Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a known complex, multi-organ system disorder with a sudden or subacute onset. ME/CFS occurs most commonly among women between 30 and 50 years of age. The current diagnostic criteria of ME/CFS, as defined by the Centers for Disease Control and Prevention, includes: profound fatigue and post-exertional malaise (>6 mo) unrelieved by rest, persistent cognitive impairment or orthostatic intolerance, and chronic unrefreshing sleep.

Despite reported associations between ME/CFS onset and exposure to infectious agents (viral, bacterial, or fungal), the pathophysiology of ME/CFS remains unknown. In this prevalence study, we investigated the rates of Aspergillus-derived toxin levels, Aflatoxin (AF), Ochratoxin A (OTA), and Gliotoxin (GT), in the urinalysis of 236 ME/CFS patients with a history of chronic exposure to mold (i.e., from water-damaged buildings).

Among ME/CFS patients reporting chronic exposure to mold, we found evidence of exposure in 92.4 percent of patients, with OTA being the most prevalent mycotoxin. Mold distributions (OTA, AF, and GT) in the urinalysis all demonstrated right skewness, while the distribution of age of ME/CFS patients diagnosed showed no deviation from normality.

This study aims to provide preliminary, epidemiological evidence among ME/CFS patients who were diagnosed in South Florida with a history of exposure to mycotoxins. Based on these findings, we proposed how future control studies should approach investigating the association between chronic mold exposure and the diagnosis of ME/CFS.

Source: Wu TY, Khorramshahi T, Taylor LA, Bansal NS, Rodriguez B, Rey IR. Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients. Int J Environ Res Public Health. 2022 Feb 12;19(4):2052. doi: 10.3390/ijerph19042052. PMID: 35206241. https://www.mdpi.com/1660-4601/19/4/2052 (Full text)

Building-related illness (BRI) in all family members caused by mold infestation after dampness damage of the building

Abstract:

Introduction: In 2010, dampness damage in a single-family house caused a massive mold infestation. In the further course, the 5 family members developed severe health problems. This report investigates the extent and cause of the water damage. In addition, the various visible fungal infestations were analyzed in a specialized laboratory.

Results: Due to building construction errors, starting from the basement, an increased moisture penetration of the residential building was detected. Within 2 years, massive mold infestation occurred. In 2016, the following species were detected: Cladosporium sphaerospermum, Chaetomium globosum, Penicillium chrysogenum, Scopularis brevicaulis, Acremonium furculum, A. charticola and A. sclerotigenum, Trichomonascus apis Aspergillus versicolor and Debaryomyces hansenii. Additionally, different black molds were macroscopically detected. The severity of the disease process varied, probably due to the different daily exposure of the family members, and possibly influenced by age. The children presented acute episodes with nocturnal cough, associated with sleep disturbances and respiratory infections with severe rhinitis. In addition, general fatigue was noticeable. The course of the disease was complicated by recurrent nightly nosebleeds. The mother developed a much more severe course as chronic fatigue syndrome. Additionally, the following continuous complaints occurred: sore throat and headache, nocturnal irritable cough, chronic rhinitis, difficulty concentrating, increasing forgetfulness and word-finding disorders, cognitive impairment with reduced short-term memory, extremely dry eyes with red sclerae, morning stiffness, dyspnea, disturbed temperature regulation (chills), increased feeling of thirst, and menstrual disorders. The father’s building-related illness (BRI) was comparatively mild due to much lower exposure, with nocturnal irritable cough, rhinitis, and marked fatigue. In 2018, after moving out of the house, the father was symptom-free after 2 weeks, the three children after 6 months, but the mother only after 18 months.

Discussion: The symptoms are consistent with reports from the literature, according to which fatigue, sleep disturbances, lack of concentration and headache as well as recurrent infections of the upper respiratory tract are caused by microbial volatile organic compounds (MVOCs) released by molds. The association with recurrent nosebleeds in childhood has not been described in this form before.

Conclusion: Since in all family members complete remission of symptoms occurred after cessation of the 6-year exposure, there is no doubt that the BRI was caused by the massive mold infestation.

Source: Kramer A, Wichelhaus TA, Kempf V, Hogardt M, Zacharowski K. Building-related illness (BRI) in all family members caused by mold infestation after dampness damage of the building. GMS Hyg Infect Control. 2021 Dec 7;16:Doc32. doi: 10.3205/dgkh000403. PMID: 34956824; PMCID: PMC8662741. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662741/ (Full text)

Chronic Fatigue Syndrome and Bone Marrow Defects of the Jaw – A Case Report on Additional Dental X-Ray Diagnostics with Ultrasound

Abstract:

Purpose: This paper aims to demonstrate the additional benefit of ultrasound in the diagnosis of chronic osteolysis and osteonecrosis (bone marrow defects) of the jaw shown in a clinical case report.

Patients and Methods: A case of chronic fatigue syndrome (CFS) in a young man presenting the typical, ambiguous symptoms, which were accompanied by headaches and tinnitus. X-ray techniques, namely panoramic radiographs (OPG) and cone beam computed tomography (DVT/CBCT), failed to produce any remarkable findings of bone marrow defects (BMDJ) in the jawbone. However, the measurement of bone density using trans-alveolar ultrasound (TAU) indicated a possible bone marrow defect in the lower left jawbone.

Results: Surgery was undertaken at the conspicuous area. Additional to softened, ischemic, fatty tissue, a black area was revealed, which was surprisingly subsequently identified as aspergillosis by histopathological analysis. In addition, the excessive local RANTES/CCL5 expression found in the affected area confirmed the necessity for surgical debridement and additional findings of TAU.

Conclusion: In contrast to radiography, complementary TAU imaging of the BMDJ revealed chronic inflammatory signaling RANTES/CCL5 pathways and fungal colonization. This case report supports the need for additional diagnostic techniques beyond radiographic modalities, which can help to elucidate the diagnostic composition and knowledge of the bone manifestations of systemic diseases.

Source: Lechner, J., & Schick, F. (2021). Chronic Fatigue Syndrome and Bone Marrow Defects of the Jaw – A Case Report on Additional Dental X-Ray Diagnostics with Ultrasound. International medical case reports journal14, 241–249. https://doi.org/10.2147/IMCRJ.S306641 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064682/  (Full text)

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Abstract:

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms.

More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

 

Source: Morris G, Berk M, Walder K, Maes M. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability. Mol Neurobiol. 2016 May;53(4):2550-71. doi: 10.1007/s12035-015-9262-7. Epub 2015 Jun 17. https://www.ncbi.nlm.nih.gov/pubmed/26081141

 

Detection of mycotoxins in patients with chronic fatigue syndrome

Abstract:

Over the past 20 years, exposure to mycotoxin producing mold has been recognized as a significant health risk. Scientific literature has demonstrated mycotoxins as possible causes of human disease in water-damaged buildings (WDB). This study was conducted to determine if selected mycotoxins could be identified in human urine from patients suffering from chronic fatigue syndrome (CFS).

Patients (n = 112) with a prior diagnosis of CFS were evaluated for mold exposure and the presence of mycotoxins in their urine. Urine was tested for aflatoxins (AT), ochratoxin A (OTA) and macrocyclic trichothecenes (MT) using Enzyme Linked Immunosorbent Assays (ELISA). Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin (one in the equivocal range).

Almost 30% of the cases had more than one mycotoxin present. OTA was the most prevalent mycotoxin detected (83%) with MT as the next most common (44%). Exposure histories indicated current and/or past exposure to WDB in over 90% of cases. Environmental testing was performed in the WDB from a subset of these patients.

This testing revealed the presence of potentially mycotoxin producing mold species and mycotoxins in the environment of the WDB. Prior testing in a healthy control population with no history of exposure to a WDB or moldy environment (n = 55) by the same laboratory, utilizing the same methods, revealed no positive cases at the limits of detection.

 

Source: Brewer JH, Thrasher JD, Straus DC, Madison RA, Hooper D. Detection of mycotoxins in patients with chronic fatigue syndrome. Toxins (Basel). 2013 Apr 11;5(4):605-17. doi: 10.3390/toxins5040605. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705282/ (Full article)

 

The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures

Abstract:

Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity.

This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary.

The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity.

In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures.

 

Source: Anyanwu E, Campbell AW, Jones J, Ehiri JE, Akpan AI. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures. ScientificWorldJournal. 2003 Nov 13;3:1128-37. http://www.hindawi.com/journals/tswj/2003/307098/abs/

 

Fungal spores: hazardous to health?

Abstract:

Fungi have long been known to affect human well being in various ways, including disease of essential crop plants, decay of stored foods with possible concomitant production of mycotoxins, superficial and systemic infection of human tissues, and disease associated with immune stimulation such as hypersensitivity pneumonitis and toxic pneumonitis. The spores of a large number of important fungi are less than 5 microm aerodynamic diameter, and therefore are able to enter the lungs. They also may contain significant amounts of mycotoxins. Diseases associated with inhalation of fungal spores include toxic pneumonitis, hypersensitivity pneumonitis, tremors, chronic fatigue syndrome, kidney failure, and cancer.

 

Source: Sorenson WG. Fungal spores: hazardous to health? Environ Health Perspect. 1999 Jun;107 Suppl 3:469-72. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566211/ (Full article)