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Aspergillus infection

Category: Illness or disabilities

Type

Involuntary

Introduction and description

 

Aspergillus is a genus consisting of a few hundred mould species.

“Members of the genus possess the ability to grow where a high osmotic concentration (high sugar, salt, etc.) exists. Aspergillus species are highly aerobic and are found in almost all oxygen-rich environments, where they commonly grow as moulds on the surface of a substrate, as a result of the high oxygen tension. Commonly, fungi grow on carbon-rich substrates like monosaccharides (such as glucose) and polysaccharides (such as amylose). Aspergillus species are common contaminants of starchy foods (such as bread and potatoes).”

 

In other words if you get mouldy food, this may well be the fungi responsible. 

More than 60 Aspergillus species are medically relevant pathogens causing disease in humans and other animals.  The pathogens include  A. clavatus, A. fischerianus (Neosartorya fischeri), A. flavus, and A. fumigatus (two strains). A. fischerianus is hardly ever pathogenic, but is very closely related to the common pathogen A. fumigatus

Types of disease

There are two main types of disease and illness caused by aspergillus

  • Aflatoxin infection -  Aflatoxins are naturally occurring mycotoxins that are produced by Aspergillus species, aflatoxin is both a toxin and a carcinogen. We have a separate section for aflatoxin infection.  Please follow the link
  • Aspergillosis - Aspergillosis is the group of diseases caused by Aspergillus, generally the term excludes aflatoxin infection.  We describe Aspergillosis in this section.
 

If we look at some of the main species:

  • fumigatus is the most common species to cause disease.  This can result in  Aflatoxin infection and Aspergillosis.  The organism can be differentiated from other common mould infections based on the fact that it takes on a mould form both in the environment and in the host (unlike Candida albicans which is a dimorphic mould in the environment and a yeast in the body).
  • flavus is the major producer of carcinogenic Aflatoxins in crops worldwide and as a consequence can result in  aflatoxin infection. It is also an opportunistic human and animal pathogen, causing aspergillosis in immunocompromised individuals.  
  • clavatus can result in Aspergillosis
  • lentulus is an opportunistic human pathogen that causes invasive Aspergillosis with high mortality rates.
  •  parasiticus, can result in  Aflatoxin infection.

Symptoms

 

Aspergillosis can affect anyone where the spores of the fungi are high, and where the surroundings are badly ventilated, but it often occurs as a co-morbidity in people with asthma, COPD and those with cystic fibrosis (CF). 

It may also emerge in those with HIV. 

People who have undergone organ transplantation, especially bone marrow but also lung, heart, and other solid organ transplants are at risk because of the immunosuppressants used to stop the organ being rejected.  It is a risk factor for those who have been fitted with a stent which has been coated with immunosuppressants to stop it being rejected.  Aspergillosis may occur in those who get the ‘flu even among immunocompetent hosts.

Risks may include influenza A (H1N1) or B infections and viral-induced lymphopenia, although further studies are needed. Prompt diagnosis .. are recommended given high mortality rates.  PMID: 27704024

Aspergillus primarily affects the lungs.  But……In patients who are immunocompromised, Aspergillus may disseminate beyond the lungs via the blood.  In other words, the fungus has the capability to do far greater damage than just lung damage.

Lung disease

 

Aspergillosis can result in:

  • Asthma - In asthma, the fungi may be the cause of the disease 
  • COPD -  It can also be the cause of chronic obstructive pulmonary disease [COPD]
  • Fever - May manifest as fever
  • Cough - Patients often have a cough and produce mucous plugs, which may form bronchial casts;
  • Hemoptysis -  they may cough up blood or blood-stained mucus.  In  heavy infestations, this can be ‘massive and life threatening, in 40-60% of patients’
  • Sinus problems - Symptoms may include chronic sinusitis with ‘purulent sinus drainage’
  • Wheezing  - may be noted upon ‘auscultation of the chest’
  • Lung destruction - May manifest as an ‘asymptomatic radiographic abnormality’
  • Pneumonia – usually ‘a subacute pneumonia, which progresses and cavitates over weeks or months
  • Night sweats
  • Weight loss
  • Pleuritic chest pain
  • Shortness of breath, also known as dyspnea, that is a feeling like one cannot breathe well enough.
  • Hyperventilation – the person may have carbon dioxide imbalances in their blood - respiratory alkalosis.  This in turn may cause a number of physical symptoms: dizziness, tingling in the lips, hands or feet, headache, weakness, fainting and seizures
  • Hypoxaemia - an abnormally low level of oxygen in the blood.  More specifically, it is oxygen deficiency in arterial blood.  They may look a bit blue in colour.

Brain damage, tumours and seizures

 

A 45-year-old man had been treated for chronic alcoholism and he had fever in September 2000. He was diagnosed as lung aspergillosis from chest X-ray findings, …. generalized clonic tonic convulsion developed and the brain abscess in the left parietal lobe was found by CT. Therefore we made the diagnosis of brain abscess followed by lung aspergillosis. He also showed angular gyrus syndrome. Its capsule was thick and localized in the left parietal lobe. The patient had the surgical resection in August, 2001. Aspergillus hyphae and infiltration of inflammatory cells were seen in the brain sample, therefore the diagnosis of aspergillosis brain abscess was established.  PMID:  15379285

Arthritis and other joint and bone problems

Aspergillus arthritis is a debilitating form of invasive aspergillosis. Little is known about its epidemiology, clinical manifestations, laboratory features, treatment, and prognosis. Cases of Aspergillus arthritis were reviewed in the English literature from 1967 through 2015 for variables of arthritis with Aspergillus spp. recovered from joint and/or adjacent bone, underlying conditions, symptoms, signs, inflammatory biomarkers, diagnostic imaging, management, and outcome. Among 31 evaluable cases, 87% were males and 13% pediatric. Median age was 50 y (range 1-83 y). Seventeen (55%) patients were immunosuppressed with such conditions as hematological malignancies (26%), corticosteroids (39%), and/or transplantation (26%). Approximately one-half (52%) of patients had hematogenous seeding of the joint, and more than 80% had de novo infection with no prior antifungal therapy. Oligoarticular infection (2-3 joints) occurred in 45% and contiguous osteomyelitis was present in 61%. Clinical manifestations included pain (87%), edema (26%), and limited function (23%), with knees (35%), intervertebral discs (26%), and hips (16%) being most commonly infected. Aspergillus fumigatus constituted 77% of cases followed by Aspergillus flavus in 13%, Aspergillus niger in 3%, and not specified in 7%.  PMID:  27609563

Eye diseases

 

Endophthalmitis is an inflammation of the internal coats of the eye. It is a possible complication of all intraocular surgeries, particularly cataract surgery, with possible loss of vision and the eye itself. Various bacteria and fungi have been isolated as the cause of endophthalmitis.  Keratitis is a condition in which the eye's cornea, the front part of the eye, becomes inflamed. The condition usually involves any of the following symptoms: pain, impaired eyesight, photophobia, red eye and a 'gritty' sensation:

Aspergillus species produces a wide spectrum of fungal diseases like endophthalmitis and fungal keratitis ophthalmologically, but there has been no report about blepharitis caused by Aspergilus flavus to date. Herein, we report a 61-year-old ethnic Han Taiwanese male who had suffered from pain with burning and foreign body sensation after an insect bite on his left eye. Specimens from bilateral eyelids suggested infection of A. flavus, …. Two weeks after discharge, recurrent blepharitis and keratitis of A. flavus was diagnosed microbiologically. … Collectively, it is possible for A. flavus to induce concurrent keratitis and blepharitis, PMID:  27621301

Thyroid disease

Aspergillus, a nosocomial agent, is the most common fungal cause of suppurative thyroiditis. Most patients with Aspergillus thyroiditis have disseminated infection, primarily with lung compromise. Late diagnosis and treatment, severity of immunosuppressive state and thyroid hormone overload contribute to extremely high mortality rates.  PMID:  25412755

 Kidney failure, hallucinations and other symptoms

This list is derived from the eHealthme website

Most common Aspergillosis symptoms

  • Death - (169 reports)
  • Renal failure acute - (83 reports)
  • Fever - (80 reports)
  • Pneumonia - (73 reports)
  • Bronchopulmonary aspergillosis - (69 reports)
  • Acute kidney failure - (69 reports)
  • Sepsis - (60 reports)
  • Hallucinations - (59 reports)
  • Septic shock - (58 reports)

The hallucinations are probably caused by the brain damage described above, although we have a number of observations that show that the drugs used to treat the disease are more often to blame.

Cause

Aspergillus is a pathogen, as such we could simply say, the cause is the fungus, but cases of aspergillosis are on the increase as such we need to look at why.

Climate change

This short review discusses the need to manage climate-driven expansion of old toxins in new geographic areas (e.g., aflatoxin or fumonisin in corn in historically cooler areas, and ergot where rainfall and cropping patterns have changed). In addition, a renewed consideration of the toxins that can occur in feed sources used in cool-season dairy areas is needed (e.g., silage and distillers dry grains with solubles). ……, an increase in the area where Aspergillus flavus can thrive and the discovery of the sexual stage of this fungus have raised the potential of genetic change accelerated by climate.  PMID:  27455926

Pharmaceuticals

 

The widespread use of immunosuppressants of all kinds including anti-histamines, PPIs, antibiotics and immunosuppressants themselves produces a situation in which any fungi entering any orifice – nose, mouth and lungs, ears, and so on can spread via the blood stream to any part of the body.  Anti-biotics suppress the immunological intestinal flora of the stomach.  PPIs suppress the immunological role of gastric acid in the stomach.  Antihistamines especially nasal sprays, stop the body from sending histamine to a site of attack.

The eHealthme site collects the Adverse Drug reports submitted by doctors to the FDA and SEDA in the USA.  It then summarises them for ease of use.  We originally had a direct link to Aspergillosis and the pharmaceuticals that can cause it, but the eHealthme website frequently reorganise the site and thus break the links.  Thus in order to find out which pharmaceuticals are implicated in the various types of Aspergillosis

  • Follow the LINK to the eHealthme website
  • Using the ‘All conditions’ index find the appropriate entry
  • Now scroll down until you get to the section marked ‘Drugs that could cause

The list shows you all the drugs implicated in CAUSING Aspergillosis as well as the number of people who have made a complaint to their doctor and had their case reported by him.  Note that it is up to the doctor whether he reports or not.

As of October 2016, about 450 pharmaceuticals were in this list.

Use of fungicides in farming

Invasive aspergillosis is a life-threatening mycosis caused by the pathogenic fungus Aspergillus. The predominant causal species is Aspergillus fumigatus, and azole drugs are the treatment of choice.
Azole drugs approved for clinical use include itraconazole, voriconazole, posaconazole, and the recently added isavuconazole. However, epidemiological research has indicated that the prevalence of azole-resistant A. fumigatus isolates has increased significantly over the last decade. What is worse is that azole-resistant strains are likely to have emerged not only in response to long-term drug treatment but also because of exposure to azole fungicides in the environment. ….Environmental azole-resistant strains …. have become widely disseminated across the world within a short time period. The epidemiological data also suggests that the number of Aspergillus spp. other than A. fumigatus isolated has risen. Some non-fumigatus species intrinsically show low susceptibility to azole drugs, …. Currently, our knowledge of azole resistance mechanisms in non-fumigatus Aspergillus species such as A. flavus, A. niger, A. tubingensis, A. terreus, A. fischeri, A. lentulus, A. udagawae, and A. calidoustus is limited. PMID:  27708619

Air Pollution

It appears that air pollution has only served to increase the virulence of strains of many fungi:

Through an experimental evolution experiment, we observe that chronic hypoxia exposure results in increased virulence of A.fumigatus.  We describe here the first observation of a model-specific virulence phenotype correlative with in vitro fitness in hypoxia and pave the way for identification of hypoxia-mediated mechanisms of virulence in the fungal pathogen A.fumigatus.  PMID:  27651366

A fungi able to thrive in a hypoxic environment is one which can not only thrive in the lung, but can thrive all over the body – from intestines to the brain. 

Treatment

First find the cause and see if this can be eradicated.

The home is one of the main sources of the fungus, as such you should make absolutely sure your fridge is spotless, your house is well ventilated, and that your bathroom is regularly purged of any fungal growths.  Shower cubicles are very prone to fungal overgrowths:

A case of fatal aspergillosis due to [an] azole-resistant Aspergillus fumigatus is reported. Environmental investigations at the patient's residence led to the recovery of TR46/Y121F/T289A isolates, genotypically indistinguishable from the clinical isolate, supporting for the first time the direct role of household as potential source of azole-resistant invasive aspergillosis.  PMID:  27682064

We have provided a number of observations from PubMed and Dr Duke’s phytochemical database that might help with healing.

 

References and further reading

  • J AOAC Int. 2016 Jul;99(4):837-41. doi: 10.5740/jaoacint.16-0110.  Changing Patterns of Fungal Toxins in Crops: Challenges for Analysts.  Miller JD.
  • Med Mycol. 2016 Sep 8. pii: myw077. [Epub ahead of print]  Aspergillus arthritis: analysis of clinical manifestations, diagnosis, and treatment of 31 reported cases.  Gamaletsou MN1, Rammaert B2, Bueno MA3, Sipsas NV4, Moriyama B5, Kontoyiannis DP6, Roilides E7, Zeller V8, Taj-Aldeen SJ9, Henry M10, Petraitis V11, Denning DW12, Lortholary O13, Walsh TJ14; International Osteoarticular Mycoses Consortium.

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