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T i n s A M E R I C A N .IOUKNAL O F C L I N I C A L
PATHOLOGY
Vol. 40, N o . 1, p p . 21-33
J u l y , 1063
C o p y r i g h t © 11)63 b y T h e Williams & Wilkins C o .
Printed in
U.S.A.
THE PATHOGENETIC SPECTRUM OF ASPERGILLOSIS
JOHN H. SEABURY, M.D., AND MONROE SAMUELS, M.D.
Louisiana State University School of Medicine, and Charity Hospital of Louisiana, New Orleans, Louisiana
and secondary varieties may appear obviously satisfactory to the clinician. For example, aspergillosis may be called primary "in
the absence of underlying disease or other
predisposing factors," 2 and secondary aspergillosis is "associated with a local process,
debilitating illness, impaired host defenses,
or complicating antibacterial and/or steroid
hormone therapy." 2 Is such a classification
biologically defensible?
Classification into primary or secondary
infections on the basis of the presence or
absence of an antecedent disorder is not valid
in the light of present knowledge concerning
pathogenesis. Despite our expanding knowledge about host factors that may favor
infection, we are usually ignorant of which
ones may be operational in the natural
occurrence of human disease. We speak of
"resistance"—of various types—and even
"local immunity" to explain the infrequency
with which some people are infected even
under epidemic conditions. We know that
local tissue injury, from any cause, favors
localization of infection at the injured site,
but does not necessarily explain infection
in the first place. We know that organisms
may enter and circulate in the blood stream
without producing any recognizable evidence of disease. It is recognized that
tuberculosis and many fungous infections
are more common among diabetics than
nondiabetics, yet we believe that this
increased susceptibility to infection is not
sufficient to justify classifying tuberculosis
as secondary when it occurs in a diabetic.
In considering disease produced by facultative parasites, the dividing line between
saprophyte and parasite is often narrow
and may be undiscernible under present
limitations of knowledge. The relationship
is not firm, by definition, and may be altered
by recognized or unrecognized changes in
host or microorganism. Disease of an organ
or a system predisposes to other disease.
Rather than trying to express this relation-
The role that aspergilli may be playing
in disease is often difficult to assess. When
looked for, they are frequently found growing in chronic lung abscesses,4 either loosely
in the necrotic cavitary content or tightly
applied to the abscess wall. Under such
circumstances, the fungus appears to be
leading a purely saprophytic existence,
although the frequency of hemoptysis in
these patients is disturbing when bronchiectasis is not demonstrated. Occasionally,
an Aspergillus may penetrate the wall of
the abscess and invade pericavitary lung
tissue. The fungus can produce extensive
pneumonitis, and cerebral metastasis may
occur. In the latter situations the fungus is
clearly pathogenic.
Most of the fungi that produce disease
in man pursue a free-living existence in
nature as saprophytes. When transported to
man by whatever means, they may or may
not produce disease. These fungi are,
therefore, ordinarily saprophytic but are
facultative parasites. This is no special
property of fungi, being equally true of a
multiplicity of bacteria.
Difficulty arises in designating fungous
infections as "primary" or "secondary."
"Primary" implies that the infection is either
first in order or principal. "Secondary" may
mean second or inferior in order of time,
place, or importance. The term "secondary"
is used frequently in infectious processes to
designate a complicating infection or superinfection appearing after treatment of the
primary infection has been initiated. Classification of fungous infections into primary
Received, August 20,1962; accepted for publication, April 9,1963.
Dr. Seabury is Professor of Medicine, Louisiana State University School of Medicine and
Senior Visiting Physician at Charity Hospital.
Dr. Samuels is Clinical Assistant Professor of
Medicine and Pathology, Louisiana State University School of Medicine, and Associate Pathologist
at Charity Hospital.
21
22
Vol. 40
SEABUKY AND SAMUELS
ship as primary versus secondary, we prefer
the term "opportunistic." We would discard
the term "primary" as being unnecessary.
"Opportunistic" is preferred by us to
"secondary infection" with its previously
described connotation because "opportunistic" is free from the etymologic implications
of temporality and inferiority. It is not a
new term, but has been heard with greater
frequency in the past several years. It may
be used without implying that either the
host or microorganism has undergone
changes that can be precisely defined in
creating the opportunity for infection.
One must remember that in a very real
sense all infections are opportunistic. In an
outbreak of infection by highly virulent
Lancefield Group A streptococci under the
most favorable conditions of crowding,
there will be some persons who do not
become ill in spite of adequate exposure.
Exposure can be documented by culturing
the organism from the nose and throat of
the well persons; however, such infections
are not, and never have been, graced by the
term "opportunistic." The term "opportunistic infection" is clearly not concerned
with those factors that bring about infection
by organisms which are accepted as pathogens for the host who appears to be normal
at the time of acquiring the infection.
Emmons 1 has used the designation "versatile opportunists" appropriately for all
fungi that have a natural free-living existence as true saprophytes but may produce
disease. They are what we would call
facultative parasites. The designation of
these organisms as "versatile opportunists"
TABLE 1
PATIENTS WITH ASPERGILLOSIS*
Patient
Age
Sex
Probable Portal
of Entry
F
Bronchi
Organs Involved
Possible Predisposing
Factor
Species of
Aspergillus
yr.
O. T .
R. D.
E. F.
50
23
24
M
M
29
L. C.
I t . C.
24
42
Bronchi
Bronchi
Bronchi
M
F
L. J.
35| F
D. P.
24f
M
Bronchi
Paranasal
sinuses (?)
Mouth
Paranasal
sinuses
Both lungs
Acute myelogenous leukemia, corticoids, chloramphenicol, penicillin
Bronchiectasis,
penicillin,
Lung abscess
streptomycin, sickle cell
disease
Lung abscess and lung
Diabetes, penicillin, streptomycin, occupation,,
asthma
Lung abscess and lung
Diabetes, asthma, occupation
Lung bullae, lung, kidneys, Boeck's sarcoid, anemia,
malnutrition, penicillin,
liver, spleen
chloramphenicol, e r y t h romycin,
prednisolone
(11 days)
Brain,
cavernous
sinus, Streptomycin,
oxy t e t r a anterior clinoid process,
cycline,
erythromycin,
optic chiasm
cortisone
P a r o t i d area, frontal and None
ethmoid sinuses, eyelid,
orbit, skull, brain (?),
lung (?)
Orbits, lacrimal sac, eye- None
lids, face, maxillary and
frontal sinuses
A.
fumigatus
A.
fumigalus
A.
flavas
A.
?iiveus
A.
fumiga1'II.S
A.
fumigatvs
A.
Jlavus
A.
jlavus
* This table summarizes the essential data from the 7 patients described. The possible predisposing
factors are not listed in a sequence calculated to reflect their order of importance,
f Age at onset.
July 1963
23
ASPERGILLOSIS
is a biologic one with reference to the organism itself rather than the host.
We suggest the term "opportunistic
fungous infection" to designate those
mycotic infections that arise because of the
presence of a major abnormal host condition
which (1) predisposes statistically to the
development of infection by fungi which
rarely produce disease in normal man, or
(2) makes possible the activation of a
previously acquired mycosis that has been
latent or arrested. Some of these infections
are iatrogenic, as a consequence of the
administration of potent therapeutic agents
and the increasing use of surgical or semisurgical procedures that provide an unusual
portal of entry. Opportunism is also afforded
by metabolic and neoplastic diseases, as well
as by prolonged debilitating illness. The
most important part of the definition relates
to the presence of a major abnormal host
condition. Some of the fungi that rarely
produce disease in normal man do produce
infection in persons who seem to be normal
by available clinical evaluation and laboratory testing. Both the aspergilli and some
of the phycomycetes are in this category.
Aspergillosis and subcutaneous phycomycosis are encountered in apparently normal
persons. On the other hand, most Aspergillus
infections in man arise in the presence of a
major host abnormality, and this applies to
mucormycosis among the phycomycoses.
We have selected a small group of patients with species-identified aspergillosis to
illustrate the pathogenetic spectrum of the
infection insofar as it can be determined
from clinical, mycologic, and pathologic
studies. With this purpose in mind, the
case reports that follow are reduced to those
data which we believe to be pertinent to the
host-parasite relationships. Essential data
are listed in Table 1.
R E P O R T OF CASES
Case 1
0 . T., a 59-year-old woman, developed
progressive weakness, left lower chest pain,
and somnolence in July 1960. In August, a
small furuncle appeared on the right side of
the face and rapidly enlarged. A second
furuncle appeared above the left eye 1 week
later. She was admitted to Charity Hospital
in September 1960. Laboratory study
revealed a severe anemia attributable to
acute myelogenous leukemia. She was
treated with prednisone, prophylactic penicillin, and chloramphenicol. Chest x-rays
at the time of admission and 1 week prior
to death revealed no pulmonary abnormality. Physical signs of a left upper lobe pneumonia appeared 3 days before death and
were confirmed by chest roentgenogram.
Repeated blood, urine, and sputum cultures
were negative for significant pathogens.
She died on September 28, 1960.
Necropsy revealed multiple nodules in
the right lung. The left upper lobe was
completely consolidated and contained numerous red nodules with central necrosis.
Scattered nodules of a similar nature were
present in the left lower lobe. Histologically,
all areas were either Aspergillus lung abscess
or Aspergillus pneumonia. A typical abscess
about a central hyphal mass is illustrated
in Figure 1. Invasion of the blood vessels
was frequent. Culturally, all areas gave
rise to pure cultures of Aspergillus fumigatus.
This case represents an example of one of
the increasingly common associations between lymphomatous and leukemic disease
and aspergillosis. Although no antimetabolites or myelodepressive drugs were administered, the reticuloendothelial system
was extensively altered by the leukemic
process. Host factors were such that multiple
antibiotics and corticoid therapy in large
doses was sufficient to permit rapid invasion
and growth of an opportunistic fungus
which manifested no clinical evidence of its
presence until 3 days prior to death. A.
fumigatus was highly pathogenic in this
patient, probably being the immediate
cause of death. No definite portal of entry
was found, and it is entirely possible that
the Aspergillus did not enter the respiratory
tract until a few days before death. The
situation would seem to be similar to that
demonstrated by Sidransky and Friedman 6
in mice treated with antibiotics and cortisone.
Case 2
R. D., a 23-year-old man, first developed
pneumonia at age 8. Resolution was delayed
24
SEABURY AND SAMUELS
and accompanied by the production of
large amounts of green sputum. Sickle cell
disease was first recognized at age 12.
There was a subsequent history of repeated
attacks of pneumonia for which he was not
hospitalized. In October 1951 he was admitted to Charity Hospital at age 23 because of right lower lobe pneumonia. He was
febrile and had a leukocytosis of 26,800
per cu. mm. Treatment with sulfonamides
was complicated by sickle cell crisis.
In December 1954 he was readmitted
with the same complaints and x-ray findings
as were present in 1951. X-ray of the chest
in January 1955 revealed persistence of
the right lower lobe density despite treatment with penicillin and streptomycin.
Numerous sputum specimens and bronchial
washings were negative for mycobacteria,
malignant cells, and pathogenic fungi
(including aspergilli). When cavitation appeared in the area of pneumonitis, it was
decided to resect the right lower lobe.
The resected lobe contained a 5-cm.
cavity that was filled with friable material
within a firm wall. Fibrosis, bronchiectasis,
and chronic bronchitis were present elsewhere in the removed lobe. A portion of the
cavity and underlying lung was removed
aseptically and sent in a sterile container
to the laboratory. Cultures were negative
for bacteria, but all gave rise to a pure
strain of A. fumigatus. Histologic sections
of the cavity wall and adjacent lung revealed
a heavy mycelial mat lining the cavity and
extending into but not beyond the cavity
wall. Histologic appearance suggested that
the Aspergillus was saprophytic within the
abscess. Figure 2 illustrates the relation of
the fungus to the abscess wall.
Antibiotic administration was never prolonged and no corticoids were ever administered. We believe that this represents a
bronchiectatic abscess of bacterial origin in
which the saprophytic presence of an
Aspergillus was related to the chronic
bronchitis and bronchiectasis rather than to
prolonged antibiotic treatment.
Case 8
E. F., a 24-year-old man, developed diabetes mellitus in November 1951. During
Vol. 40
the autumn of 1954 his diabetes became
difficult to regulate, he began to lose weight,
and fever developed. A chest roentgenogram revealed an area of pneumonitis and
cavitation in the anterior segment of the
right upper lobe. This was believed to be a
lung abscess, and no specific organisms were
cultured. The immediate response to treatment with penicillin was good, but he had
numerous short episodes of acute respiratory
infection after his discharge. Fever, productive cough, and right anterior chest pain
recurred in August 1955. Chest x-rays
revealed the same abscess cavity in the
anterior segment of the right upper lobe.
The right upper lobe was not resected until
March 1956. The abscess cavity measured 6
cm. in diameter.* The cavity communicated
with an anterior segmental bronchus and
its wall was composed of glistening, tough
material. No fungous ball was present.
Cultures from the cavity revealed a pure
strain of Aspergillus flavus. Microscopic
study demonstrated a mycelial mat lining
the abscess cavity, with numerous extensions of the hyphae into the subjacent lung,
which contained nonspecific inflammatory
tissue.
In our opinion, this lung abscess differs
from that of Patient R. D., inasmuch as the
role of the Aspergillus is not positively
purely saprophytic. It is unlikely that A.
flavus was responsible for the original
formation of the abscess, but the fungus
had penetrated beyond the abscess wall at
the time of resection and the lung showed an
inflammatory reaction to invasion. Poorly
controlled diabetes may have contributed
to the presumed transformation from
saprophyte to pathogen. Inasmuch as this
patient was a medical technologist with
long-standing asthma, these factors may
also have been important.
From 1956 until 1961 this patient was
completely asymptomatic except for difficulty in controlling his diabetes. In September 1961 a routine chest x-ray revealed a
thin-walled cavity in the apex of the right
lung. No etiology could be found. Sputums
* We are indebted to Dr. Henry Ransom,
Lafayette, Louisiana, for the gross pathology and
tissue blocks.
F I G . 1 (upper). P a t i e n t 0 . T. Acute abscess and granulation tissue in t h e lung surrounding a central
hyphal mass of Aspergillus fumigatus. Hematoxylin and eosin. X 300.
F I G . 2 (lower). P a t i e n t R . D . Mycelial mat of A. fumigatus lining the wall of t h e lung abscess. H y p h a l
fragments can be seen in the cavitary wall, b u t did not penetrate it. Methenamine-silver. X 300.
25
26
SEABURY AND SAMUELS
and bronchial washings were negative for
aspergilli or other significant organisms.
He had received no antibiotics.
The right middle lobe and apical segment
of the right lower lobe were resected. There
was a very large cavity present with ropy
material lying within it. The pleura was
grossly thickened. A mycelial mat lined the
cavity throughout. The lung inferior to
the cavity was non-air-containing, and
there was no visible separation between
the middle lobe and apical segment of the
lower lobe. Figure 3 illustrates a section
taken from deep within the lung inferior to
the cavity. Hyphae had penetrated well
beyond the cavity, and the Aspergillus is
here seen to be clearly invasive.
There has been no evidence of recurrent
infection in a 6-month period after surgery.
We believe that his diabetes and occupation
as a medical technologist were probably the
principal factors providing the opportunity
for Aspergillus infection; however, no
definite reason for the development of this
second abscess was evident clinically or
bacteriologically.
It might be suggested that the early
parasitism evident in the sections of the
first abscess was the real explanation for the
development of the abscess 5 years later. It
might be argued that the Aspergillus
remained dormant only to become active
later and invade. If this were true, the
second episode would represent either
"primary secondary" aspergillosis or "secondary primary" aspergillosis, depending
upon one's state of confusion. Culture from
the abscess and underlying right middle lobe
revealed that this clearly invasive Aspergillus was Aspergillus niveus, an entirely
different species. Consequently, there is no
relation between the first and second
episodes of aspergillosis other than the host
susceptibility. We are unaware of any
similar case report.
Case 4
L. C , a 24-year-old man, had an abnormal
survey chest x-ray in 1957. In February
1958 severe bilateral uveitis appeared and
required hospitalization. The ocular findings
Vol. 40
were regarded as compatible with Boeck's
sarcoidosis, and bilateral pulmonary infiltration was present. Skin tests for tuberculosis and fungi were negative. Numerous
sputum cultures were negative. Axillary
lymph node biopsy revealed reactive hyperplasia with a small granuloma containing
giant cells. No specific diagnosis could be
made. His uveitis responded to topical
corticoids, but relapsed when they were
discontinued.
Cough and blood-streaked sputum developed in May 1959, and were followed by
chills, fever, night sweats, and weight loss.
Sputum cultures were negative for Mycobacterium tuberculosis, significant pyogens,
and all fungi other than Candida. Skin
tests for fungi and tuberculosis were again
negative. He became afebrile during 11 days
of treatment with prednisolone and was
then discharged. Symptoms recurred almost
immediately and became progressive.
He was readmitted to Charity Hospital
on August 19, 1959. Chest x-rays revealed
bilateral peripheral cystic changes with
pericystic infiltration. Hilar lymphadenopathy was obvious. He was emaciated and
anemic. Sputum cultures were repeatedly
positive for hemolytic Micrococcus aureus,
which was thought to be the primary cause
of his fever. Candida was still present in
the sputum. Complement-fixation studies
at this time were positive for histoplasmosis
in a dilution of 1:64. Treatment with penicillin, chloramphenicol, and erythromycin
did not alter his clinical course. Drill biopsy
of the lung, entering one of the peripheral
cysts, revealed a non-specific granulomatous
reaction, and A. fumigatus was isolated by
culture of the biopsy material. He died on
October 6, 1959.
Necropsy revealed pulmonary aspergillosis with intracavitary hemorrhage. There
was miliary aspergillosis of the kidneys,
liver, and spleen. The basic pulmonary
infiltrate was regarded as the result of
sarcoidosis, and the hilar and aortic lymph
nodes were histologically compatible with
Boeck's sarcoid. Necropsy cultures were
positive for A. fumigatus. No histoplasma
were isolated, and none was seen by means
of periodic acid-Schiff stains. Figure 4
, -41
'fL
F i o . 3 (upper). P a t i e n t E . F . A section of lung several centimeters inferior to the cavity in
the middle lobe. H y p h a e of Aspergillus niveus are numerous. Methenamine-silver. X 450.
F i o . 4 (lower). P a t i e n t L. C. Internal margin of a peripheral cystic lesion of the lung with
the conidiophore, vesicle, sterigmata, and spores of Aspergillus fumigalus. Hematoxylin and
eosin. X 450.
27
28
SEABURY AND SAMUELS
illustrates a vesicle with conidia in a lung
cyst.
The administration of multiple antibiotics
and a brief course of prednisolone may have
been important in the pathogenesis of
aspergillosis. The peripheral pulmonary
bullae were typical of those seen in advanced
sarcoidosis and offered considerable opportunity for infection to any organism which
might have been present in the bronchial
tree. If one assumes that the initial infection
of the bullae with A. fumigatus was essentially a saprophytic relation, then the subsequent invasion and dissemination might
reasonably be attributed to multiple antibiotic therapy, malnutrition, anemia, brief
corticoid therapy, and those unknown altered host factors which may be produced by
extensive sarcoidosis. Invasion of blood
vessels by the hyphae of Aspergillus was
evident histologically and probably related
to the persistent hemoptyses.
Case 5
R. C , a 42-year-old woman, developed
pharyngitis, malaise, and fever of 3 weeks'
duration without medication. She was then
treated with penicillin for 2 days. Two days
later a universal erythematous rash appeared; she became irrational and was admitted to Charity Hospital. She was semicomatose, incontinent, and completely
irrational. Slight erythema of the left tympanic membrane, meningismus, and enlarged
and hyperemic palatine tonsils were present.
Spinal fluid was normal and blood cultures
were negative. She became increasingly
febrile and developed swelling of the right
side of the neck. Treatment with oxytetracycline, streptomycin, and 22 days of cortisone acetate altered neither her febrile course
nor her clinical deterioration. The spinal
fluid was re-examined, skin and muscle
biopsies were obtained, and a search made
for L.E. cells. None of these studies was abnormal. She gradually became afebrile and
was discharged on the 46th hospital day.
Two months later she developed enlargement of the left pupil and marked loss of
visual acuity, 0 . S. Left retro-orbital pain
developed and increased during the following months. Papilledema was observed.
Vol. 40
Readmission to the hospital for numerous
studies revealed only an irregular enlargement of the left optic foramen and some
slight decrease in filling of the right lateral
ventricle by pneumoencephalogram.
Orbital symptoms progressed and exophthalmos on the left became measurable. A
carotid angiogram was normal. Orbital exploration was unrevealing.
Four months later she developed motor
aphasia and right hemiplegia. At the time
of readmission the spinal fluid was under
increased pressure, contained 6 cells per cu.
mm., and manifested a paretic colloidal gold
curve. Cerebral angiography revealed a block
in the left internal carotid. The patient died
shortly after left frontal lobectomy with excision of a brain abscess.
Histologic examination revealed a granulomatous lesion of the brain, containing giant
cells, multiple small abscesses in which there
were numerous branching septate hyphae.
A portion of one of the abscesses is illustrated in Figure 5. Multiple cultures from
the brain and abscess grew out a pure strain
of A. fumigatus.
Necropsy revealed an additional lesion in
the left parietal area with erosion of the anterior clinoid process and destruction of the
optic chiasm. Aspergillus was found invading the cavernous sinus and this was believed to be the initial intracranial focus. No
lesions were found in the lungs, liver, or
spleen.
The lesions in the brain were granulomatous and did not suggest pyogenic bacterial origin. The symptoms which prompted
her initial admission to the • hospital may
have been the result of a penicillin reaction.
Nevertheless, the semicomatose state, incontinence, irrationality, and meningismus lead
one to suspect that cerebral aspergillosis
may have been present before cortisone or
any broad spectrum antibiotics were administered. The clinical course suggested the
cavernous sinus was involved relatively
early. There was no underlying metabolic
or neoplastic disease. The Aspergillus was
highly pathogenic. The clinical course makes
us unwilling to regard this as an opportunistic fungous infection related to either broad
7>#
F I G . 5 (upper). P a t i e n t R. C. Central portion of a chronic brain abscess with hyphae of Aspergillus
fumiqalus in a septum of the cerebrum traversing t h e cavity of the abscess. Hematoxylin and eosin.
X 300.
F I G . 0 (lower). P a t i e n t L. J. Section of the right orbital mass witli septate hyphae of Aspergillus
flavus surrounded by a liistologic reaction t h a t consisted chiefly of dense fibrotic tissue. Periodic acidSchiff. X 584.
29
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SEABURY AND SAMUELS
The Aspergillus seemed to behave much as
in the preceding case. It was pathogenic but
very slowly invasive and of low virulence.
This case also illustrates the fallacy of identifying all aspergilli isolated from human
tissues as A. fumigalus.
DISCUSSION
Species of the genus Aspergillus are very
common in our general environment. The
nature of their spores is admirably suited to
aerial dissemination. They are common and
annoying laboratory contaminants. These
saprophytes are common in soil and upon
vegetation of various sorts. In one way or
another, man must come in contact with the
aspergilli with great frequency, yet visceral
aspergillosis is a relatively rare disease in
man. A. fumigatus and A. niger have been
recognized as potentially pathogenic to
birds and mammals for many years. Unfortunately, there are many instances in
which A. fumigatus or A. niger were reported
as human pathogens without the tedious
cultural study necessary for species identification.
As medical mycology has improved, it has
become evident that human pathogenicity
is not restricted to A. fumigatus and A. niger.
Indeed, there is one report7 of concurrent infection by 3 species of Aspergillus in a single
host. A. flavus is being isolated with increasing frequency from human aspergillosis. We
do not believe that this is attributable to any
biologic change in A. flavus. Aspergilli found
in cultures of biopsy or necropsy specimens
should not be discarded as contaminants until careful microscopic study of properly
prepared sections demonstrates an absence
of hyphal elements morphologically compatible with these fungi. If histopathology
and cultures indicate the presence of an
Aspergillus, the isolate should be submitted
to a competent mycologist for identification of species. If this were done routinely,
it is probable that additional species of
Aspergillus would be added to the list of
facultative parasites.
Although the aspergilli lead much the
same free-living, saprophytic existence as
Coccidioides and Histoplasma, they are not
as restricted geographically and produce
recognized human disease much less fre-
Vol. 40
quently. They manifest no dimorphic
adaptability to tissue existence.
The aspergilli have a low order of infectivity and seem to be an excellent genus for
the study of host factors permitting infection. In severely debilitated patients who
may have been moribund for days, necropsy
sometimes reveals aspergilli forming small
abscesses with peripheral hyphal extension
into air sacs or bronchioles. Fructification
has been seen under these circumstances. In
such patients the Aspergillus is undeniably
pathogenic, but only because of the severely
altered host resistance. The bacterial population in such abscesses and the occasional
finding of other fungi, such as Candida, in
association with the aspergilli strongly suggest that these abscesses are caused by
aspiration.
The statistical relation of severe diabetes
to fungous infections is well known. The observations of Sheldon and Bauer 5 on cutaneous mucormycosis in rats made acutely
diabetic and acidotic by alloxan are probably
equally applicable to Aspergillus infection in
severely diabetic man. They observed that
acute alloxan diabetes with acidosis in rats
inhibited the normal function of mast cells,
delayed and decreased inflammatory response to the fungus, and permitted rapidly
progressive and invasive fungous growth.
Sidransky and Friedman 6 demonstrated
beautifully the marked infectivity and virulence of inhaled A. flavus spores in cortisonized and antibiotically treated mice; this
condition was entirely absent in similarly
exposed normal mice. Similar experimental
studies on fungous infection have been made
in relation to leukemic animals and those
with reticuloendothelial systems damaged by
therapeutic agents used in the treatment of
cancer.
Our patients Avere selected to illustrate the
variable relation which the common saprophyte, Aspergillus, may have to human disease. Patient 0. T. had many host factors,
especially acute leukemia, permitting the
invasion and rapid extension of an Aspergillus which probably did not infect until a
very few days before death. Patient R. D.
had a chronic lung abscess and bronchiectasis. The Aspergillus probably entered this
cavity during ventilation and continued to
July 1963
33
ASPERGILLOSIS
pursue a purely saprophytic existence. The
same basic relation probably existed initially
in Patient E. F.; however, he had a disease
(asthma) which promotes obstruction of the
smaller airways, and distal infection. His
diabetes was severe. Under these conditions,
tlie saprophytic Aspergillus began to invade
the lung beyond the abscess wall during his
first illness and was much more invasive
during the second. These 2 observations suggest that patients with cavitary lesions containing fungous balls should certainly have
the lesions resected, if possible, in the presence of any major host abnormality which, in
itself, would not produce death within several years.
Patient L. C. had well established sarcoidosis before developing aspergillosis.
Although the association of aspergillosis
with Boeck's sarcoid has been previously reported,3 there is no statistical evidence
at present to implicate sarcoidosis as a major
host abnormality for opportunistic infection
by aspergilli. It is more likely that anemia,
malnutrition, multiple antibiotic therapy,
and brief treatment with prednisolone were
tlie factors creating the opportunity for invasion and dissemination.
Patient R. C. can not be said to have had
an opportunistic fungous infection. Although
she received multiple antibiotics and cortisone for several weeks, the clinical and
pathologic evidence suggest that infection
with Aspergillus may have occurred before
treatment. Progression and extension of her
infection may have been augmented by
drugs.
Patients L. J. and D. P. were both free
from any host abnormalities known to predispose to fungous infection. Mechanical
factors may have been present in the case of
Patient D. P. It is intriguing that in this
milieu Patient L. J. harbored her disease for
17 years before succumbing to it, and Patient D. P. died from other causes after 16
years of infection.
SUMMARY
1. Seven patients with culturally identified aspergillosis have been presented to illustrate some of the host-parasite relations of
Aspergillus in man.
2. The aspergilli are common saprophytes
which may, as they did in one of our patients,
enter the human body and continue a purely
saprophytic existence.
3. Aspergilli may begin their life in man as
saprophytes, becoming parasitic and pathogenic if the presence of major host abnormalities creates the opportunity for invasion.
4. The aspergilli, although ordinarily
saprophytic, are facultative parasites which
may produce disease in man in the absence of
host factors known to predispose to infection.
SUMMARIO I N I N T E R L 1 N G U A
1. Es presentate septe casos de aspergillosis de identification cultural pro illustrar
certes del relationes inter hospite e parasite
que es characteristic de Aspergillus in le
homine.
2. Le aspergillos es commun saprophytes
que pote, como illos lo faceva in facto in un
de nostre patientes, entrar in le corpore
human e continuar un existentia purmente
saprophytic.
3. Aspergillos pote comenciar lor vita in le
homine como saprophytes e postea devenir
parasitic e pathogene si le presentia de
major anormalitates del hospite crea le opportunitate pro un invasion.
4. Le aspergillos, ben que ordinarimente
saprophytic, es parasites facultative que pote
causar morbiditate in le homine in le absentia de factores de hospite que cognoscitemente predispone al contraction de infectiones.
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