SWELLING DISEASE (Swelsiekte)-The role of the Inflammatory process
By Dr Mackie Hobson BSc(Agric),BVSc

1. Diseases
2. Field Studies

SWELLING DISEASE (Swelsiekte) - Role of the inflammatory process

The first cases of swelling disease in South African Angora goats have been reported during the early 1970s.  A number of trials have been conducted to investigate the cause of this disease over the subsequent years. The consistent finding in studies have been:

• The presence of a low Total Serum Proteins (TSP) and Albumin
• An elevated white blood cell count(Wbc)

This is reflected in previous trials and samples taken from swelsiekte cases.

• Bath (1983),Vermeulen (1984) ,Bath & Vermeulen (1988) and De Wet & Bath (1994)

                Total white cell counts are usually elevated

• Mitchel, Hattingh, Ganhoa (1983), White blood cells were  20X10⁹/L

• A small sample size (n=10) collected by Dr Johan Van Rooyen (Grootfontein) from goats with swelsiekte (n=7) and non-swelling goats (n=3). Swelling goats showed a Stress Leucogram (High Neutrophils, High Monocytes. Low Lymphocytes, Low Eosinophils)

Investigation and collection of data 2015

Swelling disease (hypoproteinaemia) can be seen as an acute onset when a number of individuals show clinical signs within a day or two as well as in chronic cases where individuals/small numbers occur over an extended period of a few weeks (such as in the case of brown stomach worm and coccidiosis). See website https://www.angoras.co.za/article/the-impact-of-brown-stomach-worm-and-coccidiosis-on-angora-kids.

Recovery time can vary and in some cases, it takes up to 2 months for Albumin levels to return to normal. See the website https://www.angoras.co.za/article/treatment-of-hypoproteinemia-swelsiekte-following-brown-stomach-worm-and-cocidiosis-infection.

In these more chronic forms of the disease it is a common and almost certain finding in weaned kids that there is a degree of Lymphocytic-Plasmacytic -enteritis. See website https://www.angoras.co.za/article/lymphocytic-plasmacytic-enteritis-lpe-in-angora-goats

In 2015 the South African Mohair Growers Association (SAMGA) Veterinarian (M.Hobson) sampled 3 outbreaks of ‘Swelsiekte’ on 3 different farms under different conditions where no significant levels of internal parasites were detected.

• Young ewes grazing on the veld, recently shorn
• Old ewes kraaled during cold weather after shearing

• Young ewes grazing on Lucerne lands.

Goats with and without clinical signs of ‘Swelsiekte’ (n=60) were sampled.

Any farmer will know that when catching out 60 Angora goats there is some likelihood that there may be some overlap ‘grey area’ between those goats with ‘swelsiekte’ and those without or just starting to swell.

Graph below: scatter graph of Wbc pattern in relation to Albumin levels

• ORANGE Dots (Non-Swelling goats),
• BLUE Dots (Swelling Goats)

Light green box (normal reference range wbc x10^{9 g/l} IDEXX)

Dark green box (normal reference range Albumin g/i)

The difference in the inflammatory response between Kids and adult Ewes

It is well known in the Angora goat industry that angora kids between weaning and 18 months are the goats in which we see most of the swelling. Angora kids have an abnormal immune response to various antigens. Lymphocytic-Plasmacytic-Enteritis (LPE) is very common in kids between weaning and a year old.

It is also known that kids up to a year have a very poor acquired immunity. See the website

https://www.angoras.co.za/article/immunity-in-angora-goats

It is therefore interesting to see that the WBC response in swelling kids (n=20) is slightly higher than that of ewes  (n=10)

• Swelling Kids: ave 30.1 x10⁹
• Swelling ewes ave 22.1 x10^{9 (}

Non-Swelling ewes and kids had similar Wbc :

• Non-Swelling Ewes ave 17.3 x10^o
• Non-Swelling Kids ave 16.7 x10⁹

EWES inflammatory response in the SWELLING goats was not as pronounced as that of the WEANED KIDS. ORANGE dots (EWES) BLUE Dots Weaned kids

What are the normal Wbc count (leukogram) of an Angora goat?

The Wbc counts of ‘normal’ Angora goats samples by Grootfontein and the SAMGA vet (n=51) and normal % differential (n=15).

 Swelling goats sampled by J.Van Rooyen, Grootfontein and Mohair SA showed a similar leucogram pattern.  (n=8)

This pattern is very similar in both a Stress Leucogram and an inflammatory leucogram

The samples from Grootfontein (Van Rooyen) there is a mild Left shift (n=7)

The STRESS leukogram pattern

Stress resulting in increased corticosteroids causes neutrophilia, lymphopenia, monocytosis, and eosinopenia. (Reflected in the table).

Not all of these changes will be present in any given animal. The most consistent finding is lymphopenia, followed by a mature neutrophilia (increase in segmented neutrophils, but not usually bands).

Left shift or blood shift is an increase in the number of immature cell types among the blood cells in a sample of blood. Many (perhaps most) clinical mentions of left shift refer to the white blood cell lineage, particularly neutrophil-precursor band cells

However, the cortisol levels of both swelling and non-swelling goats over 3 outbreaks (n=60) were not significantly different with the swelling group at 35.9nmol/l while the non-swelling group averaged 34.6nmol/l.

The distribution of the cortisol levels between the kids (n=40) can be compared in the scatter graph below with the orange dots (non-swelling) and blue dots (swelling). The normal reference ranges (Idexx) are marked in light green (cortisol) and dark green (Albumin).

Separating the 2 kid groups,  veld and lands BLUE Swelling, Orange non-swelling

The expectations that a sick animal (Swelling) should show a stress leucogram and increase in cortisol level? Similarly, a stressed goat should show an increased cortisol level? This does not appear the case.

An increased cortisol level should also result in an increased blood glucose level (hyperglycaemia), in cases of sepsis hypoglycemia may be evident.

Blood samples from Grootfontein indicate a lower glucose level in swelling goats (n=13) of 1.65mmol/l compared to non-swelling goats of 3.13 mmol/l.

Wiese (1990) considered a hypothesis that Angora goats either have too low-fat reserves, or they are unable to mobilize their fat reserves quickly enough to maintain their blood glucose levels during stress.

The answer may lie in the fact that 90% of circulating Cortisol is protein-bound, changes in binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of this hormone.

Therefore stressed goats with a presumably normal adrenal function but decreased cortisol-binding proteins will have lower-than-expected concentrations of serum total cortisol but appropriately elevated free cortisol levels.

The Inflammatory leukogram,

An inflammatory response results in a neutrophilia with a left shift (with fewer bands than segmented neutrophils.

Neutrophilia, Monocytosis may or may not be part of an inflammatory leukogram. A monocytosis is usually seen with inflammation when it is more long-standing or resolving. However, the monocytosis can be quite mild.

Lymphopenia (with or without eosinopenia) frequently accompanies an inflammatory leukogram, but this does not always happen. We usually attribute this due to concurrent endogenous stress (corticosteroid release), although inflammatory cytokines may directly cause lymphopenia In some cases, a mild lymphocytosis may be seen with chronic inflammatory conditions.

Inflammation can cause changes in albumin and globulins: This is usually comprised of low albumin/high globulin. The low albumin concentration is due to reduced production by the liver and increased production of globulins. In swelling goats, we see a reduction in both Albumin and Globulin.

Stress or inflammation?

Both stress and inflammation can manifest with similar leukogram patterns, Swelling disease surveys and history have often suggested a component of stress such as after shearing or housing during cold weather. What role does stress play in the significant inflammatory response to swelling disease?

Perhaps intense stressors over-activate the immune system? Young weaned Angora goats under 18 months are known to have an over reactive immune response (Lymphocytic-Plasmacytic-Enteritis).

Other trials where swelling occurred after a stressor was observed after shearing (M.Snyman, A. Snyman Grootfontein). The goats were shorn during Week 10 of the experiment. In week 12 of the study, 19 of the goats developed some subcutaneous oedema. Just prior to the swelling a hot day was followed by cold rainy conditions. The number of goats that developed oedema was fairly evenly distributed among the various treatment groups.

Both stress and inflammation can manifest with similar leukogram patterns, i.e. a mature neutrophilia (no left shift or toxic change), monocytosis and lymphopenia and eosinopenia (although all changes may not be present in every animal). Other lab data may help distinguish (e.g. hyperglobulinemia, hypoalbuminemia).

• In swelling goats the A: G ratio DECREASES by 0.22 (0.66 to 0.44) in the plasma. This is due to albumin concentration reducing to a greater extent than globulin in the plasma compartment so the A: G ratio decreases. See the website https://www.angoras.co.za/article/swelsiekte-swelling-disease-in-angora-goats

Large bodies of evidence indicate that stress can activate an inflammatory response in humans (and rats)

• Recent researchers have proved that Cortisol can also have a pro-inflammatory impact on the immune system. Rats with higher basal plasma corticosterone levels show fewer anti-inflammatory factors after acute stress (Pérez-Nievas et al., 2007).
• Acute stressors seem to enhance immune function, whereas chronic stressors are suppressive. Intense stressors over-activate the immune system, leading to the imbalance of inflammation and anti-inflammation. (Miller et al., 2009).
• In common, an over-activated immune system, increased activity through sympathetic nerve pathways and reduced Cortisol responsiveness may work together in the activation of inflammatory responses during stress.

What has Post Mortems on Swelling goats indicated?

The splenic changes may indicate that a systemic inflammatory response took place, but a cause cannot be determined from the findings and may also be parasite related or due to terminal septicaemia/endotoxaemia.  DR E C DU PLESSIS-( Idexx Pathologist)

The potential role of the inflammatory response “Capillary leak syndrome”

“Capillary leak syndrome” occurs in systemic inflammatory response syndrome (SIRS). Due to widespread damage to the capillary endothelium, there is increased loss of medium to high molecular weight compounds, particularly albumin, into the extravascular space.

The more permeable the capillary barrier is to proteins, the higher the interstitial oncotic pressure and increased swelling of the goat.

For more information on the Capillary leak syndrome as a possible result of the inflammatory response. SEE THE WEBSITE https://www.angoras.co.za/article/swelsiekte-swelling-disease-in-angora-goats

REFERENCES:

• The role of Brown stomach worm (Ostertagia circumcincta), coccidiosis and dietary protein level in the development of swelling disease in Angora goat kids. M.A. Snymana * & A.E. Snyman
• Vermeulen SO 1986    Die etiologiese rol van bruinmaagwurm (Ostertagia circumcincta) ten opsigte van swelsiekte by Angorabokke          Karoo Agric, Vol 3, No 7, 1986, 45-50
• Snyman MA, Herselman MJ    2004    Investigation into the probable cause, predisposing factors and effective treatment of swelling disease in Angora goats  The Angora Goat and Mohair Journal, 46(1): 27-37
• Bath (1983),Vermeulen (1984) ,Bath & Vermeulen (1988) and De Wet & Bath (1994)
• Mitchel, Hattingh, Ganhoa (1983),
• Dr Johan Van Rooyen (Grootfontein)
• com, Cornell University
• Rohleder, 2014; Calcia et al., 2016). Inflammation: The Common Pathway of Stress-Related Diseases.Yun-Zi Liu, Yun-Xia Wang, and Chun-Lei Jiang 2017
• Corticosterone as a marker of susceptibility to oxidative/nitrosative cerebral damage after stress exposure in rats.BG Pérez-Nievas, B García-Bueno, JR Caso 2007
• Transient responses of inflammatory cytokines in acute stress . Author links open overlay panelKaoriYamakawaaMasahiroMatsunagabcTokikoIsowadKentaKimuraeKunioKasugaicMasashiYonedacHiroshiKanekobHidekiOhiraa