Select Committee on Science and Technology Written Evidence

Memorandum by Dr D W Denning, University of Manchester

  There are two major fungal diseases of man which are life threatening—candidiasis and aspergillosis. The former occurs primarily in intensive care unit and surgical patients with a smaller number of cases occurring in premature neonates, leukaemia and bone marrow transplant patients as well as medical patients receiving total parenteral nutrition often with diabetes and/or renal failure or intravenous drug addicts. Invasive aspergillosis is usually an opportunistic infection occurring in those with damaged immune systems including transplant recipients and patients undergoing chemotherapy for leukaemia or other tumours, steroid treated patients (chronic obstructive airways disease, severe renal disease, systemic lupus erythematosis, etc) and patients with AIDS. Invasive candidiasis is mostly acquired endogenously in the hospital, aspergillosis both in the community and hospital. Throughout the western world the incidence of these infections has been rising although there is no useful data from the UK. In the US invasive aspergillosis (using conservative diagnostic criteria) costs the economy $600 million annually.


  There are no surveillance systems in the UK for the monitoring of these fungal diseases. An attempt is made by the Communicable Disease Surveillance Centre to collect blood culture data on Candida but this is rarely tabulated and is never complete. The most common cause of candidaemia is endogenous spread from individuals, but approximately 10 per cent of cases are nosocomially acquired and there are occasional outbreaks. There are no services available nationally for molecular or other typing systems for Candida.

  Invasive aspergillosis is frequently a hospital acquired pathogen but many cases are acquired in the community. Faulty air flow systems in hospital lead to additional cases. There are some guidelines for the monitoring of air quality in hospitals but no national system for checking on these data or system for enforcement of improved measures. This is particularly important in operating rooms, burns units, intensive care units and leukaemia treatment centres. See the attached official responses from Hansard 16 and 18 January 2002.

  Early diagnosis of serious fungal infection is essential to survival. The overall mortality of invasive candidiasis is 40 per cent and is approximately 75 per cent for invasive aspergillosis. Under recognition and therefore late diagnosis of these diseases is a major issue in treatment outcome. Adequate surveillance in hospitals could alert clinicians to a break in air quality and raise the level of awareness and the more rapid institution of appropriate diagnostic measures or prophylactic approaches for particularly high risk individuals.

  Clearly a much better understanding of the frequency of serious fungal infections and whether these are related to cross infection or hospital air problems would greatly improve strategies for the prevention of these life threatening infections.

  Approaches to the surveillance of serious Candida infections could relate simply to collection of blood culture data. This would underestimate the size of the problem by approximately one third as blood cultures are only 50-75 per cent sensitive for diagnosing candidaemia and ivasive candidiasis.To capture all the cases other microbiology records, histology (including autopsy) and radiology would be required together with clinical interpretation. If surveillance of oesophageal candidiasis (which is very common in hospitalised and AIDS patients) was undertaken and endoscopy records would be required. Surveillance for candidiasis could probably best be organised as a sentinel surveillance system rather than national comprehensive surveillance system.

  Invasive aspergillosis is equally difficult to document accurately. There are probably 4-500 cases nationally each year and may be as many as 1,000 most of which are fatal currently. Surveillance of invasive aspergillois would require access to microbiology, histology, radiology, serology and clinical records. If a major effort was made in the hospital to try and identify all cases using these records probably 60-80 per cent could be identified ante-mortem (assuming the hospital uses modern techniques for diagnosis), again this would probably be best set up as sentinel centres rather than doing a national survey.

  There are very preliminary efforts for a Candida vaccine being undertaken in the USA but no efforts in the UK. There are no efforts to undertake a vaccine project in invasive aspergillosis although this would certainly be a desirable objective for patients waiting for transplantation and for leukaemic patients between cycles of chemotherapy and patients with AIDS.

  A new diagnostic for invasive aspergillosis using Aspergillus antigen testing is available. It has been used on the continent for several years and has been found to be useful in the early diagnosis of invasive aspergillosis in haematology patients (but not others). This has barely been applied in the UK because of funding restrictions. The consequence of this is overuse of some very expensive antifungal agents, which are the single largest item on many hospital pharmacy budgets (eg 1M annually at the Royal Free Hospital).

  There is substantial increased awareness of the risks of invasive aspergillosis. The public are much more aware than previously of aspergillosis in particular. The Aspergillus website ( has an extremely high usage (ranked 11,000 internationally out of three billion websites and more heavily used than football club websites, the University of Manchester website, BT and others). The introduction of two new drugs for invasive aspergillosis (caspofungin, Merck Sharp and Dohme; voriconazole, Pfizer) will substantially increase the awareness of invasive aspergillosis and candidiasis amongst the medical fraternity. These drugs are very expensive and will shortly catch the attention of health service administrators. The introduction of these drugs in my hospital is estimated to cost £250,000 extra annually.


  Serious fungal diseases are increasing in frequency; four per cent of patients dying in modern European teaching hospitals from invasive aspergillosis and probably 1 to 2 per cent from invasive candidiasis. Diagnosis is suboptimal, surveillance is effectively non-existent. Means of preventing these infections include reduction of cross infection and very careful control of air quality in hospital environments. Poor diagnostic capabilities contribute to substantial additional deaths and additional antifungal therapy, which is very expensive.


    —  Set up sensible surveillance centres for invasive candidiasis and aspergillosis in perhaps 10 hospitals nationally.

    —  Ensure the introduction of new diagnostics for invasive aspergillosis in haematology patients.

    —  Ensure national standards for air quality in hospitals treating immunocompromised patients are applied in all operating rooms, intensive care units, burn and haematology units nationally.

    —  Encourage the additional study of new diagnostics and vaccines for serious fungal diseases.

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