The Story of Facial Eczema Research

New Zealand Journal of Agriculture, Volume 97, Issue 3, 15 September 1958, Page 202

The Story of Facial Eczema Research

By

J. F. FILMER,

Director,

Animal Research Division, Department of Agriculture, Wellington

LOSSES from facial eczema in 1955 and 1956 were serious and widespread and similar outbreaks have occurred periodically during the last 60 years or more. It is therefore natural that farmers and others should ask what research has been conducted to determine the cause of this disease and the best methods of preventing it. It is understandable that they are not satisfied with the results obtained and are demanding an extension and intensification of the research programme. This article tells the story of facial eczema research, recounts' the difficulties that have been met and shows how some of them have been overcome, reviews the gradual accumulation of knowledge, and indicates the ways in which it is planned to continue the investigations.

THE first official reference to facial eczema is in the annual report of the Department of Agriculture for the year ended 31 March 1908. The late Dr J. A. Gilruth, the Dominion’s first Chief Veterinarian, reported: “Almost simultaneously from different districts of the North

Island outbreaks of this disease [facial ' eczema] were reported, especially during the month of April .... The outbreaks are generally concurrent with a rich '“ g upon 1 ? e bresking up of a more or less nrolonsrpd neriod nf rl-rxr weather prolonged period of dry weather during which the sheep were devoid of succulent fodder. In all these respects the history is identical with that of similar cases observed- by me nearly 10 years ago. He further reported:

“Various experiments were conducted at the laboratory [Wallaceville] in the attempt to transfer the disease from each of the 5 sheep received with the affection in different stages but without success. As to the bacterial flora

of the lesions naturally this was abundant, especially on the excoriated surfaces. As regards the vesicular eruption, tubes inoculated from the youngest vesicles occasionally remained sterile, but those inoculated from older and more or less purulent lesions always developed numerous

colonies of staphylococci and various bacilli none of which, however, proved virulent when inoculated into healthy sheep, either by «earifirafinn nr mibeutan’enuqlv A similar fate attended all attempts , . j-i •» . to transfer the disease by inocui a +j on of the actual material f atlon ot tae actual material through scarification or otherwise direct from . sheep to sheep. Furthermore when the affected sheep were placed with others in no case was the disease trans- . “ „ ml e "

These experiments at Wallaceville initiated the facial eczema research campaign which is still going on. During the next 30 years, as occasion offered, the pathology of the disease was studied at Wallaceville and observations were made of the conditions

under which the disease occurred in the field. The Wallaceville studies indicated the nature of the skin lesions and revealed the presence of liver damage, It was found that skin damage occurred only on white or lightly coloured skin which was not covered by wool and that affected animals part kin ifsiom; and suggested that photosensitisation was Klved. This is a process whereby skin is rendered unduly sensitive to light which normally would cause no damage. Many photosensitising agents are known, a numher of them being contained in plants of which St. John’s wort is a well

known example in parts of the South Island. The liver damage was found to be °f a particular type which is easily recognised by microscopic examination and. this enables facial eczema to be and this enables facial eczema to be readily differentiated . from other diseases in which iver damage occurs diseases m which liver damage occurs, Field studies confirmed Gilruth . s observations that facial eczema fol . lowed warm autumn rains and was ... . , .. , , . more likely to occur after hot, dry summer periods in which pasture

growth was depressed. In an article published in the February 1938 issue of the “Journal of Agriculture” J. E. Mcllwaine, now Director of the Animal Industry Division of the Department of Agriculture,

after referring to the serious outbreak of 1935, wrote:

“Although one does not wish to enter the sphere of the prophet in predicting an outbreak of the disease this year, at the same time we are advised that the summer is likely to be a dry one and in such circumstances the outbreak of 3 years ago was a very serious matter for sheep owners.”

In the 2 months after the publication of this article New Zealand experienced its most disastrous outbreak of facial eczema.

Facial Eczema Management Committee

After this outbreak the Government set up a Facial Eczema Management Committee to plan and direct a longterm programme of investigations with a view to determining the cause of the disease and providing methods of control. Ample funds were provided and since then succeeding Governments have met all the requests made for money to finance facial eczema research.

At the end of the 1938 outbreak the following, knowledge was available: The primary lesion was in the liver and the losses from facial eczema were due to the effects of liver damage. In severe cases this damage was so great that there was no possibility of the liver regaining its normal condition. In less severe cases sufficient regeneration occurred to enable the liver to function normally unless it was exposed to some unusual strain such as that imposed by lambing or calving. The liver damage was sometimes but not always associated with jaundice and photosensitisation. Outbreaks of facial eczema occurred after warm autumn rains and more frequently on improved pastures than on hill country carrying pastures dominant in danthonia and browntop. All efforts to transmit the disease from affected to healthy sheep had failed and there was no reason to consider that facial eczema was infectious.

Work in South Africa on a related disease known as geeldikkop (literally, yellow bighead) had shown that the photosensitisation in that disease was due to phylloerythrin. This is a substance produced from chlorophyll in the gut of the grazing, animal. In normal animals it is excreted in the bile, but certain types of liver damage cause it to accumulate in the blood and render the animal photosensitive. It was suspected that the photosensitisation in facial eczema was due to phylloerythrin.

With this background of knowledge it was decided to undertaken investigations along the following lines:

1. Field surveys to define as accurately as possible the conditions under which facial eczema occurred. 2. Studies of the after effects of facial eczema in ewes to indicate how they should be handled. 3. Studies of the photosensitisation to determine if phylloerythrin was in fact responsible. ‘

4. Experiments designed to discover what caused the liver damage.

5. Attempts to discover practical methods of controlling the disease.

The investigations conducted under these headings ..will be described separately, but it should be realised that they were often undertaken concurrently.

Field Surveys

Very detailed surveys were made of a number of affected farms in the Waikato district in 1938 by five veterinarians and five agriculturists working in pairs. These surveys began on 30 March 1938 between the two outbreaks which occurred in that year and continued for 2 months. Surveys were also made by officers of the Grasslands Division of the Department of Scientific and Industrial Research in both the Waikato and Bay of Plenty

districts and reports from officers of the Fields Division from all North Island districts were correlated by the Director, Grasslands Division. .

In July 1938 one veterinarian and one agriculturist began a 2-year study of 12 affected farms in the Waikato district concerning which they made detailed monthly reports. In November 1938 a physicist was appointed to supervise the keeping of weather records on these farms and on the research stations. Grass minimum and earth thermometers and rain gauges were - supplied to the farmers and a very full range of weather observations was made on the research stations. « <

From these surveys and from field observations and weather recordings made since, much valuable information has been obtained. This has served as a basis for the investigations conducted at the special facial eczema research stations and in the laboratories. This is the natural sequence in research. Field surveys point the way for the investigation and their continuance is seldom justified after the planned investigation has been started.

Unfortunately such investigation is confined to a few' places and seldom comes under the notice of farmers whose stock are affected and who are inclined to believe that research workers would learn more from studying field outbreaks than from experiments conducted in laboratories or research stations. Experience does not support this view.

Studies of After Effects of Facial

Eczema in Ewes

Forty-four ewes which all showed skin lesions of facial eczema during April 1938 were kept under continuous observation at Ruakura. Nineteen of these were classified as severe cases. Jaundice continued for a relatively short period and could be detected in only a few cases by the end of May. Skin lesions had all healed by the end of June, but some eye lesions were permanent, probably due to infection or injury. There were a number of recurrences of photosensitisation during the spring of 1938 and a few in subsequent autumns and springs. The mortality rate and lambing record are summarised in the following table:

Alive at Lambs Lambs Year lambing Lambed dropped fattened 1938 ..44 19 22 17 1939 ..24 15 17 16 1940 ..19 9 9 9

A further 4 ewes died after lambing in 1940. At the end of this year there were thus 15 survivors from the original 44. All survivors were then in good condition.

Most of the deaths occurred during winter or immediately after lambing. Heavy infestations with the large stomach worm (Haemonchus contor-

tus) occurred during autumn. Survivors regained condition each summer. Lambs grew at normal rates. and fattened well. *

At the end of 1938, 9 deaths had occurred from facial - eczema and' 3 from other causes and 17 lambs were fattened. There would thus have been available for sale 32 ewe fleeces, 32 ewe carcasses, and 17 lamb carcasses.

In a subsidiary Experiment at Ruakura a concentrate supplement was fed to half of a group of affected ewes to determine if this would hasten recovery. There . was no significant difference in the recovery rate of the concentrate-fed ewes and those which received pasture only. In a later, outbreak Ruakura studied 50 clinical and 50 sub-clinical cases. The 50 clinical cases were all suffering from severe photosensitisation and loss of condition. The 50 sub-clinical showed no photosensitisation, but their condition was typical of ewes with badly affected livers. They were derived from a flock of 1,200 ewes from which a sample killing of 100 ewes, showing no photosensitisation

and selected at random, showed 100 per cent severely affected livers. The following results were observed:

Alive at Died Lambs Lambs lambing later Lambed dropped fattened Clinical .... 32 ' 6 77 7 ' Sub-clinical .. 41 6 15 17 15

From these and other observations it has been concluded that a conservative policy should be adopted in dealing with affected ewes. All but the worst of these should be given a chance to fatten rather than being sacrificed while still affected. It is doubted, however, if survivors should

be again mated, especially if they lose condition at or after the first lambing after they contract facial eczema. Studies of Photosensitisation From 1938 to 1943 a comprehensive series of experiments was conducted at Wallaceville. These involved the injection of phylloerythrin into normal sheep, the chemical examination of the blood and urine from these sheep and from cases of facial eczema, and the determination of the types of light which produced photosensitisation in facial eczema and in sheep injected with phylloerythrin. It was demonstrated that phylloerythrin is the photosensitising agent in

facial eczema. As this substance accumulates in the blood only when the

liver is not functioning properly, it was concluded, that liver damage is responsible for the photosensitisation. As liver damage is also responsible for loss of condition

and death in sheep which do not show skin lesions, it is obvious that it is the important factor

in facial eczema. Cases in which photosensitisation does not accompany liver damage are probably due to the liver being able to divert phylloerythrin into the bile when liver damage occurs slowly, even though it may eventually be quite severe.

Search for Liver-damaging Factor More than 20 different diseases have been described in various parts of the world in which liver damage and photosensitisation occur. In nearly all of these a plant is known or suspected to cause the liver damage. It was therefore natural to suspect a plant as the cause of facial eczema. Careful examination by botanists and a mycologist of paddocks in which facial eczema occurred in 1938 failed to incriminate any weed or fungus. The hypothesis was therefore propounded that facial eczema was caused by a liver-damaging factor developing in one or more pasture species after warm autumn rains.

It was also realised that the liverdamaging factor could have resulted from a variation in the concentration of some of the normal ■ constituents of pasture. This prompted a comprehensive series of analyses of pasture samples from .. paddocks in which facial eczema had occurred or was expected to occur and a parallel series of analyses of samples of normal pasture. This involved the whole-time efforts of a considerable number of chemists for about 2 years. It produced useful information about the relative composition of mature and immature pasture.'

Rapidly growing autumn pasture was also examined for the presence of unusual compounds and a series of hitherto undescribed alkaloids was discovered. It was shown, however, that these were not responsible for the liver damage.

It is not surprising that chemists at this stage made no progress toward identifying the liver-damaging factor, as it is doubtful if any of the pasture examined by them contained it. Field evidence showed that if healthy lambs were introduced into a paddock as soon as sheep grazing in it showed signs of facial eczema, the new lambs

remained healthy. This meant that if facial eczema was caused by the eating of toxic pasture, the pasture did not always remain toxic after symptoms had appeared. Pasture therefore had to be collected before symptoms appeared, but first it had to be shown that facial eczema was in fact caused by a liver-damaging factor in pasture.

The first attempts to do this were made on an area of 40 acres leased on a farm at Karamu, about 10 miles south-west of Hamilton. These attempts failed because, though facial eczema was reported to have occurred annually for a number of years on the area, no clinical facial eczema and very little liver damage occurred there in 1939 and 1940. This situation recurred many times in the course of the facial eczema investigation.

The first significant success was achieved in 1941 on 10 acres leased at Whakaki, about 10 miles east of Wairoa; A serious outbreak of facial eczema occurred in experimental lambs grazing this area during. March. Pasture was mowed daily from the area from January to April and fed green to penned lambs. Definite liver damage was produced in some of these. This greatly strengthened the hypothesis that liver damage was due to a substance in the pasture, but before the chemists could start their task some means had to be found of preserving the pasture which did not destroy the liver-damaging factor.

Freezing had been tried at Karamu in 1939 and 1940, but results were inconclusive because the growing pasture was only slightly toxic. With the removal of the experimental area to the east coast freezing appeared to be less attractive, as the transport of frozen grass in large quantities to the chemistry laboratories at Waiiaceville and Ruakura would have presented difficulties.

In 1942 grass was preserved by boiling _ and sealing in tins and small quantities were preserved in alcohol. No liver damage occurred in lambs grazing on the experimental area in that year.

To determine whether grass remained toxic after preservation, it had to be fed to lambs and experience showed that from 100 to 250 lb. of green grass was necessary for a test with a single lamb. This presented real difficulties with preservation in alcohol, which for obvious reasons would have to be evaporated off before feeding. This method was continued only on a small. scale which proved very useful for the alkaloid extraction already mentioned.

In 1943 grass was preserved by boiling and by drying. Boiling presented many problems. Kerosene tins were first used but were not strong enough to stand the strains set up during heating and cooling. Eventually, with helpful advice from commercial canneries, grass was successfully pre-

served in 378 tins holding approximately 6 lb. of green grass each. Grass, was dried by drawing air from a coke furnace by an electric fan and forcing it through layers of pasture held in trays. In this year about 2 tons of . grass was dried from the experimental area at Whakaki and from selected paddocks in Gisborne and

Wairoa districts. Fortunately severe liver damage occurred in lambs grazing these areas. . The preserved grass was sent to Wallaceville, where it was fed to lambs and guinea pigs. The boiled grass produced only very mild liver damage in 1 of 2 lambs and in none of 6 guinea pigs. Dried grass produced liver damage in varying degree in 10

out of 11 lambs and in 13 out of 39 guinea pigs. It was thus shown that the toxicity of grass could be preserved to at least some extent by drying. Another forward step had been made.

The relatively small percentage of guinea pigs showing liver damage made this animal appear unreliable for test purposes. This was unfortunate, as the daily ration for even a mature guinea pig is only about 1/10 that for a lamb. Since 1943 heat drying, has been adopted as the standard method for preserving pasture and a total of about 6 tons of dried toxic grass has been obtained.

Test for Toxic Pasture

A method of determining which pasture was toxic had to be developed. The only test available was the reaction of the grazing lamb. It was hoped that a test could be found which would show when the liver suffered damage. A number of different methods were tried involving many thousands of individual tests, but none detected liver damage unless this was accompanied by jaundice.

Eventually the system which is now used was evolved. Five 2-acre paddocks which have a bad history for facial eczema are kept short during summer by either overgrazing or mowing. In January some 300 lambs are bought from a hill farm before any liver damage occurs. From 40 to 60 of these are placed in one of the 2-acre paddocks and then. rotated through the 5 paddocks, spending 2 days in each. The remaining lambs are grazed on crops, usually turnips or thousand-headed kale, which do not produce facial eczema, until they are required.

When the first autumn rains fall 10 lambs are introduced into the experimental paddocks and thereafter a further 10 are introduced each week until the weather cools, usually late in April. Two of the large group are removed each week; 1 is killed immediately and the second is grazed for 3 weeks on crops and then killed. The latter procedure has been adopted because it has been found that liver damage progresses after feeding on toxic pasture has ceased.

The smaller groups are removed after 3 weeks in the experimental paddocks. Five are killed immediately and the remaining 5 after 3 weeks’ grazing, on safe crops. All livers are carefully examined for damage.

From the time of the first autumn rains until cold weather follows in late autumn pasture is mowed daily and dried. Each day’s cut is labelled, with paddock number and date. The dried grass which was toxic when growing can thus be identified; for example, in 1950 the livers of all lambs killed up to 27 March were normal and livers of all lambs which entered the paddock on or after 4 April were normal. Livers of lambs which grazed during

the intervening period showed some damage and it was thus obvious that pasture was toxic during some part of that period and non-toxic before and after it. Chemical Investigations Ever since it was demonstrated in 1943 that the liver-damaging factor could be preserved in dried grass chemists have been endeavouring to isolate the responsible substance. They had no clue to its identity and its only known characteristic was that it produced liver damage. Every extract prepared had to be fed to a lamb. At least 25 lb. of dried grass was required for each test and it had to be fed over a period of 3 weeks or more.. Supplies of toxic grass became available at irregular intervals, the toxicity was often rather low, and it tended to disappear when the grass was kept for long periods. This is now prevented by keeping the dried grass in cold storage. The irregularity of supply is indicated by the following data from the Manutuke experimental area. 1944 Toxic grass collected on 36 days 1945 Toxic grass collected on 51 days 1946-48 No toxic grass collected

1949 Toxic grass collected on 19 days 1950 Toxic grass collected on 17 days 1951 Toxic grass collected on 9 days 1952-54 No toxic grass collected 1955 Toxic grass collected on 1 day 1956 Toxic grass collected on 1 day 1957 Toxic grass collected on 21 days Before 1952 the toxicity of the dried grass could be tested only by feeding it to lambs and the toxicity of each day’s collection could not be tested. The probable toxic period was determined by reference to the liver damage which occurred in lambs grazing the experimental area. Grass collected during this period was mixed and fed to lambs. The results in 1955 and 1956 were most disappointing. Grazing lambs developed liver damage over considerable periods and clinical cases occurred in both years. The same dryer and the same techniques were used as in previous years. However, feeding experiments with the dried grass showed that toxicity had been preserved on only 1 day in each year. Fortunately small supplies of toxic grass became available from some areas in the Waikato. In 1957 over 2 tons of toxic dried grass was collected from Manutuke and other

Poverty Bay areas and at present adequate supplies are available for the first time. The difficulty of collecting toxic pasture early prompted efforts to grow it by simulating the weather under which facial eczema occurs. As early as 1939 efforts were made to grow toxic pasture under glass and on artificially heated soil outside. Further efforts were made in 1956 and 1957 with improved facilities. Unfortunately these efforts have so far failed, but they are being continued. . The first toxic extracts were produced in 1952 and since then considerable progress has been made. This was greatly assisted by the discovery that very young guinea pigs. are fairly sensitive to the liver-damaging factor. Tests can be made with them using extracts from about 2 lb. of dried grass. Toxic extracts have now been prepared which contain only a 1/100,000th of the original dry matter. However, even at this concentration the chemical reactions are very similar to those from extracts made from nontoxic grass. Only feeding tests can differentiate with certainty between corresponding extracts from toxic and non-toxic grass. Identification of the liver-damaging factor is proving very difficult.

. There has, . however, been one encouraging chemical development. During the extraction of toxic pasture it was observed that a deposit appeared on the walls of the beaker in which the extract was evaporated. This gave rise to the so-called “beaker test”. The deposited substance is not the liver-damaging factor and is in fact not toxic, but its presence indicates toxicity with reasonable accuracy at least in the earlier part of a toxic period. As the test requires only about 2 oz. of dried grass and can be completed in a few hours, it promises to be very useful. It is hoped to use it in spotting toxic pastures for collection and perhaps in identifying toxic species, in following the development and the level of toxicity in relation to weather, and, possibly in breeding non-toxic strains of ryegrass.

Development of Means of Preventing Disease From 1941 to 1944 comprehensive daily weather observations were recorded at the experimental area at Whakaki and similar observations have been made at Manutuke since 1945. It has thus been possible to

correlate the occurrence of liver damage with weather over 18 years. From these data three observations have emerged. Facial eczema tends to occur more frequently after summers which are hotter than normal. In those years it is precipitated by warm autumn rains. Not all warm autumn rains induce facial eczema and there is still no means of differentiating between those which are followed by facial eczema and those which are not. The demonstration of a liver-damag-ing. factor in pasture and its association with weather has enabled preventive measures to be devised. As facial eczema is caused by the consumption of toxic grass, it can obviously be prevented by ensuring that toxic grass is not eaten. This can be done in a variety of ways. Brassica crops and pure white clover swards do not produce facial eczema, so sheep can be grazed safely on them during dangerous periods. Where safe crops are not available stock can be protected by being concentrated in small areas and thus reducing the consumption of toxic grass to a minimum. Hay and/or silage are fed to prevent undue loss of condition. By this means facial eczema has been prevented at Ruakura during the

last 15 years, though it is known that pasture was dangerous in 6 of those years.

It may well be that some means will be discovered of preventing pasture from becoming toxic. In 1938 it was observed that mature pasture was less toxic than the rapidly growing pasture which appeared after warm autumn rains. Efforts were made to provide mature pasture for autumn grazing by shutting up paddocks in summer. This procedure did not prove successful, probably because sheep tended to graze the areas in patches and then to concentrate on the young pasture growing on those patches.

Field observations in the Waikato from 1943 onward have shown that this method cannot be relied on to prevent facial eczema. The method, however, may well prove useful as a means of reducing the incidence of

the disease on hill country and it will be further tested for this purpose. It has been suggested.that the application of trace elements, such as copper and cobalt, might prevent facial eczema. In a small experiment conducted by the Grasslands Division of the Department of Scientific and Industrial Research the application of these elements did appear to give some protection, but copper was applied at a dangerously high level. In a larger experiment at Manutuke neither copper nor cobalt nor the two combined gave any protection when applied at safe levels. Fungi or other micro-organisms growing in the soil or on the plants have frequently been suggested as the cause of facial eczema. It can be stated with some certainty that facial eczema is not due to infection of the animal by any living organism. The concentrated extracts which have pro-

duced liver damage certainly do not contain any living infection. However, a fungus or other microorganism could produce the liverdamaging factor either in the soil or in the plant. It has been suggested that the heavy dressings of copper may have succeeded by acting as a fungicide. Experiments in which other fungicides beside copper will be used are planned to test this hypothesis. Substances are now available which depress rates of growth of plants. The effects of these are being tested to see if they can be used to control facial eczema.

This article has been written to give readers some idea of what is involved in the study of a problem as intricate as facial eczema. . Though progress has been slow, the position has been reached where the problem has been fairly clearly defined and knowledge and techniques are now available to attack it intelligently. It would be foolish to forecast spectacular and early success, but the assurance can be given that the investigation will be continued with perseverance and vigour until the cause of facial eczema is clearly understood and the most effective possible means of control provided.