Fungi cause catastrophic diseases such as diabetes and heart disease

[Guest guest]

http://www.knowthecause.com/sciencefungus.html By: Doug A. Kaufmann

 

The following is based largely on The Fungus Fighters: Two WomenScientists and Their Discovery, written by Richard Baldwin in 1981.The book chronicles the discovery of nystatin, and it develops howfungi have come to be largely ignored by the world of medicine,despite the many cases and studies that document their role in causingdisease.

 

Elizabeth Hazen and Rachel Brown teamed up in the late 1940s todevelop a safe, effective antifungal for use in medicine. Hazen hadalready had a long career as a microbiologist and as a mycologist, orfungi specialist, while Brown specialized in organic chemistry. Theirresearch was funded by the New York State Division of Laboratories andby the N.Y. Health Department. The two scientists tested theeffectiveness of a wide variety of agents against two, particularlydangerous fungi: Cryptococcus neoformans and Candida albicans.

 

By 1949, Brown and Hazen had discovered nystatin. The agent workednot only against the targeted microbes, but against fourteen otherfungi, as well. The second part of this last statement is important,because it counts as one of many incidences in which nystatin has beenshown to work as a broad-spectrum antifungal. Unfortunately, the FDAhas only approved the drug for use in treating Candida found in themouth (thrush) or on the skin. Clearly, that approval should bebroadened.p.78 Even if it never is, however, the FDA's stance is notmuch of an obstacle. Remember, once a drug is approved for use intreating one disease, doctors have license to use it to treat otherconditions as they see fit.

 

Nystatin is produced by the fungus, Streptomyces noursei. The drug isnamed after the organization that funded Hazen and Brown's research -N.Y. State. Although it is, in fact, a mycotoxin, it has yet todemonstrate any of the harmful side effects, including cancer andatherosclerosis, found in the mycotoxins produced by other fungi.

 

Hazen and Brown found that for efficient, mass production ofnystatin, peanut meal turned out to be the ideal substance for growingStrptomyces noursei.p.14 This is hardly surprising today - evenpeanuts grown for human consumption are notorious for fungalcontamination. Among other contaminants, the nuts have to befrequently screened for a mycotoxin called aflatoxin.

 

The two scientists presented their findings at the National Academy ofSciences regional meeting in Schenectady in the fall of 1950.p.79Squibb Inc. - now known as Bristol-Myers Squibb - got the nod forfurther 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 withina month. Nystatin was described as "the first broadly effectiveantifungal antibiotic available to the medical profession." It wasrecommended for the prevention and treatment of intestinal moniliasis,or candidiasis, especially for patients taking oral antibacterialantibiotics for prolonged periods. It was also recommended forprevention of intestinal moniliasis in intestinal surgery. Researchersreported that Mycostatin could clear up established yeast infectionsin patients' digestive tracts within one to two days; a full course oftreatment typically lasted 21-30 days.

 

Hazen and Brown created a nonprofit organization to receive theirshare of the royalties from the sale of nystatin, which over the spanof their 16-year patent eventually came to almost $7 million. TheBrown-Hazen grants program became the United States' largest, singlesource of non-federal funding for research and training in combattingfungal disease.p.103 Hazen and Brown accepted not even a dime fortheir personal use.

 

Today, nystatin is widely available in both as a brand name and as ageneric drug. According to Bristol-Myers Squibb's website, worldwidesales through 2001 of the pharmaceutical company's Mycostatin alonetotaled $15.3 billion.

 

Squibb later combined nystatin with the antibiotic, tetracycline. Thenew drug, Mysteclin, was designed to offset the yeast overgrowth thatoften happens from taking antibiotics. Other manufacturers followedsuit. The host of combination drugs that arose were later banned bythe FDA for "lack of proof of efficacy," though they continue to besold in other countries. In its decision, it seems that the FDA mayhave ignored a number of studies in the 1950s and 1960s that clearlydocumented not only that antibiotic administration often leads to theovergrowth of intestinal yeast, but that combining nystatin withantibiotics could stop such growth in its tracks.2

 

In 1960, Squibb came out with a more soluble antifungal calledFungizone (amphotericin B) that could be administered both orally andthrough an I.V.p.124 Amphotericin-B was also combined with antibioticsby various drug manufacturers - one such combination, Mysteclin F, canstill be found overseas. Unfortunately, even though it proved safewhen taken in pill form, amphotericin turned out to have harmful sideeffects over the long term when administered intravenously. Today,although safer, systemic antifungals have been developed, amphotericinremains a key drug used to treat a number of life-threatening, fungalinfections.

 

The Prevalence and Seriousness of Fungal Diseases Hazen and Brown's work was sparked by their awareness of the growingdanger of fungal illnesses. Remember, however, that then, as now,doctors have not been required to report fungal diseases, which makesan exact quantification of the true extent of fungi-caused diseaseimpossible.

 

That said, the National Health Survey performed by the U.S. PublicHealth Service showed that by the early 1970s, 8 percent, or 16million Americans, were suffering from skin conditions caused byfungi.p.24 These numbers qualify such infections as an unofficialepidemic. The same health service reported that "unknown numbers ofpeople, regardless of occupation or location, have contracted one oranother of the most serious of the fungus diseases - the deep,systemic mycoses - which can disable and kill." This number remainsunknown not just because doctors are not required to report fungaldisease, but also because such infections are often misdiagnosed asother diseases.p.25

 

The ability of some of the more serious, fungal diseases to mimicother, common diseases encountered in medicine is no small problem.Indeed, some scientists believe that fungal pathogens account for moreupper respiratory infections than bacteria and viruses combined. Fungican cause all of the symptoms associated with low-grade, upperrespiratory infections, such as mild fever and cough, chills,sweating, and headache. Examination of more serious, fungal infectionsoften 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 theirtreatments upon the inaccurate diagnoses, addressing the symptomsinstead of the actual cause of the disease at hand. In cases in whichantifungal measures are finally applied as a last resort, the point atwhich such an approach would have been most effective has often longsince passed.

 

Health care professionals often rush their patients into medicinal orsurgical treatments in order to control rapidly worsening conditionsin time. We should remember that such haste could increase the chanceof a wrong diagnosis, which then makes the quickly delivered treatmentworse than meaningless.

 

Wilhelm R. Rosenblatt of the Tuberculosis Control Program, New MexicoHealth and Environment Department, echoes this point. He comments thatphysicians often mistake coccidioidomycosis and histoplasmosis of thelungs for tuberculosis. He adds that when patients suffering fromfungal, lung infections have inadvertently been sent to tuberculosishospitals, they often contracted tuberculosis in addition to theiralready-misdiagnosed fungal lung infection.p.30

 

Several studies supported by the Brown-Hazen grants have centered onthe fungus Histoplasma capsulatum, the agent responsible for thetuberculosis-mimicking histoplasmosis. Many of these studies haveconcluded that, when doctors treat their patients as though they hadcontracted tuberculosis, the underlying cases of histoplasmosis oftenworsen as a result of secondary effects of the antibiotics used totreat tuberculosis.p.140 This happens all too often today, whenphysicians prescribe antibiotics to treat other conditions, such aschronic sinusitis, which is typically caused by fungi and notbacteria. The antibiotics only assure the chronicity of theunderlying, fungal problem.

 

So, how do we contract histoplasmosis, and how could it possibly bemistaken for tuberculosis? As it turns out, although most people inareas where H. capsulatum is widespread breathe the fungi's sporeswith no apparent damage, others suffer harm for reasons still notfully understood. The pathogenic fungi thrive in their lungs, wherethey form lesions that calcify. These calcified lesions leave apattern that, when X-rayed, is almost impossible for doctors todistinguish from tuberculosis and its own, calcium formations.p.145

 

Histoplasmosis is sometimes missed to the point that the fungalinfection behind it ends up killing the patient. Even then, the realcause of death is often still overlooked. This happens because, unlessa fungal infection is suspected initially, pathologists tend not totest for them. Autopsies end up fingering tuberculosis, pneumonia oreven cancer as the cause of death, and not the fungus that wasactually the problem.p.29

 

Given this tendency to misdiagnose, it's worth taking a closer lookat some of the more common, fungal diseases.

 

Cryptococcosis is a frequent cause of secondary disease in AIDSpatients. It is not isolated to any one specific, geographic area. Infact, according to one authority, it can be found wherever there arelaboratories equipped to test for it!p.26 The diseasecoccidioidomycosis 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. Asoil fungus called Coccidioides immitis causes the disease. Whenpeople breathe contaminated dust kicked up by the wind, the fungusinfects their lungs. Coccidioides immitis is apparently so hardy andso widespread that even flying over the above mentioned areas canexpose airline passengers to its spores!p.158

 

Most victims of coccidioidomycosis come down with mild cases thatinvolve cough, fever, and chest pain, all of which clear up on theirown, given time. The more severe, progressive variety of the diseasespreads from the lungs throughout the body, impregnating skin, bones,and vital organs. At that point, if not treated the disease becomeshighly malignant, with a death rate of close to 50 percent.P.158

 

The North Central and Southeastern United States are home to thedisease blastomycosis, while the central Mississippi and Ohio Rivervalleys have histoplasmosis to contend with-as does anyone who worksaround or with birds, as the fungus is commonly found in birddroppings.

 

Aspergillus is another, common species of fungi capable of infectingboth the healthy and the sick. Aspergillus spores can be foundairborne virtually everywhere, including hospitals and environmentallycontrolled, clinical laboratories.p.28,197

 

Fungi Forgotten Despite the growing threat to public health, scientists, physiciansand many of their patients continue to display a surprising lack ofknowledge and interest in fungi. Ironically, the use of drugs againstother illnesses, including antibiotics, has only increased the dangerswe face.p.23 Since the 1940s, dependence upon broad-spectrumantibiotics has led to an increase in the number of patients sufferingfrom fungal diseases.p.44 Corticosteriods have been overprescribed, aswell, in that doctors often use them to control symptoms such asinflammation without investigating what caused such symptoms in thefirst place. Used correctly, antibiotics and corticosteroids such asprednisone can bring a person back from close to death. When they aregiven with no thought to the causes of a given illness, they can setthe stage for fungi to take over.

 

Libero Ajello was director of the Mycology Division, LaboratoryBureau, of the CDC in Atlanta in the early 1970s He echoes ourfrustration with medicine's inability to quantify fungal diseasesbecause doctors are not required to report cases they treat.p.30

 

The Centers for Disease Control (CDC) did try to bridge thisinformation gap back in 1969. Administrators began gathering,organizing, and publishing data on fungal diseases voluntarilysupplied by physicians and investigators around the country who hadmaintained their own records. Four years on, the program ended whenfunds for the CDC were slashed. Additionally, the CDC was forced toclose its Kansas City field station - an outstanding center forresearch and training physicians to recognize and treat fungaldiseases - and a number of similar programs in place at otherinstitutions.p.31

 

Ajello has also noted that, about the same time the effort to collectinformation maintained voluntarily was launched, the 2nd NationalConference on Histoplasmosis passed a resolution recommending that theCDC 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 diseasescaused by fungi were made throughout the 1970s. In 1974, theCommission on Professional and Hospital Activities reported that 2,192patients in the United States had developed fungal diseases. Theybased their figure on stats provided by a third of the United States'non-federal, acute-care hospitals.p.32 In 1978, 27 states combined toreport 2,119 cases of fungal infections requiring hospitalization -twice the number they'd reported the prior year.p.33 Deaths fromcandidiasis and aspergillosis accounted for slightly more than half ofthese 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 infectionsreported to the CDC by these few hospitals in 1977 dwarfed the numberof deaths ascribed to such reportable diseases as hepatitis,meningococcal infections, encephalitis, and rheumatic fever.

 

Meanwhile, Brown and Hazen continued to work to educate health careprofessionals about fungi. The research fund they established fueled aprogram begun in 1970, designed to train more physicians in medicalmycology.p.133 High on the program's needs list were physicians whocould correctly diagnose fungal diseases, and lab techs who couldidentify disease-causing fungi in specimens sent to them foranalysis.p.135 Back then, many medical schools did not includelectures in Medical Mycology, while others might cover Mycology in twoor three lectures during required courses in Microbiology. As aresult, most med techs and microbiologists knew nothing about fungi'srole in disease. Even biologists specializing in mycology continued tostudy fungi from a botanical standpoint, as a subject separate frommedicine.

 

Samuel B. Guze is a former vice chancellor for medical affairs atWashington University's School of Medicine. In 1973, he wrote thatmany of the frustrations patients and physicians experience withmedical care could be solved by better training.p.140

 

Sadly, more than 30 years later, fungi remain excluded from mostmedical school curriculums - just check the course schedule of anymajor medical school. Of course, classes on fungal mycotoxins-theharmful, chemical byproducts produced by fungi-are practicallynonexistent. Finally, most laboratories remain incapable of performingrapid, accurate diagnostic tests for fungal diseases.

 

The Brown-Hazen program was eventually cancelled. Absent itsreplacement, today the U.S. Department of Health and Human Services'National Institute of Allergy and Infectious Disease (NIAID) hasbecome virtually the sole provider of funds for work in mycology atuniversities, 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 Societyof Microbiology greeted the grants with enthusiasm.

 

"The creation of these units reflects recognition," it said, "thatfungal infections have become an increasingly important cause ofdisability and death in this country. The emergence of this problemreflects the darker side of new treatments for malignant orimmunological disorders [such as antibiotics and chemotherapy drugs];such treatments often appear to weaken the defense mechanisms thatordinarily prevent such infections."

 

Despite such recognition, neither the program at UCLA nor itscounterpart at Washington University would last very long. Theircancellations were not the losses they might have been - NIAID hadspecified that none of the funds it provided could be used to actuallytrain physicians. How could paying scientists to analyze mushrooms inthe lab benefit med students and doctors, let alone the outside world?What's more, funding levels had been a joke. In fact, NIAID devotedless than 2 percent of its yearly budgets to mycology, despite thebillions spent to research viruses and bacteria.

 

Does this mean that fungi are not the threat the Brown and Hazenbelieved 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 commonthere. The storm raised soil and fungal spores and carried them as farnorth as Sacramento, some 300 miles away.p.196 A year later, anepidemic of coccidioidomycosis broke out near where the clouds of soilhad finally come to rest.

 

Soon thereafter, Indianapolis experienced an outbreak of nearly 350clinical cases of acute pulmonary histoplasmosis, from which 14 peopledied. Most cases during the epidemic were reported from neighborhoodslocated downwind from heavy construction. In other words, fungiliberated by digging equipment more than likely caused the infections.

 

Environmental disturbances - some caused by human activity - thatspread fungi comprise the common denominator between incidences likethose in California and Indianapolis. Remember this next time when youor someone you know gets sick. Time spent in or around constructionsites could be to blame.

 

While incidences such as those in California and Indianapolis added tothe evidence that the fungal diseases required more attention, CDCinvestigators were working to get some measure as to how widespreadthe problem had actually become. The center's report was published inthe 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 showedthat the number of candidiasis cases had risen 9 percent, whileAspergillus had risen 158 percent. Contributing factors in the rise ofcases of coccidioidomycosis, cryptococcosis, and aspergillosisincluded the use of immune-system suppressing drugs, populationincreases in areas where fungal infections had become endemic, andsimple aging. Histoplasmosis and coccidioidomycosis combined to causemore than 75 percent of all reported cases of systemic fungal disease,while aspergillosis, candidiasis, and cryptococcosis caused thelongest duration of hospitalization and the highest death rates. Thetotal cost of these fungal diseases was estimated at $27 million in1976.p.198 Clearly, fungal diseases were out of control. Given this,the small number of antifungal drugs developed since then and the evergrowing use of antibiotics, the situation has not improved to date.

 

Although doctors are key in any effort to generate better data as tothe impact of fungal diseases, federal law continues to exempt themfrom reporting such diseases to the CDC. What's more, when the stateswrite their own laws as to which diseases require reporting tostate-based disease organizations, they exclude fungi, as well.p.199

 

It appears that the United States does not stand alone with regard tothis problem. Speaking before a Biological Conference in Israel in1976, the CDC's Ajello maintained that fungal diseases remainedunreported worldwide.

 

Why is it important to require that fungal diseases be reported?Moreover, why has the study of viruses and bacteria received so muchfunding, while fungi remain virtually ignored? The answer is that,without proper stats, increased funding for training and diagnosticcenters, as well as research, is difficult if not impossible toobtain. Researchers who study fungi must compete for the limited fundsavailable for disease research in general. In this they are at adisadvantage. While scientists who study bacteria and viruses canpoint to convincing, up-to-date, concrete data on sickness and deathrates, until fungal diseases are changed to reportable status,scientists who study fungi are forced to use old data and anecdotesthat may or may not still be relevant.

 

NIAID put together a fact sheet in September of 1996. "Although stilloutnumbered by their bacterial and viral counterparts," the sheetstates, "fungal pathogens are responsible for an increasing number ofemerging infectious diseases." The fact sheet goes on to say thatbetween 1985 and 1995, NIAID more than doubled the number of fungaldisease research grants and contracts it supports from 42 to 95. Italso more than quadrupled funding for such research, from $6.5 toalmost $29 million. The increase in spending is encouraging. And yet,at least according to the 1996 Fact Sheet, the objectives of NIAIDfunded research appear to remain unchanged since the 1970s. Ratherthan focus upon training physicians how to recognize fungal diseases,it would seem that NIAID has chosen to continue its focus onlaboratory research. The question is, what is the focus of thisresearch? Are they studying fungi that attack insects and plants, orare they truly addressing the human pathogens? NIAID's 1996 Fact Sheetfails to answer this question. Finally, though the millions of dollarsspent on fungal research may sound generous, again, it is stilldwarfed by the billions spent studying bacterial and viral pathogens.

 

We have outlined in this book how fungi cause catastrophic diseasessuch as diabetes and heart disease. We look forward to the scientificcommunity's response. We challenge scientists to perform the vitalresearch necessary to prove to us we are wrong. We believe that in theprocess, our position will only be strengthened, and that all ofhumanity will come closer to winning its fight against the fungi.

 

1.Baldwin, Richard S. The Fungus Fighters: Two Women Scientists andTheir Discovery. Cornell University Press. Ithaca and London. 1981. 2.Tewari, S.N., Fletcher, R. The Efficacy of Mysteclin andTetracycline. The British Journal of Clinical Practice. Vol. 20 No 12.Dec. 1966.