Case studies to illustrate good practice in the management of non-tuberculous mycobacterial pulmonary disease

Pulmonary disease caused by non-tuberculous mycobacteria (NTM-PD) can be a complex condition for health care providers to manage, and delayed diagnosis and treatment failure are common. Here we present three case studies that illustrate key challenges in the diagnosis and treatment of NTM-PD, and provide guidance on these issues. In addition, we make recommendations on how the overall management of NTM-PD may be improved, through strategies such as physician education to recognise NTM-PD, and the development of multidisciplinary teams and patient-support groups

The roles of neutrophils in non-tuberculous mycobacterial pulmonary disease

Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is an increasingly recognised global health issue. Studies have suggested that neutrophils may play an important role in controlling NTM infection and contribute to protective immune responses within the early phase of infection. However, these cells are also adversely associated with disease progression and exacerbation and can contribute to pathology, for example in the development of bronchiectasis. In this review, we discuss the key findings and latest evidence regarding the diverse functions of neutrophils in NTM infection. First, we focus on studies that implicate neutrophils in the early response to NTM infection and the evidence reporting neutrophils' capability to kill NTM. Next, we present an overview of the positive and negative effects that characterise the bidirectional relationship between neutrophils and adaptive immunity. We consider the pathological role of neutrophils in driving the clinical phenotype of NTM-PD including bronchiectasis. Finally, we highlight the current promising treatments in development targeting neutrophils in airways diseases. Clearly, more insights on the roles of neutrophils in NTM-PD are needed in order to inform both preventative strategies and host-directed therapy for these important infections

Uniting to end the TB epidemic: advances in disease control from prevention to better diagnosis and treatment.

Tuberculosis is a major global cause of morbidity and mortality. Despite recent advances in containing the epidemic, several challenges continue to slow progress towards elimination including the continuing impact of drug resistant disease, and the lack of appropriate tools. Curtailing the transmission of tuberculosis remains a challenge especially in high burden countries. New developments in measuring correlates of protection are urgently needed to support the evaluation of vaccines. Similarly, despite progress in molecular diagnostics, better tools are required to identify resistance to antibiotics in multi and extensively drug resistant tuberculosis. Whole Genome Sequencing may lead to the next generation of assays to rapidly detect resistance and evaluate transmission. Advances on shortening treatment are hampered by the lack of a biomarker of cure which obviates the current long wait for relapses in trials. New research is urgently needed to support development of new vaccines and better diagnostics tools and shorter treatment for drug sensitive and resistant tuberculosis

Anticipating the impact of the COVID-19 pandemic on TB patients and TB control programmes.

The COVID-19 pandemic has currently overtaken every other health issue throughout the world. There are numerous ways in which this will impact existing public health issues. Here we reflect on the interactions between COVID-19 and tuberculosis (TB), which still ranks as the leading cause of death from a single infectious disease globally. There may be grave consequences for existing and undiagnosed TB patients globally, particularly in low and middle income countries (LMICs) where TB is endemic and health services poorly equipped. TB control programmes will be strained due to diversion of resources, and an inevitable loss of health system focus, such that some activities cannot or will not be prioritised. This is likely to lead to a reduction in quality of TB care and worse outcomes. Further, TB patients often have underlying co-morbidities and lung damage that may make them prone to more severe COVID-19. The symptoms of TB and COVID-19 can be similar, with for example cough and fever. Not only can this create diagnostic confusion, but it could worsen the stigmatization of TB patients especially in LMICs, given the fear of COVID-19. Children with TB are a vulnerable group especially likely to suffer as part of the "collateral damage". There will be a confounding of symptoms and epidemiological data through co-infection, as happens already with TB-HIV, and this will require unpicking. Lessons for COVID-19 could be learned from the vast experience of running global TB control programmes, while the astonishingly rapid and relatively well co-ordinated response to COVID-19 demonstrates how existing programmes could be significantly improved

World TB Day 2016: an interview with leading experts in tuberculosis research.

In this interview, we talk to leading tuberculosis (TB) experts from University College London and the London School of Hygiene and Tropical Medicine about the current challenges in TB research. The video of this interview is available here: https://www.youtube.com/watch?v=75Die7MQBec&feature=youtu.be . The video can also be downloaded via Additional file 1

Investments in respiratory infectious disease research 1997–2010: a systematic analysis of UK funding

Objectives: Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain. Setting: The UK. Participants: Institutions that host and carry out infectious disease research. Primary and secondary outcome measures The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size. Results: We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I–IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden. Conclusions: The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats