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In 2012, around 19,500 kidney transplant operations were performed in the UK and USA. The greatest infection risk to transplant recipients is from cytomegalovirus (CMV), the standard 2-4 week treatment for which involves an average of 5 days as an inpatient, which can cost up to £13,000. University of Glasgow research has led to revised standards of care for the prevention and treatment of CMV disease in kidney transplant recipients (KTRs). First, that antiviral treatment with oral valganciclovir for 200 days can be used to prevent CMV disease in postoperative KTRs and is twice as effective as treatment for 100 days. Secondly, the team found that the use of oral valganciclovir was a practical and cost-effective alternative to intravenous ganciclovir for treatment of mild CMV disease in solid-organ transplant recipients. Since 2009, the use of these therapies has been recommended in key national and international guidelines for the care of KTRs. The research also provided the evidence base that was used for evaluating, and subsequently amending, the marketing authorisation of oral valganciclovir for use in preventative treatment of CMV disease in KTRs in the UK and USA.
T lymphocytes recognise antigens in the form of an HLA-peptide complex. HLA-peptide tetramers consist of a fluorescent HLA protein and peptide which together bind to, and therefore identify, T cells that recognise this HLA-peptide complex. As such they have proven to be a revolutionary reagent in immunology. Professor Paul Moss at the University of Birmingham has played an integral role in the clinical and commercial application of tetramers, particularly around the cytomegalovirus (CMV)-specific immune response in the context of monitoring immune recovery after transplantation and pioneering a new approach for cellular immunotherapy. The impact of this research relates to the clinical management of CMV infection in immunosuppressed patients and the creation of Cell Medica, a UK Biotech company pioneering tetramer-based cell therapy, thus demonstrating impact on clinical practice and the UK economy.
Cytomegalovirus (CMV) causes life-threatening disease, particularly in immunocompromised individuals. CMV antivirals are toxic and before 2010 there was no standard for quantifying patients' viral load to enable precise use of these drugs. Research at Cardiff University led to the isolation and characterisation of wild-type CMV strain Merlin. The strain was recognised by the WHO in 2010 as the best source of the CMV genome and adopted as the international prototype strain and PCR standard. All major pharmaceutical companies offering CMV testing swiftly recalibrated their kits, and now market the assays as standardised against the strain. As a consequence, the Standard is improving clinical CMV disease definition and regulation of antiviral therapy, aiding the management of toxicity and resistance worldwide.
Viral infections pose a significant risk of long-term disease and death to cats. In Europe alone, over 30 million domestic cats are vaccinated each year against three core pathogenic viruses. Research performed at the University of Glasgow has systematically supported the development of key technologies against major feline viral diseases. This work has delivered incremental but wide-reaching benefits to veterinary healthcare and animal welfare by providing: (i) reagents used in the diagnostic industry; (ii) viral screening services for big cat conservation programmes; (iii) developmental input into the creation of one of the most efficacious and widely used vaccines against feline leukaemia virus; (iv) testing of feline vaccines for efficacy and safety; and (v) development of best practice guidelines and training for veterinary practitioners on feline viruses.
The human influenza A (H5N1) infection emerged in China in 2003 and quickly spread throughout Asia, killing more than half of those infected. Researchers at the Oxford University Clinical Research Unit in Vietnam (OUCRU) provided rapid information to the World Health Organization (WHO) on the pathological and clinical features of H5N1 infection in humans, as it emerged in Vietnam. The WHO used this front line information to inform recommendations for the investigation, diagnosis, management, and treatment of H5N1 globally, ultimately reducing mortality by up to 19%.
Researchers from St Georges have evaluated and optimised anti-fungal therapy for cryptococcal meningitis, the commonest cause of adult meningitis in sub-Saharan Africa. They have developed a "screen-and-treat" strategy to prevent the development of clinical disease in HIV-positive patients, and with collaborators developed and tested a novel point-of-care diagnostic test. These advances have led to changes in and development of a series of international guidelines and application of these new strategies in parts of Africa. A case for reduced costs of amphotericin was advanced by the group who were instrumental in reducing these costs in South Africa, allowing wider drug provision.
Research conducted by Professor Tim Goodship and co-workers at Newcastle has had a profound effect on the prognosis for patients with atypical haemolytic uraemic syndrome (aHUS). By engaging in research on the genetic factors underlying the disease they developed an understanding of the molecular mechanisms responsible. Identifying that the majority of patients with aHUS have either acquired or inherited abnormalities of the regulation of complement (part of the immune system) led to the establishment of a UK national service for genetic screening and treatment with the complement inhibitor eculizumab. As eculizumab is now available to patients in England, the progression to end-stage renal failure can be prevented and patients already on dialysis will soon be successfully transplanted.
Globally the most important cause of encephalitis (inflammation and swelling of the brain) is the mosquito-borne Japanese encephalitis virus (JEV), which causes an estimated 70,000 cases annually across Asia. Although vaccines were developed years ago, their uptake in Asian countries has been hampered through lack of disease burden data, a consequence of poor surveillance, complicated diagnostics, and insufficient knowledge about disease outcomes. Research at the University of Liverpool has addressed each of these areas in turn, to overcome the roadblocks in vaccine implementation. The University of Liverpool (UoL), through its leading role on all the relevant WHO committees groups and meetings, has ensured that its research findings are translated through to impact by supporting new vaccination programmes across Asia. By 2013 vaccination had begun in 11 new countries, and the vaccine had reached more than 200 million people. The public health benefits, estimated from a health economic modelling study, are 854,000 cases and 214,000 deaths avoided, with an associated saving across Asia of US$ 1.024 billion.
Chronic granulomatous disease is a rare but very serious inherited disorder of the immune system that leaves sufferers vulnerable to potentially fatal bacterial and fungal infections. Researchers at Newcastle University demonstrated very high survival and cure rates following bone marrow transplantation for the disease and good quality of life for successfully transplanted patients. This led to a change in national clinical policy, and doctors at both specialist disease centres in the UK now recommend transplantation to families where previously they would not have done so. In the five years prior to 2008 there were only 11 transplants for chronic granulomatous disease in the UK and in the following five years, 36 transplants. 32 children are alive and cured of the disease.
Lung transplants represent the last hope for cystic fibrosis patients with end-stage lung disease. However, since the mid-1990s, other than in large research centres, some cystic fibrosis patients were not offered this treatment because of the variable and often poor outcome of surgery. This patient group carried a difficult to treat bacterial infection caused by the Burkholderia genus. In 2001 researchers in Newcastle published findings that demonstrated that one particular species, Burkholderia cenocepacia, was responsible for the poor outcomes and that other species of Burkholderia were not as dangerous. This finding was incorporated into international guidelines and since 2008 most transplant centres worldwide have adopted a risk stratification approach to listing patients for transplant. Consequently, more than 30 people per year worldwide now get transplants that would otherwise have been denied.