Respiratory infections

Lead Research Organisation: University College London

Abstract

Respiratory infections are infections that affect people’s breathing. They are the biggest cause infectious disease deaths worldwide. A quarter of the world’s population is estimated to have latent tuberculosis (TB). Latent TB is a TB infection without symptoms. One in ten people with latent TB will develop active TB (TB with symptoms) in their lifetime. People who are older or who have illnesses such as HIV or diabetes are at higher risk of developing active TB. To address this global public health problem, we have expanded our range of TB trials to cover the full spectrum of disease. We have new studies of
• Diagnostics (tools for diagnosing TB)
• TB preventative therapy
• Shorter and simpler treatments for different types of TB in adults and children.
Respiratory infections caused by bacteria are extremely common. They are increasing in high-income countries. They are a major driver of antibiotic use and thus antimicrobial (drug) resistance. We need better evidence to inform prescribing guidelines. To help with this, we have a number of trials aiming to work out the best dose and duration of antibiotics for children and adults with bacterial respiratory infections.
In response to the SARS-Cov-2 pandemic, we have developed a number of treatment trials. These trials use our expanded global influenza network. The trials cover the patients severely ill in intensive care, hospitalised patients with mild-moderate infection and in those with early disease at risk of progression. Embedded substudies are exploring the timing and number of doses of SARS-Cov-2 vaccine needed in those who have been hospitalised with COVID-19.

Technical Summary

Respiratory infections continue to cause the greatest number of infectious disease deaths worldwide. A quarter of the world’s population is estimated to have latent tuberculosis, with a 10% lifetime risk of developing active TB, further increased by co-morbidities such as HIV or diabetes mellitus and exacerbated by the effects of aging. In response to this public health emergency, in this quinquennium, we have expanded our portfolio of tuberculosis trials to cover the full spectrum of disease, with new studies of latent tuberculosis diagnostics and tuberculosis preventative therapy, as well as addressing antimicrobial resistance through trials testing shortened treatment (improving adherence) and more effective regimens for both drug-sensitive and drug-resistant tuberculosis disease. Paediatric tuberculosis has historically been neglected, particularly in terms of identifying the right drug doses and appropriate formulations. We have been at the forefront of international activity in this area, conducting a programme of relevant phase III paediatric tuberculosis trials in Africa and Asia, ensuring that children are represented in research.
Bacterial respiratory infections are extremely common, and estimated to be increasing in high-income countries, making them a major driver of antibiotic use and thus antimicrobial resistance. Better evidence is needed to inform prescribing guidelines. Antibiotic trials pose numerous methodological challenges which our programme is addressing. For example, the relatively weak evidence base for treating pneumonia in both adults and children, particularly regarding choice of drug, dose and duration means that appropriately designed trials addressing questions about narrowing and shortening of antibiotic treatment courses need to be undertaken. We have developed a new trial design to directly estimate the optimal duration of antibiotic treatment, whose first large-scale application will be in a trial in paediatric pneumonia in LMIC.
In response to the SARS-Cov-2 pandemic, and utilising and expanding on our global influenza network, built in 2009 in response to the influenza A H1N1 pandemic, we are playing a leading role in the international response. We are testing the most promising antiviral candidates and immunomodulating agents (including passive immunotherapy using convalescent plasma and immunoglobulin) for treatment across the disease spectrum.

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