Veterinary aflatoxicosis: A comprehensive review

Introduction

Mycotoxins are naturally occurring toxic compounds produced by certain species of fungi growing on agricultural commodities before harvest, during processing, or in storage. Among the various mycotoxins identified to date, aflatoxins are considered the most significant because of their widespread occurrence, potent toxicity, and substantial impact on animal and human health (Bennett and Klich, 2003) [2] . Aflatoxins are predominantly produced by Aspergillusflavus, Aspergillusparasiticus, and, less frequently, Aspergillusnomius under conditions of high temperature and humidity (Klich, 2007) [9] . The term "aflatoxin" originated from the fungus Aspergillusflavus following the outbreak of "Turkey X disease" in England in 1960, which caused the death of more than 100,000 turkey poults fed contaminated peanut meal (Blount, 1961) [3] . Since then, aflatoxins have been recognized as major contaminants of animal feed worldwide. Their occurrence is particularly common in tropical and subtropical countries where climatic conditions favor fungal growth and toxin production (Williams et al., 2004) [15] . Veterinary aflatoxicosis refers to the disease condition resulting from ingestion of aflatoxincontaminated feed by animals. The disease may occur in acute, subacute, or chronic forms depending on the concentration of toxin consumed and duration of exposure (Hussein and Brasel, 2001) [7] . Acute intoxication is characterized primarily by severe hepatic injury, hemorrhages, and mortality, whereas chronic exposure leads to reduced productivity, impaired immunity, poor growth performance, and reproductive dysfunction (Osweiler, 2005) [12] . The economic consequences of aflatoxicosis are extensive and include decreased feed efficiency, reduced weight gain, lower milk and egg production, veterinary treatment costs, condemnation of animal products, and restrictions on international trade. Furthermore, the conversion of aflatoxin B₁ into aflatoxin M₁ in milk creates an important food safety concern for consumers (Battacone et al., 2010) [1] .

Given the increasing challenges posed by climate change, globalization of feed trade, and intensification of animal production systems, aflatoxicosis continues to represent a significant threat to animal agriculture. Therefore, understanding its etiology, occurrence, and mechanisms of toxicity is essential for developing effective preventive and control strategies.

Etiology and Sources of Aflatoxins

Aflatoxins are toxic secondary metabolites synthesized mainly by Aspergillusflavus and Aspergillusparasiticus. These fungi are widely distributed in soil, decaying vegetation, stored grains, and feedstuffs. Environmental factors such as temperature between 25 °C and 35 °C, high relative humidity, insect damage, and poor storage conditions favor fungal proliferation and aflatoxin production (Klich, 2007) [9] . The principal aflatoxins of veterinary importance include:

Among these, AFB₁ is the most prevalent and toxic compound. Metabolic derivatives such as aflatoxin M₁ and M₂ may appear in milk and other biological fluids following ingestion of contaminated feed (Battacone et al., 2010) [1] . Common feed ingredients susceptible to aflatoxin contamination include:

Contamination may occur at multiple stages, including crop growth, harvesting, transportation, storage, and feed manufacturing. Inadequate drying, mechanical damage to grains, insect infestation, and moisture accumulation are major factors contributing to toxin development (CAST, 2003) [5] . Climate change has emerged as an additional risk factor. Elevated temperatures and drought stress predispose crops to fungal colonization and increased aflatoxin synthesis, leading to greater contamination of feed resources worldwide (Medina et al., 2014) [10] .

Classification and Chemistry of Aflatoxins

Aflatoxins belong to a group of difuranocoumarin compounds derived from polyketide biosynthesis. They are chemically stable molecules capable of withstanding many feed-processing procedures, making their elimination difficult once contamination occurs (Rushing and Selim, 2019) [14] . Based on fluorescence characteristics under ultraviolet light, aflatoxins are classified into two major groups:

These compounds emit blue fluorescence and are commonly produced by A. flavus and A. parasiticus.

G-Series

 Aflatoxin G₁  Aflatoxin G₂ These toxins produce green fluorescence and are predominantly synthesized by A. parasiticus. Among all aflatoxins, AFB₁ exhibits the highest biological activity and carcinogenic potential. Following absorption, it undergoes biotransformation by hepatic cytochrome P450 enzymes to form reactive metabolites, particularly aflatoxin B₁-8,9-epoxide, which is responsible for most toxic effects (Guengerich et al., 1998) [6] . The physicochemical stability of aflatoxins allows them to persist during storage and processing. Consequently, contaminated feed may remain hazardous even after prolonged periods if appropriate detoxification measures are not implemented.

Epidemiology

Aflatoxicosis has been reported in nearly all domesticated animal species, including poultry, cattle, buffaloes, sheep, goats, pigs, horses, dogs, rabbits, and fish. However, susceptibility varies considerably among species and age groups (Osweiler, 2005) [12] . Young animals are generally more vulnerable than adults because of immature detoxification mechanisms and higher metabolic demands. Poultry, especially ducklings and turkey poults, exhibit marked sensitivity to aflatoxin exposure. Swine and calves are moderately susceptible, whereas adult ruminants demonstrate relative resistance due to microbial degradation of toxins in the rumen (Hussein and Brasel, 2001) [7] . Several outbreaks of aflatoxicosis have been documented worldwide, particularly in regions characterized by warm and humid climates. Developing countries often experience higher incidence rates because of inadequate feed storage infrastructure and limited monitoring programs (Williams et al., 2004) [15] . Risk factors associated with aflatoxin contamination include:  High environmental humidity  Elevated storage temperatures  Prolonged storage periods  Mechanical grain damage  Insect infestation  Drought stress before harvest  Poor feed management practices Seasonal variation also influences toxin occurrence, with contamination levels generally increasing during periods of high rainfall and humidity.

Pathogenesis and Mechanism of Toxicity

The toxic effects of aflatoxins are primarily mediated through metabolic activation in the liver. After ingestion, aflatoxins are rapidly absorbed from the gastrointestinal tract and transported to the liver via the portal circulation (Guengerich et al., 1998) [6] . [13] .

Major pathogenic mechanisms include Hepatotoxicity

The liver is the principal target organ because it is the primary site of toxin metabolism. Hepatic injury may manifest as:

Severe damage can lead to liver failure and death in acute cases.

Oxidative Stress

Aflatoxins increase the generation of reactive oxygen species (ROS), resulting in lipid peroxidation, mitochondrial dysfunction, and depletion of antioxidant defenses such as glutathione, superoxide dismutase, and catalase (Rawal et al., 2010) [13] .

Immunosuppression

One of the most important consequences of chronic aflatoxin exposure is suppression of immune function. Aflatoxins impair macrophage activity, reduce antibody production, inhibit lymphocyte proliferation, and decrease resistance to infectious diseases (Meissonnier et al., 2006) [11] .

Impaired Protein Synthesis

Binding of aflatoxin metabolites to nucleic acids interferes with transcription and translation processes. Consequently, protein synthesis declines, contributing to poor growth, reduced productivity, and tissue degeneration.

Carcinogenic and Mutagenic Effects

Aflatoxin B₁ can form DNA adducts that induce mutations and chromosomal abnormalities. Long-term exposure has been associated with hepatocellular carcinoma in several animal species and humans (IARC, 2012) [8] .

Reproductive and Developmental Effects

Chronic intoxication may adversely affect reproductive performance by reducing fertility, impairing embryonic development, increasing embryonic mortality, and causing teratogenic effects in susceptible species (Bryden, 2012) [4] . Overall, the pathological manifestations of aflatoxicosis result from a combination of hepatocellular damage, oxidative stress, immunosuppression, and interference with essential metabolic processes.

References

1. Battacone G, Nudda A, Palomba M, Mazzette A, Pulina G, Nicolussi P, et al. Transfer of aflatoxin B1 from feed to milk and from milk to curd and whey in dairy sheep fed artificially contaminated concentrates. J Dairy Sci. 2010;93(12):5643-5650.
2. Bennett JW, Klich M. Mycotoxins. Clin Microbiol Rev. 2003;16(3):497-516.
3. Blount WP. Turkey "X" disease. J Br Turkey Fed. 1961;9:52-77.
4. Bryden WL. Mycotoxin contamination of the feed supply chain: Implications for animal productivity and feed security. Anim Feed Sci Technol. 2012;173(12):134-158.
5. Council for Agricultural Science and Technology (CAST). Mycotoxins: Risks in Plant, Animal and Human Systems. Task Force Report No. 139. Ames (IA): Council for Agricultural Science and Technology; 2003.
6. Guengerich FP, Johnson WW, Shimada T, Ueng YF, Yamazaki H, Langouët S, et al. Activation and detoxication of aflatoxin B1. Mutat Res. 1998;402(12):121-128.
7. Hussein HS, Brasel JM. Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology. 2001;167(2):101-134.
8. International Agency for Research on Cancer (IARC). Aflatoxins. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 100F. Lyon (France): International Agency for Research on Cancer; 2012. p. 225-248.
9. Klich MA. Environmental and developmental factors influencing aflatoxin production by Aspergillus flavus and Aspergillus parasiticus. Mycoscience. 2007;48(2):71-80.
10. Medina A, Rodriguez A, Magan N. Effect of climate change on Aspergillus flavus and aflatoxin B1 production. Front Microbiol. 2014;5:348.
11. Meissonnier GM, Pinton P, Laffitte J, Cossalter AM, Gong YY, Wild CP, et al. Immunotoxicity of aflatoxin B1: Impairment of the cell-mediated immune response to vaccine antigen and modulation of cytokine expression. Toxicol Appl Pharmacol. 2006;211(2):149159.
12. Osweiler GD. Occurrence of mycotoxins in feeds and feed ingredients. In: Diaz DE, editor. The Mycotoxin Blue Book. Nottingham (UK): Nottingham University Press; 2005. p. 1-14.
13. Rawal S, Kim JE, Coulombe R Jr. Aflatoxin B1 in poultry: Toxicology, metabolism and prevention. Res Vet Sci. 2010;89(3):325-331.
14. Rushing BR, Selim MI. Aflatoxin B1: A review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. Food Chem Toxicol. 2019;124:81-100.
15. Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, Aggarwal D, et al. Human aflatoxicosis in developing countries: A review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr. 2004;80(5):1106-1122.