Persistent disease after environmental mold exposure: exposure severity, immune/metabolic risks, fungal- penetration markers & positive response to biofilm- focused antifungal therapy

Ref ID: 19370

Author:

I. H. Grant and J. F. Rini

Author address:

New York Medical College, Tarrytown, USA

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Intact tissue-barriers & cell-mediated immunity (CMI)
defend against fungal penetration. Stachybotrys (Stachy) toxic prod-
ucts/particulate debris irreversibly damage all tissues contacted.
Damaged barriers,innate immunity (1st response:monocytes/macro-
phages) or CMI is associated with infectious complications from
opportunistic molds like Aspergillus-Penicillium (Asp-Pen) that colo-
nize & infect. Since culture & microscopy routinely fail to detect mold
invasion in up to 80% of patients with severe immune defects, it is
plausible that these methods would be even less successful detecting
fungal presence with moderate or no immune deficiency. Non-
invading fungal-hyphae-biofilms support polymicrobic proliferation, persistence & elaboration of myriad destructive,inflammatory, antico-
agulating,thrombotic,immunosuppressive or carcinogenic products:
particulates & volatiles-some able to diffuse across building walls, let
alone tissues. Biofilms are difficult to eradicate. Amphotericin-B
(Ampho),the only oral antifungal that eradicates mold biofilms, can-
not cross tissue planes, is thus innocuous topically on oral, respira-
tory or GI mucosa.Since toxin-producing biofilms may cause
persistent debility long after an inoculating exposure, biofilm-directed
antifungal therapy(Rx)w/topical oral/nasal/GI Ampho was studied.
Methods Prospectively monitored 113 persistently-ill patients
removed from microbiologically-proven mold-exposure(45M, 68F,
5 mo-86 yrs),correlated symptoms (sxs) with(1)exposure severity,(2)
mold spp.(3)disease severity,(4)immune/metabolic defects,(5)specific
quantitative mold antibody response,(6)mycotoxin(MCT) excretion
(RealTime Lab.Inc.),(7)response to fungal biofilm-focused oral-nasal-
GI Ampho+/-systemic azoles or capsofungin.
Results 88(79%) exposed to Asp-Pen; 66(59%) Stachy. Severe/per-
sistent sxs occurred in 37(33%):23(20%)disabling/life-altering(neuro-
logic/pulmonary) & 10(8%) life-threatening.Those exposed to both
Stachy/Asp-Pen consistently at greater risk for more sxs. Prolonged
debility was associated with exposure intensity, impaired CMI,
MTHFR defect, multiple MCT excretion& fungal penetration-markers.
Impaired CMI risks were found in 86%: Defective innate (macro-
phage/monocyte) immunity 41% (vitamin D defic, age<5y); Defective neutrophil response 36%(protein defic 33%, steroid Rx 23%, zinc defic18%). Unique SXS:63% Nose(postnasal drip/bleeding/sinus); 54% Chronic Fatigue Syndrome (CFS); 48% Throat(pain/tightness/choking); 45% Neuro (tremors/aphasia/ataxia/seizure/stroke);42% Derm (malar/ bruises/pigment),42% GI (GERD/IBS/dysphagia);41% Lungs (asthma/ hemoptysis/nodules); 40% Ear (pain/bleeding/deaf/vertigo);38% Psych; 36% Muscle, 35% Sleep(insomnia/snoring/apnea);35% head- aches, 34% Ocular, 32% Cognitive; 27% Chemical Sensitivity, 24% Fibromyalgia (FM). A.fumigatus IgG detected in 50/50(100%)tested, elevated in 22%’ S.chartarum IgG detected in 81% tested,IgA in 3. Stachy IgE unde- tectable100%. MCT-excretion detected in 80/80(100%)tested:79% Ochratoxin [Asp-Pen immunosuppressant/renal-toxin/carcinogen], 55% Tricothecenes [Stachy-neurotoxins],19% Aflatoxin [Asp-carcino- gen]. 41 debilitated excreted multiple MCT’s. Trichothecenes excre- tion was associated with CFS, FM & persistent pain. Rx response was striking:67/78 (86%) unequivocally improved-but only after exposure stopped: 20 cured;53% residual disability;45 (58%) relapsed after Rx-interruption with 21 improving on re-Rx. 41 (53%) relapsed on mold re-exposure. Sxs-flares common on Rx-initia- tion, waning over time. Sxs improved in all categories:CFS, FM, trem- ors, vertigo, GERD, IBS, most by 3 wks; some 1-3 mo. Those with impaired CMI or fungal penetration-markers (adenopathy,nodules, calcification,pulm/GI) required prolonged(>18mo)systemic RX, relaps-
ing with interruptions. Of 13 who refused to continue RX, 6 steadily
deteriorated. Of 35 not-Rxd:19 steadily deteriorated,10 lost, 8 unable
to afford RX, 6 afraid of antifungals.
Conclusion Debility & unexplained symptoms including CFS, Fi-
bromyalgia, chronic pain parallel mold exposure intensity, impaired
host immunity/detoxification, fungal penetration-markers & MCT
excretion. The striking 86% response to biofilm-focused Rx supports
the model that toxin-producing molds can colonize mucosa causing
significant disease. Quantitative mold IgG/IgA & MCTs appear mark-
ers for persistent viable nidus or re-exposure. Studies on incidence,
pathogenesis,diagnostics,prevention & Rx are needed. Better diagnos-
tic methods are needed to detect mold presence & products both in
patients & the environment.

Abstract Number: O4.3

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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