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Mass screening with molecular diagnosis reveals a high risk of Oedema Disease with the reduction of ZnO

3 November 2021, at 3:30pm

Oedema Disease and its implications for swine production

Oedema Disease is a major problem in pig production worldwide, causing mortality and impaired productivity. The name of this disease has its origin in the fact that in the clinical form of the disease, typical cases have symptoms such as a swelling of the eyelids, together with a sudden increase in mortality. Hence, a clinical outbreak can be easily diagnosed as swine Oedema Disease on site by a swine vet.

Apart from the clinical form, two other presentations of this disease have been described (Fairbrother & Nadeau, 2019). On one hand the chronic form, which appears in herds recovering from an acute outbreak of Oedema Disease or when the E.Coli also has the potential to generate post-weaning diarrhoea. In this chronic case, typical clinical signs of oedema might not be predominant, but the animals will still have vascular lesions that produce nervous clinical signs and eventually a very significant effect on productive parameters. Finally, the subclinical form of the disease is difficult to diagnose due to the lack of symptoms. The only apparent signs may be a decrease in growth rate and congestion or mild hyperaemia found in the stomach or eyelids where capillaries are distributed. All in all, the disease may have a cost ranging from 4-5€ per pig on subclinical farms (Perozo et al. 2019) due to lower growth performance, up to devastating numbers on severely affected clinical farms with up to 80-90% mortality (Fairbrother & Nadeau, 2019).

Presentations of Oedema Disease

Clinical

Chronic

Subclinical

Sudden death

Swelling of the eyelids and forehead

Neurological disorders

Respiratory distress

Growth stops

Vascular lesions

Hyperaemia in the stomach and intestine

Possible swelling of the eyelids and forehead

Possible neurological disorders

Growth stops

Vascular lesions

Hyperaemia in the stomach and intestine

Growth stops

Mild vascular lesions

Mild hyperaemia in the stomach and intestine

To understand the broad spectrum of clinical presentations, and why the disease can present as a seasonal problem or epidemic disease, we must be aware of the disease aetiology. Oedema Disease is caused by a verotoxin-producing Escherichia Coli (VTEC) (also known as Shiga toxin-producing E.Coli (STEC)). This pathogenic bacterium has the capacity to produce the Verotoxin 2e (VT2e) or Shigatoxin (ST2e), which is absorbed into blood vessels, causing damage to vascular endothelial cells, and will be delivered to systemic organs along blood vessels.

The degree of disease severity is directly correlated to the degree of VT2e in the blood. Oanh et al. (2011) reported that the challenge of low levels of toxin in the blood (5 ng/kg) did not generate evident clinical signs, whilst severity of clinical signs and mortality increased as the levels of VT2e increased (50 ng/kg generates evident clinical signs and mortality of the piglets in 3 days, and 500 ng/kg generates mortality in less than 24h, even without the time for clinical signs to develop).

As E.Coli is a ubiquitous bacterium with a high prevalence of antimicrobial resistance (García-Meniño et al. 2018), once VTEC is introduced into a herd, bacteria will normally spread on the farm, either by the orofaecal route between animals (sows and/or piglets) or contaminated environments and will remain there. Hence, from a practical standpoint, once VTEC is introduced on to a farm, they will become susceptible or at risk of suffering Oedema Disease from then onwards.

Oedema Disease diagnosis

With regard to the diagnosis of Oedema Disease, even when clinical signs are apparent it is important to perform a laboratory diagnosis as other field conditions such as Streptococcus Suis, Glaesserella Parasuis or even salt intoxication may have similar clinical signs. Nowadays there are techniques available to evaluate the risk of the farm suffering clinical or subclinical oedema disease. This will be particularly important if we are thinking of introducing changes on our farm that could favour an E.Coli population, such as reducing antimicrobials or ZnO.

The traditional diagnostic or gold-standard method would be to sample faeces from the animal and culture them in a specific medium for E.Coli in the laboratory. By this method, we would obtain the colonies in about 24h, and from there we would select a few of them to extract DNA from this pure culture and perform a PCR to detect the pathogenic factors, such as the capacity to produce verotoxin. However, this process has the drawback of being highly time and resource-consuming.

A few years ago, HIPRA developed VEROCHECK, a simple method to improve the diagnosis of Oedema Disease by detecting the verotoxin gene in oral fluids by qPCR. The basis of the method is the well-known fact that E.Coli is transmitted by the orofaecal route, as pigs continuously interact with surfaces and other animals that are contaminated with faecal material, and this faecal material remains in their snout and mouth for some time. Oral fluids are an easily obtainable collective sample provided by a high percentage of pigs in the pen, and each individual provides faecal contamination from defecations from different pigs at different times. Therefore, one simple rope can offer a very representative image of a pen.

As demonstrated by Valls et al. (2018), the use of oral fluids showed even more sensitivity than environmental samples and individual rectal swabs. Therefore, oral fluids are a good sample for the detection of VTEC infection in pig herds.

Results of mass screening with molecular diagnosis

Since the VEROCHECK programme started in 2017, a total of 1704 farms have been sampled worldwide.

The standard procedure is that for each farm, one to five ropes are used to sample different pens (one rope per pen). Oral fluids are collected and transferred to an FTA card to finally perform a qPCR, targeting the gene encoding for verotoxin production (Frydendahl et al. 2001). Hence, the rope provides reliable information as to whether verotoxigenic E.Coli are being transmitted by the orofaecal route in the pen. As shedding may be intermittent, it is strongly recommended that different pens and ages are sampled in order to increase the probability of detecting VTEC. Finally, a farm is considered positive if VT2e is detected in at least 1 of the pens that have been sampled.

In order to display the results in an organised way, the results obtained worldwide will be divided into 3 regions: Europe and Canada (in green), Asian countries (in red) and Latin American (LATAM) countries in blue.

Figure 1. Mean prevalence results by regions.
Figure 1. Mean prevalence results by regions.

The mean prevalence of positive farms on a global basis is 62%. When assessing the prevalence by region, we can observe a high prevalence in all of them, led by LATAM countries (72% positive farms), and followed by Europe (60% positive farms) and Asia (59% positive farms). Figures 2, 3 and 4 display the country prevalence for each region:

Figure 2. Mean prevalence results in European countries and Canada.
Figure 2. Mean prevalence results in European countries and Canada.
Figure 3. Mean prevalence results in Latin American countries.
Figure 3. Mean prevalence results in Latin American countries.
Figure 4. Mean prevalence results in Asian countries.
Figure 4. Mean prevalence results in Asian countries.

When analysing the data by country, excluding countries with very limited samples (fewer than 5 samples), the top 5 countries with the highest prevalence were Brazil (85% out of 84 farms), Ireland (79% out of 38 farms), Poland (76% out of 38 farms), Mexico (76% out of 79 farms) and Argentina (76% out of 41 farms). On the other hand, the lowest prevalence was observed in Peru (14% out of 7 farms), Russia (33% out of 104 farms), Italy (36% out of 72 farms), Portugal (45% out of 40 farms) and Colombia (46% out of 35 farms).

In a previously published systematic review of 38 studies published between 1995 and 2016 assessing VTEC prevalence in healthy and unhealthy pigs (Sánchez-Matamoros and Galé (2018)), the prevalence observed by country was described as ranging approximately from 0 to 40%, except for the USA where a prevalence of over 65% of VTEC was reported. These differences could be in part due to the sampling method, whether individual samples (rectal swabs, carcass samples…) or collective samples (pools of faeces) were used; and would reinforce the use of oral fluid as an excellent method for screening VTEC, with high sensivity.

However, some relevant aspects have to be considered when interpreting the results. On the one hand, the fact that we are actively selecting farms with some kind of affection may be enhancing this prevalence, as we perform the diagnostic in farms with not only oedema clinical signs, but also high antibiotic use, relatively high total mortality, slow growth, lack of homogeneity of growing-finishing pigs… which we catalogue as oedema suspicious for having impaired productivity. Still, on the other hand, there are some factors that could be lowering the prevalence. To start with, to have the certainty and statistical power that we will detect the pathogenic E.Coli, assuming a prevalence of about 25% with intermittent excretion, at least 5% of the animals on the farm should be sampled, including different ages. However, this is often not possible due to economic limitations, and sampling has been standardised at 1 to 5 ropes per farm, assuming each rope is a pool of the majority of the animals in the pen. In addition, on the other hand, oedema disease normally affects the nursery, so many farms are sampled in nursery phases where high use of Zinc Oxide could slightly interfere with the sensitivity of the technique, as reported by Galé et al. (2019). Hence, all in all, these data could still be underestimating the real prevalence in these farms with impaired productivity.

These data may be particularly challenging in European countries, which have now drastically reduced their reliance on antimicrobial use in the nursery, often relying on therapeutic high-level zinc oxide. Zinc has been shown to be a very effective tool for preventing Oedema Disease mortality in piglets, impeding the factors associated with the cytotoxic activity of the verotoxin (Uemura et al 2017). However, due to its environmental impact, the EU has decided to ban the medicinal use of zinc. From June 2022, zinc as a feed additive will only be supplied in the feed in quantities that meet daily requirements (150 mg/kg, Regulation (EU) 2016/1095). Hence, it is expected that this reduction will probably be accompanied by an increase in clinical cases of Oedema Disease.

The positive news is that there are tools currently available on the market to tackle this situation. For instance, high-tech recombinant vaccines have been reported to be an excellent tool, not only to reduce clinical signs and mortality due to clinical disease (or even prevent it 100% with VEPURED®), but also to increase the productivity of animals affected by subclinical Oedema Disease. As published by Perozo et al.2018, a significant reduction in mortality and a more than 4 kg increase (105.54 ± 14.81 kg in non-vaccinated animals to 109.64 ± 14.35 kg (P <0.001)) in body weight gain can be observed with vaccination on farms suffering clinical Oedema Disease. Moreover, a subclinical farm without mortality attributable to oedema benefitted by nearly 4 kg (110.06 kg vs 106.24 kg) at the end of the fattening period when the piglets were immunised against the verotoxin.

Conclusions

The fact that 6 out of every 10 farms that were screened had a verotoxigenic E.Coli is unexpectedly high based on the commonly acknowledged clinical incidence of the disease. Considering the substantial costs of this disease, not only for clinical but also subclinical farms, this situation may be revealing huge hidden costs in swine production. How many farms without clinical signs will be suffering subclinical disease? How many farms will suffer clinical Oedema Disease after the removal of ZnO? Further investigation is ongoing and the number has yet to be confirmed. However, data up until today reveal that tools to prevent Oedema Disease such as vaccination will be vital for farms to enhance or maintain productivity in the near future.

References
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Galé et al. 11th Symposium ESPHM Proceedings (2019).
Sánchez-Matamoros & Galé. 10th Symposium ESPHM Proceedings (2018).
Fairbrother & Nadeau, Diseases of swine 11th Ed. (2019) 807-834.
Frydendahl et al. Molecular and Cellular Probes (2001) 15, 151-160.
García-Meniño et al. Frontiers in Microbiology (2018) 9, 2659.
Oanh et al. Infection and Immunity (2011) 469-473.
Perozo et al. Animal and Veterinary Sciences (2018) 6, 95-101.
Uemura et al. Journal of Veterinary Medical Science (2017) 79, 1637-1643.
Valls et al. 10th Symposium ESPHM Proceedings (2018).

Swine Business Unit at Hipra
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Swine Business Unit at Hipra
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