The burden of invasive and serious fungal disease in the UK
1
DW ,
2
M,
2,3
W
Denning
Pegorie
Welfare
24th European Congress of Clinical Microbiology and Infectious Diseases in Barcelona, Spain, May 2014
1
National Aspergillosis Centre, University Hospital of South Manchester and The University of Manchester, Manchester
2 Greater Manchester Health Protection Team, Public Health England
3 Manchester Academic Health Sciences Centre, University of Manchester
INTRODUCTION
Invasive fungal disease is thought to be increasing in frequency in the UK due to a variety of
factors including increased survival time from previously lethal illnesses and an increase in
prevalence of conditions and treatments leading to immunosuppression. Understanding of the
overall burden of invasive fungal disease in the UK is limited as there is no formal systematic or
mandatory surveillance programme specific to fungal infections, although active surveillance
networks exist for candidaemias (voluntary laboratory reporting1) and specifically for
candidaemias in neonates (voluntary reporting2). In addition, several debilitating chronic and
allergic fungal diseases, amenable to antifungal therapy have come to greater prominence. In
2008, the UK health Protection Agency issued a report entitled “Fungal Diseases in the UK: The
current provision of support for diagnosis and treatment: assessment and proposed network
solution”. A rough annual burden estimate of many fungal diseases was made in this report, but
not subsequently published. Given this, we have attempted to quantify this burden with improved
tools and an expanded range of serious fungal infections.
METHODS
We estimated the annual incidence of the following invasive fungal infections: cryptococcal
meningitis, Pneumocystis pneumonia, invasive aspergillosis, candidaemia and Candida peritonitis, as
well as oesophageal candidiasis. In addition, we have estimated the prevalence of chronic pulmonary
aspergillosis, allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal
sensitisation (SAFS). Information on incidence, prevalence and total burden of these conditions in
England is limited. Where such information was available, we included it in the study. One example is
data from the voluntary surveillance of candidaemia in England, Wales and Northern Ireland1.
Where the information was not available we used a pragmatic approach for each fungal condition:
1. We considered which populations were most at risk of the condition
2. We sought published estimates for incidence or prevalence measures for the condition in these
specific risk populations.
3. We applied these rates to published estimates of size of these high risk populations in the UK
Where multiple estimates were published, we considered both internal validity (quality of the study,
sample size etc.) and external validity (how similar the study population is to UK population, how
recent the study is etc.) of the studies in deciding on which estimate to use.
RESULTS
The UK population in 2011 was 62,417,000 with 17% under the age of 15 and 23% over the age of 60 years.
The following burden estimates were calculated: invasive candidiasis (IC) 4,700; Candida peritonitis complicating CAPD 88 and the
remainder captured under IC; Pneumocystis pneumonia 587 cases, invasive aspergillosis (IA), excluding critical care patients 818 to
882, and IA in critical care 359 to 8,120 patients, utilizing different external assumptions, < 100 cryptococcal meningitis cases. With
respect to allergic aspergillosis, 178,000 (50,000–250,000) ABPA cases in asthma and 873 adults and 278 children with cystic fibrosis.
Chronic pulmonary aspergillosis is estimated to affect 3,600 patients, based on burden estimates post TB and in sarcoidosis.
Infection
Oesophageal
candidiasis
Invasive
candidiasis
Candida
peritonitis
ABPA
Chronic
pulmonary
aspergillosis
Invasive
aspergillosis
Cryptococcal
meningitis
Pneumocystis
pneumonia
Total burden
estimated
Number of infections per underlying disorder per year
None
HIV/AIDS
Respiratory
Cancer/Tx
ICU
-
62
-
-
-
-
-
-
-
-
-
-
179,151
-
-
3,600
62
0.1
4,703
7.5
88
88
0.14
-
-
179,151
287
-
-
3,600
5.77
8.15
-
-
850
4,239
5,089
-
-
-
-
-
<100
0.16
-
-
-
-
587
0.94
850
4,327
193,380
310
62
182,751
CONCLUSIONS
Estimating the burden of invasive fungal infection accurately is challenging due to the lack of a
dedicated mandatory systematic surveillance system, and the wide range of incidence estimates for
one of the largest high-risk population (patients in ICU). This is likely to be compounded by the
limited sensitivity of traditional diagnostic tests used for invasive fungal illness, making it difficult to
obtain laboratory confirmation for a significant number of cases.
There is a high degree of uncertainty around the total estimate of burden due to:
diagnostic limitations, the lack of a systematic national surveillance system, the
limited number of studies published on the topic and the methodological
limitations of calculating the burden.
It was encouraging to note that for some conditions, our pragmatic approach resulted in a total
estimate not too dissimilar to estimates calculated from recently published burden studies. This was
the case for Pneumocystis pneumonia, where our pragmatic approach yielded an estimate of 522
cases, compared to an estimate of 587 cases derived from the published burden study3: a variation of
approximately 10%.
-
-
DISCUSSION
There is a significant level of inaccuracy as our estimation methods have relied on limited published
information, and there is a wide range of estimates for some of the published incidence rates.
-
Rate
Total burden
/100K
To our knowledge, this is the first attempt at a comprehensive estimation of
burden of invasive fungal infection in the UK. Further studies will likely need to
combine methods (pragmatic and surveillance-based), take into account any new
published information on specific incidence rates, and consider using alternative
data sources such as the Hospital Episodes System (HES). An accurate estimate of
total burden will ultimately rely on improved diagnostic testing and laboratory
reporting.
ACKNOWLEDGEMENTS
LIFE: Leading International Fungal Infection. http://www.lifeworldwide.org/
REFERENCES
1. Public Health England (PHE). Voluntary surveillance of candidaemia in
England, Wales and Northern Ireland: 2012. HPA, 2013.
2. http://www.neonin.org.uk/index
3. Maini R, Henderson KL, Sheridan EA, Lamagni T, Nichols G, Delpech V, et al.
Increasing Pneumocystis pneumonia, England, UK, 2000–2010. Emerg Infect
Dis , 2013.http://dx.doi.org/10.3201/eid1903.121151