Burden of serious fungal infections in China Liping Zhu, Jiqin Wu. David S. Perlin, David W. Denning Huashan Hospital, Fudan University, Shanghai 200040 China; Public Health Research Institute, Newark, NJ, USA and The University of M anchester in association with the LIFE program at w w w .LIFE -w orldw ide.org
Intr od uc tio n The incidence of serous fungal infections has been increasing over the past several decades as a result of the expanding number of im m unocom prom ised pa tien ts w ith risk factors such as HIV in fe ction , tra n sp la n ta tio n , im m unosuppressive therapy, co rtico ste ro id therapy, and b ro a d -s p e c tru m a n tib io tic m ed ica tion, etc. D espite the a v a ila b ility of new er and po tent a n tifu n g a l agents, the m o rb id ity and m o rta lity of in vasive fun gal in fe ctio n s rem ain high. U nderstanding of the burden of fungal in fe ction s is crucial to both be tte r disease prevention and treatm ent. In C hina, with the largest population in the world, p o p u la tio n -b a se d surve illan ce on various fungal infections is still lacking. However, data from spe cific high risk populations and some citie s has increasingly been reported. We have attem pted to estim ate the burden of serious fungal infection in China through literature review.
Methods
LIFE
LEADING INTERNATIONAL FUNGAL EDUCATION
All published epidem iology papers reporting fungal infection rates from China were identified. If few data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence. Population (2009), HIV (2011) and TB (2011) data were from WHO. Asthma, ABPA and CPA rates were from Denning, Bull WHO 2011, Med Mycol 2013 (ahead of print) and Ma, 2011. COPD adm issions were from Tan, Respirology, 2009. Cryptococcal m eningitis (CM) estim ate in HIV was assumed to be 1% of late stage HIV patients, and the rate of CM in other cases on the ratios reported by Chen, M ycopathologia, 2012. Pneum ocystis jiroveci pneumonia (PCP) rates were based in Hong Kong rates in HIV and in non-H IV on Wang, J Med Microbiol, 2011. Penicillium marneffei infection rate was based in HK data, adjusted for regional differences in HIV prevalence. Tinea capitis rate was on a report from Shanghai (Zhu, M ycopathologia, 2010). K eratitis rate was based on Xu in Qingdao (Chin Med J, 2012).
Results Of the 1,363M population, 20% are children (0 -1 4 years) and 12% are >60 years old. 20M Chinese (age 15-50) women are estimated to get recurrent vaginal thrush (4+ times annually). Of the 740,000 estimated HIV positive patients in 2011, 92,227 are not on ARVs (CD4 <350). Of these an estimated 83,000 develop oral thrush, 50,000 oesophageal candidiasis, 461 CM, 16,140 PCP and 1,383 P. marneffei infection. We estimate a 5 -ye a r period prevalence of 256,534 CPA cases (assuming 15% annual mortality); 80% from 893,121 cases of pulmonary TB, 20% other conditions. Asthma prevalence in adults is estim ated at nearly 20M and assuming 2.5% of asthm atics have ABPA, 491,721 patients with ABPA are likely and 648,300 have severe asthma with fungal sensitisation (SAFS). The rate of candidem ia was estim ated at 5/100,000 population (68,150 cases) and C andida pe riton itis at 19,982 cases. Invasive aspergillosis (IA) in >100,000 haem atological patients is estim ated at 8,178 cases and in the COPD 154,000 cases (11,9M adm issions). IA numbers in renal and liver transplantation and numerous other fungal diseases were not estim ated. Infectio n Oesophageal candidiasis Candidaemia Candida peritonitis Recurrent vaginal candidiasis (4x/year +) Allergic bronchopulmonary aspergillosis (ABPA) Severe asthma with fungal sensitisation (SAFS) Chronic pulmonary aspergillosis (CPA) Invasive aspergillosis Mucormycosis Cryptococcal meningitis Pneumocystis jiroveci pneumonia (PCP) Penicillium marneffei infection Fungal keratitis Tinea capitis Total burden estimated
N um ber of in fe ctio n s per u n d e rly in g diso rd e r per year None H IV /A ID S R e sp ira to ry C an ce r/Tx ICU 50,834 20,445 47,705 19,082 19.959k 491.721 648,300 265.534 8.178 154,155 2.726 922 922 461 ? 16,140 8.070 ? 1,383 _ _ _ 17.038 _ 34.075 20.010k 221k 151.822 1.405,555 37,615
To tal burden
R ate /100K
50.834 68,150 19.082 19.959 491.721 648,300 265,534 162,333 2,726 2306 24,210 1,383 17,038 34,075 21,829k
3.7 5.0 1.4 2,929 36.1 47.6 19.5 11.9 0.2 0.17 1.8 0.1 1.3 2.5
Conclusion Without any national surveys of fungal disease in China, uncertainty surrounds all these estim ates. But the burden of fungal disease is alm ost certainly one of the greatest in the world. Epidem iological studies are urgently required to validate or modify these estimates.
corresponding author: D r.L i-p in g Zhu. Email:zhulp@ fudan. edu.cn
Belfast Health and Social Care Trust
Burden of Fungal Infection in Ireland Eileen Dorgan1, David W. Denning2 , Ronan McMullan1 1. Department of Medical Microbiology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Grosvenor Road, Belfast, BT12 6BA 2. The University of Manchester in association with the LIFE program at www.LIFE-worldwide.orq
Introduction & Purpose Fungal Infections are a growing global problem that are difficult to quantify in terms of population affected, mortality, resources used and possible methods of prevention. Currently data available on fungal infections worldwide are crude estimates that have not been standardized. This project attempts to compile data from several countries worldwide that differ in terms of economic status, health care provision and ethnicity in order to form a better overall picture of the current state of fungal infection globally.
Methods For the purposes of creating a comparable data set for each country a template was provided that included demographic data and specific disease related information was gathered. Relevant published epidemiology describing fungal infection in Ireland was identified. Data were collected for 2010 from both Northern Ireland (NI) and the Republic of Ireland (ROI) and that combined data is presented here. This included some specific assumptions from published data that would allow the directly observed incidence of fungal infection to be used in conjunction with surrogate markers for fungal infection to estimate the total burden nationally. Population data were obtained from Northern Ireland Research and Statistics Agency and Central Statistic Office of Ireland, patients were categorized by age and gender. HIV/AIDS data for the Republic of Ireland was obtained from World Health Organization (WHO) “People living with HIV” report and from the Health Service in Ireland 2011 HIV report. NI data was gathered from the Public Health Agency (PHA) HIV & STI surveillance report 2011 and a direct audit of HIV attendances at specialist clinics. It is assumed that 90% of patients with HIV who are not being treated with Anti-retrovirals (ARVs) will develop oral candidiasis and it is assumed that 20% of patients with HIV not on ARVs and 5% of those on ARVs develop oesophageal candidiasis. The assumptions for oral candidiasis and oesophageal candidiasis may artificially elevate the numbers of these conditions in populations where patients are not receiving ARVs due to having a CD4 count >200 and not fitting clinical criteria that warrants ARV treatment as opposed to the unavailability of such interventions'1-2-3. Recent work has been published on Pneumocystis pneumonia in Northern Ireland and these results were adjusted to include the ROI population4. Cystic fibrosis (CF) figures were extrapolated from the CF trust (NI) and CF registry (ROI). COPD information from ROI was taken from the OECD library and asthma rates were obtained from the Asthma Society IE. There was insufficient direct data for Northern Ireland for COPD of Asthma numbers so this data was extrapolated using population figures. ABPA (Allergic Bronchopulmonary Aspergillosis) figures are determined by assuming rates of 15% of adult CF patients and 2.5% of adult asthmatics. SAFS (Severe asthma with Fungal sensitisation) assumption is that this affects 33 % of the worst 10% of adult asthmatics. Pulmonary tuberculosis (TB) data for ROI was obtained from WHO and Northern Ireland information was obtained directly from PHA with supporting HIV audit data. In order to assess the total number of chronic pulmonary aspergillosis (CPA) the assumption is that 25% of CPA is as a result of TB and therefore the figure for TB is multiplied by 4 to give the total prevalence. The prevalence of CPA in the TB population is assumed to be 20%5. The number of Acute Myeloid Leukaemia (AML) patients per year were obtained from the local cancer registry. It is assumed that non-AML haematological conditions in total have the same rate of Invasive Aspergillosis as AML patients6. ROI transplant data was obtained form 2011 Council of Europe report on organ transplant and NI data from the organ donation registry along with direct figures from the local Haematology Transplant Co-ordinator to capture the Stem Cell Transplants It is assumed that 0.5% of renal transplants, 4% lung, 6% heart 4% liver transplants also develop invasive aspergillosis and other risks such as steroid use cause negligible numbers of cases.
The national figure on critical care beds was obtained form the critical care census and included just the level 3 beds. Abdominal surgery is used as a marker for peritoneal candidasis and candidaemia the results for Northern Ireland were obtained from DHSSPSNI Statistics and Research records and the numbers were then adjusted to include ROI population.
Total Burden
Rate /100K
601
9.4
403
6.3
64
1
94,974
1484
8,961
140
11,675
182.4
449
7
13
0.2
3
0
50
0.8
196
3.1
601
Oesophageal candidiasis Candidaemia
275
128 64
Candida peritonitis
vaginitis (>4x/year)
Ireland has a population of 6,399,152. Of this, 22% are children under 16 and 8% are women over 60. The rate of recurrent candida vaginitis is between 5-8% of adult women; however in populations where a large percentage of women are over 50 this may overcall the number of cases and a downward adjustment of 80% is appropriate7. Therefore it is estimated that 94,974 women in Ireland have recurrent Candida vaginitis per year. Current total HIV/AIDS Proportion of diagnosed cases on ARVs Number of diagnosed cases not receiving ARVS New cases of AIDS per year Proportion of AIDS cases presenting with PCP Proportion of AIDS cases presenting with cryptococcal meningitis AIDS-related deaths in 2010
7374 0.79 1549 50 25% 6%
Among patients with chronic pulmonary aspergillosis (CPA) it is estimated that 25% is attributable to TB. We infer an approximate prevalence of 196 cases of CPA. Using international data, indicating that typically around 2.5% of adults with asthma have Allergic Bronchopulmonary Aspergillosis (ABPA), we have estimated 8,691 cases per year among the estimated 353,794 adults with asthma and 773 CF patients.
Ireland has approximately 7,374 people with HIV. There are few AIDS-related opportunistic infections with only around 13 HIV-positive patients developing Pneumocystis pneumonia.
Pulmonary TB (HIV positives)
20
Pulmonary TB (HIV negative)
225
Pulmonary TB total
245 10.1%
COPD admissions to hospital per year Asthma rate in adults
30720
Numbers of adults with asthma
353,794
Number of Adults with Cystic Fibrosis
7.1%
773
Figure 2. Respiratory Disease in Ireland
The candidaemia rate is approximately 6.3/100,000, which gives us a total of 403 cases of candidaemia per year. Of these, an estimated 128 occur in critical care each year, and an additional 64 cases of Candida peritonitis occur among 244,630 abdominal surgical procedures. 12% Allogenic Stem Cell Transplant Renal Transplant
61%
8,961
Allergic bronchopulmonary aspergillosis (ABPA)
There are approximately 3 patients diagnosed with AML per 100,000 population per year in Ireland. In 2010 there were a total of 192 patients with Acute Myeloid Leukaemia in Ireland.
Figure 3. Transplants in Ireland
Some countries have high rates of hisoplasmosis, coccidioidomycosis, tinea capitis and fungal keratitis but there are few resources available in the literature to five a good estimate of this for the Irish population and since these conditions are not always clinically reported there was no resource for direct calculation of these numbers in Ireland. There is a general assumption that the rate of mucormycosis is approximately 2 cases per million popluation. This and other fungal infection estimates are summarised in the table.
11,675
Severe asthma with fungal sensitisation (SAFS)
50
Invasive aspergillosis
399
13
Cryptococcal meningitis
3
Pneumocystis pneumonia
12
Chronic pulmonary
38 196
aspergillosis Fungal keratitis Tinea capitis
Total burden estimated
COPD prevalence (all GOLD stages)
Lung Transplant
94,974
Mucormycosis
12
Figure 1. HIV Data in Ireland
1%
Number of infections per underlying disorder per year None HIV/AIDS Respiratory Cancer/Tx ICU
Recurrent Candida
Results
1%
Infection
94,987
616
20,832
363
591
117,389
Figure 4. Summary Table of Results for fungal infections in Ireland
Conclusions Most fungal infections are unreported and therefore are impossible to count in absolute numbers. To have an impression of the overall fungal burden in Ireland it is necessary to make some assumptions about the population from known datasets and published literature. Based on available data approximately 1.9% of Ireland’s population will have a serious fungal infection during one year. Since most of our results are extrapolated from surrogate markers of fungal infection this model requires validation; however, it provides a standardised means of estimating and comparing the burden of disease across populations.
References 1. Matee MI, Scheutz F, Moshy J. Occurrence of oral lesions in relation to clinical and immunological status among HIV-infected adult Tanzanians. Oral Dis 2000;6:106-11. 2. Smith E, Orholm M. Trends and patterns of opportunistic diseases in Danish AIDS patients 1980 1990. Scand J Infect Dis. 1990;22(6):665-72. 3. Buchacz K, Baker RK, Palella FJ Jr, Chmiel JS, Lichtenstein KA, Novak RM, Wood KC, Brooks JT; HOPS Investigators. AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study. AIDS. 2010 Jun 19;24(10):1549-59. 4. Coyle PV, et al. Rising incidence of Pneumocysitis jirovecii pneumonia suggests iatrogenic exposure of immuno-compromised patients may be becoming a significant problem. J Medical Microbiology 2012; 61: 1009-1015. 5. Denning DW, Cole DC, Pleuvry A. Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. Bull WHO 2011;89:864-872. doi: 10.2471/BLT.11.089441 6. Lortholary O, Gangneux JP, Sitbon K, Lebeau B, de Monbrison F, Le Strat Y, Coignard B, Dromer F, Bretagne S; French Mycosis Study Group. Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005-2007). Clin Microbiol Infect. 2011;17:1882-9. 7. Sobel JD. Vulvovaginal candidosis. Lancet. 2007;369:1961-71.
Acknowledgements With Thanks to Michael Devine, Public Health Agency, Belfast, Susan Piggott , Haematology Transplant Co-ordinator Belfast Health and Social Care Trust and Yvonne Wilson Belfast Health and Social Care Trust for their help.
Estimation of the burden of chronic and allergic aspergillosis in India Arunaloke Chakrabarti, Ritesh Agarwal, Donald C. Cole, Alex Pleuvry and David W. Denning Departments of Medical Microbiology and Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; Oncalex, High Peak, U.K The University of Manchester, Manchester, UK, in association with the LIFE program at www.LIFE-worldwide.org r
r
Abstract L.
L.
-A
Objective: India is the world’s second most populous country, with high rates of TB and HIV. Comprehensive baseline data is necessary for effective
Time Population frame
prioritization of limited public health resources. Using scoping review 1976
methodology and deterministic modelling, we have estimated the incidence
Secondary and tertiary
ABPA studie
3-4
d 367
years
Comments
(4.6%)
IgE not measured, patients
? fungal
periodic infiltrates, positive skin
following TB and prevalence of allergic bronchopulmonary aspergillosis
disease
test, eosinophilia, A. fumigatus
(ABPA) complicating asthma in India.
referrals
grown from sputum and
Khan et al
per 100,000 population
2005
Sequential
NS
105
8
12 patients excluded. Healthy
Maurya et
(7.6%)
control group also evaluated.
al
referrals to
Estimated pulmonary TB rates were updated from 2007 to 2011 using WHO
a tertiary
Patients also sensitized to non-
statistics, with deaths excluded. Asthma rate in adults was estimated from
centre
fumigatus Aspergilli
2007
the country-specific prevalence of asthma from the GINA report applied to
Sequential
4.5
referrals to
years
population estimates (mean prevalence of current wheezing in children was
a tertiary
88% of adults in the countries which participated in both studies). Additional
centre 2010
Tertiary
155
Full diagnostic details not
Agarwal et
(20.5%
provided for all ABPA patients.
al
1 year
referrals
number of cases of pulmonary TB in India were 3,100K (249/100K) and the
215
15
Excluded: those in receipt
(7%)
o f steroids fo r 2 weeks in
Ghosh et al
(n=5 studies) vary from 0.7 to 3.5%, with the median being 2.5%. The number of adult asthmatics is estimated at 23,709K and ABPA at 592,719. If rates of 5%, 7% and 20% are applied, the gross numbers of ABPA patients estimated in India rises to 1,185K, 1,660K and 4,742K respectively. All estimates (n=7) of Aspergillus sensitization rates in adult asthmatics in India exceed 16% and are 50% in asthmatics admitted to ICU with asthma. Conclusion: The total burden of antifungal-responsive chronic and allergic aspergillosis in India is not known, but is likely to exceed 860,000 patients. CPA has many underlying conditions in addition to TB, which are not estimated. CPA carries an early mortality of 30% after diagnosis (Korea and Japan), emphasizing the importance of antifungal therapy to minimize death and morbidity.
Epidemiological studies are required to better
categorize the burden of these diseases in India.
X
-A
Asthma of any severity may be complicated by allergic bronchopulmonary aspergillosis (ABPA). Treated pulmonary tuberculosis (PTB) can lead to complications, including progressive loss of lung function, persistent pulmonary symptoms and the most subtle, yet the most severe, chronic pulmonary aspergillosis (CPA), Both ABPA and CPA respond well to antifungal therapy. Using scoping review methodology and deterministic modelling, we estimate the prevalence of ABPA complicating asthma; and the incidence and 5yr period prevalence of CPA following PTB, in India.
these diseases in India.
among new referrals
Deaths from CPA in subsequent y e a r(%)
References Denning DW, et aspergillosis with
al. Global burden of allergic bronchopulmonary asthma
and
its complication
chronic
pulmonary
aspergillosis in adults. Med Mycol 2013; IN PRESS 2.
Denning DW, et al. Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. Bull World Heatlth Organ 2011;89:864-
CPA 5 -ye a r period to prevalence following Surgeries for PTBa CPA in subsequent y e a r(%)
Estimated pulmonary TB rates were assessed for the year 2011 using WHO fact sheet (http://www.who.int/tb/country/data/profiles/en/index.html), with deaths excluded.
Background & Objectives L.
Epidemiological studies are required to better categorize the burden of
fo r asthm a (2.5%)
p rio r 6 months. 6 patients
mortality was 300K (24/100K). The annual estimated incidence of new CPA
ABPA complicating asthma with good denominators of referral populations
in adults
Total CPA incidence following PTB at 1 year
grew A. flavus.
cases was 85,012 while 5 year period prevalence was 267,987. Rates of
% of asthma
in India is likely to exceed 860,000 patients.
Proportion with ABPA
)
center
Results: In 2011, the population of India was estimated at 1,241,000K. The
755
X
The total burden of antifungal-responsive chronic and allergic aspergillosis
Asthma rate in adults was estimated from the prevalence of asthma from the GINA report applied to population estimates (mean prevalence of current wheezing in children was 88% of adults in the countries which participated in both studies). Additional modeling was done to accommodate several ABPA studies in India. The burden of CPA complicating pulmonary TB was made on the following assumptions [Ref. 2]:
positive Aspergillus precipitins.
Bull WHO 2011;89:864-72 and Denning et al, Med Mycol 2013. In press).
modeling was done to accommodate several ABPA studies in India.
Asthm a cases
had to have asthma and
and 5yr period prevalence of chronic pulmonary aspergillosis (CPA)
Methods: The bases for the computations have been published (Denning et al,
Reference
N 17
Conclusions
We estimated the adult burden of asthma by the GINA estimates. The prevalence of ABPA complicating asthma was estimated at 2.5% (0.7-3.5%) [Ref. 1]. The following factors were used in estimation of ABPA:
N Year
JI
/lethods
872 Khan ZU, et al. Allergic bronchopulmonary aspergillosis: A study of 46 cases with special referecne to laboratory aspects. Scand J Respir Dis 1976; 57: 73-87 4.
Maurya V, et al. Sensitization to Aspergillus antigens and occurrence of allergic bronchopulmonary aspergillosis in patients with asthma. Chest 2005; 127:1252-1259
Results
Agarwal
R, et al. Clinical significance of hyperattenuating mucoid
impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 In 2011, the population of India was estimated at 1,241,000K. The number of cases of pulmonary TB in India has fallen slightly from 3,305K to 3,100K (2,100K - 4,300K) (249/100K) and the mortality also from 331K to 300K (24/100K). The annual estimated incidence of new CPA cases has risen from 83,000 to 85,012 and 5 year period prevalence from 261,679 to 267,987. Rates of ABPA complicating asthma with good denominators of referral populations (n=5 studies) vary from 0.7 to 3.5%, with the median being 2.5% [Ref. 1]. The number of adult asthmatics is estimated at 23,709K and ABPA at 592,719. If rates of 5%, 7% and 20% are applied [Refs. 3-6], the gross numbers of ABPA patients estimated in India rises to 1,185K, 1,660K and 4,742K respectively. All estimates (n=7) of Aspergillus sensitization rates in adult asthmatics in India exceed 16% and are 50% in asthmatics admitted to ICU with asthma [Ref. 7].
patients. Chest 2007; 132:1183-1190 6.
Sarkar A, et al. Occurrence of allergic bronchopulmonary mycosis in patients with asthma: An Eastern India experience. Lung India 2010; 27:212-216
7.
Agarwal
R,
et
al.
Aspergillus
hypersensitivity
and
allergic
bronchopulmonary aspergillosis in patients with acute severe asthma in a respiratory intensive care unit in North India. Mycoses 2010; 53:138-143
LIFE
LEADING INTERNATIONAL FUNGAL EDUCATION
i f
NUH Nationaf University Hospital
NUS National University cf Singapore
Yong Loo Lin School of Medicine
Burden of Serious Fungal Infections in Singapore 1Lionel Hon Wai LUM, 1# Louis Yi Ann CHAI , Sophia ARCHULETA, 2David DENNING 1Division o f Infectious Diseases, National University Health System, Singapore 2 University o f Manchester, United Kingdom, in association with the LIFE PROGRAM at www.LIFE-worldwide.org Infection
INTRODUCTION/ PURPOSE Singapore is a cosmopolitan South East Asian country with a Gross Domestic Product of USD 240 billion and a population of 5.35 million. However, the fungal burden is poorly recognized and documented in Singapore. We aim to estimate the burden of fungal infections in the country as part of a multi-national effort to quantify worldwide fungal infections
METHODS Estimation of fungal disease burden was extrapolated from available epidemiological documents. Population statistics and respective disease distributions pertaining to HIV, malignancies, tuberculosis, chronic obstructive pulmonary disease (COPD) and asthma were extracted from Singapore Demographics Profile 2012 and Ministry of Health (MOH) releases. The total number with HIV/AIDS was estimated to be 5306 from the MOH statistics in 2011.The number of new AIDS patients per year was 183, with 47.7% presenting with Pneumocystis pneumonia and 9.2% presenting with cryptococcal meningitis ( taken from the Communicable Disease Surveillance Report in 1997). The number of AML patients per year was estimated to be 161 per year, extrapolated from the data from ICD-10 C92.0. The annual incidence of pulmonary tuberculosis was 39.2 per 100000 as estimated from MOH statistics. The prevalence of moderate to severe COPD and asthma were obtained from World COPD day- The Singapore perspective from The College Mirror :Dec 2003: Vol 29(4) and The Health Promotion Board Singapore respectively. Transplant cases were estimated from Heart Lung Registry, and from the Renal and Liver Transplant Lists in Singapore hospitals. The number of critical care beds was obtained via a manual count of the hospitals countrywide. In cases whereby local incidence of specific diseases was not known, this was reasonably extrapolated from that of neighbouring Asian countries with similar population demographics.
RESULTS 13% of the population are younger than 15 years old, and 2.12 million are women older than 15 years of age, of which 106000 (5% of adult women) are estimated to have recurrent Candida vaginitis1. The incidence of invasive aspergillosis in immunocompromised hosts is at least 33 cases annually (10% of AML, equal number of non AML hematological patients, 0.5% of renal transplant patients, 4% of lung and liver transplant patients and 6% of heart transplant patients), but many more in COPD admissions and ICU patients. On the other hand, the prevalence of chronic pulmonary aspergillosis (CPA) can, at best, be extrapolated from data in Taiwan and China. While asthma is relatively common in adults (250,000 - 5% of population), ABPA and SAFS are rarely diagnosed. Based on 183 annual new AIDS patients in Singapore in 2011, 9.2% (17) of those with AIDS have cryptococcal meningitis , 47.7% (87) have Pneumocystis pneumonia, 460 patients per year have oral candidiasis, and 265 have esophageal candidiasis. The annual incidence of candidemia is 268 per year ( 5 per 100000)2-3, with two thirds of the patients being in critical care or surgical care, and one thirds being cancer or immunocompromised patients.
Number of infections per underlying disorder per year HIV/AIDS Respirator Cancer/Tx None ICU
Total burden
Rate /100K
187
265 267
4.95 5
37
37
0.7
106,000
1,981 unknown unknown
33 10
0.6 0.2
unknown
17
0.3 1.6 0.1 0.1 unknown 1.1
y Oesophageal candidiasis Candidaemia Candida peritonitis Recurrent vaginal candidiasis (4x/year +) ABPA SAFS Chronic pulmonary aspergillosis Invasive aspergillosis Mucormycos is Cryptococcal meningitis Pneumo cy s tis pneumonia Histoplasmosis Fungal keratitis Tinea capitis Total burden estimated
-
106,000 -
265 -
-
-
80
unknown unknown
-
-
33 10
unknown -
unknown
-
-
-
17
2 6 unknown
87 2 -
unknown -
unknown 2 -
-
87 6 6 unknown
106,008
371
unknown
125
224
106,728
Table : Summary of fungal burden in Singapore
CONCLUSIONS The prevalence of medically-significant fungal infections in the population is under-recognised in Singapore. Increased awareness and surveillance will serve to enhance appropriate allocation of healthcare resources in this disease spectrum. References 1. Sobel JD. Vulvovaginal candidosis. Lancet 2007; 369: 1961-71 2. Chai et al Predominance of candida tropicalis blood stream infections in a Singapore Teaching hospital Med Mycol 2007 Aug 45(5): 435-9 3. Tan TY et al. A retrospective analysis of antifungal susceptibilites of Candida bloodstream isolates from Singapore hospitals. Ann Acad Med Singapore. 2008 Oct 37 (10) : 835-40
Correspondence: Dr. Louis Chai Division Of Infectious Diseases University Medicine Cluster 1E Kent Ridge Road NUHS Tower Block, Level 10 Singapore 119228 Email:
[email protected]
Burden of serious fungal infections in Austria, Abstract Nr. 757 Cornelia Lass Florl, V. Greil, David W. Denning and The University of Manchester in association with the LIFE program at w ww.LIFE-worldwide.org D ivisio n o f H yg ie n e and M e d ica l M ic ro b io lo g y , In n s b ru c k M e d ica l U n ive rsity, A u s tria T ir o le r La n d e sk ra n k e n a n s ta lte n , In n s b ru c k M e d ica l U n iv e rsity , A u stria N a tio n a l A s p e r g illo s is C e n tre , E d u c a tio n and R e se a rch C en tre U n iv e rsity H o sp ital o f S o u th M a n c h e s te r (W y th e n s h a w e H o sp ital), M a n c h e s te r, UK
Abstract Introduction The number of fungal infections occurring each year in Austria is not known. We have estimated these based on populations at risk, supplemented with existing data Number of infections per underlying disorder per year
Methods
Rate /100 K
All published epidemiology papers reporting fungal infection rates from Austria were identified
Results Of the 8.22M population, 14.5% are children (0-14 years) and 18% of population are >65 years old. We therefore estimate that 110,000 Austrian women get recurrent vaginal thrush (4+ times annually). 106 cases have been recorded in Tirol in 2011, a total of 1221 nationally. Of the 688 cases of pulmonary TB in 2011, 84% in HIV negative people, and that 25% of chronic pulmonary aspergillosis (CPA) cases are TB related we estimate a 5-year period prevalence of 382 CPA cases (assuming 15% annual mortality). Asthma prevalence in adults is 7% and assuming 2.5% of asthmatics have ABPA 7,537 patients with ABPA are likely and 9,949 with severe asthma with fungal sensitisation (SAFS). Of the 15,000 estimated HIV positive patients, only 45 presented with AIDS in 2010 and 100% are taking ARVs. Only 5 cases of cryptococcal meningitis were identified and it is not possible to estimate the annual incidence of Pneumocystis pneumonia, or oesophageal candidiasis which is principally in non-AIDS patients. The rate of candidemia in Austria is low at 2.63/100,000 population consistent with 209 cases, although only 165 were actually documented. Candida peritonitis is estimated at 40% of the ICU candidaemia rate, based on French data. Most cases or oral and oesophageal candidiasis were probably in non-HIV infected people. Invasive aspergillosis in haematological and transplant patients is estimated at 96 cases [which contrasts with 158 from registry data (2007/8)] and 283 in COPD patients admitted to hospital. 28 mucormycosis and 2 histoplasmosis cases were recorded
Oesophageal candidiasis
100
Oral candidiasis
100
M aterial and Methods
Underlying diseases
703 139
209
70
70
Recurrent vaginal candidiasis (&/year +)
110,000 7,537
7,537
9,949
9,949
382 Invasive aspergillosis
All published epidemiology papers reporting fungal infection rates from Austria were identified. We also extracted reported data from the International Classification of Diseases (ICD) from Ministry of Health as comparators. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence, depending on the condition. Asthma and COPD rates were from Statistik Austria, Gesundheitsbefragung 2006/2007 and OECD. 2011 HIV data was from Ministry of Health. 2011 transplantation numbers were from Gesundheit Osterreich. Infections are grouped in invasive fungal infections (cryptococcal meningitis, invasive aspergillosis, candida bloodstream infection, Pneumocystis pneumonia), chronic lung or deep tissue infection (chronic pulmonary aspergillosis), allergc fungal disease (allergic bronchopulmonary aspergillosis (ABPA), severe asthma with fungal sensitisation (SAFS)), mucosal infection (oral and oesophageal candidiasis, Candida vaginitis (thrush)) and skin, hair and nail infection (tinea capitis)
518
503 70
Substantial uncertainty surrounds these estimates except for invasive aspergillosis figures in immunocompromised patients and candidaemia, where hospital-based surveillance studies have been done. Therefore, epidemiological studies are urgently required to validate or modify these estimates
Invasive fungal diseases (IFDs) are an increasingly encountered threat among critically ill patients and are a significant cause of morbidity and mortality [1]. Worldwide, most infections are caused by the genera Candida, Aspergillus and Cryptococcus. The incidence and severity of IFD are dependent on a variety of factors including increased use of immunosuppressive agents antineoplastic agents, broad-spectrum antibiotics, prosthetic devices and grafts and hyperalimentation. Improvements in medical care have resulted in critically ill patients surviving longer rendering them vulnerable to IFD. Populations at risk for IFD include haematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients; patients with haematologica malignancy; patients with HIV/ AIDS; and intensive care unit (ICU), surgical and burn patients [1, 2, 3] Candida species have historically been the most common causative organisms. However, the epidemiology of IFD has shifted in recent years as Aspergillus species and other moulds have become increasingly important pathogens [4, 5]. Most data available are mainly derived from single-institution reports or multiple sites within countries rather than from multi-national reports. Fungi infect billions of people every year, yet their contribution to the global burden of disease is largely unrecognized. True rates are unknown because of a lack of good epidemiologica data and despite the high mortality rates of invasive fungal infections, they remain understudied and underdiagnosed as compared with other infectious diseases. Most serious fungal infections occur as a consequence of other health problems such as asthma, AIDS, cancer, transplantation and corticosteroid therapies Endemic mycoses, such as histoplasmosis, coccidioidomycosis, and penicilliosiss have a restricted geographic distribution and largely confined to areas of the world where the etiologic agents are found in nature. In recent years, however, increased domestic and international travel has led to an increase in the number of reported outbreaks and sporadic cases of mycotic diseases. In Austria, for most fungal infections we lack any surveillance data, active or passive Herein, we have estimated fungal infections based on populations at risk, supplemented with existing data from several sources
100
Candida peritonitis
Conclusion
Introduction and Background
418
1999
2009
7 992 323
8 363 040
4 130 143
4290174
3 862 180
4072866
Life expectancy at birth 2,616
121
74.8 Population older than 65 years* Population younger than 20 years’
1 231690
1 464 173
1 859 988
1 754082
382 50
283
28
333
Source: StatisticsAustria 2(
28
Cryptococcal meningitis Pneumocystis pneumonia
1221 Total burden estimated
1221 207
492
130,964
DISCUSSION Austria is a landlocked country of roughly 8.22 million people in Central Europe. The Austrian health care system is characterised by a high density of easily accessible health care facilities. In 2008 a total of 267 hospitals with about 64 300 beds were available for in-patient care. The most common discharge diagnosis in Austria are malignant neoplasms (80% cancer) for women and diseases of the circulatory system in the case of men. The latter is also the most frequent cause of death in Austria, followed by cancer and respiratory diseases. In 2009 a newborn girl had a life expectancy of 82.9 years and a newborn boy of 77.4 years. Over the past 30 years life expectancy has increased by more than eight years whereas infant mortality has decreased by more than 75%. The infant mortality rate corresponded to 3.8 deaths per 1 000 live births in 2009. In 2008 a 60-year- old man had a remaining life expectancy of 21.3 years, and in the same year a woman aged 60 could expect to live for an additional 25.1 years. Many of the se individuals will have underlying chronic illnesses and consequently, are at greater risk of developing more serious infections As shown by our study, we can conclude that several fungal infections are unreported and therefore are impossible to count in absolute numbers. To have an impression of the overall fungal burder in Austria it is necessary to make some assumptions about population from known data sets and published literature. Based on available data approximately 1.59% of Austrian's population will have serious fungal infections during one year. Recurrent vaginal candidiasis and severe asthma with fungal sensitisation (SAFS) are accounting for the most frequent infections, followed by ABPA From data available, most infections occur in immunocompromised and respiratory patients. We lack any data on Pneumocystis pneumonia and Fungal keratitis The rate of candidemia in Austria is low at 2.63/100,000 population consistent with 209 cases, although only 165 were actually documented. Candida peritonitis is estimated at 40% of the ICU candidaemia rate. Most cases or oral and oesophageal candidiasis were probably in non-HIV infected people. Invasive aspergillosis in haematological and transplant patients is estimated at 96 cases [which contrasts with 158 from registry data (2007/8)] and 283 in COPD patients admitted to hospital. 28 mucormycosis and 2 histoplasmosis cases were recorded The rate of candidemia is lower when compared to Aspergillus [1,2] infections. This might be somewhat unusual when compared to other reports; however, we are of the opinion that intensive surveillance studies on mold infections done in the past contribute to this findings. No nation-wide studies on candidemia have been done so far. Overall, we notice an increase of infections due to mucormycetes [6], the reason are not yet fully understood. However, in Austria most of the centres treating patients with hematological malignancies use extensive treatment with voriconazole and/or echinocandins, drugs, which do not target mucormycetes. Since most of our data are extrapolated from surrogate markers this model requires validation. However, it provides a standardized means of estimating and comparing the burden of disease across population. Enhanced surveillance and reporting will be critical to improve our understanding of the importance of invasive fungal infections, to enable prioritization of research and prevention efforts , and to evaluate prevention strategies.
m
I
//
References 1.Richardson C, Lass- Florl C. Changing epidemiology of systemic fungal infections. Clin Microbiol Infect 2008; Suppl 4:5-24 2. Presterl E, et al. Changing pattern of candidaemia 2001-2006 and use of antifungal therapy at the University Hospitalof Vienna,Austria . Clin Microbiol Infect 2007;13:1072-6. 3. Martino R, Subira M. Invasive fungal infections in hematology: new trends. Ann Hematol 2002; 81:233-43. 4. Auberger J, et al. Invasive fungal breakthrough infections, fungal colonization and emergence of resistant strains in high-risk patients receiving antifungal prophylaxis with posaconazole: real-life data from a single-centre institutional retrospective observational study. Antimicrob Chemother 2012; 67: 2268-2273 5. Perkhofer Set al. The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcomeof invasive mould infectionsin immunocompromised and/or immunosuppressed patients. Int J Antimicrob Agents 2010; 36:531-6 6. Auberger J, et al. Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol 2008;88:508-15
The burden of severe human fungal infections in Brazil
J i_ UFCSPA univcrsidade Federal d c Cicncias da Saude d c Porto Alegrc
V
ISANTA CASA I Id e m i s e r i c O r d i a ! PORTO
Ludmila F. Baethgen,1 Lilian C. Carneiro,1 Maria Adelaide Millington,2 David W. Denning,3 Arnaldo L. Colombo,4 Alessandro C. Pasqualotto1-5* in association with the LIFE program (www.LIFE-worldwide.org)
ALEGRE
1Universidade Federal de Ciencias da Saude de Porto Alegre, Brazil; 2Brazilian Ministry of Health, Brazil; 3University of Manchester, UK; 4Universidade Federal de Sao Paulo, Brazil; 5Santa Casa de Misericordia d
rto Alegre, Brazil.
* Corresponding author: Alessandro C. Pasqualotto MD PhD. Av Independencia 155, HDVS, Molecular Biology Laboratory, 90075150, Porto Alegre, Brazil. E-mail:
[email protected]; Phone: +55 51 99951614 r
^
r
^
Introduction S Serious human fungal infections (SHFI) are worldwide associated with high morbidity and mortality rates despite some effective treatment options; S Patients with SHFI often require hospital care, as a consequence of a difficult diagnosis and treatment - almost all fungal diseases occurs as a consequence of other health problems. Despite this, it is an internationally neglected health topic; S This situation is also a problem in Brazil where none of the SHFI are official reportable disease (except for cryptococcal meningitis). This situation hampers epidemiological survey data and masks the tragic reality of the many fungal diseases in our country.
r
Assumptions
Results
S Invasive aspergilosis: 13.4% of AML + 2.3% allo HSCT + 0.5% renal Tx (Nucci, 2012) + 13.3% lung Tx (Pasqualotto, 2010). Not available data for aspergillosis in renal, heart and liver Tx in Brazil. World: 6% Heart Tx and 1.3% liver Tx. Other steroid patients ignored. Added to: COPD admissions to hospital per year *0,013; S Chronic pulmonary aspergillosis (CPA) post tuberculosis: 64,825 TB pulmonary cases, and 59,639 alive pulmonary cases (WHO, 2011); S Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis patients: frequencies ranging from 22-23% (Carneiro, 2008; Paschoal, 2007). ABPA affects 2.15% of asmathics;
S To estimate the total burden (incidence and/or prevalence) of SHFIs in Brazil so that new decision making for monitoring, prevention and fungal disease control becomes possible.
S Oral candidosis: 90% of patients with HIV not on ARVs [possible over-estimation if a large % not on ARVs have CD4 >200 cells];
S Historical data was collected from the Ministry of Health Informatics Department System (DATASUS), from year 2011, for hospitalization admissions and/or notification cases of: cryptococcal meningitis, mucormycosis, histoplasmosis, coccidioidomycosis, paracoccidioidomycosis and blastomycosis; S Official country data was considered consistent only for fungal diseases for which there was a surveillance program in place; S Cases of cryptococcosis meningitis and PCP (for AIDS patients) were obtained from the Information System of Notifiable Diseases (SINAN).
S All data were entered into a Microsoft Excel spreadsheet for statistical analysis.
References
-J
S HIV/AIDS: the current total of HIV/AIDS cases is 608,230 which 30% are not receiving antiretroviral (ARVs). Each year are reported 34,218 annual new AIDS cases (at risk of opportunistic infections). In 2010, about 12,000 deaths were related to AIDS;
S For all kinds of Candida infections the official data in 2011 were 1,242 hospitalizations, differing absurdly of our estimation study that we should have almost 30,000 hospitalizations.
S Critical care and surgery cases: Brazil has 35,403 critical care
beds and ~11,6 million (M) of hospital admissions per year. A tota of 5,609 peritoneal dialysis were done in 2011.
S It is important to note that we exclude for our analysis all cases of severe asthma with fungal sensitization (SAFS), that could be as many as 600,000 cases. S The dermatomycoses were excluded for our study since the minority of the cases are treated in public health centers or in private clinics, making the official data collection unreliable.
Graph 2. Candida infections estimated cases 897 (0%) 28,991 ( 1%)
164,2 2 2 (6 %)
57,782 (2 %)
S Fungal keratitis: 9.01/million of inhabitants per year (based on sales distribution of antifungal eye drops; Ibrahim, 2012).
2 ,729,525 (91%)
Table 1. Estimated burden of serious fungal diseases in Brazil. disease/ Total
Fungal d isease
Cryptococcal meningitis in AIDS Pneumocystis pneumonia
□ Invasive aspergillosis
immunocompromised
Critical care +
Incidence
surgery
(100,000)
392
0.20
18,820
39.60 6,813
1,851
Candidaemia in hospitalized patients Candidaemia in outpatients
Recurrent Candida vaginitis (>4x/year)
□ CPA post TB
Total Candida
4.47 201.31
390,486
211.98
411,183 28,991
11,654
870
3,131
13,336
249.00
897 164,222
164,222
84.66
57,782
57,782
29.79
2,729,525
2,729,525
1,696
0.87
Mucormycosis*
243***
2.09**
Histoplasmosis*
255
Coccidioidomycosis*
829
2.19** •j ^ * *
Paracoccidioidomycosis*
930
7.99**
Total Prevalence
S Based on local data and literature estimates of the frequency of mycoses in susceptible populations, 1.7% of Brazilians presents some form of serious fungal disease;
2,981,416
Fungal keratitis
Total serious fungal infection burden (per year)
□ Recurrent Candida vaginitis (>4x/year)
6.20
390,486
Oesophageal candidosis
□ ABPA
138
Cancer +
12,032 Total Aspergillosis
2%
HIV/AIDS
8,664
Invasive aspergillosis ABPA
12,032 3%
392
0 . Respiratory .. 3 disease 4
other
18,820
CPA post TB
8,664
□ Candidaemia (outpatients)
□ Oesophageal candidosis
No underlying
Graph 1. Aspergillosis estimated cases
□ Candidaemia (hospital)
□ Oral candidosis
S Recurrent Candida vaginitis (>4x/year): 5% of woman (childbearing age) (75% of woman 10-49 years). Literature estimate is 5-8%;
Oral candidosis
S For aspergillosis, candidosis and fungal keratitis we conducted multiple electronic bibliographic database searches. Assumptions were derived using the frequency of these diseases from the literature and as denominator we used official data (population, respiratory diseases, cancer and immunocompromised, and critical care beds) as reported in official governmental publications;
Contrast with official data
S The official hospitalization data for aspergillosis presented 442 cases while in our estimative we have more than 400,000 aspergillosis cases. Most are in the community - allergic and chronic, but there are an estimated 8,664 invasive cases;
S Oesophageal candidosis: 20% of patients not on ARVs, and 0.5% of those on ARVs;
Methods
I
Brazilian scenario: Brazil has ~194 million inhabitants (76% adults, 51% women, and 33% are >40 years old). Knowing that almost all fungal diseases occurs as a consequence of other health problems; we used official Ministry Health as follows:
S Cancer, leukaemia, transplant and other immunocompromised patients: the AML population frequency is estimated in 5/100,000 with 25,244 AML patients reported per year. In 2011, about 700 patients had undergone allogeneic hematopoietic stem cell transplantation (HSCT) and 6,658 were submitted to solid organ Tx (renal, lung, heart and liver);
S Candidaemia in outpatients: 3% of all cases (Colombo, 2006) conservative assumption, since another publication (Pasqualotto, 2005) revealed 9%;
r
L.
S Respiratory diseases: pulmonary TB annual incidence is 36/100,000 (2010). The chronic obstructive pulmonary disease (COPD) prevalence all GOLD stages is 15.8% with 142,421 COPD admissions to hospital per year. We have an asthma rate in adults estimated in 12.4% (To, 2012). About 200 adults are reported with cystic fibrosis.
S Candidaemia in hospitalized patients: 2,49*Critical care + surgery. (2,49/1,000 hospital admissions (Nucci, 2010; Colombo, 2006);
Purpose
^
3,415,764
S Knowing that the mycoses are an internationally neglected health topic, we believe that if all fungal diseases could be officially notified the real number should be much higher than the estimated by this study; S Additional epidemiological estimates are required to validate the modelling estimates presented here.
1,76
*Numbers of cases reported to the Ministry of Health in 2011, based on hospital admission’s codes (CID10); **Incidence in 100,000 hospital admissions. For all other incidences are related to the general population; *** Adjusted value. One Brazilian state is overestimating the mucormycosis cases attended in hospitals.
(1) Brasil. Ministerio da Saude. Secretaria de Atengao a Saude. Departamento de Regulagao Avaliagao e Controle. Coordenagao Geral de Sistemas de Informagao. Fonte: Base de Dados do SIHSUS-Sistema de Informagoes Hospitalares - fornecido pelo DATASUS (tabulados pela CGSI em 17/08/2012). (2) Nucci M, et al. Clin Microbiol Infect 2012 (in press). (3) Pasqualotto AC, et al. Transplantation 2010; 90: 306-11. (4) Carneiro AC, et al. J Bras Pneumol 2008; 34: 900-6. (5) Paschoal IA, et al. Lung, 2007;185:81-87. (6) Colombo AL, et al. J Clin Microbiol 2006; 44: 2816-23. (7) Pasqualotto AC, et al. J Hosp Infect 2005; 60: 129-34. (8) Matee Ml, et al. Oral Dis 2000; 6: 106-11. (9) Smith E, et al. Scand J Infect Dis 1990; 22: 665-72. (10) Sobel JD. Lancet 2007; 369: 1961-71. (11) Ibrahim MM, et al. Plos One 2012; 7: e33775. (12) To T, et al. BMC Public Health 2012; 12: 204. (13) ABTO. Associagao brasileira de transplante de orgaos. 2011. http://tabnet.datasus.gov.br (14) http://www.gbefc.org.br/gbefc/REBRAFC_EN_2009.pdf (15) http://www.inca.gov.br/estimativa/2012/tabelaestados.asp?UF=BR (16) http://www.aids.gov.br/sites/default/files/anexos/publicacao/2011/50652/boletim_aids_2011_final_m_pdf_26659.pdf (17) http://www.who.int/hiv/pub/progress_report2011/en/index.html (18) http://www.fungalinfectiontrust.org/fungaldis.html
