What are mycotoxicosis?

The term mycotoxicosis has been defined as: 

“ingestion of a fungal toxin” (Reiss et al, 2012)

“mycotoxicoses are examples of “poisoning by natural means” and thus are analogous to the pathologies caused by exposure to pesticides or heavy metal residues” (Bennett & Klich, 2003)

“Mycotoxicoses are the animal diseases caused by mycotoxins” (Bennett & Klich, 2003)

“Mycotoxicoses are diseases caused by mycotoxins, i.e. secondary metabolites of moulds”

Since molds can be present without producing toxins, it is difficult to prove that a disease is a mycotoxicosis and even when mycotoxins are detected, it is not easy to show that they are the etiological agents in a given veterinary or human health problem. However, there is sufficient evidence from animal models and human epidemiological data to determine that mycotoxins represent an important danger to human and animal health (Bennett & Klich, 2003).

What are mycotoxins?

All mycotoxins are low-molecular-weight natural products (small molecules) produced as secondary metabolites by filamentous fungi that are toxic at relatively low concentrations. The term was coined in 1962 after an unusual veterinary crisis in England, in which approximately 100,000 turkey poults died. The finding that this mysterious turkey X disease was due to a peanut meal contaminated with secondary metabolites from Aspergillus flavus, alerted scientists of other possible occult deadly mold metabolites. There are about 300 to 400 compounds recognized as mycotoxins, of which approximately a dozen groups regularly receive attention as threats to human and animal health (Bennett & Klich, 2003). Compounds produced by different types of fungus, belonging mainly to the Aspergillus, Penicillium and Fusarium genera. Under favourable environmental conditions, when temperature and moisture are appropriate  these fungi grow and can produce mycotoxins. They enter the food chain through contaminated food and feed crops, especially cereals (efsa, 2015). Mycotoxins are produced optimally at 24-28°C. Temperature and water activity affect contamination during storage allowing ecological succession of different fungi (Breitenbach et al, 2002).

Symptoms of mycotoxicosis

The symptoms shown during cases of mycotoxicosis depend on several factors (Bennett & Klich, 2003):

·      The type of mycotoxin

·      The amount and duration of the exposure

·      The age, health, and sex of the exposed individual

·      Synergistic effects like genetics, dietary status, and interactions with other toxic compounds

Transmission

As many of the diseases that are caused by fungi, mycotoxicosis cannot be transmitted from person to person. The majority of them are ingested in contaminated foods. Some other important sources of exposure include skin contact with mold-infested substrates (cutaneous) and inhalation of spore-borne toxins (Bennett & Klich 2003, Peraica et al 1999).

Treatment

Except for supportive therapy like diet and hydration, there are almost no treatments for mycotoxin exposure (Bennett & Klich, 2003). There are no specific antidotes for mycotoxins. To eliminate further exposure the source of the toxin can be removed. Aluminosilicates have been used to effectively prevent the absorption of some mycotoxins. Contaminated products can be blended with unspoiled products to reduce the toxin concentration. Nevertheless, it should be monitored by follow-up toxin analysis and there are cases in which it is not acceptable by certain regulatory agencies (Merck, 2015).

Toxicology and Human Health

Mycotoxicoses, are categorized as acute or chronic. Acute toxicity has a rapid onset and an obvious toxic response, while chronic toxicity is characterized by low-dose exposure over a long period of time, that can result in cancers or other irreversible effects. The main human and veterinary health problems of mycotoxin exposure are related to chronic exposure. However, the best-known mycotoxin episodes are manifestations of acute effects, such as turkey X syndrome, human ergotism, and stachybotryotoxicosis (Bennett & Klich, 2003).

Mycotoxins as carcinogens

Aflatoxin B₁ is considered the most potent natural carcinogen known and is usually the major aflatoxin produced by toxigenic strains. The data on aflatoxin as a human carcinogen are more critical than the data implicating it in acute human toxicities; there is no other natural product for which the data on human carcinogenicity is so compelling (Bennett & Klich 2003, FSA 2015).

The International Agency for Research on Cancer has classified aflatoxin B₁ as a group I carcinogen. Exposure to these mycotoxins in the diet is considered an important risk factor for the development of primary hepatocellular carcinoma, especially in individuals exposed to hepatitis B. Several studies have linked aflatoxin consumption in the diet to liver cancer incidence. The results have not been entirely consistent, and the quantification of lifetime individual exposure to aflatoxin is particularly difficult. An early epidemiological study of Dutch peanut processing workers exposed to dust contaminated with aflatoxin B₁ showed a correlation between both respiratory cancer and total cancer in the exposed group in comparison with unexposed cohorts. Aflatoxin has also shown to be a pulmonary carcinogen in experimental animals (Bennett & Klich, 2003).

Incidence and Risk Factors

Mycotoxins are found worldwide as contaminants of food. Several factors affect its occurrence: geographic and seasonal factors, cultivation, harvesting, storage and transportation practices. Mycotoxin contamination has been reported on cereal plants, grasses and oilseed crops (Breitenbach et al, 2002). Mycotoxin exposure is more likely to occur in areas of the world where there are poor methods of food handling and storage, areas with malnutrition problems, and where few regulations exist to protect exposed populations. Nevertheless, even in developed countries, specific subgroups may be vulnerable to mycotoxin exposure. For example, in the United States hispanic populations tend to consume more corn products than the rest of the population, and inner city populations are more likely to live in buildings that contain high levels of molds (Bennett & Klich, 2003).  Its prevalence and concentration are sporadic and can vary annually, even in the same location. Production is affected by local weather patterns, crop damage and production practices and can be produced pre- or post-harvest (Iowa State University, 2015).

Characteristics of the most common genera that cause mycotoxicosis

The most commonly mycotoxin producer genera include: Fusarium, Aspergillus, and Penicillium. 

Examples of Mycotoxicosis Outbreaks

In the Middle Ages, outbreaks caused by ergot alkaloids from Claviceps purpurea mutilated and killed thousands of people in Europe. Ergotism was known as ignis sacer (sacred fire) or St Anthony's fire, because of the belief that a pilgrimage to the shrine of St Anthony would relief from the intense burning sensation. Victims of ergotism were exposed to a hallucinogen produced during the baking of bread made with ergot-contaminated wheat (Peraica et al 1999, Pitt 1989). The initial symptoms of the gangrenous form of ergotism are oedema of the legs, with severe pain. Paraesthesias are followed by gangrene at the tendons, with painless demarcation. The last recorded outbreak of gangrenous ergotism occurred in Ethiopia in 1978 where 140 people were affected and there was 34% mortality. The other type of ergotism is the convulsive form, which is related to intoxication with clavine alkaloids from Claviceps fusiformis. The last outbreak was characterized by gastrointestinal symptoms (nausea, vomiting and giddiness) followed by effects on the central nervous system (drowsiness, prolonged sleepiness, twitching, convulsions, blindness and paralysis), it was seen in 1975 in India when 78 people were affected (Peraica et al, 1999).

Several outbreaks of aflatoxicosis have occurred in tropical countries (Peraica et al, 1999). An example is the outbreak  observed in eastern and central provinces of Kenya (districts of Makueni and Kitui) between January and July 2004. A high case fatality rate resulted in 125 recognized deaths. It was confirmed that the outbreak was the result of widespread aflatoxin contamination of locally grown maize that was stored under damp conditions. There was an active survey on the number of cases by date between those months, showing peaks in the months of May and June (CDC, 2004). 

Economic consequences

Crops with large amounts of mycotoxins often have to be destroyed. As an alternative, contaminated crops are sometimes diverted into animal feed. But feeding contaminated crops to susceptible animals can generate reduced growth rates, illness, and death. Also, these animals can produce meat and milk that may contain toxic residues and biotransformation products, it has been found that ochratoxin in pig feed can accumulate in tissues (Bennett & Klich, 2003). Iowa State University (2015) provides detailed information on recommended concentrations of mycotoxins in animal feeds.

An important aspect of the mycotoxin problem is the ability to diagnose and verify mycotoxicoses. Several national and international organizations and agencies have special committees and commissions that set recommended guidelines, develop standardized assay protocols, and maintain up- to-date information on regulatory statutes (Bennett & Klich, 2003).  There are still some countries without regulations for mycotoxins (FAO, 2003).

Since it is impracticable to prevent the production of mycotoxins, the food industry has established internal monitoring methods. And government regulatory agencies survey for the occurrence of mycotoxins in foods and establish regulatory limits. The Food and Agriculture Organization of the United Nations has published a series of compendia summarizing worldwide regulations for mycotoxins (Bennett & Klich, 2003).

Control, Detection and Screening of Mycotoxins

Methods for controlling mycotoxins are largely preventive, including good agricultural practice and sufficient drying of crops after harvest. There is on-going research on methods to prevent preharvest contamination of crops, like developing host resistance through plant breeding and enhancing antifungal genes by genetic engineering, using biocontrol agents, and targeting regulatory genes in mycotoxin development. But since mycotoxins are “natural” contaminants of foods, their formation is often unavoidable (Bennett & Klich, 2003).

Surveillance programs have been developed to diminish the risk of mycotoxin consumption by humans and animals. Analytical techniques are used for characterization and quantitation of mycotoxins including high-pressure liquid chromatography (HPLC), thin layer chromatography (TLC), and gas chromatography (GC); enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) tests are also available. Several commercial test kits are available for field testing (Breitenbach et al, 2002).

References

Bennett, JW & Klich, M. 2003. Mycotoxins. Clinical Microbiology Reviews (16): 3. 497-516.

Breitenbach, M; Crameri, R; Lehrer, S. 2002. Fungal allergy and pathogenicity. Karger Medical and Scientific Publishers. Vol 81. 310p.

Centers for Disease Control (CDC). 2004. Outbreak of Aflatoxin Poisoning-Eastern and Central Provinces, Kenya, January-July 2004. Morbidity and Mortality Weekly Report (53):34. 790-793.

Ellis, D. 2015. Mycology Online. The University of Adelaine. Retrieved from  http://www.mycology.adelaide.edu.au.

European Food Safety Authority (efsa). 2015. Mycotoxins. Retrieved from http://www.efsa.europa.eu.

Food and Agriculture Organization of the United Nations. (FAO). 2003. Updates to FAO Food and Nutrition Paper 64. Retrieved from http://www.fao.org/3/a-y5499e.pdf.

Food Standards Agency (FSA). 2015. Mycotoxins. Retrieved from http://www.food.gov.uk.

Iowa State University. 2015. College of Veterinary Medicine: Mycotoxins. Retrieved from http://vetmed.iastate.edu.

Leslie, J; Bandyopadhyay, R & Visconti, A. 2008. Mycotoxins: Detection methods, management, public health and agricultural trade. CAB International. 476p.

Merck. 2015. The Merck Veterinary Manual: Overview of mycotoxicoses. Retrieved from http://www.merckvetmanual.com.

M. Peraica, B. Radić , A. Lucić , & M. Pavlović. 1999. Toxic effects of mycotoxins in humans. Bulletin of the World Health Organization (77): 9. 754-766.

Pitt, J. 1989. Mycotoxin prevention and control in foodgrains: An introduction to mycotoxins. A collaborative publication of the UNDP/FAO Regional Network Inter-Country Cooperation on Preharvest Technology and quality Control of Foodgrains (REGNET) and the ASEAN Grain Postharvest Programme. Bangkok, Thailand. Retrieved from http://www.fao.org/docrep/x5036e/x5036E00.htm#Contents.

Reiss, E; Shadomy, HJ & Lyon, GM. 2012. Fundamental Medical Mycology. Wiley-Blackwell. 442p.

Volk, T & Hallen, H. 2005. Tom Volk's Fungus of the Month for August 2005. Gibberella zeae or Fusarium graminearum, head blight of wheat. Retrieved from http://botit.botany.wisc.edu.

World Health Organization (WHO). 2011. Mycotoxins: Children's health and the environment. Retrieved from http://www.who.int/ceh/capacity/mycotoxins.pdf.