importance of risk factor in diagnosis ......page 30 transmission and risk group •transmission:...

Outline

Burden of SFI – the magnitude of the problem

Epidemiology – who, where & when

Risk factors & risk groups

Aspergillosis and Candidiasis

THE BURDEN OF INVASIVE FUNGAL INFECTION

Invasive fungal infections tend to be under-

diagnosed

This is partly because of non-specific signs &

symptoms

Unrecognised/untreated IFI could cause death

A significant number recognised only at autopsy

So, a high index of clinical suspicion is required.

• Diagnosis of IFI is difficult, with the sensitivity of the

gold standard tests (culture and histopathology) often

<50%.

• Therefore, physicians rely on a constellation of

clinical signs, radiography, culture, histopathology and

adjunctive tests to establish diagnosis

British Journal of Haematology, 139, 519–531

Treatment of IFI: the earlier the better

Fungal infection

• Fungal infection may knowed as mysterious and dangerous diseases, even they are often caused by fungi that are common in the environment.

• Fungi can be found in soil, on plants, trees, and other vegetation, and on our skin, mucous membranes, and intestinal tracts.

• Most fungi are not dangerous, and some can even be helpful – for example: penicillin, bread, wine, and beer use ingredients made from fungi.

Fungal infection

• The symptoms of fungal diseases depend on the type of infection and location within the body.

• Some types of fungal infections can be mild, such as a rash or a mild respiratory illness. However, other fungal infections can be severe, such as fungal pneumonia or bloodstream infection, and can lead to serious complications such as meningitis or death.

Characteristics fungal infection

• Predisposed in pts with

immunodeficiency

• Reactivated

• More frequent in pts with systemic

infection

Clinical suspected to invasive

fungal infections

• Persistent fever unresponsive to broad spectrum

antibiotics in high risk patients

• Macronodular cutaneous lession (Candidiasis)

• New pulmonary infiltrate on CXR (Aspergillosis)

• Hallo sign on CT scan or mycotic lession

• Colonization Candida or Aspergillus

• Positive serology test

Beware of fungal infections

PERSISTENT / RECURRENT FEVER, - Pulmonary infiltrates

- Neutropenia > 7 days

- Adequate AB > 3 d

- Eosinophilia

- Elevated IgE

PREDISPOSING FACTORS

14

PREDISPOSING / RISK FACTORS

• Broadspectrum antibiotics

• CVC

• Parenteral nutrition

• Hemodialysis

• Neutropenic pts

• Implantable prosthetic devices

• Immunosuppressive agents and

• Immunomodulators 15

Normal individual against

infection

• Anatomical barrier

–Skin barrier and mucosal

barrier

• Immune system

–Phagocyte

–Complement

–Cell mediated immunity

INVASIVE FUNGAL INFECTIONS IN RELATION TO IMMUNE

DEFENSE

compromised defense severely compromised

external fungal population

our body

Immune Response in Fungal Infections

(Playfair JHL, Immunology at a glance, 1996)

The others factor could be

influence in fungal infection

• Neonates : weaker

• Invasive procedure ; Catheterization

• Antibiotics

• Environments :

– Cryptococcus spp – bird dropping

– Hospital environments : water supply, hospital

food, toilet, unclean sinks, flower, plant,

parenteral nutrition, room, hospital equipment

Epidemiolgy

• Assesing incidence and prevalence of IFI

is difficult --- autopsy

• Overall incidence of nosocomial IFI has

increases 2 times in the two last decade

• The incidence of community acquired

infection by cryptococcus neoformans has

increases

Increases in the prevalence of

systemic Candida infections

Bassetti M, et al. BMC Infect Dis 2006; 6:21

Inci

den

ce o

f ca

nd

idae

mia

(e

pis

od

es/1

0,00

0 p

atie

nt-

day

s/y

ear)

Year

1999

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

2000 2001 2002 2003

Europe Data

MORTALITY DUE TO INVASIVE

MYCOSES McNeil et al. Clin Infect Dis 2001;33:641-7

0

0,2

0,4

0,6

Rate

per

100,0

00 p

op

ula

tio

n

United States, 1980-1997

Mycoses other than Candida albicans

1999 2000 2001 2002 2003

0

0,5

1

1,5

2

2,5

3

3,5

Inc

ide

nc

e (

%)

DEVELOPMENT OF FUNGAL INFECTIONS

OVER TIME

other moulds

Aspergillus

Candida

other yeasts

Increasing rate of

candidiasis in the US

Martin et al, NEJM 2003;348:1546

+300%

+300%

+600%

nu

mb

er

of

ca

se

s

0

100

200

300

400

Lethality Of The Various Invasive

Fungal Infections

cases casualties

42%

61% 53%

33%

50% 29%

487 FUNGAL INFECTIONS IN

TRANSPLANT RECIPIENTS

Pappas et al. ICAAC, Chicago 2003; abstr M-1010

Candida

Aspergillus and other moulds

Crypto Endemic Pneumocystis

BASIC RISK FACTORS FOR FUNGAL INFECTIONS

immuno-

suppression

epidemiologic

exposure

technical / anatomic factors

Adapted from RH Rubin, Boston

OPPORTUNISTS!

Figure 1: A generalized diagram displaying

infection and disease cycle caused by fungi and

oomycetes.

Mentions: In this review, we summarize common

mechanisms of pathogenesis displayed by

oomycetes and fungi. Pathogenesis by a fungus or

oomycete is a complex process. Briefly, it includes

the following steps: dispersal and arrival of an

infectious particle (usually a spore of some kind) in

the vicinity of the host, adhesion to the host,

recognition of the host (which may occur prior to

adhesion), penetration into the host, invasive

growth within the host, lesion development in the

host, and finally production of additional infectious

particles [5,6] (see Figures 1, 2). In order to

describe the entire process, we formulate a

description of pathogenesis using standardized

terms from the Gene Ontology (GO), including 256

new terms developed by members of the PAMGO

(Plant-Associated Microbe Gene Ontology)

Transmission and risk group

• Transmission: – Occurs through inhalation of airborne conidia.

– Nosocomial infections : dust exposure

– Occasional outbreaks of cutaneous infection : traced by

contaminated biomedical devices.

• Risk groups: – Severe/prolonged granulocytopenia,

– Hematologic malignancies,

– HIV/AIDS.

– Other risk factors include receipt of hematopoietic stem cell or

solid organ transplants and taking high-dose corticosteroids or

other immunosuppressive therapies.

PATIENTS RISK GROUP

• Abdominal surgery

• HIV /AIDS

• Auto immun

diseases

• Burn

• Gastroenterology

• Infectious

diseases

• Patients in ICU

• Neonatalogy

• Oncology

• Pulmonology

• Radiotherapy

• Rheumatolgy

• Transplantation

• Prolonged steroid

treatment

Risk factors fungal

infection

• Surgery : Disruption of normal barrier

• HIV /AIDS : Destroy CD4

• Chronic granulomatous diseases:

Defective neutrophile phagocyte cell

• Immunosuppressive drugs : Steroid,

cyclosporine

Malignancies patients

o Immunosuppressive drugs :

lymphophenia

o Myelosuppresive chemotherapy

Netropenia

Disease

Risk (critical illness)

• Prolonged antibiotic use

• CVP

• Prolonged stay in ICU

• Renal failure and hemodialysis

• TPN

• Abdominal surgery

• Immunosuppression

Catagories

• Opportunistic infections : Cryptococcosis

Aspergillosis

Are becoming increasingly problematic as the number of people

with weakened immune systems rises, this includes cancer

patients, transplant recipients, and people with HIV/AIDS.

• Hospital-associated infections : Especially candidemia are a leading cause of bloodstream

infections.

Advancements and changes in healthcare practices can provide

opportunities can emerge the fungal infection in hospital settings.

• Community-acquired infections: Coccidioidomycosis

Blastomycosis

Histoplasmosis

Candidiasis

• Candidiasis is a fungal infection caused by yeasts that belong to the

genus Candida.

• There are over 20 species of Candida yeasts that can cause infection

in humans, the most common of which is Candida albicans.

• Candida yeasts normally live on the skin and mucous membranes

without causing infection; however, overgrowth of these organisms

can cause symptoms to develop.

• Symptoms of candidiasis vary depending on the area of the body that

is infected.

SPECTRUM FUNGAL

INFECTION

• Spectrum fungal infection has changed

• C.Albicans : 1980 (75%)-1995 (60%)

• 1987-1992 :

– C.Albicans : 87-30%

– C.Glabrata : 2-26%

– C.parapsiosis : 9-20%

– C.Tropicalis : 2-24%

j.maertens,european journal of cancer care,2001,10

Epidemiology of candidemia

Tortorano Trick Diekema Richet Pfaller Marchetti

(n=569) (n=2759) (n=254) (n=377) (n=1134) (n=1137)

J Hosp Infect CID J Clin Microbiol CMI J Clin Microbiol CID

2002 2002 2002 2002 2002 2004

C.alb icans 58,50% 59% 58% 53% 55% 66%

C.glabrata 12,80% 12% 20% 11% 15% 15%

C.parapsilosis 14,60% 11% 7% 16% 15% 1%

C.tropicalis 6,10% 10% 11% 9% 9% 9%

C.krusei 0,90% 1,20% 2% 4% 1% 2%

Miscellaneous 7,10% 7% 2% 6% 1% 7%

Aspergilosis

• Aspergillus is a common fungus that can be found in

indoor and outdoor environments.

• Most people breathe in Aspergillus spores every day

without being affected.

• Aspergillosis is usually occurs in people with lung

diseases or weakened immune systems.

• The spectrum of illness :

Allergic reactions,

Lung infections,

And infections in other organs

• From the population-based data the infection rate of 1 to

2 cases per 100,000 people per year.

Clinical features

• Immunosuppressed hosts:

Invasive pulmonary infection, usually with

fever, cough, and chest pain. Infection may

disseminate to other organs, including brain,

skin and bone.

• Immunocompetent hosts: Localized

pulmonary infection in people with underlying

lung disease, allergic bronchopulmonary

disease, and allergic sinusitis.

Etiologic and

reservoir

• Etiologic Agent: Aspergillus fumigatus,

Aspergillus flavus,

and less commonly A. terreus, A. nidulans, and A.

niger.

• Reservoir: Aspergillus is ubiquitous in the

environment; it can be found in soil, decomposing plant

matter, household dust, building materials, ornamental

plants, food, and water.

• Early treatment initiation in patients with IFIs has a

profound impact on mortality rates, but reliable diagnostic

measures are lacking.

• Identifying high-risk patients is the first step in reducing IFI-

related mortality.

• Early diagnosis of IFIs is imperative to facilitate treatment

success.

importance of risk factor in diagnosis ......page 30 transmission and risk group •transmission:...

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