Transcript Histoplasma capsulatum

Histoplasma capsulatum
Histoplasmosis;
Ajecllomyces capsulatus
Taxonomy of Histoplasma
capsulatum:
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Superkingdom: Eukaryota
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Kingdom: Fungi
Phylum: Ascomycota / Subphylum: Pezizomycotina
Class: Eurotiomycetes
Order: Onygenales
Family: Onygenaceae
Genus: Ajellomyces
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Histoplasma capsulatum:
The Endemic Mycoses
(Pathogenic classification)
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Characterized by:
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*Caused by dimorphic
fungi which exist as
filamentous
organisms in nature
and as yeast cells in
infected tissue.
*All are endemic to
certain
geographical areas
where they can
usually be found in
the soil.
Similar Pathogens
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Blastomyces
dermatitidis
The causative
agent of
Blastomycosis
Found in the
southeastern
and middle
western areas
of the U.S.
Coccidioides immitis
Cause of
coccidioidmyco
-sis
 Found in the
southwestern
areas of the
U.S.
Diseases and targeted
tissues:
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Targets primarily the lungs and the respiratory system BUT
 The disease can progress to systemic forms affecting all of the major
organs.
Causes primary lesions in the lungs
 the most common cause of fungal respiratory infections in the
world.
 poses a particular threat to the elderly and to
immunocompromised patients such as those infected with HIV,
or to organ transplant recipients undergoing
immunosuppressant drug therapy.
 May contribute to development of secondary disease, such as
pneumonia.
Life Cycle of Histoplasma
capsulatum
HIV patients are more suceptible
to symptomatic infection. Why?
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Yeast grows more
rapidly within
macrophages from HIVinfected individuals or
within macrophages
infected in vitro with a
macrophage-tropic
strain of HIV.
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Among T-cell
populations, CD4
cells are vitally
important
Ecology/Infection Process:
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After conidia have been inhaled and settle into the
alveoli, they bind to the CD2/CD18 family of integral
protiens and are engulfed by both neutrophils and
macrophages but not killed.
In the macrophages, conidia transform into yeast
within the pulmonary parenchyma;
It then migrates to local draining lymph nodes and,
subsequently, to distant organs rich in mononuclear
phagocytes, such as the liver and spleen
Ecology of Histoplasma
capsulatum
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Histoplasma capsulatum is a
dimorphic fungus. The
mold or mycelial form
exists as a mold in the soil
where it absorbs nutrients
from dead organic matter
and produces infectious
spores.
Exists as a yeast in tissues.
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When these spores are
inhaled, they encounter
the warm moist
environment of the lungs.
In the lung, the spores are
ingested by macrophages
and become yeasts. The
disease may be
asymptomatic or, in some
cases, resemble
tuberculosis. they undergo
a transformation to the
yeast or parasitic form.
Ecology of Histoplasma
capsulatum cont.
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HOSTS : Humans, dogs, cats, cattle, horses, rats,
skunks, opossums, foxes and other animals
 INFECTIOUS DOSE: inoculation of 10 spores is
lethal in mice
 VECTORS: None
 SURVIVAL OUTSIDE HOST: Spores are resistant to
drying and may remain viable for long periods of time
 INFECTIVE STAGE: (conidia) present in sporulating
mold from cultures and in soil from endemic areas;
yeast form in tissues or fluids from infected animals
or humans
Symptoms in the Host may
include the following:
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flu-like symptoms
headache
cough
lymphadenopathy
caseating necrosis
fever
muscle pain
chest pain
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Hepatomegaly
(coughing up blood)
 erythema nodosum
 malaise
 anorexia
 dyspnea
 splenomegaly
 coin lesion
General Stats:
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Begins as lower
respiratory infections
as a result of
inhalation of the
conidia.
X-ray findings are
similar to tuberculosis
or cancer and
infections
Misdiagnosed
especially in nonendemic areas.
Most infections may
be asymptomatic in
immunocompetent
Diagnostic Testing:
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4 Preferred
Methods:
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Histoplasmin skin test
Detection of antigens or
antibody to the agent in
the blood (serology)
Complement fixation
(preferred)
Identification of cells in
the microscope
Differential
Diagnosis
Goal: Other disease or
conditions that need to
be eliminated
Other infectious diseases
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Other fungal infections
Other infections of the
respiratory tract
Miliary tuberculosis
Other problems
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Bronchitis
Emphysema
Inhalation poisoning
Serologic tests
A high serum concentration of
antibodies develops within 8
weeks of exposure in most
patients and then declines to low
or undetectable levels over a 2- to
5-year period.
Diagnostic Factors that May
be Tested:
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Growth rate as measured in , Sabouraud's
agar medium
resistance to 10% KOH
yeast in lung
microscopic examination
septate, branching hyphae
yeast in macrophages
hyphae
Histoplasma capsulatum
Culture Identification Test
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Most Common form of testing
 Rapid DNA probe Test
– Uses Nucleic Acid Hybridization for
identification when isolated from a culture
Treatment/ Prevention
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FIRST AID/TREATMENT: Amphotericin B for disseminated or
chronic pulmonary cases; conazole drugs may be added or
used in rotation for therapy in immunocompromised patients
because relapse is common
IMMUNIZATION: None
PHYSICAL INACTIVATION: Inactivated by moist heat (121° C
for at least 15 min)
Supportive care :
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Oxygen for respiratory care;
Glucorticoids to support adrenal function;
Antipyretics and antiemetics to support treatment with
antifungals;
Surgery may be needed to treat fibrosis
Epidemiology
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TRANSMISSION:
Inhalation of airborne
conidia; small size of
infective conidia (< 5 µm)
INCUBATION
PERIOD: Symptoms appear
within 3-18 days after exposure,
commonly 10 days
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COMMUNICABILITY:
Not transmitted from personto-person
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Focal infections are common
worldwide; clinical disease and
severe progressive disease less
frequent; 80% of population
show hypersensitivity to H.
capsulatum in eastern and
central North America;
outbreaks in families or groups
exposed to bird or bat
droppings or recently disturbed
contaminated soil; prevalence
increases from childhood to 15
years of age
Cites of Infection and Sources
Sources (Asymptomatic
Carriers)
Cites of Pathegenocicity:
Symptoms are Expressed
bats
respiratory tract
laboratory cultures
LRT
(71 reported cases with 1 death )
soil
immunosuppressed
birds
infants
Mississippi River valley
lung pathogen
chickens
Ohio River valley
Geographical Distribution
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In the US: Most common in the southeastern, midAtlantic, and central states and in the Ohio and Mississippi
River valleys.
Internationally: Endemic in areas of North and Latin
America but can be found throughout the world.
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Favorable Growth Conditions:
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In soil: typically are found in the temperate zone between latitudes
45° north and 30° south. Factors accounting for its geographic
distribution include humid environmental conditions and acidic
permeable soil. The organism commonly is found in bird and bat
droppings, most often where guano is decaying and mixed with
soil.
History and Background
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First was described in 1905 by Samuel Darling, a US
Army pathologist stationed in Panama.
Darling examined visceral tissues and bone marrow from
a young man from Martinique whose death originally was
attributed to miliary tuberculosis.
The organism initially was described as protozoal.
Because it lacked a kinetoplast, Darling assumed that it
was a different species of Leishmania. He termed it H
capsulatum.
In 1912, after reviewing tissue specimens, da Rocha-Lima
suggested that the organism resembled a yeast rather than a
protozoan
Morbidity and Mortality Rates:
Only 5% of infected individuals
develop symptomatic disease
after a low-level exposure to
Histoplasma. The estimated
incidence is 1 per 2000 persons
References:
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Weinberg M, Weeks J, Lance-Parker S, Traeger M, Wiersma S, Phan Q, et al. Severe
Histoplasmosis in Travelers to Nicaragua. Emerg Infect Dis. Vol. 9, No 10. 2003
Oct.{accessed 12/02/03}. Available from: http://www.cdc.gov/ncidod/EID/vol9no10/030049.htm
Fahad M Alhameed, MD, FRCPC, Consultant Critical Care and Pulmonary
Medicine, Department of Internal Medicine, Sections of Pulmonary and Critical
Care, et al. Histoplasmosis, Thoracic.. © Copyright 2003, eMedicine.com, Inc.
January 15, 2003 {accessed 12/04/03}. Available
from:http://www.emedicine.com/radio/topic344.htm
Mycology Fungi. Histoplasma capsulatum. Author not listed. Available through
Rutgars Pharmacy. {Accessed 12/06/03} . Available from:
http://pharmacy.rutgers.edu/lcr/pdfs/miller2.pdf
Office of Laboratory Security, PPHB. Histoplasmosis, essential data. Copyright,
Health Canada, 2001. 2001 March. Accessed 12/03/03. Available from:
http://www.cbwinfo.com/Biological/Pathogens/HC.html.
Histoplasma capsulatum Sequencing at the GSC in collaboration with the
University of California at San Francisco and the Department of Molecular
Microbiology here at Washington University. Last modified: November 19 2003
15:21:18.{accessed 11/29/03}. Available
from:http://www.genome.wustl.edu/projects/hcapsulatum/