Memorandum by Dr D W Denning, University
There are two major fungal diseases of man which
are life threateningcandidiasis 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
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 (www.aspergillus.man.ac.uk) 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
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
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
Encourage the additional study of
new diagnostics and vaccines for serious fungal diseases.