THE EFFECTS OF
MYCOTOXINS ON
SWINE HEALTH Francesc Accensi Centre de Recerca en Sanitat Animal (CReSA) Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Barcelona. Departament de Sanitat i d’Anatomia Animals, Facultat de Veterinària (UAB), Barcelona
M
ycotoxins are secondary metabolites, which means that they are non-essential for the survival of the organisms that produce them. They are produced by various fungal genera and species.
A mycotoxin can be produced by more than one genus or species (for example, Ochratoxin A can be produced by Aspergillus ochreaceus, A. niger or Penicillium verrucosum) and the same fungal strain can produce more than one toxin (for example, A. flavus can produce Aflatoxins and cyclopiazonic acid).
1
CLASSIFICATION OF MYCOTOXINS
FIELD MYCOTOXINS
Mycotoxins produced throughout the plant’s life before harvest (the typical example is the case of mycotoxins produced by Fusarium spp., such as Fumonisins and Deoxynivalenol).
STORAGE MYCOTOXINS
Mycotoxins produced after harvest, during the storage of the grain (this is the case of mycotoxins produced by the genera Aspergillus or Penicillium, such as Aflatoxins or Ochratoxin A).
Over time, it was observed that, even though in general it is a valid classification, the so-called field mycotoxins can appear after harvest, during the first stages of storage. On the other hand, storage mycotoxins can also be produced during the plant’s life, during the last stages of the fruit development and before harvest.
2
TYPES OF MYCOTOXIN INTOXICATIONS IN PIGS The ingestion of these mycotoxins causes a kind of intoxication called mycotoxicosis.
Mycotoxin intoxication can be acute, subacute, or chronic, with the effects depending on the dosage, exposure time and, logically, the toxin involved.
DIAGNOSIS | One of the major problems regarding mycotoxicosis is establishing a clear diagnosis.
Generally, after evaluating various options, the time when mycotoxin intoxication is proposed as the problem on the farm, it is already late to definitively establish the correct diagnosis. There are rarely any remains of the feed that was consumed by the pigs that could be associated with intoxication, which means that analyzing the presence of toxins in the feed that they are currently consuming makes no sense.
Additionally, it is important to keep in mind the importance of taking feed samples for mycotoxins detection: correct sampling at various sites and homogenization of the sample are key points for taking samples.
3
Mycotoxin
Raw material
Clinical symptoms
Lesions/Diagnosis
Liver toxicity
Aflatoxins (AFB1, AFB2, AFG1, AFG2)
Corn, cotton, wheat, peanuts, sorghum, etc...
Cholangiohepatitis
Liver necrosis
Hemorrhage
Increased serum bile acids, hyperplasia of bile ducts
Coagulopathy Stunted growth Lower of feed conversion Immune system dysfunction
Detection of AF in feed Detection of AF in liver or urine Return to normal 1-2 weeks post-exposure
AF is classified as carcinogenic
Ochratoxin A (OTA) y/o Citrinine
Trichothecenes. Group A Toxina T-2
Corn, wheat, peanuts, rye, oats, barley...
Corn, barley, wheat, rye, sorghum...
Nephrotoxicosis with polyuria and polydipsia
Gastric ulcers and renal tubular damage or fibrosis
Gastric ulcer
Detection of metabolites of OTA in kidneys
Anorexia and weight loss
High level of excretion of proteins in urine
Alteration of the immune response
The residues may persist for weeks
Hematopoietic suppression, anemia, leucopaenia, hemorrhage, diarrhoea, skin problems (irritation/necrosis) Reduced immunocompetence
Trichothecenes. Group B Deoxynivalenol (DON or Vomitoxin)
Corn, wheat, barley, sorghum...
Food rejection, vomiting, diarrhoea, depresion, strong alteration of the immune response
Ulcers in the oral cavity, lymphoid depletion Presence of mycotoxins in feed. Residues last little: 1-3 days post-exposure Clinical effects observed at 1-8 ppm Residues are quickly excreted (1-3 days)
Estrogenic
Zearalenone
Fumonisins (FB1, FB2)
Corn, wheat, barley, sorghum...
Corn
Prepuberal gilts: vulvovaginitis, rectal or vaginal prolapse, signs of heat
Enlarged vulva or uterus (gilts)
Sows: nymphomania/anoestrus (variable)
Vaginal cornification
Repetitions, pseudogestation, corpus luteum retention
Excretion in urine/milk in 1-5 days
Pulmonary edema (high doses) Liver toxicity (subacute dosage)
Table 1. Main mycotoxins that affect swine and the symptoms and lesions they produce (Osweiler & Ensley, 2012)
4
Corpus luteum retention (sows)
Histological lesions with intense interlobular pulmonary edema Apoptosis in liver and biliary retention Increased serum levels of AST, GGT, and bilirubin
TRACEABILITY | A key part of mycotoxin control When it comes to mycotoxins, we have a serious problem with traceability.
CONSUMPTION OF FEED WITH HIGH LEVELS OF MYCOTOXINS Acute intoxication (we could also include subacute intoxications) caused by the ingestion of feed with high levels (or relatively high levels) of mycotoxins is very well characterized. They rarely appear, due to the controls carried out on the feed components and raw materials. In any case, they can appear unseasonably due to negligence in the maintenance of the farm’s silos.
SUSTAINED INTAKE OF SUBCLINICAL LEVELS OF MYCOTOXINS Frequently, with the consumption of sustained subclinical levels, the detection of mycotoxicosis is complicated, with a much more non-specific effect and, thus, more difficult to control. It is commonly accepted that pigs are one of the most sensitive animals to mycotoxins. Due to the type of feed, rich in cereals, that they usually receive in our production systems, pigs are particularly exposed to these kinds of toxins.
As commented before, in most cases, the presentation of mycotoxicosis is generally chronic, which means that the signs are vague or very complicated to assess: Reproductive alterations Reduction of feed consumption Weight reduction Immunosupressionn
Hereafter, we will concentrate on this particular consequence: affectation of the immune response
EFFECTS OF MYCOTOXINS ON THE IMMUNE SYSTEM
Many of the studies carried out on the effects of subclinical mycotoxicosis in pigs have involved DON. This is due to: DON is the most prevalent toxin in the world (Schatzmayr & Streit, 2013) The particular and interesting effect that it has on the animal’s immune system.
A The exact mechanism through which DON and other mycotoxins interfere with the immune system has not been completely elucidated.
IMMUNOGLOBULIN LEVELS
One of the most characteristic effects caused by DON that has been well established in the murine model is an increase in the serum levels of IgA, as well as a decrease in the serum levels of IgG and IgM. The reason of this alteration in the production of different isotypes of immunoglobulins is that DON increases the differentiation of cells that secrete IgA in the animal’s Peyer’s patches, which has repercussions at a systemic level. There is controversy regarding if this mechanism of action also occurs in pigs, as there are some studies that report a similar pattern as the one described in mice (Pinton et al 2008, Grenier et al, 2011) while other researchers have not observed any effects on the different isotypes of serum Ig (Savard et al, 2015b).
7
B
THE EFFECTS OF DON ON VACCINATION
DISCREPANCIES BETWEEN EXPERIMENTAL STUDIES & THE PRESENCE OF MYCOTOXINS IN THE FIELD
On the other hand, what is more interesting is the effect of DON on the response to vaccination. Studies carried out by Pinton et al 2008, Grenier et al, 2011 & Savard et al 2015 indicate that this mycotoxin interferes decisively on such an important practice in modern animal health, leading to a reduction in the efficacy of the vaccination in pigs: Through experimental immunization with ovalbumin (Pinton et al 2008, Grenier et al, 2011) Using commercial vaccines, for example, against the Porcine Reproductive and Respiratory Syndrome (Savard et al 2015a)
C
SENSITIVITY TO INFECTIOUS DISEASES
It has been clearly demonstrated that pigs fed with subclinical doses of several mycotoxins are more sensitive to infectious diseases. In numerous studies, pigs intoxicated with AF, OTA, FB, or DON are more sensitive to infections with parasites, bacterias (Oswald et al. 2005), or viruses (Savard et al 2015b) than the animals that received the control diets.
8
It is interesting to point out that most of the studies carried out, are hard to interpret. Due to higher costs of animal studies and use of single mycotoxins in the trials makes it hard to conclude the effects of mycotoxins.
In the field, unfortunately, the opposite usually occurs: the animals are exposed to more than one toxin at a time, which complicates the situation.
The studies carried out so far have demonstrated the additive effects caused by co-contamination with different mycotoxins, although further studies should be carried out in order to establish the scope of the synergies.
SUBCLINICAL INTOXICATIONS
IMMUNOSUPRESSION OF THE AFFECTED ANIMALS
The intoxication with medium to high levels of mycotoxins are associated with a relatively well-established clinical picture that, comparatively, is easy to diagnose.
The intoxication with subclinical levels of mycotoxins is much more frequent and is very hard to distinguish.
INCREASED INCIDENCE OF PATHOLOGIES
ECONOMIC LOSSES (LESS PRODUCTION, INCREASED ANTIBIOTIC CONSUMPTION, ETC...)
One of the main consequences is the immunosuppression of the affected animals and, in turn, this depression of the immune system increases the incidence of pathologies, which leads to economic losses: less production and increased antibiotic consumption...
Lastly, I would like to highlight something that might be a meer “impression” -after various conversations with members of the sector”. There is a sensation that, lately, mycotoxins have become a “culprit” to which every process that remains without a reliable diagnosis is attributed to.
References available on request
9