Abstract
Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.
Highlights
Nontuberculous mycobacteria (NTM), including organisms of the Mycobacterium avium complex (MAC), represent a significant and growing threat to human health worldwide
host-directed therapies (HDTs) are an active area of investigation in the therapy of tuberculosis (TB), as well as many non-mycobacterial infectious diseases [11,12,13,14,15], there has been a relative dearth of research into the potential of HDTs as adjunctive therapies for disease caused by MAC [16]
We summarize HDT agents which are currently under investigation for MAC disease, as well as other HDTs and potentially targetable host pathways, which have not been investigated directly for MAC, but which show promise for future research
Summary
Nontuberculous mycobacteria (NTM), including organisms of the Mycobacterium avium complex (MAC), represent a significant and growing threat to human health worldwide. The most common clinical syndromes caused by MAC are pulmonary infection in patients with underlying lung disease, as well as disseminated disease in the severely immunocompromised [3, 4]. A recent review of MAC pulmonary disease worldwide reported a five-year all-cause mortality rate of 27% [5]. In the face of the increasing prevalence, high mortality, and treatment challenges associated with MAC infections, new therapeutic options are urgently needed. HDTs are an active area of investigation in the therapy of tuberculosis (TB), as well as many non-mycobacterial infectious diseases [11,12,13,14,15], there has been a relative dearth of research into the potential of HDTs as adjunctive therapies for disease caused by MAC [16]. We summarize HDT agents which are currently under investigation for MAC disease, as well as other HDTs and potentially targetable host pathways, which have not been investigated directly for MAC, but which show promise for future research
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