SWELLING DISEASE (Swelsiekte)-Theories and Trials conducted
By Dr Mackie Hobson BSc(Agric),BVSc

1. Diseases
2. Field Studies

The first cases of swelling disease in South African Angora goats were reported during the early 1970s. 

A number of theories and trials conducted have been put forward and tested as to the cause of swelling in Angora goats. From all the information available on swelling disease in Angora goats, it is obvious that it is a complex condition, of which little is known regarding the mechanisms involved in the initiation and course of the disease.

1. Glucogenesis from Albumin caused the low oncotic pressure:

• Wiese (1990)aimed to investigate the hypothesis regarding swelling disease: Angora goats either have too low-fat reserves or cannot mobilize their fat reserves quickly enough to maintain their blood glucose levels during stress conditions. Thus gluconeogenesis is started, but with the poor muscular development of Angora goats, the source for gluconeogenesis would primarily be the albumins in the blood plasma.

• However, Herselman (1995)reported results that suggest the opposite to the above-mentioned hypothesis. Trials relating to the hardiness of different small stock breeds were conducted in which blood parameters of mature Angora goat, Boer goat, Dorper sheep, Merino sheep and Namaqua Afrikaner sheep were monitored over a period of five weeks, including a seven day fasting period. Blood levels of glucose, non-esterified fatty acids, ketones, total plasma proteins, plasma albumins and albumin: globulin were measured for a five-week experimental period. All breeds, including the Angora goat, had mobilized fat reserves during the fasting period. Furthermore, total plasma proteins, plasma albumins and albumin: globulin remained virtually constant throughout the seven-day fasting period. Therefore, these results prove that Angora goats do not use blood albumin as a source for gluconeogenesis during feeding stress conditions. As fasting is a drastic stress condition, it can be deduced that Angora goats would also be able to mobilize their fat reserves instead of blood albumins under other types of stress conditions. 

2. Allergic reaction:

• Vermeulen (1986) suggested that an allergic reaction may be involved in the development of swelsiekte. However, he said that a loss of protein could not be excluded. Brown stomach worm may be able to possibly cause a protein loss and an allergic reaction, although other factors may be involved. Experiments in 1981 where brown stomach worm was dosed on Angora goats at different levels caused a few swelsiekte cases to conclude the effect of brown stomach worm on swelsiekte. The cause appears to be complex as not all cases of swelsiekte had low protein levels or a high parasitaemia. Where swelsiekte did occur, it developed when the goat's blood protein levels were at their lowest point.

• Histaminewas injected into goats with hypoproteinaemia but did not result in symptoms of swelling (Bath, Vermeulen 1983,1984)

3. Hypoadrenocorticism:

• An article by Sullivan et al. 2013reflected it has been proposed that ventral oedema may be associated with congenital hypoadrenocorticism. These animals have a reduced adrenal function with decreased cortisol production and glucogenesis in response to stress (Engelbrecht and Swart 2000).

Ventral oedema may therefore be a manifestation of stress in this breed.

The same reduced physiological response to ACTH by the adrenal cortex has also been reported to result in a significant number of mortalities of young goats during cold, wet weather, particularly after shearing (Storbeck et al, 2009).

In goats with congenital hypoadrenocorticism, the synthesis of cortisol (a glucocorticoid) is reduced due to the bioactivity of two cytochrome P450 17 alpha- hydroxylase/17,20 lyase (CYP17) isoforms identified in the South African Angora). The secretion of glucocorticoids by the adrenal cortex is a central feature of the stress response in mammals, and a functional hypothalamic-pituitary-adrenocortical axis is essential for glucose homoeostasis (Storbeck et al., 2009).

The reduced enzymatic activity of CYP17 isoforms in these animals does not allow them to maintain normal blood glucose levels under stressful conditions (Storbeck et al., 2009). Without adequate blood glucose levels, especially in cold conditions, the goats experience dangerous drops in body temperature. Without glucose as an energy source, the goats cannot thermoregulate effectively, resulting in significant mortalities.

The SAMGA Vet M.Hobson (2015) compared the cortisol levels of swelling and non-swelling goats over 3 outbreaks (n=60). The average cortisol levels were not significantly different, with the swelling group 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).

The expectation would be that the cortisol levels in sick (swelling) or stressed goats should be higher than in normal goats? Is there a lack of Glucocorticoid response? However, 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 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 to cause a physiological stress response.

• Aldosterone, the main mineralocorticoid, increases sodium absorption by epithelial cells in the kidneys, salivary glands, sweat glands and the gastrointestinal tract. A reduction in the secretion of aldosteroneresults in marked alterations in serum levels of potassium, sodium and chloride. Potassium secretion by the kidneys is reduced, resulting in a progressive increase in serum potassium (Bruyette, 2011). Hypernatraemia and hypochloraemia also result from renal tubular losses.

In a field study (M.Hobson 2015), No differences were found in Sodium levels between swelling and non-swelling goats (n=58). Average Na in swelling goats was 144.1 mmol/l compared to non-swelling goats of 145.7 mmol/l.

In the graph below, non-swelling goats have orange dots and swelling goats blue dots. Light green reference ranges of Sodium (Na) and dark green reference range Albumin (Idexx labs)

Bath and Vermeulen (1983, 1984) injected Aldosterone into goats with hypoproteinaemia to determine if insufficient aldosterone was the trigger due to ‘stress’. No symptoms, however, developed

The SAMGA Vet M.Hobson (2015) sampling 3 outbreaks of swelsiekte showed the swelsiekte goats had higher Aldosterone levels as would be expected in cases of lower oncotic pressure. On average, swelling goats had Aldosterone levels of 1280.5 pmol/l compared to non-swelling goats of 387.6 pmol/l (n=58)

Below is the distribution of Aldosterone results: Blue dots swelsiekte (n=29) Angora goats compared to Orange dots non-swelling Angora goats (n=29). Reference range (Idexx) in green  

4. Parasites

• Brown stomach worm (Ostertagia circumcincta) Vermeulen (1986)

Vermeulen conducted experiments between 1980 and 1984; Angora goats were infected with Ostertagia circumcincta (Brown stomach worm) larvae at varying doses

• All goats infected with Ostertagia circumcincta had a reduced plasma protein level in all trials. From these, it seems as if Ostertagia circumcincta could be an underlying cause for the development of swelling disease.
• However, some or other trigger mechanism (any stress-inducing condition is necessary for the goat to develop the full-blown swelling disease.
  • Brown stomach worm (Ostertagia circumcincta) and Coccidiosis. M.Snyman &A. Snyman (2005)

A trial was carried out to investigate the possible role of Ostertagia circumcincta, coccidiosis, and protein level in the diet in the development of swelling disease in Angora goat kids. Eighty Angora goat kids were bought from five producers whose flocks had a history of swelling disease. There were also no significant differences at any stage throughout the experimental period in faecal egg counts, faecal coccidial oocyst counts or any of the blood parameters between goats that developed moderate oedema, little oedema and those that did not develop any oedema. No goats developed full-blown swelling disease during the course of the experiment. It is possible that the treatments applied in this study are not inductive of the disease, or the effects of the treatments were not severe enough to induce swelling disease.

• Coccidia, M.Snyman and A.Snyman (2005)

Snyman/Snyman noted that coccidial oocyst counts in affected animals reported in the available literature were low.

• Blue lice, Howell, Walker, Nevill (1978)

Howell, walker and Neveville suggest blue lice infestations (Linognathus Africanus) caused cases of oedema (Howell, Walker, Nevill 1978).

5. Albumin loss through faeces or urine Bath, Vermeulen (1983,1984)

Radio-active marked Albumin was injected into goats with swelsiekte and normal goats. Albumin loss was at the same rate in swelsiekte and normal goats. The quantity of albumin in the faeces and urine was the same. This concluded that Albumin loss through urine and faeces was not a feature of swelsiekte.

 6. Infectious causes Bath, Vermeulen (1983,1984)

              No indication of the disease being transmissible.

Trials in laboratory animals and in goats, using different organs inoculated by various routes, have failed to give any indication that the disease can be transmitted. Various attempts to culture bacteria and mycoplasmas from affected goats have yielded no significant results.

 A disease possibly similar to ‘swelsiekte’ has been reported in the Mediterranean region (Stampa 1977), where the cause was suspected to be due to Mycoplasma agalactica however, attempts to culture the bacteria failed.

7. Reduced blood albumin levels Snyman, Herselman (2004)

7.1 Snymanand Herselman (2004) concluded that from the results of various trials the reduced blood albumin levels is the underlying mechanism responsible for accumulation of subcutaneous oedema in goats with swelling disease. They therefore suggested that any condition / factor that contributed to a lowered blood albumin level, could be a predisposing factor for swelling disease.

Low levels of Albumin/TSP were confirmed as the outcome has been confirmed by all researchers, but the mechanism has not been identified.

The possibility of many factors could that contribute to a lowered blood albumin level and indirectly to the development of the swelling disease may be involved:

Protein deficiency – reduced production of plasma proteins

• Low-quality feed (low digestibility, low % crude protein)
• Low feed intake (only irrigated pastures – too high moisture content of feed)
• Low protein absorption from the intestines (mucosa damaged by parasites or coccidia)
• Interference with the metabolism of plasma proteins

Increased protein loss

• Physiological protein loss:  Mohair production
• Increased permeability of capillary membranes:  Allergic conditions, Infectious diseases
• Internal parasites: Brown stomach worm (Ostertagia circumcincta), Wireworm (Haemonchus contortus), Coccidiosis, Conical fluke (Paramphistomum)-(E.Snyman 1988)
• External parasites: Ticks, Blue lice, blood parasites

Any stress-inducing condition

• Weaning
• Shearing
• Dipping, castrating
• Inclement weather
• Competition for food
• Change of feed

7.2 A. van Rooyen (2009), reviewing laboratory reports from the Provincial Veterinary Laboratory (PVL) at Middelburg, made a list of abnormal findings. These reports dated from 1980 to 2006 and were performed by a number of successive veterinarians.

Three sets of abnormal findings were common:

1. Decreased red blood cell count coupled with increased white blood cell count
2. Decreased lymphocytes coupled with increased neutrophils
3. Decreased albumin coupled with increased globulin.

Swelling disease occurs when one or more of the pathways are active. These can possibly be grouped into four main pathways that lead to a common end result:

1. Insufficient protein inputs
2. Loss or consumption of protein
3. Abnormal metabolic pathways
4. Increased capillary permeability.

See Website: Role of the Blood Proteins: (M.Hobson 2015) https://www.angoras.co.za/article/swelsiekte-the-role-of-blood-proteins

BLUE dots Swelling goats, Orange dots Non-swelling goats (n-60).

8. Capillary leak syndrome

 8.1 Capillary leak syndrome as a result of Hypoproteinaemia -Mitchel, Hattingh and Ganhao (1983).

Boer goats and Angora goats were used in the study. The plasma of oedematous goats shows a lower total protein concentration, a lower colloid osmotic pressure and lower albumin: globulin ratio than that of normal goats. Similarly, the interstitial fluid of oedematous goats has a lower protein concentration, osmolality and colloid osmotic pressure than the fluid from normal Boer goats (but similar albumin: globulin ratio. These results suggest that hypoproteinaemia leads to filtration of fluid and increased capillary permeability.

8.2 Capillary leak syndrome causing Hypoproteinaemia M.Hobson (2015)

A hypothesis of hypoproteinaemia as a result of a capillary leak syndrome.

Normal interstitial values were obtained for Angor goats. https://www.angoras.co.za/article/the-composition-of-interstitial-fluid-in-angora-goats

Comparisons of the Albumin: Globulin ratio of interstitial fluid from both normal and swelling Angora goats led to the conclusion that the Albumin was being lost into the interstitial fluid due to a capillary leak. This reflected findings by Mitchel, Hattingh and Ganhao (1983).

See https://www.angoras.co.za/article/swelsiekte-swelling-disease-in-angora-goats

8.3 Capillary leak syndrome as a result of an inflammatory response, M.Hobson (2015)

The inflammatory response affects the capillary membranes and could potentially contribute to a ‘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.

Graph of goats from 3 different outbreaks of swelling (n=58) comparing the blood Albumin levels and White blood cell count (Wbc).

Comparing the kids: Orange dots non-swelling goats, blue dots swelling with reference ranges of normal goats dark green (Albumin) and WBC light green.

See: https://www.angoras.co.za/article/swelsiekte-swelling-disease-in-angora-goats

Conclusive evidence as to the underlying mechanism and the cause of the disease still needs to be established.

Further investigation into the Leucocytosis and Free cortisol needs to be evaluated.

References:

• Swelling disease  GF Bath & SO Vermeulen  (1985) Grootfontein Agricultural Development Institute
• Snyman MA, Snyman AE (2005) The possible role of Ostertagia circumcincta, coccidiosis and dietary protein level in the development of swelling disease in Angora goat kids. J. S. Afr. Vet. Ass. 76(2) : 63-68
• 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) :
• Bath GF (1988) Swelling disease
• Joubert JPJ (1990) Swelling disease / Swelsiekte  Angora goat and Mohair Journal 32 (1)
• 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
• Vermeulen S (1983)  Swelsiekte by angoras ondersoek    Karoo Streeknuusbrief Herfs            
• Sullivan (student Charles Sturt University) and M Monaghan (Lithgow Veterinary Hospital) and D Ryan (NSW DPI, Menangle) and B Watt (Central Tablelands Local Land Services, Bathurst) (2013)
• INVESTIGATION INTO THE CAUSE, PREDISPOSING FACTORS AND EFFECTIVE TREATMENT OF SWELLING DISEASE IN SOUTH AFRICAN ANGORA GOATS J.A. van Rooyen. RESEARCH REPORT of the GROOTFONTEIN AGRICULTURAL DEVELOPMENT INSTITUTE (2009)
• THE COMPOSITION OF PLASMA AND INTERSTITIAL FLUID OF GOATS WITH SWELLING DISEASE G. MITCHELL·, J. HATTINGH·· and M.F. GANHAO· Journal of the South African Veterinary Association (1983)