I am a member of a group of veterinarians who all became ill within about a years time of each other, and who all were employed in the same physical location. Some of the affected veterinarians also had human and/or canine family members who also went on to develop a very similar illness to that seen in the cluster of veterinarians. The practice facility was inspected by OSHA and traditional medical work-up was done on all of those affected. No unifying etiology could be determined for the "syndrome" of illness described by those affected, but environmental chemicals and psychiatric causes were ruled out. As veterinarians and other types of scientists (affected family members), we recognized that the pattern of illness development appeared most consistent with some type of infectious process (possibly with genetic predispositions to resistance/succeptibility to the agent). The illness appeared to develop in unrelated people who worked at a common site initially, then multiple family members of some affected veterinarians developed a similar illness. Our familiarity with collecting/interpreting FNA/cytology samples allowed us to do some diagnostic tests that are not available in human reference laboratories, and with the encouragement of infectious disease physicians at Mayo and UCD medical centers we began some carefully controlled cytology tests on samples provided by those affected with the "syndrome" of illness, as well as samples from healthy control family members/colleagues.
What we have found is an incredibly consistent pattern of fibers/filaments, copiously present in the urine of those affected individuals, and completely absent in the healthy controls. Initially we suspected the filaments to be a possible nematode, but further tests demonstrated that there were also more fragile yeast-like objects and highly organized fruiting-body-like structures associated with the filaments. We also found the filaments and "spores" in subcutaneous nodules, cyst fluid, sputum, and blood cultures from those affected. These details, along with positive staining for chitin by lactophenol cotton blue and calcofluor-white, and positive staining for a thick mucopolysaccharide coat by Alacian Blue- led us to modify the hypothesis and consider that these objects could indicate a fungal or pseudofungal infection.
Many permutations of cytology tests (always coupled with control studies of the same tissues in healthy counterparts) have led us to suspect that we may be seeing some type of oomycete, somewhat similar to Pythium or Lagenisma. We have attempted sequencing, but not gotten consistent results and/or have gotten reports of sequences that are either truncated or reported as different types of fungi, none of which are obviously close relatives of oomycetes. Since this research is unfunded, we have not been able to pursue as much molecular testing as would be ideal. The UCD infectious disease physician did agree that the images were compelling, but not his primary field of study. He/we filed a report with the CDC about the possiblity of this being an emerging/novel human pathogen, but the CDC has not replied to his follow-up requests for assistance in characterizing the findings.
I realize our involvement in this research is both non-traditional and that those of us doing it have motivations beyond that which drives most research. However, we have had enough independent scientists/physicians corroborate our perception that we are seeing something "not normal" in the tissues/fluids of those affected compared to the healthy controls, and encourage us to continue to try to find answers, that I feel compelled to post our findings thus far and ask for opinions and advice. We are hoping that someone, much more expert in mycology/protistology than us might be willing to review these images and offer their perspective. Also, if there is anyone actively pursuing ( or wanting to pursue) this line of research, we are happy to share all of our data gathered thus far, in hopes that it may lead to faster and more thorough characterization of what we have found, and hopefully application to determine which chronic diseases may have this putative infection as a component of their etiology.
Thanks!
Dear Dr.Melinda,
I am attaching PDF of our Review article to your reference with a hope that it will be useful to you.
Please confirm receipt of the review on Pythiosis.
With best wishes and good luck,
Prof.Dr.Mahendra Pal
Dear Dr.Melinda,
I am distressed to know that several persons were affected with the disease of undefined etiologies. Though I worked in the field of Veterinary and Medical Mycology, I have never came across any case of Pythium as suspected by you.
I retired as University Professor and Head in early 2006. However, I still remain active in academic field.
I am attaching one review on Pythiosis that describes clinical symptoms, diagnostic tests, and treatment. You must consult the Physician before taking any drug/s.
Please feel to seek any advise from me.
Wishing you a good health and happiness.
Prof.Dr.Mahendra Pal
Dear Dr.Melinda,
I am attaching PDF of our Review article to your reference with a hope that it will be useful to you.
Please confirm receipt of the review on Pythiosis.
With best wishes and good luck,
Prof.Dr.Mahendra Pal
Thank you, @Mehendra Pal. Dr Pal, i appreciate the information on Pythiosis. Pythiosis is something we had considered as a possibility etiology. We did have a canine case of confirmed pythiosis in our practice near the time of the cluster of human infections of unknown etiology. While pythiosis has not been definitively ruled out, it is presenting differently in the cohort of affected humans than classical cutaneous or vascular pythiosis would be expected to. Some of the affected veterinarians have had small ulcerated lesions with some oozing, that might be considered draining tracts, but the more obvious clinical signs are hematuria, development of numerous tender subcutaneous nodules, dystegulation of phosphate homeostasis, non-pitting edema, and profound fatigue. The protracted, but somewhat mild clinicsl course is inconsistent with numerous reports of human pythiosis in the literature- leading us to wonder if this might be some novel oomycete, but a more distant telative than pythiosis.
@Phil Geis, Thanks for the follow-up question/thoughts! Nothing was recovered from routine bacterial/fungal culture (send out) for two of the human patients tested, though in-house culture done at 25degrees C did show odd raised "clear" colonies (absent at samples cultured at 30 degrees). It was from those "clear" raised areas on the culture plate that the images in the post labeled "from cultured blood" were obtained. Also, we are mindful that the calcofluor white staining/fluorescence could indicate cellulose or chitin, and that was one of the reasons that we have also not completely ruled out the possibility of a protozoal organism, or a "pseudofungus" such as a myxamoeba. But between the strong staining of portions of these objects with calcofluor white, lactophenol cotton blue, and Alacian blue, it seemed reasonable evidence that the target objects were not normal mammalian cells, since either chitin or cellulose would be a material not synthesized by mammalian cells/tissues. Unfortunately, in our veterinary practice laboratory, we do not have the capacity to perform either GMS silver staining or immunohistochemistry for chitin/cellulose (and/or more specifically against whatever we suspect the putative organism to be) These tests would be far more definitive.... Part of our rationale in posting these findings/this theory is to hopefully make contact with someone with similar interests, and those capabilities- with whom we might be able to collaborate.
@Mahendra Pal,
Hi Dr. Pal, My apologies- in an earlier reply to your answer I was typing from my phone where I could not see the input field- so please excuse the multiple typos there. As I was trying to say in the previous reply- We appreciate your helpful summary document about Pythiosis. I need to read it in more depth to make certain I haven't missed anything. We did consider the possibility of traditional pythiosis. We even had a case of canine intestional pythiosis treated at our practice around the time that people started getting ill (though we can't recall exactly). However, the illness "syndrome" among the affected veterinarians and some of their extended family presents fairly differently from the classic forms of cutaneous, vascular, or intestinal pythiosis. Those affected have all had persistent hematuria, with no known cause other than the presence of these "filaments" that are absent in matched controls. They have had some mild skin lesions, occasionally with subtle draining tracts- but these have all healed without intervention. Most have numerous small subcutaneous nodules that vary from painless to very tender. Several have had derangements in phosphorus levels and elevated PTH levels. Many have non-pitting or pitting edema. All have had profound fatigue. Clinical complaints have been present for years- plateauing in some individuals and progressive in others. The initial cluster of cases was linked by physical location- though mold testing at the site of the practice yeilded no evidence of exposure to pathogenic molds (or other chemicals.... beyond what all veterinarians are exposed to in the course of their work). The cases that followed in extended family members are spread across individuals in different states and even countries- with the only linking factor being that they are relatives (mostly blood relatives, but at least one step-relative) of one of the veterinarians who became ill in the original cluster at the practice. So, we don't really think this is actual pythiosis..... just that the cytology findings were similar enough to what is seen in some of the oomycetes (both free-living, non-pathogenic forms, as well as the few documented cases pathogenic in animals) that we thought it a reasonable hypothesis to pursue, and to hopefully engage the interest of specialists like yourself who know much more about the morphologies of these things than a bunch of small animal veterinarians! Thanks for your response! - Melinda
Dear Dr.Melinda,
Many thanks to your kind words. If possible, I advise you to please send stained and unstained smears and also histopathological slides to The Division of Mycology, CDC, Atlanta, Georgia, USA. I know that CDC has all facilities to confirm the diagnosis. Before sending to CDC, please ask whether diagnosis will be made free or on payment.
I wish you a grand success in your mission.
Prof.Dr.Mahendra Pal
MVPH, Ph.D.,D.Sc.
In these images show a pathogenic consistent of w/oomycetes /myxomycetes /fungus.
The oomycetes also known as water molds are group of several hundred organism that included some of the most devastating plants pathogens.the disease they cause include seeding blights,damping off,root rots,foliar blights and downy mildews.some notable diseases are the late blight of potato,downy mildew of grape vine ,sudden oak death,and root and stem not of soybean.
Because of their filamentous growth habit ,nutrition by absorption and reproduction via spores ,oomycetes were long regarded by plant pathologists as lower fungi.however as our understanding of evolutionary understanding of evolutionary relationship has grown,it now clear that this group of organisms is unrelated to true fungi.
Indeed fungi appear more closely related to animals than to oomycetes and oomycetes and oomycetes are closely related to algae to green plants.myxomycetes the true slime molds,are highlighted in research and teaching that emphasizes various stages of life cycle as experimental modules ,past and current phylogenetic classifications of myxomycetes on the tree of life are presented .life cycle stages are illustrated described and discussed .simple laboratory demonstrations and experiments are describe that include spore germination ,spore releases and moist chamber cultures utilizing .Aeroallergens include fuligo septica
The plasmodial stage of physarum prolycephalum has been used as a model research system to study responses to gravity in outer space ,solve the shortest pathway through a maze exhibiting primitive intelligence.
Despite the presence of human parasite within the same per class as the myxomycetes and evidence for flagellate protistica as phytopathogens these groups are distantly related and there is no evidence that myxomycetes are parasite or phytopathogenic .the most remarkable e.g of myxomycetes enabling cancer treatment is with a non toxic ,non immunologenic,and biodegradable nanoconjugate drug delivery system called plycetin.
Polycetin is synthesized from purified poly(B-L-malic acid )(BY -P.polycrphalum)and is subsequent.
Pathogenic fungi are fungi that cause disease in humans or other organisms.approximately 300 fungi are known to be pathogenic to humans is called medical mycology although fungi are microorganisms.
The study of fungi and other organisms pathogenic to plants is called pathology
Melinda Sarte
Members of Myxomycetes are presently grouped under different kingdoms, such as oomycetes are grouped under Kingdom- Straminipila. I have seen one of your images some chlamidospores may have a single flagellum which is in agreement with features of myxomycetes . So if this infectious microorganism has some similarities with myxomyctes you can go for another analysis of cell wall composition (to detect wheather it contain cellulose or not as it is a typical feature of Oomycetes ) and analysis of flagella characteristics (number, position, type and movement) which are key criteria for grouping a certain microrganism under myxomycetes. A myxomycetes human pathogen is a quite rare and novel discovery. Best of Luck Mam.
Dear Dr.Melinda, Hope you will be well. Did you inquire from the Director of The Division of Mycology, CDC, Atlanta, Georgia, USA to help you in confirming an unequivocal diagnosis ? I wish you a grand success in your mission. Prof.Dr.Mahendra Pal MVPH, Ph.D.,D.Sc.
Founder Director of Narayan Consultancy
Mahendra Pal , Hi Dr. Pal. We did file a report with the CDC, both directly by myself and by the Infectious Disease physician at UC Davis Medical Center, who is the main contact point between the CDC and our research group. Unfortunately, despite three relatively recent follow-up messages he has left with the CDC, he has not received any follow-up regarding where to send the images, or actual slides, for CDC review. He was told that due to COVID demands, our report would likely not be pursued very quickly. However, even our initial reports were made quite a while prior to the onset of the COVID pandemic, and we were having trouble getting much engagement from the CDC even before COVID was an issue. Sadly, we learned that the first report I filed was not even logged in, as intake secretary at the CDC immediately dismissed any possibility that these findings were significant. The second report (made by the UCD ID physician), was logged in, but hasn't been pursued as far as we can tell.
I do understand how far-fetched sounding a scenario it is to suggest that a group of veterinarian/scientists in other disciplines could have noticed something that has not been recognized yet by academic pathologists/infectious disease physicians etc.... However, I do think that this scenario might be possible since the cytology techniques routinely used by veterinarians are different (preserve/highlight different details) than the histopathology techniques routinely used by clinical laboratories in human medical systems. Most veterinarians prepare and interpret cytology preparations for infectious/neoplastic screening on a daily basis, and we have a different skill set that makes veterinarians alert to patterns that fall outside the norm for what should be present in mammalian tissue and fluid samples (plus my additional training in ultrastructural studies).
While I haven't yet specifically reached out to the Mycology Division of the CDC (in following their policy of allowing the report to be processed through the channels they determine appropriate), the general CDC gatekeepers have definitely been badgered by both myself and the ID physician overseeing the cluster- without any reply or direction provided by the CDC in response. I was hoping to be more certain that this was a fungus/pseudo-fungus before attempting to contact the mycology department specifically, but if you know people there and think that they would be open-minded to such a query, I would be happy to reach out to them directly.
Many thanks for your time and suggestions!
Dear Dr.Melinda,
It is very unfortunate that the problem of confirming the diagnosis is still not solved. Earlier, I was knowing Dr.Ajello who was Director of Mycology Division CDC, Atlanta. After the demise of Dr.Ajello, I do not know who is currently on the chair. Dr. Ajello was a very good person who helped me several times.
You can see on Google search whether Dr.Arvind Padhye, Indian born but settled in USA, is still working in the Division of Mycology at CDC, Atlanta.Though I have no personal relation, I can still request for you.
You may please also try to contact the following Institutes.
1.International Mycological Institute, Bakecham Lane,Egham, Surrey TW209TY, UK
2.Mycological Reference Laboratory, Public Health Laboratory Service, Myrtle Road, Kingsdown,Bristol BS28EL, UK
3. Australian National Reference Laboratory in Medical Mycology, Royal North shore Hospital, Pacific Highway, St.Leonards,NSW2065, Australia
4 .Laboratory of Mycology, Pasteur Research Institute, Paris, France
I wish and pray to God that you get an early diagnosis.
With kindest warm regards,
Prof.Dr.Mahendra Pal
Dr. Melinda,
I stumbled across your post today after researching this same unknown illness for the past year. I too, suffer from this and have no answers and no help. My family and 3 separate homes that I frequent are also now all experiencing the same side effects both personally as well as the same damage being contained in our yards and homes.
v/r,
Sarah
Dear Dr.Melinda,
I am really very sorry that your problem is not yet solved.
I had requested you earlier to contact few Institutes, which are working of fungi.
I am again mentioning the address of four Institutes. 1.International Mycological Institute, Bakecham Lane,Egham, Surrey TW209TY, UK 2.Mycological Reference Laboratory, Public Health Laboratory Service, Myrtle Road, Kingsdown,Bristol BS28EL, UK 3. Australian National Reference Laboratory in Medical Mycology, Royal North shore Hospital, Pacific Highway, St.Leonards,NSW2065, Australia 4 .Laboratory of Mycology, Pasteur Research Institute, Paris, France
Please try to contact these Institutes with the hope that some positive answer may come. I wish and pray to God that you get an early diagnosis. With kindest warm regards, Prof.Dr.Mahendra Pal
@ Sarah Rueff,
Thsnk you for your interest in our research and for sharing your similar history.
We have recently found a method of culturing the putative organism from blood and tissue samples of the affected individuals. The cytology from these colonies show an organism with some fungal-like attributes (hyphae ir pseudohyphae formation upon rehydration of cultured “spores”, and some protozoal attributes (encysted/spore-form that seems capable of “hatching” to form an amoeboid form that appears to migrate with amoeba-like motility), snd even some algae-lije attributes (geometric patterns with sharo edges in some of the forms that seemingly form colonies or even maybe aggregations). We hypothesize that it may be some tupe of novel stramenopile?
We are in the process of sending samples out for TEM and sequencing, and are hopeful that this will help significantly with identification/characterization.
We suspect that the organism is more widespread than just our little “cluster”. While it seems that most humans/dogs exposed to the putative organism do not become ill, we sispect that there is a, not insignificant, humsn population that is succeptible to infection.... either by genetic predisposition, other co-morbidities, or simply exposure to massive load of organism. If our sequencing/TEM studies are supportive of this theory, we will be trying to form a network of researchers interested in learning of the research, snd hopefully attempting to characterize the distributiin of affected cases/clusters. We had hoped that the CDC would take over that responsibility, but unfortunately, the CDC has been unresponsive to requests for assistance in attempting to vslidate or refute the data and hypotheses that have been proposed thus far.
Since we have had little response from public health personal, we would appreciate the involvement of sny private sector or academic researchers who might be able to attempt to replicate our findings snd/or collaborate to advance the understanding of this, possibly important novel organism.
Please feel free to message me through Researchgate messaging to discuss further.
PS, please excuse all of the typos in my previous replies... working from my phone, which for some reason does not allow me to scroll down to see the area in which I am typing.
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