Other infectious diseases of global public health significance

Antibiotic resistance, viral hepatitis and infections which can cause a global epidemic such as influenza, place major burdens on human health. Our research focusses on the following:
1) Antibiotic resistance. One of objectives is to see if we can treat common infections such as pneumonia with shorter courses of antibiotics. Another is to see if using two antibiotics for a short time might improve outcomes when people have blood infections. Last, whether we can find new uses for older antibiotics that are no longer widely used but might be very effective for resistant bugs that have become more common in hospitals;
2) Hepatitis C. There are now several very well tolerated oral drugs which cure >90% of patients with Hepatitis C with just 12-24 weeks of treatment. However, they are very expensive and not widely available. We are planning a study to see if people can be cured with even shorter treatment courses of between 4-6 weeks.
3) Infections that ‘go global’. The 2009 ‘swine flu’ outbreak, only 6 years after SARS, reminded us of how important it is to prepare for global epidemics. We are part of two international influenza studies trying to understand how influenza changes over time and what factors predict who will do badly if they get flu. We are now trialling a new treatment (FLU-IVIG) for those severely ill, hospitalised with influenza.

Antimicrobial resistance, viral hepatitis and infections with pandemic potential place a major burden on human health. Our research focusses on:
1) Antibiotic-resistance – which increases morbidity/mortality for the individual and has huge public health implications. Our research aims to i) demonstrate in well-conducted trials that narrower spectrum antibiotics do not lead to poorer clinical outcomes; ii) assess the role of shorter antibiotic courses as a mechanism to reduce antibiotic selection pressure (CAP-IT) and the utility of short course dual antibiotics to effect more rapid bacterial kill in bacterial sepsis syndromes with high morbidity and mortality (ARREST);
iii) investigate the role of old, now rarely used narrower spectrum antibiotics and/or repurpose existing narrower spectrum antibiotics as alternatives to broad spectrum antibiotics; iv) investigate novel point-of-care biomarkers to more clearly distinguish bacterial from viral infection and avoid using antibiotics inappropriately.
2) Viral hepatitides, in particular hepatitis C where a number of very potent, low toxicity oral direct acting antivirals (DAA) are able to cure >90% of patients with just 12-24 weeks of treatment. This offers the chance of global elimination because treatment could be shifted to the community and the brevity of the treatment means hard-to-reach populations could be treated successfully. There is a major caveat, in that these DAA are very expensive and hence not universally available, and moreover, do not prevent re-infection. We aim to explore a strategy of treating immediately vs. deferring in those with minimal liver disease to better understand the clinical benefits of treatment; a second study exploring the utility of even shorter DAA courses is also planned.
3) Emergent infections with pandemic potential. The 2009 influenza pandemic, only 6 years after the SARS coronavirus outbreak in 2003, served to illustrate the importance of a world-wide rapid-response infrastructure ready for future pandemics. MRC CTU as part of the INSIGHT network, established two observational studies in influenza, in the hospital (FLU003 Plus) and out-patient (FLU002 Plus) settings in direct response to this pandemic. These studies, along with the genetic substudy (INSIGHT-004) aim to inform on the longitudinal changes in clinical presentation of differing influenza strains, understand influenza strain drift/shift, antiviral resistance and the genetics that underpin poorer outcomes. We are now trialling a passive immunotherapy (FLU-IVIG) for those severely ill and hospitalised with influenza. This represents a novel treatment, which if found to be effective is likely to be developed into a commercialised polyclonal antibody product.