Why Physicians No Longer Know About Fungi: An Expose On Nystatin

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Why Physicians No Longer Know About Fungi: An Expose On Nystatin

The following is based largely on **The Fungus Fighters: Two Women

Scientists and Their Discovery**, written by Baldwin in 1981. The book

chronicles the discovery of nystatin, and it develops how fungi have come to be

largely ignored by the world of medicine, despite the many cases and studies

that

document their role in causing disease.

Hazen and Brown teamed up in the late 1940s to develop a

safe, effective antifungal for use in medicine. Hazen had already had a long

career as a microbiologist and as a mycologist, or fungi specialist, while

Brown specialized in organic chemistry. Their research was funded by the New

York

State Division of Laboratories and by the N.Y. Health Department. The two

scientists tested the effectiveness of a wide variety of agents against two,

particularly dangerous fungi: Cryptococcus neoformans and Candida albicans.

By 1949, Brown and Hazen had discovered nystatin. The agent worked not only

against the targeted microbes, but against fourteen other fungi, as well. The

second part of this last statement is important, because it counts as one of

many incidences in which nystatin has been shown to work as a broad-spectrum

antifungal. Unfortunately, the FDA has only approved the drug for use in

treating Candida found in the mouth (thrush) or on the skin. Clearly, that

approval should be broadened.p.78 Even if it never is, however, the FDA*s

stance

is not much of an obstacle. Remember, once a drug is approved for use in

treating one disease, doctors have license to use it to treat other conditions

as

they see fit.

Nystatin is produced by the fungus, Streptomyces noursei. The drug is named

after the organization that funded Hazen and Brown*s research - N.Y.State.

Although it is, in fact, a mycotoxin, it has yet to demonstrate any of the

harmful side effects, including cancer and atherosclerosis, found in the

mycotoxins produced by other fungi.

Hazen and Brown found that for efficient, mass production of nystatin,

peanut meal turned out to be the ideal substance for growing Strptomyces

noursei.p.14 This is hardly surprising today - even peanuts grown for human

consumption are notorious for fungal contamination. Among other contaminants,

the nuts

have to be frequently screened for a mycotoxin called aflatoxin.

The two scientists presented their findings at the National Academy of

Sciences regional meeting in Schenectady in the fall of 1950.p.79 Squibb Inc. -

now known as Bristol-Myers Squibb - got the nod for further testing and the

eventual production and marketing of the drug. Four years later, the FDA

approved Squibb*s Mycostatin oral tablets. Doctors began writing their patients

prescriptions for the drug within a month. Nystatin was described as **the

first

broadly effective antifungal antibiotic available to the medical

profession.** It was recommended for the prevention and treatment of intestinal

moniliasis, or candidiasis, especially for patients taking oral antibacterial

antibiotics for prolonged periods. It was also recommended for prevention of

intestinal moniliasis in intestinal surgery. Researchers reported that

Mycostatin

could clear up established yeast infections in patients* digestive tracts

within

one to two days; a full course of treatment typically lasted 21-30 days.

Hazen and Brown created a nonprofit organization to receive their share of

the royalties from the sale of nystatin, which over the span of their 16-year

patent eventually came to almost $7 million. The Brown-Hazen grants program

became the United States* largest, single source of non-federal funding for

research and training in combating fungal disease.p.103 Hazen and Brown

accepted not even a dime for their personal use.

Today, nystatin is widely available as a generic drug. According to

Bristol-Myers Squibb*s website, worldwide sales through 2001 of the

pharmaceutical

company*s Mycostatin alone totaled $15.3 billion.

Squibb later combined nystatin with the antibiotic, tetracycline. The new

drug, Mysteclin, was designed to offset the yeast overgrowth that often happens

from taking antibiotics. Other manufacturers followed suit. The host of

combination drugs that arose was later banned by the FDA for **lack of proof of

efficacy,** though they continue to be sold in other countries. In its

decision, it seems that the FDA may have ignored a number of studies in the

1950s

and 1960s that clearly documented not only that antibiotic administration often

leads to the overgrowth of intestinal yeast, but that combining nystatin

with antibiotics could stop such growth in its tracks.2

In 1960, Squibb came out with a more soluble antifungal called Fungizone

(amphotericin that could be administered both orally and through an

I.V.p.124

Amphotericin-B was also combined with antibiotics by various drug

manufacturers - one such combination, Mysteclin F, can still be found overseas.

Unfortunately, even though it proved safe when taken in pill form, amphotericin

turned out to have harmful side effects over the long term when administered

intravenously. Today, although safer systemic antifungals have been developed,

amphotericin remains a key drug used to treat a number of life-threatening,

fungal infections.

The Prevalence and Seriousness of Fungal Diseases Hazen and Brown*s work was

sparked by their awareness of the growing danger of fungal illnesses.

Remember, however, that then, as now, doctors have not been required to report

fungal diseases, which make an exact quantification of the true extent of

fungi-caused disease impossible.

That said, the National Health Survey performed by the U.S. Public Health

Service showed that, by the early 1970s, 8 percent, or 16 million Americans,

were suffering from skin conditions caused by fungi.p.24 These numbers qualify

such infections as an unofficial epidemic. The same health service reported

that **unknown numbers of people, regardless of occupation or location, have

contracted one or another of the most serious of the fungus diseases - the

deep, systemic mycoses - which can disable and kill.** This number remains

unknown, not just because doctors are not required to report fungal disease,

but

also because such infections are often misdiagnosed as other diseases.p.25

The ability of some of the more serious fungal diseases to mimic other,

common diseases encountered in medicine is no small problem. Indeed, some

scientists believe that fungal pathogens account for more upper respiratory

infections than bacteria and viruses combined. Fungi can cause all of the

symptoms

associated with low-grade, upper respiratory infections, such as mild fever and

cough, chills, sweating, and headache. Examination of more serious fungal

infections often leads to mistaken diagnoses of pneumonia, tuberculosis,

meningitis, rheumatoid arthritis or even brain tumors.

Although fungi lie at the root of the problem, physicians base their

treatments upon the inaccurate diagnoses, addressing the symptoms instead of

the

actual cause of the disease at hand. In cases in which antifungal measures are

finally applied as a last resort, the point at which such an approach would

have been most effective has often long since passed.

Health care professionals often rush their patients into medicinal or

surgical treatments in order to control rapidly worsening conditions in time.

We

should remember that such haste could increase the chance of a wrong diagnosis,

which then makes the quickly delivered treatment worse than meaningless.

Wilhelm R. Rosenblatt of the Tuberculosis Control Program, New Mexico Health

and Environment Department, echoes this point. He comments that physicians

often mistake coccidioidomycosis and histoplasmosis of the lungs for

tuberculosis. He adds that when patients suffering from fungal lung infections,

they

have inadvertently been sent to tuberculosis hospitals, and then contract

tuberculosis while there! p.30

Several studies supported by the Brown-Hazen grants have centered on the

fungus Histoplasma capsulatum, the agent responsible for the

tuberculosis-mimicking histoplasmosis. Many of these studies have concluded

that, when doctors

treat their patients as though they had contracted tuberculosis, the

histoplasmosis often worsens as a result of secondary effects of the

antibiotics used

to treat tuberculosis.p.140 This happens all too often today, when physicians

prescribe antibiotics to treat other conditions, such as chronic sinusitis,

which is typically caused by fungi and not bacteria. The antibiotics only

assure the chronicity of the underlying, fungal problem.

So, how do we contract histoplasmosis, and how could it possibly be mistaken

for tuberculosis? As it turns out, although most people in areas where H.

capsulatum is widespread breathe the fungi*s spores with no apparent damage,

others suffer harm for reasons still not fully understood. The pathogenic fungi

thrive in their lungs, where they form lesions that calcify. These calcified

lesions leave a pattern that, when X-rayed, is almost impossible for doctors

to distinguish from tuberculosis and its own calcium formations.p.145

Histoplasmosis is sometimes missed to the point that the fungal infection

behind it ends up killing the patient. Even then, the real cause of death is

often still overlooked. This happens because, unless a fungal infection is

suspected initially, pathologists tend not to test for them. Autopsies end up

fingering tuberculosis, pneumonia or even cancer as the cause of death, and not

the fungus that was actually the problem.p.29

Given this tendency to misdiagnose, it*s worth taking a closer look at some

of the more common, fungal diseases.

Cryptococcosis is a frequent cause of secondary disease in AIDS patients. It

is not isolated to any one specific, geographic area. In fact, according to

one authority, it can be found wherever there are laboratories equipped to

test for it!p.26 The disease coccidioidomycosis occurs mostly in the

Southwestern United States* more arid regions, including southwestern Texas,

southern

New Mexico, Arizona, and parts of California, especially the San Joaquin

Valley. A soil fungus called Coccidioides immitis causes the disease. When

people

breathe contaminated dust kicked up by the wind, the fungus infects their

lungs. Coccidioides immitis is apparently so hardy and so widespread that even

flying over the above mentioned areas can expose airline passengers to its

spores!p.158 This is an example of how adaptable fungi can be. When you think of

fungus or mold, you likely think of environments that are warm and moist, not

warm and dry! Yet, here is one that shows up in a place which may otherwise

be unsatisfactory for fungi to flourish.

Most victims of coccidioidomycosis come down with mild cases that involve

cough, fever, and chest pain, all of which clear up on their own, given time.

The more severe, progressive variety of the disease spreads from the lungs

throughout the body, impregnating skin, bones, and vital organs. At that point,

if not treated, the disease becomes highly malignant, with a death rate of

close to 50 percent.P.158

The North Central and Southeastern United States are home to the disease

blastomycosis, while the central Mississippi and Ohio River valleys have

histoplasmosis to contend with-as does anyone who works around or with birds,

as the

fungus is commonly found in bird droppings.

Aspergillus is another, common species of fungi capable of infecting both

the healthy and the sick. Aspergillus spores can be found airborne virtually

everywhere, including hospitals and environmentally controlled, clinical

laboratories.p.28,197

Fungi Forgotten

Despite the growing threat to public health, scientists, physicians and many

of their patients continue to display a surprising lack of knowledge and

interest in fungi. Ironically, the use of drugs other than just antibiotics,

has

only increased the dangers we face.p.23 Since the 1940s, dependence upon

broad-spectrum antibiotics has led to an increase in the number of patients

suffering from fungal diseases.p.44 Corticosteriods have been over prescribed,

as

well, in that doctors often use them to control symptoms such as

inflammation without investigating what caused such symptoms in the first

place. Used

correctly, antibiotics and corticosteroids such as prednisone can bring a

person back from near death. When they are over prescribed with no thought to

the

causes of a given illness, they can set the stage for fungi to take over.

Libero Ajello was director of the Mycology Division, Laboratory Bureau, of

the CDC in Atlanta in the early 1970s He echoes our frustration with

medicine*s inability to quantify fungal diseases because doctors are not

required to

report cases they treat.p.30

The Centers for Disease Control (CDC) did try to bridge this information gap

back in 1969. Administrators began gathering, organizing, and publishing

data on fungal diseases voluntarily supplied by physicians and investigators

around the country who had maintained their own records. Four years on, the

program ended when funds for the CDC were slashed. Additionally, the CDC was

forced to close its Kansas City field station - an outstanding center for

research, training physicians to recognize and treat fungal diseases - and a

number

of similar programs in place at other institutions.p.31

Ajello has also noted that, about the same time the effort to collect

voluntarily-maintained information was launched, the 2nd National Conference on

Histoplasmosis passed a resolution recommending that the CDC require doctors to

report fungal diseases. Despite this, histoplasmosis remains a non-reported

disease even today.

Other, scattered attempts at defining the true scope of diseases caused by

fungi were made throughout the 1970s. In 1974, the Commission on Professional

and Hospital Activities reported that 2,192 patients in the United States had

developed fungal diseases. They based their figure on stats provided by a

third of the United States' non-federal, acute-care hospitals.p.32 In 1978, 27

states combined to report 2,119 cases of fungal infections requiring

hospitalization - twice the number they*d reported the prior year.p.33 Deaths

from

candidiasis and aspergillosis accounted for slightly more than half of these

numbers, more than doubling over a ten year period. Aspergillosis deaths alone

jumped dramatically between 1976 and 1977.

To put things in perspective, the 688 deaths from fungal infections reported

to the CDC by these few hospitals in 1977 dwarfed the number of deaths

ascribed to such reportable diseases as hepatitis, meningococcal infections,

encephalitis, and rheumatic fever.

Meanwhile, Brown and Hazen continued to work to educate health care

professionals about fungi. The research fund they established fueled a program

begun

in 1970, designed to train more physicians in medical mycology.p.133 High on

the program*s needs list were physicians who could correctly diagnose fungal

diseases, and lab techs who could identify disease-causing fungi in specimens

sent to them for analysis.p.135 Back then, many medical schools did not

include lectures in Medical Mycology, while others might cover Mycology in two

or

three lectures during required courses in Microbiology. As a result, most

med techs and microbiologists knew nothing about fungi*s role in disease. Even

biologists specializing in mycology continued to study fungi from a botanical

standpoint, as a subject separate from medicine.

B. Guze is a former vice chancellor for medical affairs at

WashingtonUniversity*s School of Medicine. In 1973, he wrote that many of the

frustrations patients and physicians experience with medical care could be

solved by

better training.p.140

Sadly, more than 30 years later, fungi remain excluded from most medical

school curricula - just check the course schedule of any major medical school.

Of course, classes on fungal mycotoxins-the harmful, chemical by-products

produced by fungi-are practically nonexistent. Finally, most laboratories

remain

incapable of performing rapid, accurate diagnostic tests for fungal diseases.

The Brown-Hazen program was eventually cancelled. Absent its replacement,

today the U.S. Department of Health and Human Services* National Institute of

Allergy and Infectious Disease (NIAID) has become virtually the sole provider

of funds for work in mycology at universities, hospitals, and other

nongovernmental institutions.p.193

NIAID has made two, major grants to fund centers for medical mycology - UCLA

and Washington University at St. Louis.194 The American Society of

Microbiology greeted the grants with enthusiasm.

**The creation of these units reflects recognition,** it said, **that fungal

infections have become an increasingly important cause of disability and

death in this country. The emergence of this problem reflects the darker side

of

new treatments for malignant or immunological disorders [such as antibiotics

and chemotherapy drugs]; such treatments often appear to weaken the defense

mechanisms that ordinarily prevent such infections.**

Despite such recognition, neither the program at UCLA nor its counterpart at

WashingtonUniversity would last very long. Their cancellations were not the

losses they might have been - NIAID had specified that none of the funds it

provided could be used to actually train physicians. How could paying

scientists to analyze mushrooms in the lab benefit med students and doctors, let

alone the outside world? What's more, funding levels had been a joke. In fact,

NIAID devoted less than 2 percent of its yearly budgets to mycology, despite the

billions spent to research viruses and bacteria.

Does this mean that fungi are not the threat the Brown and Hazen believed

them to be? Not necessarily.

Late in 1977, a dust storm occurred over California's San JoaquinValley. As

we've mentioned, the disease coccidioidomycosis is common there. The storm

raised soil and fungal spores and carried them as far north as Sacramento, some

300 miles away.p.196 A year later, an epidemic of coccidioidomycosis broke

out near where the clouds of soil had finally come to rest.

Soon thereafter, Indianapolis experienced an outbreak of nearly 350 clinical

cases of acute pulmonary histoplasmosis, from which 14 people died. Most

cases during the epidemic were reported from neighborhoods located downwind

from

heavy construction. In other words, fungi liberated by digging equipment

more than likely caused the infections.

Environmental disturbances that spread fungi comprise the common denominator

between incidences like those in California and Indianapolis. Remember this

next time when you or someone you know gets sick. Time spent in or around

construction sites could be to blame.

While incidences such as those in California and Indianapolis added to the

evidence that the fungal diseases required more attention, CDC investigators

were working to measure how widespread the problem had actually become. The

center*s report was published in the Journal of the American Medical

Association (JAMA) in late 1979, paraphrased below.p.197

From 1970 to 1976, studies of a third of American hospitals showed that the

number of candidiasis cases had risen 9 percent, while Aspergillus had risen

158 percent. Contributing factors in the rise of cases of coccidioidomycosis,

cryptococcosis, and aspergillosis included the use of immune-system

suppressing drugs, population increases in areas where fungal infections had

become

endemic, and simple aging. Histoplasmosis and coccidioidomycosis combined to

cause more than 75 percent of all reported cases of systemic fungal disease,

while aspergillosis, candidiasis, and cryptococcosis caused the longest

duration of hospitalization and the highest death rates. The total cost of

these

fungal diseases was estimated at $27 million in 1976.p.198 Clearly, fungal

diseases were out of control. Given this, the small number of antifungal drugs

developed since then and the ever growing use of antibiotics, the situation has

not improved to date.

Although doctors are key in any effort to generate better data as to the

impact of fungal diseases, federal law continues to exempt them from reporting

such diseases to the CDC. What's more, when the states write their own laws as

to which diseases require reporting to state-based disease organizations,

they exclude fungi, as well.p.199

It appears that the United States does not stand alone with regard to this

problem. Speaking before a Biological Conference in Israel in 1976, the CDC*s

Ajello maintained that fungal diseases remained unreported worldwide.

Why is it important to require that fungal diseases be reported? Moreover,

why has the study of viruses and bacteria received so much funding, while

fungi remain virtually ignored? The answer is that, without proper stats,

increased funding for training and diagnostic centers, as well as research, is

difficult if not impossible to obtain. Researchers who study fungi must compete

for the limited funds available for disease research in general. In this, they

are at a disadvantage. While scientists who study bacteria and viruses can

point to convincing, up-to-date, concrete data on sickness and death rates,

until fungal diseases are changed to reportable status, scientists who study

fungi are forced to use old data and anecdotes that may or may not still be

relevant.

NIAID put together a fact sheet in September of 1996. **Although still

outnumbered by their bacterial and viral counterparts,** the sheet states,

**fungal pathogens are responsible for an increasing number of emerging

infectious

diseases.** The fact sheet goes on to say that between 1985 and 1995, NIAID

more than doubled the number of fungal disease research grants and contracts it

supports from 42 to 95. It also more than quadrupled funding for such

research, from $6.5 to almost $29 million. The increase in spending is

encouraging.

And yet, at least according to the 1996 Fact Sheet, the objectives of NIAID

funded research appear to remain unchanged since the 1970s. Rather than focus

upon training physicians how to recognize fungal diseases, it would seem

that NIAID has chosen to continue its focus on laboratory research. The question

is, what is the focus of this research? Are they studying fungi that attack

insects and plants, or are they truly addressing the human pathogens? NIAID*s

1996 Fact Sheet fails to answer this question. Finally, though the millions

of dollars spent on fungal research may sound generous, again, it is still

dwarfed by the billions spent studying bacterial and viral pathogens.

We challenge scientists to perform the vital research necessary to combat

human illness. We believe that in the process, our position will only be

strengthened, and that all of humanity will come closer to winning its fight

against the fungi.

1.Baldwin, S. The Fungus Fighters: Two Women Scientists and Their

Discovery. CornellUniversity Press. Ithaca and London. 1981.

2.Tewari, S.N., Fletcher, R. The Efficacy of Mysteclin and Tetracycline. The

British Journal of Clinical Practice. Vol. 20 No 12. Dec. 1966.

Mycotoxins: Risks in Plant, Animal, and Human Systems. Task Force Report No.

139. Jan 2003. Council for Agricultural Science and Technology (CAST). Ames,

IA. ISBN: 1-887383-22-0. Phone 515-292-2125. _cast@..._

(mailto:cast@...) . _www.cast-science.org_

(http://www.cast-science.org)

.. 199 pp.

The Fungalbionic® Series: The Fungal/Mycotoxin Etiology of Human Disease, by

A.V. Costantini, et al.

Website for ordering: click here (it’s best to call the number to order)

Clinical Mycology. (Chapter 30: Mycotoxins and Human Disease) Anaissie, Elias,

et al.

Churchill Livingstone. Philadelphia, PA. 2003. ISBN: 0-443-07937-4. 608 pp.

Cover N/A

Mycotoxins, Cancer, and Health. PenningtonCenter Nutrition Series, Vol. 1.

Bray, and , Donna, eds. LouisianaStateUniversity Press, Baton Rouge

and London. 1991. ISBN: 0-8071-1679-3. 331 pp

Principles and Practice of Clinical Mycology. C.C. Kibbler, et al. eds.

Wiley and Sons, West Sussex, England. 1996. ISBN: 0-471-961043. 275 pp.

Fundamentals of the Fungi. 4th ed. -Landecker. Prentice Hall.

Upper Saddle River, New Jersey. ISBN: 0-13-376864-3. 1996. 574 pp

A Practical Guide to Medically Important Fungi and the Diseases they Cause.

Sugar, A & Lyman, C. Lippincott-Raven. Philadelphia and New York. ISBN:

0-397-5186-X. 1997. 153 pp.

The Scientific Validation of Herbal Medicine. Mowrey, Dan, PhD. Keats

Publishing. New Canaan, Connecticut. ISBN: 0-87983-534-6. 1986. 316 pp.

RELATED INFO

....In September 1999, s Hopkins medical researchers confirmed that

virtually all chronic sinus infections were due to fungus. Not all findiings

are

that solid. As a matter of fact, few are. Rather, scientists seem confused and

startled at their own discoveries with regard to fungus. Fungus makes

poisonous byproducts called mycotoxins. Antibiotics are one class of

mycotoxins.

Without this knowledge, however, many questions are raised when researchers

stumble onto this seemingly elementary fact. Recently, researchers have

discovered that antibiotics are contributing to everything from 2nd heart

attacks to

breast cancer. It is our hope that someday when discoveries like these are

made, logic will supercede confusion.