1. Epidemiology and surveillance of fungal infections: an overview
David W. Warnock
Centers for Disease Control and Prevention
Atlanta, Georgia

2. Healthcare Public Health
At this point, it is pertinent to ask: ‘what is public health?’ This is a difficult concept to define, and many well-educated individuals find it difficult to distinguish between clinical medicine and public health. In simple terms, public health can be defined as the prevention of illness in a population.
In clinical medicine the focus is on the individual, on the diagnosis of illness, and on its management. In contrast, in public health the focus is – for the most part – on the population, on the prevention of infection, and on its control.
We depend on the effectiveness of clinical medicine to cure us when we get sick, but we depend on public health to prevent us from becoming ill.
Focus on:
individual
diagnosis
treatment
Focus on:
- population
prevention

3. The cycle of disease prevention

4. The cycle of disease prevention

5. The cycle of disease prevention

6. The cycle of disease prevention

7. 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

8. The spectrum of public health surveillance
Population
Data collection
Case definition
Sentinel surveillance
Passive surveillance
Syndromic surveillance
Population-based surveillance
Laboratory-based surveillance
Active surveillance

9. 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

10. Number of reported cases of coccidioidomycosis United States, 200777 24 3 12 3 72 68
2991 9
4832 23 3
Morbid Mortal Wkly Rep 2007; 56 (no 53) (published July 9, 2009)

11. 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

12. 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

13. 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

14. Incidence of Candida bloodstream infections (per 100,000 population)
7.1
7.1
6.0
24.0
25.0
Looking at the distribution of spinach packages with culture-positive spinach samples and the lot code P227, reported by patients,
we can see that the packages were distributed across a wide region of the United States.
Therefore P 227 could explain cases throughout the wide geographical regions over the course of the outbreak.
8.7
14.0
Diekema et al. 2002; Hajjeh et al. 2004; Kao et al. 1999

15. Incidence of Cryptococcus gattii infection British Columbia, Canada
Average incidence 1999–2006:
Vancouver Island: 2.8 cases per 100, Mainland: 0.65 cases per 100,000
Cases per 100,000 population
Source: BC Centre for Disease Control 2007

16. Estimated population-based incidence of Candida bloodstream, by race
Atlanta, GA, and San Francisco, CA
Cases per 100,000 population
Connecticut, and Baltimore, MD
Kao et al. 1999; Hajjeh et al. 2004

17. Population-based surveillance Cohort 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

18. 12-month cumulative incidence (%)
Incidence of invasive fungal infections after stem cell transplant, (TransNet)
12-month cumulative incidence (%)
Kontoyiannis et al submitted for publication

19. 12-month cumulative incidence (%)
Incidence of invasive aspergillosis after allogeneic stem cell transplant, (TransNet)
Overall incidence: 1.6%
12-month cumulative incidence (%)
Transplant center

20. 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

21. 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

22. Incidence of Candida bloodstream infections (per 10,000 hospital admissions)
Sweden
3.2
Canada
4.0
France
2.0
United States
8.0
Spain
5.3
Italy
3.8
Brazil
24.9
Australia
2.1
Almirante et al. 2005; Colombo et al. 2005; Chen et al. 2006; Hajjeh et al. 2004; Laupland et al. 2005; Tortorano et al. 2004;

23. 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

24. Chang et al. Infect Control Hosp Epidemiology 2008; 29: 25-30
Comparison of the use of administrative data with an active system for surveillance of invasive aspergillosis in a single hospital,
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

25. Bitar et al. Emerg Infect Dis 2009; 15: 1395-1401
Incidence of zygomycosis in France based on analysis of hospital records,
Cases per 100,000 population
Bitar et al. Emerg Infect Dis 2009; 15:

26. 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

27. FoodNet Foodborne Diseases Active Surveillance Network
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.
2009 : 10 sites, 45 million persons, 15% of population

28. FoodNet trends: E. coli O157 infections
Incidence per 100,000 population
1.30
National objective
0.90
Make y axis horizontal. Looks better with white background.
Healthy People 2010 Objective: 1.0 illness per 100,000 persons

29. 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

30. 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’
This article had been cited on 2350 occasions through
Mead et al. Emerg Infect Dis 1999;5:607-25

31. 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:

32. Estimated annual cases of HIV-associated cryptococcosis
Eastern Europe & Central Asia
27,200
Western & Central Europe
500
North America
7,800
East Asia
13,600
North Africa
& Middle East
6,500
Caribbean
7,800
South
& South-East Asia
120,000
Sub-Saharan Africa
720,000
Latin America
54,400
Oceania
100
Global total: 957,900 cases (range: 371,700 – 1,544,000)
Park et al. AIDS 2009; 23:

33. Estimated annual deaths from HIV-associated cryptococcosis
Eastern Europe & Central Asia
15,000
Western & Central Europe 45
North America
700
East Asia
1,200
North Africa
& Middle East
3,600
Caribbean
4,300
South
& South-East Asia
66,000
Sub-Saharan Africa
504,000
Latin America
29,900
Oceania 10
Global total: 624,700 deaths (range: 125,000 – 1,124,900)
Park et al. AIDS 2009; 23:

34. Estimated deaths in Sub-Saharan Africa from cryptococcosis and other infectious diseases*
WHO estimates
* Excluding HIV AIDS

35. 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

36. Thank you for your attention
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