FUNGAL DISEASES:
A SERIOUS THREAT TO HUMAN EXISTENCE IN
RECENT TIMES
BY
PROF. JOSEPHINE IFEYINWA OKAFOR
1.1
INTRODUCTION
It is with joy and in thanksgiving to God and also to the
University Administration for giving me this opportunity to
deliver my inaugural lecture today to this distinguished
audience.
My area of specialization is Medical Microbiology with
special interest in Medical Mycology which is the study of
fungi that cause diseases in man. For about thirty years, I
have carried out extensive research on fungi and also taught
my students all that I learnt and discovered about fungi
which are responsible for many diseases of man. During all
these years, I have also learnt that fungi have shifted their
position from being agents of non-significant human
diseases to agents of serious and life-threatening human
diseases.
Unfortunately, many people including those in medical
profession, particularly in the developing countries like
Nigeria, are yet to be convinced that fungi are major causes
of morbidity and mortality in the world today. I have,
therefore, decided to give this public lecture in order to
inform people of Nigeria in particular that fungi are indeed
responsible for many fatal diseases of man.
1
1.1.1 What are fungi?
They are a group of non-photosynthetic micro-organisms
which live as saprophytes in the soil and on dead organic
matter or as parasites of plants and animals including man.
Fungi are found everywhere: in the soil, in decaying
vegetation, in the air and in the waters. They are seen to
grow on foods (bread, cooked food), damp clothes, wet
walls, house roofs, damp leather materials (shoes, bags,
boxes) and even in harsh environments like hot desert soil,
hot spring waters, snow fields, hot compost pits and bottom
of deep waters (oceans, seas, great lakes) with very low
temperatures and high pressures and also in the
refrigerators. They also form part of the microbial flora of
both outside and inside of living organisms including man,
animals and plants.
Most fungi produce spores in large numbers which are
useful for their survival and distribution. The spores are
usually light and so can remain floating in the air for long
periods and often blown for a distance of about 500km by
strong winds. From the air, they are forced into houses
through suction mechanism or into the exposed human
tissues (cuts in the skin) and into the nose during breathing.
Most fungi are microscopic multi-cellular filaments,
consisting of septate or non-septate hyphae while a few are
unicellular in form (yeasts). A few are macroscopic in size
(mushrooms).
2
1.1.2 Nutrition in fungi
Every living organism requires energy for its metabolic
activities (growth, movement, reproduction). Fungi, being
non-photosynthetic organisms, obtain their energy by
feeding saprophytically on dead organic matters which
contain high energy compounds (carbohydrates) or
parasitically on living organisms which contain stored
energy compounds (sugars, proteins, fats) in their tissues.
Their parasitic activities cause a lot of damage to their
hosts and these actions often give rise to different types of
diseases of plants and animals including man.
1.1.3 The beneficial roles of fungi
Fungi, as saprophytes, are very useful to man in many
ways:
i)
They are important in the decomposition of huge
organic matters that are regularly formed within the
environment and which after decomposition, serve as
food for the living plants.
ii) They are important in the recycling of inorganic
substances (potassium, sodium, calcium etc.) which
are trapped in the dead organic matter and then make
them available to living plants.
iii) They are important in the production of fermented
foods, wines, alcohols, and acids in homes and
industries.
3
iv) Some of them produce antibiotics (penicillin) as part
of the products of their metabolic activities, which are
useful in the treatment of some diseases of man.
1.1.4 The defence mechanisms against fungal invasion
of the human tissue
The human body is constantly putting up strong resistance
against any organism including fungi that tries to gain entry
into the tissue to feed and live in it. This body defence is a
combined action of many components of the body known
as “immune system.”
The first line of defence consists of the protection by the
skin and mucous membrane. The skin which covers the
outer body of man and the mucous membrane which covers
the mouth, nose and exposed part of the female genital
organ, as long as they are intact, provide protection against
most pathogenic fungi that constantly attempt to enter the
human tissue.
There are also as part of this defence, a group of microorganisms that include fungi, bacteria and protozoa which
are known as “microflora”, “microbiota” or “commensal
organisms,” which colonize the skin and mucous
membrane. They feed on substances that are excreted from
the body without causing any harm to the host and remain
there throughout the life of the host, preventing the
establishment of other organisms including the pathogenic
ones.
The second line of defence consists of two major
components of the immune system, namely B-lymphocytes
4
and the T-lymphocytes which play key roles in destroying
these fungi. Any cut on the skin and membrane (knife cut,
surgery, gun shot, nail or thorn prick), will allow fungi (and
other micro-organisms) to enter the tissue. However, the
normal immune system, particularly in healthy individuals,
will prevent the establishment of these fungi.
The B-lymphocytes produce different types of soluble
substance called “antibodies” (IgA, IgG, IgM, IgE, IgD)
which are capable of destroying many micro-organisms
including fungi. The T-lymphocytes, also known as T-cells,
are of different types: T helper (CD4), T cytotoxic, T
suppressor, and T delayed cells; and they have various
functions in the elimination of the invading organisms. T
helper cells are the most important of the T cells for they
have multiple functions including helping in the maturity of
B-lymphocytes and stimulating T cytotoxic cells to destroy
micro-organisms and tumour cells.
There are also a group of other immune cells called
“phagocytes” (white blood cells, macrophages) or “cell
eaters” which singly or in combination with some T cells
destroy large numbers of organisms in the tissue in a
process called “phagocytosis.”
1.1.5 Establishment of fungi in the human tissue
Despite the immune defence that operates within the
human tissue, some pathogenic fungi are still able to enter
the tissue, establish there, and cause various diseases in
man due to the following:
5
i)
They are capable of producing various substances
which include enzymes and toxins that they use in
destroying human tissues.
ii) Some of them possess protective coats (capsules)
which prevent their being engulfed and destroyed by
phagocytes.
iii) Regular and prolonged use of some drugs, including
antibiotics often reduce the effect of the immune
system and so allow the establishment of some
pathogenic fungi.
iv) Some micro-organisms (viruses) are able to attack
some of the immune cells and so prevent them from
playing their role in tissue defence.
1.1.6 Classification of fungal diseases (Mycoses)
Fungal diseases, also called “mycoses,” are classified
according to the degree of tissue involvement and mode of
entry into the tissue. These are:
Superficial or cutaneous mycoses
Subcutaneous mycoses
Deep or systemic mycoses
Opportunistic mycoses
1.2
SUPERFICIAL MYCOSES
These are fungal diseases which are limited to the
outermost part of the body (skin, mucous membrane, nails
and hair). Some important superficial mycoses are:
i)
Dermatophytosis: A group of fungi collectively called
dermatophytes are known to attack the outer layer of
6
the skin including the hair and nails to cause
superficial lesions on the skin known as ringworm or
tinea. Ringworm disease was initially thought to be
caused by worms and that was how the disease got the
name. It was only after some researchers identified
some fungi as being the cause of this disease that fungi
were added to the list of agents of diseases in man.
Ringworm disease is common in children and it is
usually seen as scaly lesions on their head. In most
cases, children overgrow this disease since it often
heals spontaneously without treatment. In adults the
lesions are usually on the skin, feet (athlete’s foot),
groin, beard, or nails. The disease may be chronic but
not serious and also does not go beyond the upper part
of the skin. This disease is very common in this
country. We have published some of our work on
dermatophytosis, particularly among children in
Nigeria.
ii)
Superficial candidiasis: Candida, a species of the
group of unicellular fungi which are called yeasts,
normally form part of the microflora of the human
body and live on waste products of the body without
causing any harm to the host tissue. However, under
certain conditions in the human body, this “commensal
organism” may become an “opportunistic pathogen”
sometimes growing out of proportion to produce
superficial lesions on the skin and mucous membranes
particularly in infants, old people, pregnant women,
diabetics and women on oral contraceptives. Many of
you are familiar with some common diseases such as:
diaper rash in infants
7
oral thrush (membranous white growth) on the
tongue of infants, diabetics and old people
white growth or discharges often from the genital
organs of diabetics, pregnant women or those on
oral contraceptives.
These diseases are usually caused by Candida. In most
cases the lesions remain at the superficial part of the
body, not serious but may be chronic, causing a lot of
discomfort if not treated. In some of our studies, we
identified Candida as a normal flora of the skin of
healthy individuals. We also found them to be
responsible for skin rashes and oral thrush in infants as
well as vaginal candidiasis which is very common
among women in this country.
iii) Tinea versicolor (“ngwo” in Igbo): This is also caused
by a species of the yeast called Pityrosporum. The
lesions appear as patches of discolouration of the skin
particularly on young adults. This is a common
disease which we are familiar with. In some of our
studies we were able to isolate this fungus from some
patients and also identified some of the factors that aid
its pathogenicity.
Other superficial mycoses are caused by spores of fungi
found floating in the air which manage to enter the
superficial area of the body. Some of them can cause
superficial lesions in the external part of the ear or on the
cornea of the eye but these diseases are not serious
mycoses and can be easily treated.
8
1.3
SUBCUTANEOUS MYCOSES
These are fungal diseases that are limited mostly to the
tissue just below the skin which is the dermis but they
rarely affect the deeper tissues. Some important ones are:
i)
Basidiobolomycoses. This disease is caused by a
fungus called Basidiobolus. The organism exists
naturally in the soil, decaying vegetation and also as
part of the microflora in the intestine of reptiles
(lizards, wall gecko) and amphibians (toads, frogs).
The spore enters the tissue of man through cuts in the
skin, grows slowly to produce a hard and enlarged
lump under the skin, often in the legs and arms. The
disease, if not treated may spread to the deeper tissue
sometimes affecting vital organs. In some serious
cases amputation of the affected limb is carried out to
avoid the spread to vital organs like brain which will
result in death of the patient.
ii)
Conidiobolomycosis. This disease is caused by a
fungus called Conidiobolus and it is in the same class
of fungus as the Basidiobolus. It exists naturally in the
soil and decaying plant vegetation. The spore of this
fungus is believed to gain entry through a cut likely in
the area of the nose of man where it grows slowly to
produce a hard and enlarged lump under the skin. As
the disease progresses, it causes excessive
inflammation of the nasal area including the nose,
upper lip and part of the upper face so that the patient
9
eventually looks like a monster. The inflammation
may eventually cause blockage of the nasal passage to
prevent breathing through the nose. Death may occur
if the disease is not well treated.
My M.Sc. and Ph.D. research work were mainly on these
two fungi. In the first part of this work, I identified the
prevalence of Basidiobolus in soil (including river sand),
plant vegetation and in the intestinal tracts of animals
(lizards, toads, turtle, wall gecko) both here in Nigeria and
also in Florida in the United States of America where I did
part of my work. The high prevalence of this fungus within
these different environments, shows a high possibility of
the spore entering the tissue of any body with a cut in the
skin. This also explains why we have many cases of
basidiobolomycosis especially in children in the tropical
areas of the world (where we have the majority of the
reported cases) who often play outside (with cuts not
usually taken care of). This disease occurs mostly in
children in rural areas where it is often treated successfully
by native doctors who simply remove the fungal lump
under the skin. However, in few cases especially where the
lump is in the neck area, the organism may spread to the
brain to cause death of the patient even when the patient is
undergoing medical treatment.
10
Figure 1: Right picture is a plate culture of Basidiobolus sp.,
which is cream coloured and shows radial furrows. It has been
isolated from African lizard (Agama agama). Left picture shows
conidia from a young culture of Basidiobolus sp. as seen under
the microscope, X375.
Figure 2: Scanning electron micrograph of Basidiobolus
haptosporus showing primary globose conidium and a slender
conidiophore, X1200.
11
Figure 3: A typical clinical picture of
Basidiobolus infection causing massive
subcutaneous swelling of the thigh.
Conidiobolomycosis, although it is a more serious disease
than basidiobolomycosis and is also prevalent in the soil
(including river sand), appears to be rare even in Nigeria
which is a tropical country. However, we were able to
identify one case recently at the University of Nigeria
Teaching Hospital (UNTH), Enugu. I can also recall that
over thirty years ago while I was still in the college, I saw a
man with features of this disease who was consulting a
medicine dispenser in one of the villages in Enugu State.
We have tried to make inquiries on the existence of this
disease in some villages in Enugu, Abia and Ebonyi States
but so far we have not identified any. This paucity of
identified cases may not necessarily mean that the disease
does not exist in Nigeria, but may be due to poor diagnosis
and poor record keeping in hospitals. It is also possible that
patients with this disease often consult native doctors since
12
such weird diseases are usually attributed to poison by
enemies or evil forces.
Figure 4: Conidia of Conidiobolus coronatus isolated
from Nigerian soil.
13
Figure 5: Typical clinical pictures of
rhinoentomophthoromycosis caused by Conidiobolus coronatus.
Note the subcutaneous swelling on the face.
1.4
DEEP OR SYSTEMIC MYCOSES
These are fungal diseases that affect deeper tissues
including the muscles, bones, and body organs (lungs,
liver, kidney, heart, and brain). Some important ones are:
i)
Maduromycosis (mycetoma). This is caused by a
variety of soil-borne fungi. The disease occurs when
the spore of any of these fungi enters the tissue
through a cut especially in the leg or hand, germinates
and develops into a typical form. A typical form of the
disease is characterized by excessive enlargement of
the affected part which is followed by massive
destruction of the affected tissue including the muscles
and in severe cases, the bones. As the disease
progresses, a large amount of pus is produced which
contains the fungus in the form of coloured granules
(“sulphur granules”) oozing out through openings in
the cracked skin. This disease is common among
outdoor workers, particularly in developing countries
(including Nigeria) where protective shoes and gloves
are not worn especially during farming. In severe
cases, other organisms including bacteria may also be
involved and this often leads to rapid spread of the
organisms towards vital organs which may sometimes
require amputation of the affected limb so as to
prevent death of the patient. Cases of mycetoma are
very common in Nigeria and we recently identified a
case at UNTH, Enugu. In the course my teaching of
14
mycology I have continued to isolate various species
of fungi responsible for mycetoma from the soil with
ease and these are what we use for the students’
mycology practical lessons.
ii)
Dimorphic fungi involved in respiratory diseases.
Dimorphic fungi are a group of fungi that can exist in
two morphological forms (unicellular forms or
filamentous forms) which often help them to live as
parasites in one form and as saprophytes in another
form. As parasites, they often cause serious respiratory
diseases similar to tuberculosis. These fungi occur as
saprophytes in the soil where they grow as filaments
and produce numerous spores that can be inhaled by
man. The spores, if not destroyed in the human tissue,
will germinate to develop into the parasitic form
which may be a yeast form (as is the case in
Histoplasma and Blastomyces) or in the form of
endospores (as is the case in Coccidioides). In healthy
individuals who have active immune system
(“immunocompetent” individuals), the inhaled fungal
cells are often destroyed by the immune cells and so
the disease fails to occur. However, in individuals with
defective immune system (“immunocompromised”),
the fungal cells will grow to attack the lung tissue and
from there may spread to other vital organs. Whenever
these fungi are left to spread uncontrollably, as many
as 90% of the affected patients often die of the fungal
invasion of the vital organs.
15
Figure 6: Maduromycosis (mycetoma) of the right leg. Note the
swelling with induration of the subcutaneous tissue. (Courtesy of
Dr. E. R. Ezeome, Department of Surgery, UNTH, Enugu)
Figure 7: Maduromycosis. This is the surgical excision
specimen from the patient in Figure 6. Note the whitish fibrotic
lesion destroying the subcutis and skeletal muscle and which
contains the characteristic yellow granules (“sulphur
16
granules”) of the fungal elements. (Courtesy of Dr. O.C.
Okafor, Department of Morbid Anatomy, UNTH, Enugu)
1.5
OPPORTUNISTIC MYCOSES
Healthy individuals with active immune system which
helps them to resist fungal invasion of their tissues are said
to be “immunocompetent individuals.” However,
individuals whose immune system is defective, such that
they are not able to resist fungal spread are said to be
“immunocompromised individuals”. Some important
factors
that
lead
to
the
development
of
immunocompromised state in some individuals include:
i)
immature or genetically inherited defective immune
system
ii) long therapy (use) of antimicrobial antibiotics
iii) prolonged use of immunosuppressive drugs
particularly in patients who received organ transplant
(to prevent rejection of transplanted organ)
iv) debilitated disease conditions including diseases like
diabetes mellitus, tuberculosis, cancer, and acquired
immunodeficiency syndrome (AIDS).
As a result of a significant increase in the number of
immunocompromised individuals in the past one or two
decades, fungal diseases which earlier on did not constitute
any serious problem to man have now become important
causes of morbidity and mortality in man. The death rate
due to fungal diseases is alarming and so needs to be
addressed. A number of fungal diseases are now in the list
of life threatening mycoses and they include:
i) Systemic candidiasis
17
ii)
iii)
iv)
v)
vi)
vii)
viii)
ix)
Cryptococcosis
Trichosporonosis
Invasive aspergillosis
Invasive mucormycosis
Histoplasmosis
Coccidioidomycosis
Blastomycosis
Mycotoxicosis
2
SYSTEMIC INFECTIONS
2.1
CANDIDIASIS
Candida is a unicellular fungus and it is normally a
member of the microflora of the body including the gut and
intestine. In these parts of the body they are known to coexist with other micro-organisms which include other fungi
and some “beneficial bacteria” in a manner that the growth
of each group is under control so that none is allowed to
grow out of proportion.
Various studies on the microflora of the body have shown
that the growth of Candida is controlled by other microorganisms that constitute the microflora (which is the case
under normal conditions). However, certain conditions may
cause a drastic change that can allow Candida in the body
to grow out of control and this will result in a disease
condition generally called candidiasis. There are a number
of conditions that can predispose a healthy individual to
have candidiasis and one of them is prolonged use of
antibiotics especially antibacterial antibiotics. In recent
times, development of resistance of some pathogenic
18
bacteria to the conventional antibiotics has forced
physicians to prolong the period of treatment and also use
different antibiotics to cure their patients. Unfortunately,
this long antibacterial therapy as well as the use of different
types of antibiotics have increased the chances of
eliminating both the pathogen as well as the beneficial
bacteria that co-exist with Candida and other yeasts in the
human body. This often results in an excessive proliferation
of Candida cells.
In developed countries, antibiotics are administered only
through doctor’s prescription but in developing countries
like Nigeria, there is no restriction to their purchase and
use. Hence, there is a serious abuse of the use of antibiotics
which allows untrained medicine sellers to administer
antibiotics to any one who requests for them. Also many
sick people easily self-administer antibiotics without
doctor’s prescription or laboratory tests. A very common
example of this uncontrolled use of antibiotics in Nigeria is
seen in the treatment of “typhoid fever” where patients
consume all kinds of antibiotics for weeks often without a
confirmatory test to prove that the patient actually has the
disease. Many such patients continue to feel sick despite
the prolonged antibacterial therapy and quite often they
develop serious complications.
This gross abuse and overuse of antibiotics has been found
to cause a serious elimination of most beneficial bacteria in
the gut and intestine and this is often followed by an
excessive growth of Candida. This uncontrolled growth of
Candida has given rise to a newly discovered and
challenging unhealthy condition called “chronic
19
candidiasis syndrome” or “leaky gut syndrome” (LGS). It
was discovered that Candida, during this excessive growth
in the gut, changes from its unicellular form to a mycelial
form. In this mycelial form, Candida appears as a “plantlike structure” and develops “root-like structures” called
“rhizoids” (long burrowing legs). The rhizoids hook into
and penetrate the mucous membranes into the gut to cause
serious bowel pains and distress. Later, the rhizoids burrow
right through the intestinal walls to produce “microscopic
holes” which will allow toxins, undigested food particles,
particularly digested proteins, yeasts cells and some other
micro-organisms to enter the bloodstream.
2.1.1 Leaky gut syndrome (LGS)
LGS is a common problem of modern society partly due to
abuse of antibiotics and other non-inflammatory drugs. The
gut, which is made up of both small and large intestines,
hosts many hundreds of different kinds of beneficial
bacteria as well as fungi and viruses. These bacteria are
important for healthy metabolism and immune response
within the human intestines. They use their enzymes to
transform the human and microbial wastes (bile, toxins,
chemicals etc.) before they are finally discharged from the
body. “Bile” which is found in the liver plays an important
role of elimination of many toxins that accumulate in the
liver. Bile is extremely caustic to large intestine epithelium
but the beneficial bacteria in the small intestine are able to
breakdown the bile salts into less caustic compounds before
they enter the large intestine. However, elimination of these
bacteria due to prolonged use of antibiotics will allow free
passage of bile from the small intestine into the large
20
intestine which will eventually cause serious damage to the
large intestine. Damage to the large intestine has been
found to be one of the causes of “colon cancer.”
Beneficial bacteria in the intestines also metabolise
hormones like “oestrogen” which are discharged from the
liver into the small intestine. Absence of these bacteria and
presence of leaky gut, allows the hormones to be
reabsorbed and carried to different parts of the body.
Excess oestrogen is known to bind to sensitive areas such
as the breast, uterus, and ovaries and this has been found to
contribute to fibrosis and tumours in these organs. These
tumours may sometimes become malignant (cancerous).
The damage to intestinal barrier due to LGS allows
absorption of partially digested food particles, toxins,
chemicals and micro-organisms especially Candida cells
into the bloodstream to different parts of the body. Candida
is known to produce 79 distinct toxins. Increased
absorption of “toxins” by the liver will place great stress
on this vital organ which may lead to liver inflammation
and toxic hepatitis. Some of the toxins will move to the
brain cells where they can be mistaken for
neurotransmitters to cause brain fog. Some will move to
the skin to cause rashes.
In immunocompromised individuals, Candida cells which
enter the bloodstream through the leaky gut will grow
profusely and eventually develop into systemic candidiasis
and so travel through the blood stream to other parts of the
body including the mouth, sinuses, throat, reproductive
organs, lungs, and heart. In most severe cases of systemic
21
candidiasis, the organism causes a type of blood poisoning
called “candidal septicaemia” or “candidaemia”. This will
cause the organism to invade every organ in the body
which in turn may result in death due to shock and renal
shut down. A high mortality rate of up to 40% has been
reported. The body defence system also attacks the
undigested food particles and produces antibodies against
them for future attack. This will result in the development
of allergic reactions to these food particles. Some
antibodies can give rise to autoimmune diseases in an
attempt to destroy any foreign matter.
What started as a gut barrier problem can escalate to a
serious problem of tissue toxicity and with time can cause
pains in the muscles and joints, brain fog, drop in energy
production and body temperature. This will result in
conditions such as:
Opportunistic infections
Arthritis
Brain fog, inability to concentrate
Chronic fatigue
Cancer (particularly of the liver, breast, ovary and
uterus)
Stressed immune system
Other causes of LGS include:
Consumption of allergic food
Radiation therapy
Alcohol (depletes N-acetyl glucoseamine) and caffeine
Excess sugar (leads to excess growth of yeast)
HIV infection
22
Excess stress
LGS is hardly tested for or diagnosed by doctors in general
practice especially in the developing countries. But its
effects are seen in many unrelated symptoms. Researchers
give it different names; for example Gibere calls it
“intestinal terrorist” while Gellend calls it “vicious cycle”.
Crook (1986; 1998) has written two popular books: “The
Yeast Connection” and “The Yeast Connection and the
Woman” in which he discussed the disturbing role of yeasts
in human diseases.
Figure 8: Pseudohyphae and a few yeast cells of Candida
albicans from growth in corn meal agar, X825.
2.1.2 Candida - Cause of diarrhoea in immunocompetent
individuals
23
Excessive growth of Candida in the guts of
immunocompetent individuals even in the absence of LGS
has also been found to cause chronic persistent diarrhoea
sometimes associated with abdominal cramps. It was found
that the symptom continued in most patients until
antifungal treatment was administered which cured them of
the disease. Some doctors in Georgetown University
Hospital, Washington DC, who handled some of these
cases, lamented that many hospitals even in developed
countries rarely request for yeast identification in stool
samples. Furthermore, even the well trained laboratory
technologists often do not report the presence of yeasts they
come across during their investigation even when the
number seen are abnormally very high. Chronic diarrhoea
if untreated, may lead to serious dehydration that can be
fatal especially in children.
2.2
CRYPTOCOCCOSIS IN
IMMUNOCOMPROMISED PATIENTS
Cryptococcus neoformans is a capsulated yeast which lives
as a saprophyte in the soil particularly one contaminated
with faeces of birds (pigeons). This fungus can enter the
human tissue through inhalation of soil containing the
organism which is eventually carried into the lungs. In a
healthy individual the organism will not be able to grow
and to spread in the lungs because the immune cells
(particularly T cells) will be able to destroy it. However, in
immunocompromised individuals particularly those
suffering from “acquired immunodeficiency syndrome”
(AIDS), the immune cells are no longer effective, hence,
the organism will grow slowly in the lung tissue to produce
24
a disease called cryptococcosis. The disease initially
presents as pneumonia but later the organism moves to the
meninges and to the brain to cause cryptococcal meningitis.
The disease is usually fatal in AIDS patients and patients
with organ and bone marrow transplants. Such patients
usually have low CD4 lymphocyte counts (low T cells)
which are not enough to destroy the capsulated organism.
2.3
TRICHOSPORONOSIS IN
IMMUNOCOMPROMISED PATIENTS
Trichosporon beigelii is an ubiquitous yeast which inhabits
the soil and also lives as part of the microflora of the skin,
nose and the intestinal tract of man. Ordinarily, it causes a
superficial infection of the hair called “white piedra”
(loose white fungal ball attached to the hair shaft) which is
common among farmers in the tropical and subtropical
regions in the world. Recently, this organism has been
found to cause fatal systemic mycoses called
“trichosporonosis” in immunocompromised patients. Most
of the patients affected are:
AIDS patients
Bone marrow and organ transplant recipients
Low birth weight and premature infants
Patients with in-dwelling devices (catheter)
Patients on prolonged broad spectrum antibiotics
Cancer patients.
T. beigelii in these patients is known to grow
uncontrollably all over the body and also invades the blood
vessels to cause various disease conditions which include:
Peritonitis especially in AIDS patients
25
Chronic meningitis in cancer patients
Hepatitis (liver infection)
Fungaemia (wide spread of the yeast in the entire body
system)
Most patients with this disease are known to die in spite of
the antifungal therapy.
2.4
INVASIVE ASPERGILLOSIS IN
IMMUNOCOMPROMISED PATIENTS
Aspergillus is an ubiquitous filamentous fungus found
naturally in the soil and produces numerous spores which
are easily aerosolised. The spores are very light and so can
remain suspended in the air in very large numbers and
spread all over the environment and for long distances by
wind. They are also found regularly on surfaces of most
materials including furniture, water, vegetations, cooked
and raw foods as well as on bodies of plants and animals.
They can enter human tissues through inhalation or cuts on
the skin. There are many species of Aspergillus which
include A. niger, A. flavus, A. fumigatus, A. orizae and A.
parasiticus. In healthy individuals, Aspergillus can cause
superficial mycoses like keratitis (infection of the cornea)
and external otitis (infection of the external ear) which are
easily treated with antifungals. Constant inhalation of airborne spores of Aspergillus occurs daily in every
individual. In immunocompetent individuals, these inhaled
spores are regularly destroyed by the immune cells to
prevent their growth and spread. However, in
immunocompromised patients inhaled spores germinate
26
and grow to produce, in many cases, a fatal disease called
“invasive aspergillosis.”
Invasive aspergillosis has been on the increase in the last
decade and death rate has been extremely high despite
antifungal therapy. The disease occurs in severely
immunocompromised patients such as:
Patients with acute leukaemia (cancer of the blood)
AIDS patients with very low CD4 lymphocyte count
Patients with heart, kidney, liver, and bone marrow
transplant.
For organ recipient patients, the highest risk period is the
first two to three months after transplant often due to high
dosage of immunosuppressive therapy. These groups of
patients are usually hospitalised and become infected
through inhalation of Aspergillus spores which occur in
large numbers in dust particles from construction work
(demolished hospital buildings) that often occur during
hospital expansion or renovations. In one hospital in the
State of Pennsylvania in the United States of America,
three patients who had undergone cardiothoracic surgery
died due to invasive aspergillosis. These patients (through a
thorough investigation by the Hospital Administration)
were found to have died of invasive aspergillosis contacted
as a result of the fungal spores inhaled. These spores were
traced to the dusty air from a building construction in the
hospital which was going on at the time of surgery.
The organ most affected in invasive aspergillosis is the
lung, with growth of the fungus in the lung tissue followed
by severe damage to the pulmonary blood vessels which
27
may eventually cause a collapse of the affected lung. The
fungus may also invade other blood vessels to cause skin
and gastrointestinal ulceration. It may also spread to other
organs especially the kidneys, heart, and brain. These
activities of the invading fungus often result in the
formation of microabscesses within multiple organs,
blockage of the blood vessels and stroke which often cause
death of the patient. Despite adequate treatment, invasive
aspergillosis carries a high mortality.
Pillows can serve as reservoirs for Aspergillus spores. A
research carried out at the University of Manchester in
England which was funded by “Fungal Research Trust”
revealed that millions of fungal spores are literally under
our noses particularly in our pillows. They found that
spores of A. fumigatus were the most isolated fungal spores
from pillows. They dissected both feather and synthetic
pillows and identified several thousands of spores of
fungus per gram of used pillow. They also discovered that
pillows used between 17 months and 20 years, contain
more than a million spores per pillow. They, therefore,
concluded that immunocompromised patients particularly
those that have undergone organ transplant may develop
invasive aspergillosis through inhalation of Aspergillus
spores in their pillows.
Most hospitals in developed countries provide patients with
plastic covered pillows to protect them from direct contact
with fungal spores in pillows. Patients may get infected
when they go home and use unprotected pillows. In
developing countries like Nigeria, the chances of
immunocompromised
patients
contacting
invasive
28
aspergillosis are very high since most homes and many
hospitals may not provide plastic pillows for them.
Figure 9: Conidiophores of Aspergillus fumigatus with flaskshaped vesicles bearing sterigmata in single series and chains of
conidia, X550. This is an isolate from Nigerian soil.
Figure 10: These are autopsy specimens from a 39-year-old
female who died from cancer (lymphoma). Histology confirmed
the presence of circulating hyphae of Aspergillus within and
29
around the wall of blood vessels in the lungs (top), kidneys
(bottom left), spleen (bottom right), and brain. (Courtesy of Dr.
O.C. Okafor, UNTH, Enugu).
2.5
INVASIVE MUCORMYCOSIS IN
IMMUNOCOMPROMISED PATIENTS
Many fungi in the order Mucorales, which include Mucor,
Rhizopus and Absidia, are saprophytes in the soil. They
produce large quantities of spores which are continually
inhaled by man during normal breathing. In healthy people,
the immune cells prevent the growth of these spores. But in
immunocompromised patients, some of these spores
especially those of Mucor can grow uncontrolled to cause a
disease called mucormycosis. This disease may occur as a
pulmonary infection with destruction of the lung tissue, a
rhino-cerebral infection with the destruction of the brain
cells or disseminated infection which spreads through the
blood stream to destroy vital organs (liver, heart, kidney)
and eventually causing death of the patient. Patients who
are at risk of developing mucormycosis are:
AIDS patients
Patients with organ transplant
Poorly controlled diabetic patients
It is believed that in diabetic patients with ketoacidosis,
acidosis interferes with phagocytic processes of the
phagocytes and thereby prevents them from destroying the
fungal cells in the tissues.
30
Figure 11: Mucormycosis diagnosed in the right eyeball and
peri-orbital tissue from a 41-year-old HIV-positive male. He
presented with right eye swelling, loss of vision, and copious
yellowish-white discharge from the eye. (Courtesy of Dr. O.C.
Okafor, UNTH, Enugu)
2.6
HISTOPLASMOSIS
This is caused by Histoplasma capsulatum var. capsulatum
(American histoplasmosis) and H. capsulatum var.
dubuosii (African histoplasmosis). These fungi are usually
found in black bird roosts, chicken houses (soil
contaminated chicken droppings), as well as bat droppings.
31
H. capsulatum var. capsulatum, the causative agent for
American histoplasmosis, enters the human through
inhalation of spores of the fungus. Many cases of the
disease are common in people who spread chicken manure
in their gardens. The spores are able to grow and cause
disease only in immunocompromised patients especially in
AIDS patients where there is dissemination to other vital
organs (spleen, liver, and bone marrow) with fatality rate
up to 90%.
H. capsulatum var. dubuosii, (the causative agent for
African histoplasmosis) is endemic in West, East, and
Central Africa. The exact portal of entry of this fungus is
unknown but direct inoculation into the skin and inhalation
through the respiratory tract have been incriminated. It
commonly affects the skin, subcutaneous tissue, and bone;
occasionally it may cause disseminated disease involving
the liver, spleen, lungs, and other vital organs.
Figure 12: African histoplasmosis diagnosed in the axillary
lymph nodes of a 21-year-old female who presented with
32
enlarged axillary lymph, night sweat, and weight loss nodes of 6
months duration. (Courtesy of Dr. O.C. Okafor, UNTH, Enugu)
2.7
COCCIDIOIDOMYCOSIS
This is also primarily a pulmonary disease caused by
Coccidioides immitis. The fungus is usually found in hot
desert soil, pottery, archaeological middens, cotton, as well
as rodent burrows. Their spores are produced in large
numbers and many are found floating in the air and spread
to hundred of miles by dust storms. The fungus is common
in desert areas of northern part of America where many
cases
have
been
identified
particularly
in
immunocompromised patients. The disease is usually
progressive, chronic, and fatal particularly in AIDS patients
where the skin, lymph nodes, spleen, liver, bones, kidneys,
meninges and brain are mostly affected.
2.8
BLASTOMYCOSIS
This is again primarily a pulmonary disease caused by
Blastomyces dermatitidis. The fungus is usually found in
soil containing rotting wood, animal droppings, and plant
materials. The fungus infects mostly people collecting
firewood, tearing down old buildings or engaged in other
outdoor activities which disrupt soil. The disease is also
fatal in immunocompromised patients when the vital
organs are seriously affected.
The last three genera of fungi are not well known to cause
disease in Nigeria. One of the reasons for this observation
is that, with the exception of H. duboisii which we have
33
isolated from soil here, there is so far no documented report
on the presence of the other ones here. Secondly, many
doctors here in Nigeria rarely request for the detection of
these fungi in the clinical specimens (sputum) sent to the
laboratory for investigation. Hence, the laboratory
scientists rarely make report on the presence of yeast cells
(characteristic of Histoplasma or Blastomyces) or
spherules/ endospores (characteristic of Coccidioides)
which they may encounter in the clinical specimens.
2.9
MYCOTOXICOSES
Mycotoxins are natural by-products of some filamentous
fungi which are toxic to human and other animal tissues
when introduced (mostly by ingestion) in low
concentrations. Mycotoxins are usually produced in plants
such as maize, wheat, barley, rye, as well as groundnut
while still growing in the field, after they have been
harvested, during storage and also when they are processed
into food or animal feed concentrates. There are about
twenty mycotoxins which are known to occur naturally in
foods and feeds at significant levels.
Human intake of mycotoxins occurs mainly through
ingestion of mycotoxin-contaminated foods as well as
contaminated animal-derived foods like milk, cheese, and
certain fermented meat products. Recently, mycotoxin
contamination of food and feeds has become a world-wide
problem. It is now believed that as much as 25% of the
world food crops are affected annually by variable levels of
mycotoxins. This has caused serious economic problems
34
for individual crops, livestock producers, grain handlers,
processors, as well as consumers.
The effects of mycotoxins on human health are complex
and not well understood. Human mycotoxicoses have been
mainly associated with ingestion of contaminated foods and
some scientists have been able to link some mycotoxins to
certain human cancer. There is also some scientific proof
that several mycotoxins can damage components of human
immune system especially cellular immunity. The parts
involved are the T lymphocytes as well as the non-specific
humoral factors. Some important mycotoxins which are
known to cause serious human diseases are:
Ergotamine and ergonomine produced by Claviceps
purpurea
Amatoxin
produced
by
Amanita
phalloides
(mushroom)
Aflatoxin produced mainly by Aspergillus flavus and A.
parasiticus.
2.9.1 Ergotamine and Ergonomine
These two toxins produced by Claviceps purpurea were
first discovered in Europe in the “middle ages” when rye, a
staple food of the peasant population was somehow
connected with a deadly disease called “ergotism.” A close
study of the implication of rye in the many deaths revealed
that a fungus called Claviceps purpurea grew in some of
the developing seeds of rye and eventually replaced them
with hard fungal mass called ergot. At maturity, both the
ergot and the good rye seeds were all harvested, ground
together and eaten as food. A detailed study of the ergot
35
revealed that it releases a “Pandora’s box” of deadly
poisons which include ergotamine and ergonovine which
often led to death of consumers.
Most medical historians noted that ergot mycotoxins
exerted a major role in preventing population expansion in
the middle ages in Europe. However an increase in the
population of Europe was noted in the 16th and 17th
centuries, and this has been attributed to the introduction of
wheat and potatoes as staple food and also the reduction in
the consumption of rye.
2.9.2 Mushroom Toxins (Amatoxins)
Mushrooms which are composed of a group of
macroscopic fungi that grow in the soil often serve as meat
for the poor especially in developing countries.
Unfortunately some species produce deadly toxins which
kill human beings on consumption. The most deadly of
these toxins are the amatoxins (known to be among the
deadliest mushroom toxins in our planet) which are
produced by Amanita phalloides (“death cap”) and has no
known antidote. The toxins are found to destroy the liver
and kidney and death usually occurs within 3 to 7 days
following consumption.
Fortunately, most people in the developing countries no
longer eat mushroom for fear of consuming the deadly
ones. Hence, only few cases of death from mushroom
meals are now reported. However, in developed countries,
mushrooms are eaten as special delicacies since mushroom
farmers grow safe species for marketing.
36
2.9.3 Aflatoxins
Aflatoxins are toxic metabolites produced by certain fungi
in or on foods and feeds. Aflatoxins were discovered
accidentally in 1960 when over one hundred thousand
(100,000) young turkeys on poultry farms in England died
in the course of a few months from an apparently new
disease which was then called “Turkey X Disease.” The
disease was not limited to turkey but also affected
ducklings and young pheasants (large birds with long tails).
A detailed investigation of these outbreaks revealed that the
birds were fed on groundnut feeds from Brazil which
happened to contain aflatoxins that killed the turkeys. The
toxins were later found to be produced by a fungus
identified as Aspergillus flavus which influenced the
naming of these toxins (aflatoxins). Other species of
Aspergillus namely A. niger, A. parasiticus and A. nomius
were also found to produce aflatoxins.
I still recall that I first knew about aflatoxins in 1972 in my
final year in the Department of Botany where I got my first
degree. I presented two seminars as part of the
requirements for the B.Sc. degree in Botany. I chose to talk
on “Yeasts” in my first seminar. In the second one I talked
on “Aflatoxins” which I found very interesting and
revealing and my presentation was highly commended by
staff and students in the department. After my graduation,
my good results as well as these two seminars I presented
helped me to earn a job and a University Scholarship as a
37
“Junior Fellow” in the Department of Microbiology. The
department wanted to train somebody in the area of
Medical Mycology as part of the University Academic
Staff Development. During the interview, the Vice
Chancellor then, Prof. H. C. Kodilinye of blessed memory,
who was the Chairman of the interview panel was so
impressed with my discussion on aflatoxins that he wanted
to know if I had travelled to England to get all the facts I
presented on the toxins. I then told him that I did not go
any where but read about them from books and journals.
His reply was: “Well read, well read,” and soon after this I
was offered the job and the scholarship.
Aflatoxin-producing fungi infect plants while still growing
in the farms and after harvest, especially during storage if
the crops are not properly dried. Insects and rodent
infestations facilitate their invasion into the crops in storage
places. Favourable conditions for crop infection are high
moisture content and high temperature. Crops with the
highest risk of infestation are cereals (corn, sorghum,
millet, rice and wheat), oil seeds (peanuts/groundnuts,
soybean, sunflower, and cotton), spices (pepper and ginger)
and tree nuts (almond, walnut, and coconut). Corn which is
the staple food of many countries is of great concern for its
aflatoxin contamination because it is grown in climates that
are likely to have perennial contamination with aflatoxins.
Again aflatoxins are stable or moderately stable in most
food processes from where they enter the human tissues
through food ingestion. The toxins can also be found in the
milk of animals which are fed with aflatoxin-contaminated
feed. The disease they cause in man is called
“aflatoxicosis.”
38
Acute aflatoxicosis has been reported in developing
countries like Taiwan, Uganda, and India. The disease is
characterised by vomiting, abdominal pain, convulsion,
coma with serious involvement of the lungs, liver, kidneys,
heart, brain and death may occur in severe cases.
Conditions that favour development of acute aflatoxicosis
in humans include limited availability of food,
environmental conditions that favour aflatoxin-producing
fungi in crops and commodities and lack of regulatory
systems for aflatoxin monitoring and control.
It is now accepted that aflatoxins are undoubtedly human
carcinogens and not only of birds. A World Bank report
has strongly incriminated mycotoxins especially aflatoxin
as a significant modulating factor in childhood diseases and
deaths. A number of epidemiological studies done in Africa
have demonstrated a positive association between dietary
aflatoxins and “primary liver cell cancer” (PLCC). Other
investigations also revealed that aflatoxin ingestion through
contaminated foodstuffs is one of the major etiological
factors in PLCC in China and Sub-Saharan Africa. In
certain regions of these countries, at least 250,000 deaths
from PLCC are known to occur annually. For almost four
decades, National Institute of Environmental Health
Sciences (NIEHS) funded scientists who conducted
research on the role of aflatoxins in the promotion of liver
cancer. NIEHS-funded scientists at the Massachusetts
Institute of Technology (MIT) in the U.S.A. were among
the first to show that exposure to aflatoxins can lead to liver
cancer. From their work it has been discovered that high
39
level of aflatoxins exposure produces an acute necrosis,
cirrhosis, and carcinoma of the liver.
No animal species, man inclusive, is immune to acute
effects of aflatoxins. However, humans have been found to
have an extraordinarily high tolerance level to aflatoxin
exposure and so, rarely succumb to acute aflatoxicosis.
Children are particularly affected by aflatoxin exposure
which usually leads to stunted growth and delayed
development. Chronic exposure also leads to high risk of
developing liver cancer through aflatoxin M1. In 2001,
many reports appeared in the news media in South Africa
on what was described as “poison in the peanuts”. These
reports were based on the discovery of high levels of
aflatoxins which caused serious health problems in school
children fed on aflatoxin-containing peanut butter used in
preparing their sandwich meal. Following this report, The
South African Medical Research Council, an internationally
recognised centre of excellence on mycotoxins, made some
recommendations on the ways to control aflatoxins in
peanut butter.
It is difficult to avoid consumption of aflatoxin
contaminated foods because fungal growth in foods is not
easy to prevent. However, the ability of aflatoxins to cause
cancer and related diseases in human given their
unavoidable occurrence in foods and feeds, makes the
prevention and detoxification of these mycotoxins one of
the most challenging toxicology issues in recent times
particularly in countries with high temperature and
humidity. In developed countries like United States of
America, foods with high levels of aflatoxins are not
40
allowed to be sold in their food stores. Agencies like Food
and Drug Administration (FDA) have specific guidelines
on acceptable levels of aflatoxins in human foods and
animal feeds. This step had to be taken because aflatoxins
are considered unavoidable contaminants of food and feeds
even where good manufacturing practices have been
followed.
Studies on human populations exposed to diets naturally
contaminated with aflatoxins revealed a direct relationship
between the high incidence of liver cancer in Africa and
some other places and dietary intakes of aflatoxins.
Following these findings, careful control of aflatoxins in
foods has been recommended for each country. Effective
control and monitoring of levels of aflatoxins in foods and
feeds can, therefore, be handled by agencies such as:
National Agency for Food and Drug Administration
(NAFDAC)
Ministry of Health
Ministry of Agriculture
Natural Environment Committee Board
Food and Agricultural Organization
I have a postgraduate student who is currently looking at
some common staple foods consumed in Nigeria to
determine the levels of aflatoxin contamination in them.
The results will help to determine the safety of some of our
foods with regards to aflatoxin contamination.
41
3.
CONCLUSION AND RECOMMENDATIONS
I will not like any one to have the impression, after
listening to this lecture, that fungi are a group of dangerous
organisms which must be eliminated. Surely this is not true
since I had earlier in this lecture, listed the beneficial
aspects of fungi. Some of them are the decomposition of
refuse in the environment which has helped to give us clean
environment and subsequently provide food for plants and
other organisms. The production of antibiotics and other
useful metabolites by some species of fungi have helped to
save humanity from serious harm and even death by some
other pathogens. One must not fail to accept the fact that
fungi are naturally saprophytic organisms and can live their
lives by depending solely on organic matters within our
environment. Living organisms including man are
colonised by fungi only if they are able to gain entry into
their tissues and also if they are able to overcome the
defence mechanisms of their host tissues.
The immune status of every individual is a key factor in the
prevention or establishment of fungal diseases. Healthy
individuals
with
effective
immune
system
(“immunocompetent”) are able to overcome most fungal
invasion. However, individuals with defective immune
system (“immunocompromised”) are rarely able to resist
the dissemination of fungal cells throughout the entire body
even in the presence of appropriate drugs. This situation is
a great concern for the medical group who are now faced
42
with so many treatment problems including resistance of
many pathogens to the best available drugs. The emergence
of “human immunodeficiency virus” (HIV) which is
destroying the CD4 lymphocytes (that are most effective in
the destruction of fungal pathogens) has given rise to AIDS
in man. The numbers of individuals with full blown AIDS
are on the increase each year. Many fungi which were mere
members of the body microflora, are now causing death (at
a high percentage) in patients with advanced stage of
AIDS.
We are all aware that AIDS is real and that AIDS patients
have the highest risk of being easily infected by
opportunistic fungi. It is therefore, very necessary that
everyone should take every adequate precaution to avoid
infection by HIV. A word is enough for the wise.
Prolonged use and abuse of antibiotics have elevated the
status of some fungi like Candida found normally in the
intestines of man, from being a harmless commensal
organism to a serious pathogen that now causes systemic
candidiasis and the subsequent “leaky gut syndrome.”
This now calls for an effective control of both the sale and
the administration of antibiotics in this country. The
medical personnel particularly the Medical Doctors and the
Pharmacists must, therefore, be more cautious in the
administration of antibiotics to patients to avoid the
elimination of the other important members of the
microflora of the human body. Every Nigerian who
treasures his or her life must know that self medication
(especially of antibiotics) is very risky and can create
43
serious complications that can lead to the death of the
individual. In developed countries, there are effective laws
preventing the purchase of antibiotics at pharmacy shops
without the doctors’ prescription and everyone obeys
because the people there are disciplined. Unfortunately, in
Nigeria, I am not aware of any law preventing the purchase
of any drug from any medicine store without doctors’
prescription. Even if there is one, no one is enforcing it.
Moreover, most Nigerians are not disciplined enough to
obey such laws. The only effective option left at the
moment (before Nigerians realise the need to do things
properly) is for every sensible Nigerian to avoid taking
antibiotics at the slightest discomfort so as to prevent
diseases like systemic candidiasis. Medical Doctors and
Pharmacists are now challenged to champion an effective
law that will stop the abuse of drugs particularly antibiotics
in this blessed country.
It is now clear from all we have learnt about aflatoxins that
it is impossible to avoid contamination of foods and animal
feeds by these toxins. We have also learnt that the crops
most affected by the aflatoxin-producing fungi are corn and
groundnut. Let us reflect for a moment, on the rate of
consumption of corn in this country as a major staple food
(corn flour, pap, roast and boiled corn, corn flakes, corn
cakes and corn bread) and imagine the health implications
if corn is highly contaminated with aflatoxins before it is
eaten as food. We should also be concerned about the rate
at which groundnut is being consumed in this country, as
snacks in schools, work places and in homes as soup
ingredient and the health hazard associated with aflatoxincontaminated groundnuts. Groundnut is also popular as
44
peanut butter (“ose oji” in Igbo) for kola nuts. Since it is
now confirmed that aflatoxins are highly implicated in
cases of liver cancer particularly in Africa, one may not be
wrong in suggesting that consumption of corn and
groundnut containing high levels of aflatoxins, may be
partly responsible for some of the many cases of liver
cancer being reported recently in our country.
Nigeria, therefore, needs to established effective agencies
(as is the case in most developed countries) which will
monitor the levels of aflatoxins in our foods and animal
feeds. The Director of NAFDAC, Prof. Dora Akunyili, can
be appealed to, so that she can institute aflatoxin
monitoring in foods and animal feeds to save lives
regularly lost through aflatoxicosis. This is another
challenge particularly to Pharmacists in this country.
Part of the health problems created by fungal diseases is
poor diagnosis of many diseases where fungi are the major
cause. In many such cases especially in developing
countries like Nigeria it is usually the culture methods that
are used. In most developed countries the more advanced,
faster, and more specific non-culture methods such as
serological test, detection of fungal antigens in the infected
tissue and detection of specific nucleic acid or distinctive
fungal metabolites are used. Again many doctors do not
request for search for fungi as possible aetiological agents
in most of the clinical specimens. The doctors and
laboratory scientists should therefore, look out for fungal
cells (yeast cells, spherules and fungal balls) in clinical
specimens which include sputum, faeces and urine
collected for diagnosis. Very often the medical laboratory
45
scientists rarely report the occurrence of fungal cells even
when they are seen in an abnormally large numbers. There
is now need for them to do so.
Many doctors are yet to accept the fact that fungi have
moved from being confined to the superficial part of the
human body to a new position of penetrating into deeper
tissues and organs, challenging the immune system
effectively, and establishing fatal and systemic diseases. A
number of other conditions such as AIDS have facilitated
this development. Doctors should therefore, pay more
attention to fungal diseases and not mostly on bacterial
diseases so as to save lives of those facing death due to
fungal diseases.
One of the problems facing medical doctors recently in the
successful treatment of fungal diseases is the emergence of
fungal resistance to the available antifungal drugs. The
Chemists are now challenged to discover new effective
drugs that can destroy these invaders of the human
territory. Unfortunately, fungi, being also eukaryotic
organisms, share the same cellular structure as human
beings with the result that many antifungal drugs produced
are toxic to human tissues. Hence research into antifungal
drugs is more challenging.
Scientists working on medicinal plants (Pharmacists,
Chemists and Microbiologists) are also challenged to
identify medicinal plants that can serve as cheaper and
safer alternative drugs that can be used for the treatment of
fungal diseases especially for the large population of the
masses in developing countries who will not be able to
46
afford the expensive prescription drugs. I know that people
are working on anti-microbial medicinal plants but more
work is needed particularly on the antifungal ones. I have
done some work on both antibacterial and antifungal plant
extracts with some of my colleagues and students and the
results obtained so far are promising.
The Nigerian government needs to be more involved in
tackling many health problems caused by fungi so that
Nigerians can also enjoy high quality lives like other
people in developed countries. There is need for modern
and well equipped research and diagnostic laboratories for
efficient and quick diagnosis of fungal diseases particularly
the deadly systemic ones. Funds should, therefore, be
provided by the government for these. There is also need to
establish effective laws with the support of the national
legislators, for the control of sale of drugs with doctors’
prescriptions to avoid the serious abuse of drugs in this
country.
Finally, the Government needs to establish agencies that
will monitor the levels of mycotoxins, particularly
aflatoxins in foods and animal feeds sold to the public. If
the various effective arms of the government , the medical
people, the scientists and the Nigerian populace can act
effectively towards the fight against fungal attack on
humanity, Nigerians can join the rest of the developed
countries in the global plan to save humanity from
extinction by these silent but energetic destroyers, the
fungi.
47
4. ACKNOWLEDGEMENTS
I will not like to end this lecture without expressing my
appreciation to all who have in one way or the other played
key roles in my academic achievements so far.
My highest honour and thanksgiving go to God, the Creator
and Provider of all good things to humanity. I will for ever
cherish the numerous blessings He has bestowed on me, the
challenges He allowed me to experience and for making it
possible (out of His mercy) for me to be alive today to
deliver this lecture as a testimony of his goodness to me. I
also thank my Spiritual Directors, Very Rev. Msgr. Prof. F.
C. Okafor, Rev. Fr. Dr. A. O. Onyeneke, Rev. Fr. Prof. E.
M. Nwabuisi and Rev. Fr. Prof. A. Ekwunife for their
prayers and my spiritual guidance.
I am most grateful to the Vice Chancellor, Ven. Prof. C. O.
Nebo and the other members of the University
Administration who made sure that assessment for my
professorship was followed up and released after many
years of undue delay just as he did for many others with
similar experience. May God reward them for putting
smiles on the faces of many who were unjustly treated in
this University. I also wish to thank him and his
Administration for financing these series of inaugural
lectures which have given lecturers the opportunity to
enlighten the general public on their research findings and
experience in life.
48
Next in my list are members of my family starting with my
parents, late Mr. Joseph Igboko and late Mrs. Christiana
Igboko who nurtured me right from birth with so much
love and care. Despite the fact that they had many other
children including two brilliant sons just behind me and
also at a time when education for women was considered
unprofitable, they were determined to give me the best
education. My dad being a dedicated teacher coached me
thoroughly for the highly competitive secondary school
entrance examination particularly to good colleges. This
was what made it possible for my name to appear top on
the merit list published in one of the daily newspapers of
thirty brilliant young girls who gained admission into one
and only Federal Government Girls College, east of the
River Niger which was then called “Queens School
Enugu”. At the end of my first year in this college, I was
awarded a college scholarship which I enjoyed all through
the rest of my stay in the college (both for the secondary
school and higher school education). Six months after
completing my college education, my parents made sure
that I got into the university before getting married because
they believed that education is a major key to success in
life. Unfortunately my mum died at a young age but God
allowed her to see her first two grand children and she also
witnessed my B.Sc. graduation. However, I thank God that
my dad lived long enough to see the success of his labour
for he saw my six children and also witnessed the
graduation ceremonies for my B.Sc., M.Sc. and Ph.D.
degrees before God took him at the ripe age of 84 years.
Another member of my family whom I owe so much
gratitude is my darling husband, Prof. Charles Okafor, a
49
renowned academic and a great achiever to whom I got
married at the end of my first year in the university. At the
time we got married, he was a young lecturer, just back
from the United States of America after his brilliant
academic records, with First Class Honours Degree in
Chemistry from the University of London and a Ph.D.
degree also in Chemistry from Michigan State University,
East Lansing, Michigan, U.S.A. Although he was very
much involved in teaching, research and administration, he
was still able to accommodate a student wife and babies
who were born into the family during the many years I had
to study for my B.Sc. degree in Botany, M.Sc. and Ph.D.
degrees in Microbiology. Each time I reflect on the level
of support and encouragement I received from him, I count
myself as one of the happiest and luckiest wives in the
whole universe. At a certain time during my undergraduate
programme, he reminded me that spending too much time
with our children, would prevent me from earning a good
degree which he felt I could make easily on merit judging
from my previous academic performance, by working hard.
This message from him clicked in my brain and so I started
working as hard as I used to and finally got the second best
result in the B.Sc. degree examination. This was the result
that gave me a job as a “Junior Fellow” in the Department
of Microbiology and a university scholarship to pursue a
higher degree in microbiology any where in the world
although I opted to study here so that I would be able to
take proper care of my family. My husband continued to
give me strong support until I finally got my Ph.D. degree.
Soon after my B.Sc. degree, he took me on holidays to
Harvard University Cambridge, Massachusetts, U.S.A.
where he did his Post-doctoral Fellowship following an
50
invitation from a Nobel Prize winner in Chemistry, the late
Prof. R. B. Woodword. Incidentally, my husband was
nominated twice in 1985 and 1994 by the Royal Swedish
Academy of Science for consideration for the award of
Nobel Prize in Chemistry. You can now see that behind this
lecturer who gave you an inaugural lecture is a loving and
caring great man who happens to be my husband.
I will also want to thank my lovely children for being very
submissive and cooperative which made it possible for me
to combine my studies with home management. The eldest
among them is Dr. Okechukwu Charles Okafor, a
Consultant Pathologist at the University of Nigeria
Teaching Hospital and a Senior Lecturer in the Collage of
Medicine UNTH, Enugu. His brilliant academic career
made him a model for his siblings. Others are Mrs. Nnenna
Ofordu, an Assistant Manager with Zenith Bank PLC,
Ikeja, Lagos, Mrs. Ifeoma Ezuma - Ngwu, a Senior
Benefits Analyst with Metropolitan Transit Authority,
Houston, Texas, U.S.A., Dr. Chidi Okafor, M.D. and a
Resident Doctor, specialising in Internal Medicine at St
Vincent Charity Hospital, Cleveland, Ohio, U.S.A., Mrs.
Amaka Awanye, an Assistant Lecturer in Pharmacy at the
University of Port Harcourt and Mummy’s handbag,
Obioma Okafor who, by the grace of God, will be
graduating with Doctor of Pharmacy degree (Pharm. D.)
from the University of Houston, Houston, Texas, U.S.A.
early next year, 2009. I also want to extend my gratitude to
my wonderful sons-in-law, Mr. Cyprain Ofordu, a
Chartered Accountant in a Federal Ministry at Abuja, Mr.
Nnanna Ezuma - Ngwu, a Real Estate Consultant, Houston,
Texas and Mr. Emeka Awanye, a Chartered Accountant
with Elf Petroleum Company as well as my cute
51
grandchildren: Masters Kenechukwu, Ugochukwu and
Ikechukwu Ofordu, Master Chikezie, Miss Chisom and
Amaka Ezuma - Ngwu, Miss Ogochukwu, Ogechukwu and
Master Obichukwu Awanye who have brought so much joy
to the family.
I will also like to express my gratitude to my siblings, Arc.
Chris Igboko, Engr. Godwin Igboko, Dr. (Mrs.) Ijeoma
Iloeje, Prof.(Mrs) Nnenna Kanno, Mrs. Tessy Ekwunife,
Mrs. Cecilia Asika, Barrister Gab. Igboko, Mr. Patrick
Igboko, Barrister (Mrs.) Angela Emesih, Dr. Charles
Igboko, Mrs. Nkechi Nwafor, Pharm. Ikechukwu Igboko
and Miss Ujunwa Igboko, who are always available for
their big “Sister Joe”.
I cannot fail to thank my nice parents–in-law, Mr. Thomas
Okafor of blessed memory and Mrs. Agnes Okafor who
accepted me and treated me as one of their daughters ever
since I got married to their son. Many thanks also go to my
sweet sisters–in-law, late Justice Monica Edozie, Barrister
(Mrs.) Betty Madike, Mrs. Ngozi Nwosu, Prof. Chinyere
Grace Okafor as well as my brothers-in-law, Dr. Emeka
Okafor, Dr. Tony Illo and many others.
I cannot forget the amicable support I continue to enjoy
from other close relations particularly from my wonderful
brother-in-law, Prof. O. C. Iloeje , a Commissioner in the
Electricity Regulatory Commission, Abuja, Engr. Val
Emesih of Houston Electricity Corporation, Texas, U.S.A,
Mr. Rich Ekwunife, Engr. Ogbonnia Nwafor as well as my
52
lovely sisters-in-law, Mrs. Nnenna Igboko, Engr. Ngozi
Igboko, Barrister Chinelo Igboko and Dr. Ifeoma Igboko.
I also wish to express my sincere gratitude to my dedicated
teachers who taught me at different levels of my academic
career. I remember, in particular, some of my teachers at
Queens School, Enugu, namely, Mrs. Kirk Patrick, my
Principal and Mathematics teacher, Mrs. Iwobi, my
Chemistry teacher and Miss Penny, my Biology teacher at
the Higher School. I am ever grateful to my lecturers in the
Department of Botany, especially to Prof. J.N.C.
Maduewesi who made me to develop keen interest in
Mycology, late Prof. Eni Njoku, our one time ViceChacellor and great scholar, late Prof. S. N. C. Okonkwo
and Akunne O. C. Mozie as well as late Prof. A. N. U.
Njoku Obi and Prof. Nduka Okafor for their inspiring
lectures in Microbiology. My special thanks go to my
supervisor for my M.Sc. and Ph.D. degrees, Prof. H. C.
Gugnani who guided me effectively and who also made it
possible for me to study in Nigeria and also to take care of
my family especially my young children who could have
derailed in my absence. I am also indebted to my other cosupervisors in the United States of America, Prof. Diane.
TeStrake of the Department of Biology and Dr. B. G.
Yangco of the Department of Medicine, Division of
Infectious and Tropical diseases, College of Medicine both
of University of South Florida, Tampa, Florida, U.S.A.
I will also like to acknowledge the contributions of my
research collaborators, Prof. I. C. Ononogbu, Prof. O. U.
Njoku both of the Department of Biochemistry and Prof.
Maria O. Nwosu of the Department of Botany as well as
53
my postgraduate students especially Mr. E. I. Nweze and
Mr. E. A. Eze who are most likely to obtain their Ph.D.
degrees in Microbiology before the end of the year. I also
owe my gratitude to the staff in my faculty particularly to
Prof. Jasen Obeta, Prof. Chris Iroegbu, late Dr. A. C.
Emeruwa and late Dr. Joe Oguike who were very helpful to
me during the period I was the Head of the Department of
Microbiology. I cannot end without thanking Dr. (Mrs.)
Ifeoma Ezeonu, my former student and now a professional
colleague, for being a good ambassador of the department.
I am also very grateful for the cooperation I received from
other colleagues: Prof. L. C. Eze and Dr. Eddy Alumanah
both of the Department of Biochemistry, Prof. J. C.
Ogbonna, my current Head of department, Drs. Jerry
Ugwuanyi, Chukwudi Anyanwu and many others. I also
wish to thank Dr. O. C. Okafor (my son) and Dr. E. R.
Ezeome both of UNTH, Enugu who provided the clinical
pictures of some patients with fungal diseases. To all of
you I say thank you and thank you and thank you and may
you all be blessed in Jesus name.
54
5. LIST OF PUBLICATIONS
(i)
1.
2.
3.
Chapters in Books
Anyanwu, B.N. and Okafor, J.I. (1981). Man and
Microorganisms. In: Nwankiti, O.C. (ed). Man and
His Environment. Longman Group Ltd., Essex,
England, pp. 38-42.
Okafor, J.I. (1981). Terrestrial and Cosmic Life. In:
Nwankiti, O.C. (ed). Man and His Environment.
Longman Group Ltd., Essex, England, pp. 81-83.
Okafor, J.I. (1999). Morphology of Bacteria. In:
Maduewesi, J.N.C. and Iheagwam, E.U. (eds).
College Laboratory Manual of Tropical Biology.
Ihem Daris Press 8 Ltd, Owerri, Nigeria, pp 12-16.
(ii)
Refereed Journal
Conference Papers
Articles/
International
4.
Njoku-Obi, A.N.U., Okafor, J.I. and Gugnani, H.C.
(1976). Yeast-like fungi recovered from normal
human skin in Nsukka (Nigeria). Anotnie Van
Leeuwenhock Journal of Microbiology and
Serology. 42: 101-105.
5.
Gugnani, H.C and Okafor, J.I. (1980). Mycotic flora
of the intestine and other internal organs of certain
reptiles and amphibians with special reference to
55
6.
characterization of Basidiobolus isolates. Mykosen.
23: 260-268.
Okafor, J.I. (1981). Bacterial and Fungal pathogens
from Intestinal tracts of cockroaches. Journal of
Communicable Diseases. 13: 128-131.
7.
Okafor, J.I. and Gugnani, H.C. (1981).
Dermatophyte and other keratinophilic fungi
associated with hairs of rodents in Nigeria. Mykosen.
24: 616-620.
8.
Okafor, J.I., Testrake, D.I. and Mushinsky, H. R.
(1982). Ecological studies on Basidiobolus spp.
Presented at the Florida Academy of Sciences 22nd24th April at Stetson University, Deland, Florida, U.
S. A.
9.
Okafor, J.I., Testrake, D.I. and Yangco, B.C. (1982).
Physiological studies on Basidiobolus isolated from
South Florida and Nigeria. Presented at 33rd Annual
Meeting of the American Institute of Biological
Sciences (AIBS) 6th-12th August at Pennsylvania,
U.S.A.
10. Ibekwe, A.O. and Okafor, J.I. (1983). Pathogenic
organisms in chronic suppurative otitis media in
Enugu, Nigeria. Tropical and Geographical
Medicine. 35: 389-391.
11. Okafor, J.I., Yangco, B.C. and Testrake, D.I. (1983).
In Vitro antifungal susceptibility studies of human
and wild isolates of Basidiobolus sp. and
56
Conidiobolus sp. Presented at the 83rd Annual
Meeting of the American Society for Microbiology
6th-12th March at New Orleans, Louisiana. U.S.A.
12. Testrake, D.I., Beker, V., Yangco, B.C. and Okafor,
J.I. (1983). The effect of nutrition on morphology and
pigment production of Basidiobolus sp. Presented at
the 3rd International Mycological Congress 28th
August-3rd September at Tokyo, Japan.
13. Okafor, J.I., Testrake, D.I., Mushinsky, H.R. and
Yangco, B.G. (1984). A Basidiobolus sp. and its
association with reptiles and amphibians in Southern
Florida. Sabouraudia. 22: 47-51.
14. Yangco, B.G., Testrake, D.I. and Okafor, J.I. (1984).
Phialophora richardisae isolated from infected Human
Bone: morphological, physiological and antifungal
susceptibility studies. Mycopathologia. 86: 103-111.
15. Yangco, B.G. Okafor, J.I. and Testrake, D.I. (1984).
In vitro susceptibility of human and wild isolates of
Basidiobolus and Conidiobolus sp. Antimicrobial
Agents and Chemotherapy. 25: 413-416.
16. Yangco, B.G., Nettlow, A., Okafor, J.I. Park, J. and
Testrake, D.I. (1986). Comparative Antigenic studies
of species of Basidiobolus and other medically
important fungi. Journal of Clinical Microbiology.
23: 679-682.
57
17. Okafor, J.I. Gugnani, H.C. Testrake, D.I. and
Yangco, B.G. (1987.) Extracellular Enzymes of
Basidiobolus and Conidiobolus isolates on solid
media. Mykosen: 30: 404-407.
18. Okafor, J.I. and Gugnani, H.C. (1992). Lipase
activity of Basidiobolus and Conidiobolus species.
Mycoses. 33: 81-85.
19. Okafor, J.I. (1994). Purification and characterization
of protease enzymes of Basidiobolus and
Conidiobolus species. Mycoses. 37: 265-269.
20. Okafor,
J.I.
and
Okunji,
P.O.
(1994).
Cryptosporidosis in patients with diarrhoea in five
hospitals in Nigeria. Journal of Communicable
Diseases. 26: 75-81.
21. Nwosu, M.O. and Okafor J.I. (1995). Preliminary
studies of the antifungal activities of some medicinal
plants against Basidiobolus and some other
pathogenic fungi. Mycoses. 38: 191-195.
22. Okafor, J.I. and Okunji, P.O. (1996). Prevalence of
Cryptosporidium oocysts in feacal samples of some
school children in Enugu State, Nigeria. Journal of
Communicable Disease. 28: 49-55.
23. Okafor, J.I. and Uka, N.A. (1996). Extracellular
Enzyme Activities by Pityrosporum ovale on solid
media. Journal of Science, Engineering and
Technology. (Accepted for Publication).
58
24. Okafor, J.I. and Okonowo, N.O. (1997). Some
pathogenic fungi involved in serious cases of urinary
tract
infections
in
Nigeria.
Journal
of
Communicable Diseases. 29: 101-107.
25. Njoku, O.U., Onongbu, I.C. and Okafor, J.I. (1997).
Constituents of fixed oils of Piper guinense and
Xylopia aethiopica. Journal of Natural Products
and Medicine. 1:41-43.
26. Okafor, J.I. and Agbugbaeruleke, A.K. (1998).
Dermatophytosis among school children in Aba, Abia
State, Nigeria and some physiological studies on the
isolated etiologic agents. Journal of Communicable
Diseases. 30: 44-49.
27. Njoku, O.U., Okeke, U., Ezugwu, C.O. and Okafor,
J.I. (1999). Preliminary Investigation on some
Nutritional and Toxicological properties of
Caesalpinia crista seed and oil. Bollenttino Chimico
Farmaceutico. 138: 552-554.
28. Njoku, O.U., Ezugwu, C.O. and Okafor, J.I. (1999).
Investigation of some important nutritional and
phytochemical properties of Averrhoa carambola
fruit. Journal of Pharmaceutical Research and
Development. 4: 109-112.
29. Okafor, J.I., Eze, E.A. and Njoku O.U. (2001).
Antifungal activities of the leaves of Baphia nitida,
Cassia alata, Ficus exasperata and Gossypium
59
arboreum. Nigerian Journal of Natural Products
and Medicine. 5: 59–60.
30. Okafor, J.I. and Ngwogu A. (2002). Keratinolytic
activities of five Human isolates of the
dermatophytes. Journal of Communicable Diseases.
32: 300-305.
31. Okafor, J.I., Eze, E.A. and Njoku, O.U. (2002).
Antibacterial activities of the extracts of leaves of
Baphia nitida, Lodd, Cassia alata Linn, Ficus
exasperata Vahl and Gossyupium arboreum Linn.
Applied Natural Sciences Research. 4: 1-5.
32. Okafor, J.I., Nweze, E. and Njoku, O.U. (2002).
Antimicrobial activities of the methanolic extracts of
Zapotica
portericensis
Benth
and
Cissus
quadrangularis Linn. Nigerian Journal of Pure and
Applied Science. (Accepted for publication).
33. Okafor, J.I. and Ngwogu, A. (2002). In vitro effects
of three metallic salts and carbon black (soot) on the
growth of five of dermatophytes. Journal of Medical
Investigation and Practice. (Accepted for
publication).
34. Nweze, E.I., Okafor, J.I. and Njoku, O. (2003).
Antimicrobial activities of methanolic extracts of
Trema guineensis (Shumm and Thorn) and Morinda
lucida Benth used in Nigerian Herbal Medicinal
Practice. Bio-Research. 2: 39-46.
60
35. Nweze, E.I. and Okafor, J.I. (2005). Prevalence of
dermatophytic fungal infections in children: A recent
study in Anambra State, Nigeria. Mycopathologia.
160: 239-243.
36. Nweze, E.I., Okafor, J.I. and Njoku, O.U. (2005).
Antifungal activities of pair combinations of extracts
from Morinda lucida Benth by decimal additive
assay. Bio- Research. 3: 99-104.
61
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Crook, W.C. (1986). The Yeast Connection. Vintage
Book. New York.
2.
Dismukes, W.E. (1988). Cryptococcal meningitis in
patients with AIDS. J. Infect. Dis. 157: 624-628.
3.
Anon. (1989). Mycotoxins, Economic and Health
Risks. Council for Agricultural Science and
Technology. Report No. 116, pp. 91.
4.
Woods, G.L. and Goldsmith, J.C. (1990). Aspergillus
infection of the central nervous system in patients
with acquired immunodeficiency syndrome. Arch.
Neurol. 47: 181-184.
5.
Denning, D.W., Follansbee, S.E., Scolaro, M., Norris,
S, et. al. (1991). Pulmonary aspergillosis in acquired
immunodeficiency syndrome. N. Engl. J. Med. 324:
654-662.
6.
Saral, R. (1991). Candida and Aspergillus infections
in immunocompromised patients: an overview. Rev.
Infect. Dis. 13: 487-492.
7.
Pappas, P.G., Pottage, J.C., Powderly, W.G., Fraser,
V.J., et al (1992). Blastomycosis in patients with
acquired immunodeficiency syndrome. Ann. Intern.
Med. 116: 847-853.
Lecciones, J.A., Lee, J.W., Navarro, E.E., et al
(1992). Vascular catheter- associated fungemia in
8.
62
patients with cancer: analysis of 155 episodes. Clin.
Infect. Dis. 14: 875-883.
9.
Fraser, V.J., Jones, M., Dunkel, J., Strofer, S.,
Medoff, G., Dunagan W.C. (1992). Candidemia in a
tertiary hospital: epidemiology, risk factors and
predictors of mortality. Clin. Infect. Dis. 15: 414421.
10. Crook, W.C. (1994). The Yeast Connection and
Women. Jackson T.N. Professional Books.
11. Girmenia, C., Gastaldi, R. and Martino, P. (1995).
Catheter-related cutaneous aspergillosis complicated
by fungemia and fatal pulmonary infection in an HIVpositive patient with acute lymphocyte leukaemia .
Eur. J. Clin. Microbial. Infect. Dis. 14: 524- 526.
12. Chandenier, J., Goma, D., Moyen, G., SambaLefebvre, M.C., et al (1995). African histoplamosis
due to Hisloplasma capsulatum var. duboisii:
relationship with AIDS in recent Congolese cases.
Sante 5: 227- 234.
13. Jones, J.L.,Fleming, P.L., Ciesielski, C.A., Hu, D.J.,
et al (1995). Coccidioidomycosis among persons with
AIDS in the United States. J. Infect. Dis. 171: 961966.
14. Dunkin, M.M., Connolly, P.A., Wheat, L.J. (1997).
Comparism of radioimmunoassay and enzyme-linked
immunoassay methods for detection of Histoplasma
63
capsulatum var. capsulatum
Microbiol. 35: 2252-2255.
antigen.
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Clin.
15. Verweij, P.E., Poulain, D., Obayashi, T., Ptterson,
T.F., Denning, D.W., Ponton, J. (1998). Current
trends in the detection of antigenaemia, metabolites
and cell wall markers for the diagnosis and
therapeutic monitoring of fungal infections. Med.
Mycol. 36: 146- 155.
16. Berry, C.L. (1998). The Pathology of Mycotoxins. J.
Path. 154: 301- 311.
17. Erer, B., Galimberti, M., Lucarelli, G., Giardini, C.,
Polchi, P., Baronciani, D., Gaziev, D., Angelucci, E.,
and Izzi, G. (2000). Trichosporon beigelii: a lifethreatening pathogen in immunocompromised hosts.
Bone Marrow Transplant. 25: 745-749.
18. Ebright, J.R., Fairfax, M.R. and Vazquez, J.A. (2001).
Trichosporon asahii, a non-Candida yeast that caused
fatal septic shock in a patient without cancer or
neutropenia. Clin. Infict. Dis. 33: 28-30.
19. Girmensia, C.M., Nucci, M. and Martino, P. (2001).
Clinical significance of Aspergillus fungemia in
patients with haematological malignancies and
invasive aspergillosis. Br. J. Haematol. 114: 93-98.
20. Raad, I., Hanna, H., Huaringa, A., Sumoza, D.,
Hachem, R., Albitar, M. (2002). Diagnosis of
invasive pulmonary aspergillus using polymerase
64
chain reaction-based (PCR) detection of Aspergillus
in BAL. Chest. 121: 1171-1176.
21. Williams, J.H., Phillip, T.D., Jolly, P.E., Stiles, J.K.,
Jolly, C.M., Aggarwal, D. (2004). Human
aflatoxicosis in developing countries; a review of
toxicology, exposure, potential health consequences
and interventions. Am. J. Clin. Nutr. 80: 1106-
65
Figure 13: Professor Okafor working in Professor TeStrake’s
Laboratory in the Department of Biology at the University of
South Florida, Tampa, FL. U.S.A.
Figure 14: Professor Okafor working under the hood in Dr,
Yangco’s Lab in the College of Medicine, Univ. of South
Florida, Tampa, FL. U.S.A.
66
Figures 15: Professor Okafor working with a scanning electron
microscope in the Department of Biology, University of South
Florida, Tampa, Florida, U.S.A.
67
Figure 16: Professor Okafor preparing her paper for
presentation at the Florida Academy of Sciences at Stetson
University, Deland, Florida, U.S.A.
Figure 17: Professor Okafor at work in the Microbiology
Laboratory, University of South Florida, Tampa, Florida,
U.S.A.
68