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Incomplete understanding of the complex microbe\u2013host interactions has hindered the identification of suitable biomarkers to expedite the development of diagnostic tools, drugs and vaccines. The field effectiveness of directly observed therapy\u2013short course has been compromised by the intrinsic limitations of sputum microscopy and suboptimal adherence to the long duration of treatment amid the <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TB<\/jats:styled-content> syndemic and various socioeconomic constraints. While molecular tools are transforming the diagnostic processes, especially for multi\u2010drug\u2010resistant (<jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content>)\u2010<jats:styled-content style=\"fixed-case\">TB<\/jats:styled-content>, drug development and service provision for <jats:styled-content style=\"fixed-case\">MDR\u2010TB<\/jats:styled-content> seriously lag behind. Inappropriate management of detected <jats:styled-content style=\"fixed-case\">MDR\u2010TB<\/jats:styled-content> cases may amplify drug resistance, jeopardizing future control. Targeted screening and treatment of latent infection with <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>.\u2009tuberculosis<\/jats:italic> with the currently available immunodiagnostic tools and treatment regimens aim more for personal protection than major epidemiological impact or elimination. The interferon\u2010\u03b3 release assays (<jats:styled-content style=\"fixed-case\">IGRA<\/jats:styled-content>) are not affected by cross\u2010reaction to the bacillus <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>almette\u2013<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>u\u00e9rin (<jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content>) vaccine and are increasingly used for such screening before initiation of biologics for treatment of rheumatoid arthritis and other autoimmune disorders. <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> offers only partial and unreliable protection against pulmonary <jats:styled-content style=\"fixed-case\">TB<\/jats:styled-content> in adults, the crucial transmission link for this airborne infection. Systems biology and vaccinomics may speed up vaccine research. 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