Abstract
Tuberculosis is a bacterial infectious disease that is mainly transmitted from human to human via infectious aerosols. Currently, tuberculosis is the leading cause of death by an infectious disease world-wide. In the past decade, the number of patients affected by tuberculosis has increased by ~20 percent and the emergence of drug-resistant strains of Mycobacterium tuberculosis challenges the goal of elimination of tuberculosis in the near future. For the last 50 years, management of patients with tuberculosis has followed a standardized management approach. This standardization neglects the variation in human susceptibility to infection, immune response, the pharmacokinetics of drugs, and the individual duration of treatment needed to achieve relapse-free cure. Here we propose a package of precision medicine-guided therapies that has the prospect to drive clinical management decisions, based on both host immunity and M. tuberculosis strains genetics. Recently, important scientific discoveries and technological advances have been achieved that provide a perspective for individualized rather than standardized management of patients with tuberculosis. For the individual selection of best medicines and host-directed therapies, personalized drug dosing, and treatment durations, physicians treating patients with tuberculosis will be able to rely on these advances in systems biology and to apply them at the bedside.
Highlights
Tuberculosis is the leading cause of death attributed to a single microbial pathogen world-wide [1]
Drug resistances in M. tuberculosis complex strains are exclusively mediated by genomic variants, mainly single nucleotide polymorphisms (SNPs) and small insertions/deletion
Resistant phenotypes of M. tuberculosis complex strains mainly have a clear genetic correlate, which means SNPs can be used for resistance predictions with very high precision and are expected to replace phenotypic drug susceptibility testing (DST) in the future [13]
Summary
Tuberculosis is the leading cause of death attributed to a single microbial pathogen world-wide [1]. Tuberculosis patient care may be individualized in at least 4 areas (Figure 1): (I) generation sequencing of microbial M. tuberculosis DNA can predict drug susceptibility in the first week of diagnosis [6]; (II) host immunity can be detrimentally suppressed and need augmenting or it can be detrimentally exuberant and need to be suppressed [7,8,9]; or other forms of host genetic variability that may be addressed by immune-based interventions [10], (III) individualized drug concentrations that can guide antimicrobial dosing [11], and (IV) biomarkers that predict relapse-free cure and can guide duration of required therapeutics [12] (Figure 1) Such stratified therapies are within reach and could soon become available for the clinical management of tuberculosis. Mutations will potentially allow genotypic DST to replace phenotypic DST for a large fraction of clinical M. tuberculosis complex strains
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