Tuberculosis Infectiousness and Host Susceptibility

Turner, Richard; Chiu, Christopher; Churchyard, Gavin J.; Esmail, Hanif; Lewinsohn, David; Gandhi, Neel R.; Fennelly, Kevin P.

doi:10.1093/infdis/jix361

Cited by 77 publications

(65 citation statements)

References 85 publications

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“…Our Respiratory Aerosol Sampling Chamber (RASC) effectively functions as a personal clean-room, enabling collection and concentration of particulate material released by an individual patient during normal respiratory activity, including from natural (non-induced) cough (29,37). Through multiple iterations informed by our preliminary experimental and clinical observations, we have equipped the RASC to address systematically the comprehensive TB transmission research agenda outlined by others (38). Key questions posed include: When are viable, infection-competent bacilli released by Mtb-infected individuals?…”

Section: Introductionmentioning

confidence: 99%

Capture and visualization of liveMycobacterium tuberculosisbacilli from tuberculosis bioaerosols

Dinkele

Gessner

Koch

et al. 2019

Preprint

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authors contributed equally to this work. Abstract:The tuberculosis (TB) pandemic demands urgent interventions such as those designed to interrupt Mycobacterium tuberculosis (Mtb) transmission, a challenge exacerbated by our poor understanding of the events enabling successful transfer of infectious bacilli between hosts. To address this problem, we developed the Respiratory Aerosol Sampling Chamber (RASC), a personal clean-room equipped with high-efficiency filtration and sampling technologies that allow biosafe capture and isolation of particulate matter -including Mtb bacilli -released by patients during natural breathing and (non-induced) cough. Here, we demonstrate the use of DMNtrehalose labelling to detect and quantify live Mtb bacilli among complex bioaerosol samples arrayed in a bespoke nanowell device following capture in the RASC. A pilot study identified Mtb in more than 85 % of known TB patients, improving significantly on previous work which has relied on animal infection and cough sampling to estimate transmission events. Moreover, intrapatient comparisons of bioaerosol and sputum samples indicated that Mtb aerosols likely derive from a compartment other than sputum. These results support the utility of the RASC platform for research aimed at interrupting Mtb transmission, including the non-invasive detection of Mtbinfected individuals who are predicted to contribute to bacillary spread despite the absence of clinical symptoms.

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Section: Introductionmentioning

confidence: 99%

Capture and visualization of liveMycobacterium tuberculosisbacilli from tuberculosis bioaerosols

Dinkele

Gessner

Koch

et al. 2019

Preprint

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“…Torres-Gonzalez et al 29 , for example, found a high prevalence of latently infected dairy farm and abattoir workers in a high bTB cattle prevalence district of Mexico associated with occupational exposure. The factors affecting latency, and reversion to active disease, are complex and poorly understood for TB 30,31 , reducing our capabilities to project future infection outcomes. Neither should there be assumptions that M. bovis could not in future emerge as a more virulent pathogen than to date through the emergence of new strains, or the Pre-print accepted version: Veterinary Record -July 2019 21 possibility that newly emerging co-infections or co-morbidities such as diabetes mellitus could not change the epidemiology and pathophysiology of M. bovis infection in humans, making it a more prevalent and fearsome proposition.…”

Section: Discussionmentioning

confidence: 99%

Farmer and veterinarian attitudes towards the risk of zoonotic Mycobacterium bovis infection in Northern Ireland

Robinson

2019

Veterinary Record

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Based on a qualitative social science research methodology using semi-structured interviews, this paper examines the attitudes of farmers and veterinarians in Northern Ireland around the risk of acquiring tuberculosis caused by Mycobacterium bovis from infected cattle and drinking raw milk. This region has traditionally had one of the highest rates of bovine tuberculosis in the United Kingdom and among the highest in Europe. The research finds that the risk is often downplayed and considered so rare that it is no longer a significant public health risk due to the pasteurisation of milk and intensive surveillance on farms through systematic testing and removal of positive animals, as evidenced by the low recorded human incidence. Although the incidence of tuberculosis in humans caused by M bovis is only around 1% of all annual human tuberculosis cases, this paper argues that M bovis may be underestimated as a human pathogen and makes the case for a renewed perspective. Discourses surrounding the disease may need to be re-orientated to remind relevant stakeholders that human infection with M bovis is a hazard that needs to be treated with more caution on the front line of control.

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“…Additionally, regulatory T cells (Tregs) may inhibit protective immunity. 5,6 Theoretically, each of these pathways constitutes potential and 'druggable' targets. However, this notion is complicated by the complex course of progressive TB disease, including stages such as initial infection, protracted latency and overt disease 7,8 Furthermore, other factors such as genetic diversity and co-morbidities (e.g.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic host-directed strategies to improve outcome in tuberculosis

2020

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Bacille Calmette-Guérin (BCG) is the only licenced tuberculosis (TB) vaccine, but has limited efficacy against pulmonary TB disease development and modest protection against extrapulmonary TB. Preventative antibiotic treatment for Mycobacterium tuberculosis (Mtb) infections in high-prevalence settings is unfeasible due to unclear treatment durability, drug toxicity, logistical constraints related to directly observed treatment strategy (DOTS) and the lengthy treatment protocols. Together, these factors promote nonadherence, contributing to relapse and establishment of drug-resistant Mtb strains. Although antibiotic treatment of drugsusceptible Mtb is generally effective, drug-resistant TB has a treatment efficacy below 50% and can, in a proportion, develop into progressive, untreatable disease. Other immune compromising co-infections and/or co-morbidities require more complex prevention/treatment approaches, posing huge financial burdens to national health services. Novel TB treatment strategies, such as host-directed therapeutics, are required to complement pathogen-targeted approaches. Pre-clinical studies have highlighted promising candidates that enhance endogenous pathways and/or limit destructive host responses. This review discusses promising pre-clinical candidates and forerunning compounds at advanced stages of clinical investigation in TB host-directed therapeutic (HDT) efficacy trials. Such approaches are rationalized to improve outcome in TB and shorten treatment strategies.

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Tuberculosis Infectiousness and Host Susceptibility

Cited by 77 publications

References 85 publications

Capture and visualization of liveMycobacterium tuberculosisbacilli from tuberculosis bioaerosols

Capture and visualization of liveMycobacterium tuberculosisbacilli from tuberculosis bioaerosols

Farmer and veterinarian attitudes towards the risk of zoonotic Mycobacterium bovis infection in Northern Ireland

Therapeutic host-directed strategies to improve outcome in tuberculosis

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