sputum NAAT, though only able to diagnose pulmonary TB, reduced projected pediatric TB deaths by 13.3% (UR: 4.6-15.7%) and adult EPTB deaths by 8.4% (UR 2.0-9.3%) simply by averting transmission of disease. POC non-sputum NAAT had the greatest effect, lowering pediatric TB mortality by 34.7% (UR: 26.8-38.7), and adult EPTB mortality by 38.5% (UR: 30.7-41.2). The relative impact of a POC sputum NAAT (i.e., enhanced deployability) versus NAAT-EPTB (i.e., enhanced ability to specifically diagnose TB-NSP) on adult EPTB mortality depends most strongly on factors that influence transmission, with settings of higher transmission (e.g., higher per-person transmission rate, lower diagnostic rate) favoring POC sputum NAAT.Conclusion: Although novel tests for pediatric TB and EPTB are likely to reduce TB mortality, major reductions in pediatric and EPTB incidence and mortality also require better diagnostic tests for adult pulmonary TB that reach a larger population.
AB - Background: Extrapulmonary tuberculosis (EPTB) and most pediatric TB cannot be diagnosed using sputum-based assays. The epidemiological impact of different strategies to diagnose EPTB and pediatric TB is unclear. Methods: We developed a dynamic epidemic model of TB in a hypothetical population with epidemiological characteristics similar to India. We evaluated the impact of four alternative diagnostic test platforms on adult EPTB and pediatric TB mortality over 10 years: (1) Nucleic acid amplification test optimized for diagnosis of EPTB (“ NAAT-EPTB“ ); (2) NAAT optimized for pediatric TB (“ NAAT-Peds“ ); (3) more deployable NAAT for sputum-based diagnosis of adult pulmonary TB (“ point-of-care (POC) sputum NAAT“ ); and (4) more deployable NAAT capable of diagnosing all forms of TB using non-invasive, non-sputum specimens (“ POC non-sputum NAAT“ ). Results: NAAT-EPTB lowered adult EPTB mortality by a projected 7.6% (95% uncertainty range [UR]: 6.5-8.8%). NAAT-Peds lowered pediatric TB mortality by 6.8% (UR: 4.9-8.4%). POC sputum NAAT, though only able to diagnose pulmonary TB, reduced projected pediatric TB deaths by 13.3% (UR: 4.6-15.7%) and adult EPTB deaths by 8.4% (UR 2.0-9.3%) simply by averting transmission of disease. POC non-sputum NAAT had the greatest effect, lowering pediatric TB mortality by 34.7% (UR: 26.8-38.7), and adult EPTB mortality by 38.5% (UR: 30.7-41.2). The relative impact of a POC sputum NAAT (i.e., enhanced deployability) versus NAAT-EPTB (i.e., enhanced ability to specifically diagnose TB-NSP) on adult EPTB mortality depends most strongly on factors that influence transmission, with settings of higher transmission (e.g., higher per-person transmission rate, lower diagnostic rate) favoring POC sputum NAAT.Conclusion: Although novel tests for pediatric TB and EPTB are likely to reduce TB mortality, major reductions in pediatric and EPTB incidence and mortality also require better diagnostic tests for adult pulmonary TB that reach a larger population.
KW - Diagnostics
KW - Extrapulmonary
KW - Modeling
KW - Pediatrics
KW - Tuberculosis
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U2 - 10.1186/1471-2334-14-477
DO - 10.1186/1471-2334-14-477
M3 - Article
C2 - 25186052
AN - SCOPUS:84907284058
VL - 14
SP - 1
EP - 10
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
SN - 1471-2334
IS - 1
M1 - 477
ER -