epidemiology and surveillance of fungal infections: an overview david w. warnock centers for disease...
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Epidemiology and surveillance of fungal infections: an overview
David W. Warnock
Centers for Disease Control and PreventionAtlanta, Georgia
Public HealthHealthcare
Focus on:- individual- diagnosis- treatment
Focus on:- population- prevention
The cycle of disease prevention
Identify risk factors fordisease and potentialprevention measures
Measure the effectivenessof prevention strategies
for the disease
Conduct surveillance todetermine burden of adisease in a population
The cycle of disease prevention
Identify risk factors fordisease and potentialprevention measures
Measure the effectivenessof prevention strategies
for the disease
Conduct surveillance todetermine burden of adisease in a population
The cycle of disease prevention
Identify risk factors fordisease and potentialprevention measures
Measure the effectivenessof prevention strategies
for the disease
Conduct surveillance todetermine burden of adisease in a population
The cycle of disease prevention
Identify risk factors fordisease and potentialprevention measures
Measure the effectivenessof prevention strategies
for the disease
Conduct surveillance todetermine burden of adisease in a population
Public health surveillance
● ‘The ongoing systematic collection, analysis and interpretation of information about a disease’[1]
● ‘The reason for collecting, analyzing and disseminating information on a disease is to control that disease’ [2]
● ‘Collection and analysis should not be allowed to consume resources if action does not follow’ [2]
[1] Langmuir N Engl J Med 1963;268:182-92[2] Foege Int J Epidemiol 1976;5:29-37
The spectrum of public health surveillance
Sentinel surveillance
Population-based
surveillance
Population
Passive surveillance
Active surveillance
Syndromic surveillance
Laboratory-based
surveillance
Case definitionData collection
Comparison of surveillance systems
● Active surveillance– Investigator-initiated– Dedicated staff needed– Extensive case finding
performed– Extensive clinical and
laboratory information– Audits performed– High cost
● Passive surveillance– Provider-initiated– No dedicated staff needed– Limited case finding
performed– Limited clinical and
laboratory information– No audits performed– Lower cost
Number of reported cases of coccidioidomycosis United States, 2007
2991
4832
72
23
0
68
324
3
277
Morbid Mortal Wkly Rep 2007; 56 (no 53) (published July 9, 2009)
12
9
3
Mycotic diseases: passive surveillance
● Healthcare providers feel no need to report fungal infections since no immediate public health action is required
● Limitations of current diagnostic tests hinder the development of case definitions
● As a result these infections are under-diagnosed and under-reported
In 2007, CSTE adopted a modified case definition for coccidioidomycosis: a single positive serologic test for IgG is
now adequate for definition of a case
Mycotic diseases surveillance: case definitions
● A standardized case definition is needed to perform reliable surveillance for a disease
● In some diseases, a positive culture is indicative of colonization rather than infection
● Consensus case definitions for clinical trial enrollment of immunocompromised patients are too complicated for surveillance and not generalizable to other patient groups
Population-based surveillance
● Provides the most representative information on a disease in the entire population of a defined geographic location, and specific groups within that population
● All cases of the disease in the catchment area are identified, but only cases among residents are counted
● Incidence is calculated as the number of new cases occurring in a defined time period divided by the total population
● Active population-based surveillance to determine trends in disease incidence is expensive to conduct, and difficult to sustain for long periods
Incidence of Candida bloodstream infections(per 100,000 population)
Diekema et al. 2002; Hajjeh et al. 2004; Kao et al. 1999
6.01998-2001
7.11992-1993
8.71992-1993
7.11998-2000
24.01998-2000
14.02008-2009
25.02008-2009
Incidence of Cryptococcus gattii infection British Columbia, Canada
00.5
11.5
22.5
33.5
1999 2000 2001 2002 2003 2004 2005 2006
Vancouver Island Mainland
Source: BC Centre for Disease Control 2007
Cas
es p
er 1
00,0
00 p
opul
a tio
n
Average incidence 1999–2006:Vancouver Island: 2.8 cases per 100,000 Mainland: 0.65 cases per 100,000
Estimated population-based incidenceof Candida bloodstream, by race
Kao et al. 1999; Hajjeh et al. 2004
Cas
es p
er 1
00,0
00 p
opul
atio
nAtlanta, GA, and San Francisco, CA
1992-1993
Connecticut, and Baltimore, MD
1998-2000
Population-based surveillanceCohort studies
● In cohort studies, the population is defined as a particular group of individuals (e.g. persons with AIDS or transplant recipients)
● Adequate follow-up is essential to determine the presence or absence of infection and therefore inclusion as a case of disease or non-case
● These studies are most useful when only a subset of the population is at risk for a particular disease
● Information is more broadly representative than reports from single centers
Incidence of invasive fungal infections after stem cell transplant, 2001-2006 (TransNet)
12-m
on
th c
um
ula
tiv
e in
cid
enc
e (%
)
Kontoyiannis et al. 2009 submitted for publication
Incidence of invasive aspergillosis after allogeneic stem cell transplant, 2001-2005
(TransNet)
12-
mo
nth
cu
mu
lativ
e in
cid
enc
e (
%)
Transplant center
Overall incidence: 1.6%
Sentinel surveillance
● Conducted at selected medical centers or sites, rather than in the entire population of a geographic location
● Total burden of disease in the general population cannot be estimated, but useful for diseases where the at-risk population is captured
● Less expensive and easier to perform than population-based surveillance
Sentinel surveillance
● Hospital are good sites for sentinel surveillance of invasive fungal infections because good denominators are available
● Useful for monitoring trends in incidence of particular pathogens and infections, species distribution, and antifungal drug resistance
● Site selection can be biased, so information may not be representative of the general hospital population
Incidence of Candida bloodstream infections (per 10,000 hospital admissions)
Canada4.0
United States8.0
Brazil24.9
Australia2.1
Spain5.3
Sweden3.2
France2.0
Italy3.8
Almirante et al. 2005; Colombo et al. 2005; Chen et al. 2006; Hajjeh et al. 2004; Laupland et al. 2005; Tortorano et al. 2004;
Administrative data as sources of information
● Hospital discharge and death records, based on ICD codes, are widely available, and permit application of common definitions to similar data from different institutions,
● Use of these data minimizes ascertainment bias when investigators use diverse methods for case finding
● Helpful for investigating long-term trends in disease incidence rates
● Limitations include diagnostic errors, inconsistent disease coding, and undetected duplicate reporting of cases
Comparison of the use of administrative data with an active system for surveillance of invasive
aspergillosis in a single hospital, 2001-2005
● 64 of 1736 transplant recipients had ICD-9 codes consistent with IA, triggering medical record review; 3 cases detected by other methods
● 48 of 67 patients reviewed had other or no infections, or had insufficient evidence to be classed as proven or probable IA
● 14 of 19 patients reviewed and classed as having IA identified by both methods; 3 identified by active surveillance only; 2 identified by ICD-9 code only
Chang et al. Infect Control Hosp Epidemiology 2008; 29: 25-30
Incidence of zygomycosis in France based on analysis of hospital records,1997-2006
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Bitar et al. Emerg Infect Dis 2009; 15: 1395-1401
Cas
es p
er 1
00,0
00 p
opul
a tio
n
Disease registries as sources of information
● Provide useful information about clinical details of rare fungal infections, or infections occurring in special hosts, such as transplant recipients
● Limited value for public health surveillance because meaningful and appropriate denominator data are not available
● Subject to ascertainment bias: variable participation or case finding leads to unrepresentative results
● Should not be interpreted as being representative of broader populations
● Established in 1996 as a collaboration among CDC, USDA, FDA, and state health departments
● Conducts population-based, active surveillance for laboratory-confirmed infections caused by 9 pathogens commonly transmitted through food– Campylobacter spp., Listeria monocytogenes, Salmonella
spp., Shigella spp., STEC O157, Vibrio spp., Yersinia enterocolitica, Cryptosporidium spp., Cyclospora spp.
FoodNet Foodborne Diseases Active Surveillance Network
2009 : 10 sites, 45 million persons, 15% of population
0
0.5
1
1.5
2
2.5
3
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Inci
denc
e pe
r 10
0,00
0 po
pula
tion
National objective
1.30
0.90
Healthy People 2010 Objective: 1.0 illness per 100,000 persons
FoodNet trends: E. coli O157 infections
Estimating the burden of disease
● Most surveillance systems do not capture the total burden of disease in a population
● This is because the reporting of a case depends on a number of steps: the patient must visit a doctor; the doctor must collect a sample; the sample must be tested; the pathogen must be identified; and the test result must be notified
● The proportion of cases that are detected and reported differs from disease to disease
Food-related illness and death in the United States
‘Foodborne diseases cause 76 million illnesses, 325,000 hospitalizations, and 5000 deaths in the United States each year’
Mead et al. Emerg Infect Dis 1999;5:607-25
This article had been cited on 2350 occasions through 9.21.09
Estimating the global burden of HIV-associated cryptococcosis
● Literature search for studies reporting estimates of incidence among HIV populations since 1996
● Median incidence for each UNAIDS geographic region multiplied by the HIV population to estimate number of cases
● To estimate number of deaths, assumed a 3-month case fatality rate
– 9% in high-income regions– 55% in low- and middle-income regions– 70% in Sub-Saharan Africa
Park et al. AIDS 2009; 23: 525-30
Western & Central Europe
500
North Africa & Middle East
6,500
Sub-Saharan Africa
720,000
Eastern Europe & Central Asia
27,200
South & South-East Asia
120,000
Oceania100
North America7,800
Caribbean7,800
Latin America54,400
East Asia13,600
Global total: 957,900 cases (range: 371,700 – 1,544,000)
Estimated annual cases of HIV-associated cryptococcosis
Park et al. AIDS 2009; 23: 525-30
Western & Central Europe
45
North Africa & Middle East
3,600
Sub-Saharan Africa
504,000
Eastern Europe & Central Asia
15,000
South & South-East Asia
66,000
Oceania10
North America700
Caribbean4,300
Latin America29,900
East Asia1,200
Global total: 624,700 deaths (range: 125,000 – 1,124,900)
Estimated annual deaths from HIV-associated cryptococcosis
Park et al. AIDS 2009; 23: 525-30
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
Mala
ria
Diarrh
eal d
iseas
es
Childh
ood-
cluste
r dise
ases
Crypt
ococ
cosis
Tuber
culos
is
STDs exc
luding
HIV
Tropic
al-c
luste
r dise
ases
Hepat
itis B
Non-C
rypt
o M
enin
gitis
Hepat
itis C
Estimated deaths in Sub-Saharan Africa from cryptococcosis and other infectious diseases*
WHO estimates
* Excluding HIV AIDS
In conclusion:
● Similar burden of disease estimates need to be developed for other fungal infections
● These estimates would allow for comparison with other diseases
● These estimates would help set public health and healthcare priorities, and determine resource allocations
The findings and conclusions in this presentation are those of the author and do not necessarily represent the views of
the Centers for Disease Control and Prevention
Thank you for your attention