Pantothenic-acid Deficiency In Pigs 16uo

J.

COMPo PATH.

1962.

VOL. 72 .

SOME CLINICAL AND EXPERIMENTAL OBSERVATIONS ON NATURALLY-OCCURRING PANTOTHENIC-ACID DEFICIENCY IN PIGS By

R. F. W. Department qf

Vel£rina~y

GOODWIN

Clinical Studies, Universi!y of Cambridl!.e INTRODUCTION

Pantothenic-acid deficiency in the pig has been studied experimentally for a number of years but, as with other vitamin deficiencies, the earlier work was handicapped by uncertainty concerning the true nature of the deficiency states observed. Briggs and Daft (1954) concluded that, even as late as 1941, the deficiency signs produced by experimental diets could have been due to a shortage of other factors in addition to an insufficiency of pantothenic acid, but from subsequent work, involving more complete diets, they felt that they could safely list the gross clinical and pathological signs of the experimental disease. Reports of the naturally-occurring disease, such as that of Schulze (1960) , have been few and , as might be expected, they have not approached the standard of the experimental observations in defining the condition being described. Doyle (1937) encountered a condition that might have been pantothenic-acid deficiency, but he favoured an infective aetiology. Hughes (1942) stated that goose-stepping in pigs had been reported "from many sections of the country" (U.S.A.), and Hughes, Crampton, Ellis and Loeffel (1944) suggested that "the frequent occurrence of 'goose-stepping' in farm swine herds may be evidence of a pantothenic-acid deficiency". The availability of a large herd of pigs, apparently suffering from pantothenic-acid deficiency, and at the same time free of enzootic pneumonia (which otherwise might have interfered seriously with controlled nutritional trials), provided the writer with a very favourable opportunity to study this deficiency disease under field conditions. Once the presence of the disease had been established in this herd, other herds were investigated and some wider conclusions were drawn on the influences that might now be governing the pattern of the field disease. The that follows appears to be the first report of pantothenic-acid deficiency in British pigs. METHOD

To estimate the pantothenic-acid content of meals, 5 g. samples of meal were shaken with 500 ml. of phosphate buffer solution (pH6·6) at 5 min. intervals during half an hour. The extract was then filtered, diluted, and assayed with Lactobacillus arabinosus againt a calcium Dpantothenate standard. The results obtained, therefore, have been related to calcium pantothenate, rather than pantothenic acid.

R. F. W. GOODWIN

21 5

RESULTS

HERDQ

General History

This herd of pedigree Landrace pigs comprised about 40 breeding females and their offspring, the latter being fattened for bacon production. It had been apparently free of enzootic pneumonia for some years and by 1960 had fully complied with the standards of the Association for the Advancement of Virus Pneumonia Free Pigs*. The first signs of the disease that is more fully described later appeared in a litter born in December, 1957: the whole litter showed varying degrees of weakness in the hind legs, associated with scouring and unthriftiness, before weaning. A few other litters were similarly affected during 1958, and by January, 1959, a litter born in the previous October had become severely affected: the scouring which had been present before weaning, was now bloodstained; there was also anorexia and marked posterior weakness, and one animal had died. The number of clinical cases decreased during the next 4 months, but by June, I959, it appeared that the disease was becoming both more common in the growing pigs and more severe, in that the litters were now showing clinical signs at a younger age. Thus, a litter born in mid-May was scouring by 6 days of age and showing posterior weakness when just over 2 weeks old. In July, 126 pigs over weaning age were examined: of these, 49 were obviously affected neurologically, and 6 more might have been showing early signs-an incidence based on neurological involvement alone of nearly 50 per cent. As the pig is not an easy subject for detailed clinical examination, particularly when neurological signs are being recorded, all tests in which the animal's response was questionable have been omitted. The essential clinical features of the disease, however, were as follows. Clinical Signs in Weaned Pigs

Although the scour rarely became extremely watery, some fluidity of the faeces was common, and this usually preceded other signs. One of the earliest neurological signs was difficult to detect, as it was merely a slightly faulty action of the hind legs, including a mincing gait or a somewhat stiffer movement than is usual. Slight abnormalities of this type are sometimes seen in pigs, particularly Landrace animals, on diets not deficient in the B-group vitamins. When the disease did not progress beyond this stage, therefore, it could not be certain that some hereditary factor was not involved. Many cases that were first diagnosed in this way, however, proceeded to advanced posterior inco-ordination. Another mild sign was

* See Goodwin and Whittlestone (1960) for the nomenclature used in respiratory diseases, and for the regulations and standards of the Association.

216

PANTOTHENIC-ACID DEFICIENCY IN PIGS

muscular tremor over the hind quarters when standing still. In several other animals, one of the earliest signs was a slight snatching movement in the hind legs on walking but, as pigs normally move with a slightly stilted hind-leg action compared with other species, the first signs of abnormality were, once again, not always clear-cut. One of the next stages in the condition was swaying of the hind quarters. Some pigs so affected stood with their hind legs slightly more apart than usual, and a few showed a dip in the back at the lumbar region. Thereafter, the clinical signs were more obvious, but in referring to them it should be ed that, in such a large number of affected animals, there were many intermediate variations in the present set descriptions. In the main, the abnormalities of movement fell into 2 groups: first, exaggerated actions with the hind legs and, secondly, progressive paralysis of the hind legs. The exaggerated action usually commenced as a slight snatch as the hind feet left the ground. This became progressively more marked and was commonlyassociated with a forward-reaching movement of the leg as the feet returned to the ground. The combination of a very high lift of the hind leg with the reaching forward under the abdomen produced the so-called "goose-stepping" movement (Figs. I, 2, 3 and 4). In several cases this action became so great that the hock t approached the ground (Fig. 8); this necessitated a lowering of the pelvis. Pigs thus affected often moved quite rapidly with a peculiar waddling, rolling, duck-like action. It was observed that some of the animals that goose-stepped when moving, periodically snatched their hind legs from the ground when standing still (Fig. 6). Behaviour similar to this was observed by Hughes and Ittner (1942) and Colby, Cunha, Lindley, Cordy and Ensminger (1948) in the experimentally-produced disease. When the signs were largely of the second type, the earlier swaying action advanced to marked inco-ordination (Figs. 10 and 1 I), the hind quarters often collapsing to one side. On a slippery surface, this collapse was more frequent, the hind legs commonly being splayed out anteriorly on the ground (Fig. 12). Fairly advanced cases of this type could not raise their hind quarters from the ground unaided (Fig. 10), but they could sometimes stand once they had been assisted to that position. In the most advanced cases, the hind legs were incapable of ing the body; pigs thus affected often propped themselves up on their forelegs and sat with both hind legs to one side. Nearly all such cases managed to move about fairly well, and no case became immobile. The only animal with any involvement of the forelegs showed a completely atypical movement (see later, test I), and at post-mortem examination an abscess was found in the cervical vertebrae; it is probable, therefore, that this case was unrelated to the main problem. Occasionally, however, the forelegs became distorted and the carpal t more flexed, as a consequence of a long-standing grossly abnormal posterior gait

R. F. W. GOODWIN

21

7

(Fig. 9). Wintrobe, Miller and Lisco (1940) reported that some of their experimental cases were affected in the forelegs, but they gave little further information on the clinical nature of the abnormality. Some of the pigs that dragged their hind legs, protested violently and withdrew the appropriate limb sharply when a needle was stabbed into the skin near the coronet. Other such cases, however, responded sluggishly to this test, while a few others showed no reaction at all, not even an awareness that the test was being performed. These latter cases, like all the other affected animals, never developed a totally flaccid paralysis; whether any increased tone was present in these animals was difficult to determine. The various abnormalities described above did not necessarily follow in a set sequence. Furthermore, the disease could become clinically arrested at any point. Thus, many animals never progressed beyond the milder stages, even though they remained on the same diet for many weeks after showing their severest signs. No definite instance of improvement was seen by the author, although the owner believed that 2 pigs went off their hind legs for a week or so, but later walked again with difficulty. Many of the severely-affected animals remained in surprisingly good condition; they rarely had the bloom of normal pigs but, by dragging themselves to feed, they managed to grow and keep reasonably well-fleshed. This was not always so, however, as several pigs lost condition and developed a wrinkled skin which, on occasions, was a slightly-yellow colour. The above clinical signs were suggestive of pantothenic-acid deficiency. Before describing the investigation of this probability, however, it is convenient to mention briefly the effects of the disease in sows and young litters. Clinical Signs in Sows and Young Pigs The sows themselves remained free of clinical signs. However, the owner believed that, in addition to the obvious scouring and checking in growth that commonly developed after a few weeks, the litters were becoming increasingly less viable at birth. Another sign of note in young pigs was a characteristic loss of hair. As the growth of many litters was retarded, the hair was often longer than usual. The areas of baldness, therefore, which were first seen between the ears and on the nape of the neck, were all the more striking; thereafter, the baldness spread rapidly down the spine, and then outwards over the ribs and flanks. A similar distribution of the alopecia in experimentally-produced cases has been noted by Hughes and Ittner (1942), Wintrobe, Miller, Follis, Stein, Mushatt and Humphreys (1942), Wintrobe, Follis, Alcayaga, Paulson and Humphreys (1943), Moustgaard and Thorbek (1949) and Wiese, Lehrer, Moore, Pahnish and Hartwell (1951). This phase was followed by one of new hair-growth, in which the pigs had an unusual appearance, because much of the skin, notably on the anterior part of the body, was covered with a fine, short stubble (Fig. 13).

218

PANTOTHENIC-ACID DEFICIENCY IN PIGS

Pathological Findings Only two aspects of the laboratory examinations will be mentioned here. First, haematological observations on a few advanced neurological cases in fattening pigs revealed no noteworthy degree of anaemia. Secondly, the main gross lesions seen post mortem were in the alimentary tract. In early cases there was a catarrhal enteritis; longer-standing cases often showed a necrotic enteritis or thickening of the lower ileum (Figs. 15, 16 and 17). Not infrequently there were varying degrees of gastritis (Fig. 14), and occasionally these alimentary changes were complicated by peritonitis or bowel rupture. Nutritional Investigations The Diet All the pigs on the farm had been fed home-mixed rations of constant composition since about mid-1956 (Table 1). It is relevant to record that the owner had been advised that these diets would be adequate, a point that will be returned to in the discussion. The No. 1 ration was fed, after a short period of creep-pellet feeding, until the pigs reached about 120 lb. liveweight; the No.2 ration was fed thereafter until slaughter. To all three rations, a supplement of vitamins A and D 3 , a mineral supplement, and a vitamin B12 supplement were added, according to the manufacturer's instructions. TABLE

I

RATIONS FED IN HERD Q

Constituent

l_s~1

No.

6

Barley meal

6

I

Ground wheat ..

2

I

Sharps (fine to medium bran)

I

NO.2

6 2

a

White fish meal

!

Soya bean meal

1!"

1

!

t

Bean meal

t

!

!

"

A sample of the No. 1 meal was collected at the beginning of the investigation and a further sample in late October, 1959. Both were analysed for pantothenate: they agreed closely in their content, and yielded a maximum of about 2'25 mg.jlb. of food (5/Lg.jg.). A sow-and-weaner meal, made up with a proprietary concentratebalancer, was analysed at the same time, and this yielded just over 5 mg.jlb. of meal (11 ·3/Lg.jg.). Almost a year later (in August, 1960), the farm-mixed meal was sampled again and analysed by the same method. The agreement on parallel samples showed a greater variation, due perhaps to inadequate mixing on the farm, but the

21 9

R. F. W. GOODWIN

mean of 2 mg. jIb. (4'5 fLg.jg.) was not very different from the earlier analyses. The sample of farm-mixed meal collected in October, 1959, had been kept and this was re-analysed, as also was a meal made with the same proprietary concentrate referred to earlier: the results were similar to those of the previous year.

Prophylactic Supplementation with Calcium Pantothenate The simplest way to confirm the suspected aetiology was to supplement the diet with the pure vitamin under controlled conditions. All the 4 tests described below were made on the farm in the normal fattening pens. Apart from the prophylactic supplements, the management was unaltered. Supplementation after weaning (Test I). This test began on January 29th, 1960. Each of 3 litters was divided between groups A and B. Group B received the basic diet; group A received in addition 20 g. calcium pantothenate/t ton of meal for the first week, and IO g. calcium pantothenatej! ton of meal thereafter. Table 2 summarizes the results. In all the 4 tests of this type the pigs were killed at about 200 lb. liveweight unless they had become casualties earlier. As both groups continued to scour after weaning, it seemed probable that the deficiency was already developing in utero or during suckling. To reduce this variable in future tests, without recourse to supplementing the sow's diet, those animals in each litter earmarked to receive the fortified ration after weaning were injected intramuscularly with 12· 5 mg. of panthenol * every other day. TABLE

2

PANTOTHENATE SUPPLEMENTATION AFTER WEANING IN HERD Q

Animals starting test

Group A B (Controls)

Animals developing neurological signs

Scouring

11*

Persisted for 6 weeks

1**

12

Persisted for 6 weeks

5t I

* Reduced to 8 by fortuitous causes during the first 6 weeks. * * This animal had an abnormal gait after 12 weeks; the forelegs

were involved and post-mortem examination revealed an abscess extending into the lower cervical vertebrae. t Swaying of hind quarters, goose-stepping and difficulty in standing.

Panthenol injections bifore weaning (Test 2). This test began on March 3rd. Two litters of 9 pigs each were divided and cross-mixed. Those animals going into group A received their first panthenol injections at 4 to 5 weeks of age. From 8 weeks of age, the latter group received a calcium pantothenate supplement at the rate of IO g.!! ton of meal. Table 3 summarizes the results.

* Bepanthen

: Roche.

220

PANTOTHENIC-ACID DEFICIENCY IN PIGS TABLE 3 PANTHENOL INJECTIONS BEFORE WEANING IN HERD Q

Group

Animals starting test

Scouring

Animals developing neurological signs

---~---~--

A B (Controls)

st 10

None Marked

0

5*

One pig died suddenly after 7t weeks. sixth pig was probably an early case. Four of these 5 cases were litter-mates, indicating that the 2 litters had been differently conditioned before 4 weeks of age, probably by the nutritional status of their dams.

t

*A

Panthenol injections soon after birth (Tests 3 and 4). Test 3 began on April 7th. Because of the need to mix litters of comparable size, only 15 pigs were available in 2 litters. Group A received panthenol injections from the first week of life and a supplement of calcium pantothenate at IO g./! ton of meal when going on test after weaning. None of the 7 animals in group A scoured or developed neurological signs. No neurological signs appeared in the 8 controls, but this group scoured for about a month after weaning. In this test, therefore, there was little over-all difference between the 2 groups. This could not be explained by a difference in maternal diet; for although many sows on the farm were now receiving a fortified ration during pregnancy, both the dams of these litters had continued on the unfortified ration. Test 4 was a repeat of test 3. Three litters of 9, 10 and 7 pigs, were split between groups A and B (13 pigs in each group). They were weaned on May r rth, those animals going into group A having had panthenol injections thrice-weekly from the first week of life. Due to a mistake, group A received 2t per cent dried yeast, in addition to the above supplement of calcium pantothenate, for the first 20 days of the test; thereafter, the yeast was omitted. All the dams were fed the unfortified ration throughout pregnancy. In neither group did neurological signs appear. Group A scoured a little, but the controls scoured severely for at least 6 weeks. Other Observations Relating to Herd Q, Attempts at Therapy Until the controlled tests just described could be organized, the many affected animals in herd Q provided an opportunity to ascertain whether any amelioration of the clinical signs could be initiated by a change in diet. Neurologically, there was little hope of such an improvement, but it seemed worthwhile to confirm this and, at the same time, observe any other effects of treatment.

R. F. W. GOODWIN

221

The farm was visited on August 1st, 1959, and 9 pens of pigs were selected in which the animals were not yet close to slaughter weight. Each pig in these pens was examined and the degree and type of clinical affection recorded. In all, there were 79 pigs, of which 55 were showing neurological signs. A total of 32 pigs, of which 27 were affected neurologically, then had their basic diet fortified with 2 per cent dried yeast; a further 41 pigs, of which 28 were affected neurologically, had their diet fortified with calcium pantothenate-to give each pig a total daily intake of about 200 mg. of the vitamin; a pen of 6 pigs, all of which were at that time unaffected neurologically, continued on the basic diet unchanged. The improved diets were first fed on August 3rd, and 46 days later all the pigs were again clinically examined. In the group receiving yeast, one animal was definitely worse and 2 animals appeared to be less affected; otherwise, there was very little change neurologically. The scouring in this group, however, was less marked. Of those receiving calcium pantothenate, 5 seemed definitely worse, 2 were rather better, and the remainder were much the same neurologically; again, however, the scouring was noticeably better. The control group of 6 pigs had shown only some scouring at the first examination; 4 of the 5 animals remaining alive, however, now showed definite neurological signs. In the main, therefore, there was little change in the degree of neurological involvement, once the diet had been fortified with either yeast or calcium pantothenate; on balance, perhaps, a slight deterioration had occurred. During the same period, however, nearly all the animals in the small untreated group had obviously worsened. These results are more in keeping with those of Wintrobe et al. (1943), who checked the scouring but obtained only some improvement of the ataxia on treating experimentally-produced cases, than of Wiese et al. (195 I), who implied that high doses of calcium pantothenate produced a complete recovery in very young pigs. Feeding Experiments in a Different Environment

In parallel with the last experiment, and again until such time as the more precise diagnostic experiments were undertaken on the farm, some feeding experiments were carried out in Cambridge. Fifteen weaners from 2 litters born in an experimental herd in Cambridge were fed on the basic diet that was being mixed on the farm. The experimental herd supplying the 2 litters was chronically infected with enzootic pneumonia and, as a result, the average rate of growth of the fattening pigs in this herd was slower than in herd Q. Another difference was that the 15 weaners were not Landrace pigs and, furthermore, they were born from sows that had been fed a meal during pregnancy made up with the proprietary concentratedbalancer referred to earlier. Eleven pigs went to slaughter after being on the unfortified (herd Q) diet for 4t months, and the remaining 4 pigs went a month later. Throughout this time all 15

222

PANTOTHENIC-ACID DEFICIENCY IN PIGS

animals appeared completely normal, ate well and had very firm dung. The disease was not readily reproducible, therefore, when the same diet was fed to weaners in another herd. The second main feeding experiment in Cambridge was with weaners moved from the affected farm. A total of 25 pigs, 14 being 8 weeks old and I I being 7 weeks old, was split into 2 groups of 13 and 12; the first group was fed the basic, herd Q ration (mixed on the farm) and the second group was fed an identical ration, but with dried brewer's yeast added at the rate of 2 lb. per I 12 lb. * Unfortunately, it was not possible to house these 25 pigs in complete isolation; instead, they went into 4 rooms opening into a central corridor, with the 15 pigs probably infected with enzootic pneumonia, mentioned above, in 2 nearby rooms opening into the same corridor. It seemed but a question of time, therefore, before the imported weaners contracted enzootic pneumonia. Three to 4 weeks after the experiment started, both groups of weaners from herd Q developed profuse diarrhoea, associated with pyrexia; 2 pigs died in the group receiving yeast, leaving IO to finish the test, and 4 pigs died in the group without yeast, leaving 9 to finish the test. The exact cause of this trouble was not clear, and it could well have been due to a combination of a deficiency state with the onset of enzootic pneumonia; both groups were coughing some weeks later. Once the crisis had ed, however, the group receiving yeast continued well; there was no further scouring and no neurological involvement at any time. In the group not receiving yeast, however, 3 out of the 9 survivors developed neurological signs: these first appeared after 9t weeks, and eventually consisted of a swaying gait in one animal, a high-stepping walk in a second and an inability to stand on the hind legs unaided in the third. The test lasted for 20t weeks, when all the survivors were slaughtered. It thus appeared that not only were neurological signs prevented by a low level of dried brewer's yeast in the ration, but that a check in growth rate might reduce the severity of the clinical disease (see Discussion) . Subsequent Events During 1960, apart from those in-pig sows whose litters were to be used for the controlled trials above, the herd was gradually changed over to a supplemented ration. At first, the supplement was dried yeast, but this was later replaced by a multiple vitamin-B mixture. Thereafter, no further neurological evidence of pantothenic-acid deficiency was seen, and the average rate of growth was satisfactory. This can be shown by the growth rate of the litters that entered the fattening pens after the beginning of test 4. During May and June, 1960, a total of 67 pigs that were not required for any

* Yeast was used because it was not then known that pantothenate alone would prevent the condition. The rate of yeast supplementation was low, but such a supplemented diet would, theoretically, supply about 25 per cent more pantothenate than the unfortified ration.

223

R. F. W. GOODWIN

test were weaned and fattened under normal conditions; 65 of these reached bacon weight. The exceptions were a pig that died shortly after weaning, and a very small weaner that was slaughtered at a lighter weight because it lagged behind its litter-mates. Figures are available for 61 of the bacon pigs: the average dead-weight was 157 lb. at an average age of 175 days. Because it seemed probable that the deficiency condition in herd Q was partly related to the high average rate of growth of the fattening pigs, compared with most pig herds, a number of other herds, also free of enzootic pneumonia, were examined to see whether they too showed any signs ofpanthothenic-acid deficiency. Three out of the 9 herds examined somewhat superficially contained pigs that appeared to be so affected clinically. In the first herd (herd N) there was swaying of the hindquarters in some young litters and a number of cases of slight snatching of the hind legs among the older pigs in the fattening house. Herd N also contained Large White pigs that were housed and fed exactly as were the Landrace; none of the ~arge white animals developed neurological signs of pantothenicacid deficiency. In 2 other herds (MG and DO), the main sign was posterior weakness, the affected fattening pigs subsequently losing the use of their hind legs. All the 3 affected herds consisted entirely (MG and DO) or largely (N) of purebred Landrace pigs, like herd Q, and all were likewise being fed on home-mixed rations; they all also had an average rate of growth very similar to that in herd Q. TABLE 4 RATIONS FED IN HERDS N, MG AND DO

Constituent

HerdN

Herd MG

Herd DO

·.

38

II

14

·. .. ..

25

6

4

-

I

Groundnut meal

·. ·. ·. ·. ·. ·. ..

Grass meal

·.

..

Barley meal Wheat meal Molassine meal White fish meal Soya bean meal Maize meal

·. ·.

6

I

25

-

6

-

-

It

It

-

..

-

-

i

t

All 3 rations contained a mineral supplement. In herds MG and DO, vitamins A,

Da and B2 were added, but in herd N, only vitamins A and D3 were incorporated, and

then only in the winter months. In herd N, pigs over about 100 lb. in weight were fed the same ration as the younger animals, except that the fish meal was reduced to 2t parts and the groundnut meal increased in compensation. H

PANTOTHENIC-ACID DEFICIENCY IN PIGS

224

The ration being fed in each herd is shown below (Table 4). Herd MG was of special interest, because the suckling and fattening pigs had suffered severely from widespread parasitism, which had resulted in a poor over-all growth rate; steps were then taken to prevent the development of parasitism, and the time taken to reach bacon weight improved strikingly. In parallel with this removal of the burden of parasitism, the clinical cases of nutritional deficiency arose. A clinical pattern was emerging, therefore, of pantothenic-acid deficiency on home-mixed rations and where the rate of growth of the fattening pigs was above average. This was not always so, however; for the disease was subsequently seen in other herds where the average rate of growth was more conventional. HERD /0

One of these herds (10) was of particular interest. It consisted of about 60 Wessex sows and produced either purebred Wessex litters or first-cross WessexJLandrace litters, mainly for heavy-hog production. The litters were farrowed in huts at pasture and, when about 3 weeks old, they were moved with their dams to fenced paddocks. The herd was almost certainly chronically infected with enzootic pneumonia, although complete observations were not made to establish this fact. For many years the general feeding policy had been to incorporate a high percentage of waste products in the home-mixed ration. Thus from 1953 to 1956, biscuit crumbs formed about 20 to 25 per cent of the diet. At the end of 1956, a year's supply of dried potatoes TABLE 5 RATIONS FED IN HERD 10

Constituent

Suckling pigs

Weaners (to I6 weeks)

Fattening pigs

Sows

Biscuit-wafer meal

2

Ii

I

Bread-crust crumbs

4

3

4

Middlings

I

2

2

10

10

II

Soya bean meal

I

I

White fish meal

Ii

Ii

I

Ii

I

I

I

Barley meal

Mollassine meal

-

Grass meal

-

i 3

Ii II

-

i

I

i

-

All 4 rations were supplemented with a mineral mixture and vitamins A, D3 and B .. except for the fattening ration, where the vitamin A was omitted.

R. F. W •. GOODWIN

225

was purchased as a substitute and, when this was exhausted, a reversion was made to biscuit-wafer meal, to which bread-crust crumbs were then added. From early 1958, the rations varied slightly from time to time, but they were broadly of the pattern shown in the specific examples (Table 5). During the winters of 1956/57 and 1957/58 a multiple vitamin-B supplement was added, to supply 2·5 g. of pantothenic acid per ton of meal. No such supplement was added again until April, 196 I. An economic problem became obvious in 1960. Before this date, the situation had been acceptable, an average of 9·3 pigs being reared from 125 litters during the year ending on September 30th, 1958, and 8·7 reared from 132 litters during the year ending on the same date in 1959. In the spring of 1960, however, the suckling pigs seemed less vigorous and when these litters came into the fattening yards after weaning they progressively worsened: scouring became widespread and serious, and many animals developed a goose-stepping gait; some lost the use of their hind legs. By October, 1960, a crisis had developed: many fattening pigs died or had to be sent for casualty slaughter, and the state of the new-born litters augured ill for the future. Thus, the average number of pigs per litter born alive during the year ending on September 30th, 1960 (130 litters) was 7.81, compared with 9·45 for the previous year (132 litters); and this figure dropped to 7.36 for 80 litters born between September 30th, 1960, and April 13th, 1961, resulting in an average of only 6 weaned. In the 4 months between midDecember, 1960, and mid-April, 1961, 46 litters were born; although, as has been shown above, these litters were, on average, small in numbers, 142 pigs were either born dead or died shortly after birth-an average of just over 3 per litter. Unfortunately, the records in this herd did not distinguish between stillbirths and early neonatal losses at this date. It may be significant that during the winter of 1960/61, the coughing among the fattening pigs became very severe and almost universal. The writer was consulted in March, 1961, and the farm was first visited at the end of that month. The litters running at pasture showed a marked incidence of scouring; often the pigs were longhaired and unthrifty. In several litters, aged 3 weeks and upwards, pigs were found that were losing their hair, usually starting between the ears and at the back of the neck, as in herd Q. It was said that this progressive baldness in litters had been associated with the development of partial paralysis of the hind legs at about 3 weeks of age. Groups of weaners running in a wood were examined: several of these showed similar degrees of baldness and varying degrees of faulty hind-leg action; coughing was particularly severe in these litters. Chronic scouring was common among the older fattening pigs in yards, and a number of the pigs approaching bacon weight showed a snatching or slight goose-stepping gait with the hind legs. A clinical diagnosis of pantothenic-acid deficiency was made, but as

PANTOTHENIC-ACID DEFICIENCY IN PIGS

the herd was already suffering severely and was uneconomic, and as the presence of another chronic disease would probably have made the interpretation of controlled trials (using pantothenate) difficult, the diet was fortified on a wider basis at once. Wheat and barley were substituted for the bread-crust crumbs and biscuit-wafer meal in all but the fattening ration immediately, and a multiple vitamin mixture was incorporated in all the rations at the rate of 28 lb. per ton. The manufacturer's analysis of the vitamin supplement is shown in Table 6: this is the same supplement as used in the winters of 1956/57 and 1957/58. All the herd was receiving the new formulations by about April 1st. Although the diet had now been improved, sufficient quantities of the previous constitutents remained to make up small samples of meal similar to the rations being fed on the farm earlier in 1961 (Table 5). These were analysed for their pantothenate content by the same method as before. The sow mix yielded 3.6 fLg.jg. (1.6 mg. jIb. ); the weaner mix yielded 4.0 fLg.jg. (1.8 mg. jIb. ); and the fattening mix yielded 3.0 fLg.jg. (1'4 mg.jlb.). These figures, ranging from 3'0 to 4.0 fLg.jg. were notably lower than the figure of 5.0 fLg.jg. obtained with the fattening mix being fed at the height of the trouble in herd Q. The dietary improvements just described were followed by a progressive disappearance of those clinical signs specifically associated with pantothenic-acid deficiency, and there was a concommitant marked increase in the general economic efficiency of the herd.

TABLE 6 VITAMIN SUPPLEMENT USED IN HERD

Constituent

Thiamin

Vitamins per

II!!

224

mg.

Riboflavin

6000

mg.

Pyridoxine

560

mg.

Vitamin B12

1000 28000

mg.

Pantothenic acid

10000

mg.

2000

LV.

3350

mg.

179200

mg.

Vitamin E Vitamin K Choline

lb.

mcgm.

Nicotinic acid

10

R. F. W. GOODWIN

227

DISCUSSION

In herd Q, the development of neurological signs in the fattening pigs was completely prevented, under the controlled conditions in tests I and 2, by adding only calcium pantothenate to the ration. Taking these 2 tests together, no neurological signs referable to pantothenic-acid deficiency occurred among the 15 surviving animals receiving calcium pantothenate, whereas at least IO neurological cases occurred among the 22 controls. This fact, coupled with the analytical evidence that the unfortified ration was somewhat low in this vitamin, suggests that the main cause of the disease condition was an inadequate dietary intake of pantothenic acid. Whether any other deficiency states were contributing to the clinical picture concurrently is not known, but it is clear that they were of no great importance; for, although scouring continued in the first test group being fed the fortified ration, it was possible largely to prevent this scouring if the vitamin supplement were given soon after birth (tests 2, 3 and 4). The ration fed in herd Q was not particularly abnormal. It had not been criticized by nutritional advisers to whom it had been submitted and it was probably superior to the very crude rations associated with nutritional enteritis in the U.S.A. (Luecke, Thorp, McMillen, Dunne and Stafseth, 1949); many comparable homemixed rations must be in use throughout the country. The diet was inadequate in this instance, however, probably because the average growth-rate of the fattening pigs was very good. When a herd is freed of enzootic pneumonia, the most striking results occur at the fattening stage-the pigs usually growing faster and more evenly than is customary in infected herds. It might be expected, therefore, that the first signs of nutritional deficiency would appear in the growing pigs. The sows and new-born litters, on the other hand, had no exaggerated dietary demands and as a result, they showed little clinical abnormality. That the rate of growth after birth was not the sole factor involved, however, is suggested by the observation that the litters became affected at a progressively younger age. Furthermore, the incidence of the disease steadily widened in the herd, and there was some evidence that litters born from gilts were more readily affected than those born from sows; these facts point to an increasing pre-natal/lactational effect with time. Perhaps the level of pantothenic acid was barely adequate, even for the adult stock-a situation that would have ed unnoticed had the growing pigs not been free of chronic respiratory disease. The feeding tests made in Cambridge, although very limited, this general hypothesis. The unfortified ration had no effect on slower-growing animals born from dams fed a more balanced diet, while pigs transferred from herd Q and kept in a more diseased environment did not develop such marked clinical signs as did comparable and parallel groups kept for a shorter time on the basic

PANTOTHENIC-ACID DEFICIENCY IN PIGS

ration at their home farm. This, therefore, is a different general situation from that postulated by Luecke, McMillen and Thorp (1950) in which, by improving the diet without increasing the pantothenic-acid level, the growth rate is stimulated to induce a deficiency state. It is probable that many pig herds are now on the borderline of pantothenic-acid deficiency, and that any widespread improvement in mean growth rates (as are now occurring from a greater appreciation of the importance of disease control), unless accompanied by a corresponding compensation in dietary intakes of pantothenic acid, and perhaps other factors also, could result in economic losses. Preliminary evidence from herds N, MG and DO suggests that a proportion of the herds that are free from enzootic pneumonia have already moved into the clinical fringe of this particular deficiency. Apart from improved health standards, however, other factors appear to favour the development of deficiency signs. The first is home-mixing of rations. Because it is common among farmers to fortify pig rations with only riboflavin, among the main group-B vitamins, the levels of pantothenic acid in pig meals will largely depend on the nature of the main constituents. Analysis of meals marketed by 2 large, commercial compounders showed a considerably higher level of pantothenic acid than in the home-mixed ration of herd Q. However, it is a simple matter to fortify home-mixed rations with a wider range of group-B vitamins, and any present advantage in commercially-produced meals in this respect could readily be equalled on the farm. A second possible factor is variation in breed susceptibility. Herd Q, as also herds N, MG and DO, consisted of purebred Landrace pigs, and the disease has not yet been seen by the writer in Large White herds that are free of enzootic pneumonia. It is interesting that in herd 10 the farmer believed that a variable incidence of the disease had occurred; in effect, most neurological cases were seen in the three-quarter Landrace pigs, fewer cases occurred in the half-bred Landrace pigs, and even less in the purebred Wessex litters. Nevertheless, at the height of the herd trouble, cases of hind-leg weakness were certainly seen in purebred Wessex pigs, indicating that a sufficiently severe deficiency of the vitamin must inevitably affect any pig, regardless of its breed, and even though it is suffering from another disease that might retard its growth. Breed differences in susceptibility under experimental conditions, Durocs being more readily affected than Hampshires, have been reported by Luecke, Thorp, McMillen and Dunne (1949), and Ullrey, Becker, Terrill and Notzold (1955). Other, less understood factors might also have been influencing the over-all incidence of the disease in herd Q. The number of cases declined in the Spring of 1959, then surged to their greatest impact during the summer of that year; thereafter, the severity of the neurological signs appeared to wane-very few animals going right off their hind legs in 1960. In the last 2 controlled tests (tests 3 and 4,

R. F. W. GOODWIN

229

starting in April and May, 1960, respectively), no neurological cases appeared in the deficient groups. It is possible, therefore, that this decline in incidence, occurring at the same time as the decline in 1959, was more than a chance coincidence, and the importance of the control groups-even in work of this type-is underlined. Rather more information than is available here would be required to warrant open speculation on the possible causes of a seasonal variation in the effects of pantothenic-acid deficiency, but the simplest explanation, a variation in diet, was partly eliminated by analysing meal samples taken on 3 widely-spaced dates. These analyses, however, were made only for pantothenic acid, and interrelationships between pantothenic-acid requirements and the levels of other dietary constituents have been reported under experimental conditions. Thus protein (Luecke, Hoefer and Thorp, I952), and chlortetracycline (McKigney, Wallace and Cunha, 1957) appear to spare pantothenic acid, while biotin (Colby, et at., I94B) and other additives (Luecke et at., I 950) hasten the appearance of clinical signs. In herd 10, a somewhat different situation obtained. The dietary deficiency, as judged by analyses, was more marked, and sufficient to produce clinical effects even in a herd with an indifferent average growth rate. Under these circumstances, the deficiency signs might have been expected to appear throughout the herd, rather than in one section of it (as in herd Q), and this is what occurred: the neonatal losses were more severe, and the scouring and hairlessness among suckling pigs more marked. Compared with herd Q, it is more probable-because of the waste products in the ration-that some other deficiency might have contributed to the losses but, even so, the nature and pattern of the clinical signs strongly suggest that pantothenic-acid deficiency was the dominant aetiological factor. Unfortunately, time, distance and the economic state of herd IO did not allow a detailed study of a succession of new-born litters for the interesting clinical signs reported by Ullrey, Becker, Terrill and Notzold (I954, I955). These latter authors (I955), as well as Hodgskiss, Ensminger, Colby and Cunha (I950) , when studying the effects of pantothenic-acid deficiency on breeding performance, also produced clinical signs in adult pigs comparable with those seen in young growing animals, but in none of the herds mentioned in this paper were the adults seen to be affected to this degree. Little need be added concerning the clinical signs of the disease. The most consistent was scouring and, because this sign preceded most others in the growing a nd fattening pigs, it is possible that lowgrade pantothenic-acid deficiency could be playing some part in the general scouring problems that are such a feature of pig farming today. Many of the weaners and young fattening pigs that showed a grossly corrugated or necrotic terminal ileitis, and necrotic colitis at autopsy would, with their clinical history of unthriftiness and chronic scouring, have been frequently diagnosed as cases of infective necrotic enteritis or paratyphoid in general farm practice.

PANTOTHENIC-ACID DEFICIENCY IN PIGS

In herd Q, the economic effects of the disease could well have been limited by the absence of any other major disease burden. Thus, on a herd basis, the effects of the scouring alone were not as severe as expected, and many of the pigs that were affected neurologically reached slaughter weight without a gross retardation in growth. There was, nevertheless, a cumulative and intolerable economic loss over many months in the fattening pens, excessive losses among the suckling pigs, and a very serious loss due to interference with the selection and sale of breeding stock. How the herd might have fared had it also been affected with enzootic pneumonia is unknown, but there is some evidence from the feeding trials in Cambridge to suggest that the 2 conditions together could have been worse than the combined effects of each alone. Whether the increase in coughing at the height of the problem in herd 10, however, was due entirely to an increase in the incidence and effect of enzootic pneumonia can be questioned; for, in herd Q, coughing was likewise fairly common in many fattening pens when the deficiency signs were most wide-spread. There was a slight lung-worm problem in herd Q at the time, but the extent and degree of the lung-worm infestation was not of the order that would normally be expected to produce persistent coughing in litters kept on concrete since weaning and approaching bacon weight. CONCLUSIONS

In a herd of Landrace pigs in which the average growth rate was high, signs of pantothenic-acid deficiency appeared: lack of vigour in the new-born litters, loss of hair in young growing pigs, scouring, and varying degrees of neurological involvement. Analysis of the home-mixed diet showed a deficiency of pantothenic acid. In controlled experiments on the affected farm, half the pigs in a number of litters were given a supplement of calcium pantothenate. All the clinical signs were prevented, provided that the supplement was given early enough. Although other deficiencies might have existed at a lower level, pantothenic acid was probably the prime deficiency. The disease was subsequently eliminated from the herd by fortifying the diet routinely with a commercial mixture of the group-B vitamins. Therapeutic experiments, using dried yeast or calcium pantothenate, had no significant effect on the neurological signs, but brought some improvement in the scouring. Other herds with a high average rate of growth were then examined, and a proportion of these showed clinical evidence of pantothenic-acid deficiency on a smaller scale. A second form of pantothenic-acid deficiency was seen in herds in which the rate of growth of the fattening pigs was not unusually high. In one such herd, a marked vitamin deficiency, as shown by dietary analysis, was probably due to the excessive use of biscuitwafer meal and bread-crust crumbs in the home-mixed meal.

R. F. W. GOODWIN

Neonatal losses were more severe and loss of hair in suckling pigs more common; the fattening pigs showed scouring and neurological signs, as in the first herd investigated. The serious effects of the disease were arrested by fortifying the diet with a multiple mixture of the group-B vitamins. The implications of these findings are discussed in relation to the developing pattern of the British pig industry. ACKNOWLEDGMENTS

I am pleased to record the kind assistance and interest of several people and organisations. Mr. A. R. Jennings co-operated in this work by making pathological observations on a number of the cases that were brought to Cambridge; his collect,i on of neurological specimens will probably form the basis of a separate communication. M y colleague, Dr. J. T. Abrams, has been most helpful at all times. Mr. G. H. Clement of Roche Products Ltd. supplied the calcium pantothenate and arranged for Hoffmann-La Roche & Co. (Switzerland) to place their experience at my disposal. Mr. S. A. Price of Vitamins Ltd. carried out all the assays for pantothenic acid. The still photographs were taken by Miss. J. Minns, who also prepared the prints originating from 16 mm. cine-film. The latter film was taken by Mr. H. D. Williamson. Most of the expenses were met by a grant from the Agricultural Research Council. REFERENCES

Briggs, G. M., and Daft, F. S. (1954). The Vitamins, vol. II, p. 664, ed. Sebrell, W. H. , and Harris, R . S. Academic Press; New York. Colby, R. W., Cunha, T.J., Lindley, C. E., Cordy, D. R., and Ensmingel·, M . E. (1948). }. Amer. vet. med. Assoc., 113, 589. Doyle, L. P. (1937). Ibid., 43,656. Goodwin, R. F. \V., and Whittlestone, P. (1960). Vet. Rec., 72, 1029. Hodgskiss, H. W. , Ensminger, M. E., Colby, R. W., and Cunha, T. J. (1950). J. animo Sci., 9,6 19. Hughes, E. H. (1942). ] . agric. R es., 64, 185. Hughes, E. H., Crampton, E. W., Ellis, N. R., and Loeffel, W ..J. (1944). Report qf the Committee on Animal Nutrition. II Recommended Nutrient Allowancesfor Swine. National R esearch Council; Washington, D.C. Hughes, E. H., and Ittner, N. R. (1942) .]. animo Sci. , 1,116. Luecke, R. W., Hoefer,J. A., and Thorp, F. (1952). Ibid., 11, 238. Luecke, R. W., McMillen, W. N., and Thorp, F. (1950). Ibid. , 9, 78. Leucke, R. W., Thorp, F., McMillen, W. N., and Dunne, H. VV. (1949). Ibid., 8, 464. Leucke, R. W., Thorp, F., Mc11illen, W. N ., Dunne, H. W., and Stafseth, H. J. (1949). Technical Bulletin 21 I. State College Agricultural Experiment Station; Michigan. M cKigney, J . 1., Wallace, H. D ., and Cunha, T. J. (1957). ]. animo Sci., 16,35· Moustgaard, J., and Thorbek, G. (1949). Report XIVth Int. vet. Congress, London, 3, 63. Schulze, W. (1960). Dtsch. tieriir::.tl. Wschr., 67, 245. Ullrey, D. E., Becker, D. E., Terrill, S. W., and Notzold, R. A. (1955) . ]. Nutr., 57,401.

PANTOTHENIC-ACID DEFICIENCY IN PIGS

Wiese, A. C., Lehrer, W. P., Moore, P. R., Pahnish, O. F., and Hartwell, W. V. (1951). J. animo Sci., 10, 80. Wintrobe, M. M., Follis, R. H., Alcayaga, R., Paulson, M., and Humphreys, S. (1943). Johns Hopk. Hosp. Bull., 73, 313. Wintrobe, M. M., Miller, J. L., and Lisco, H. (1940), Ibid., 67,377. Wintrobe, M. M., Miller, J. L., Follis, R. H., Stein, H. J., Mushatt, C., and Humphreys, S. (1942). J. Nutr., 24, 345. [Received for publication, December 13th, 1961]

R. F. W. GOODWIN

Platf

Fig. 1. Fig. 2. Fig. 3· Fig. 4· Fig. 5· Fig. 6. Fig. 7· Fig. S. Fig. 9· Fig.

10.

Fig. Fig.

II.

12.

I

Marked goose-stepping, side-view. l\1arked goose-stepping, rear-view. Very exaggerated goose-stepping in a running pig, showing lack of flexibility in the hock t. Moderate but obvious goose-stepping in 2 pigs from group B, test I. (Fed the" unfortified ration.) Normal gait, for comparison, in 2 con trol pigs from group A, test 1. (Fed the same ration as the pigs in Fig. 4, except for a supplemen t of calcium pantothenate.) Sudden snatching-movement with a hind leg while stand ing still. Similar isolated movement while standing still in anoth er pig, but here there was a sudden backward, horse-like kick. Abnormally low position of the hocks. Deformation of the forelegs, with goose-stepping of the hinds, giving a tip-toe movement.

The pig on the ri ght could j ust walk , the hind quarters being con tinuously on the verge of collapse. The left-h a nd pig required assistance to stand. Marked sway ing of hind qu a rters, with splaying of the hind legs. Sudden collapse on turning q uickly. The shock of collapse has thrown the ears well up.

Note. F igs.

I

to

12

were prepared from

16

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PANTOTHENIC-ACID DEFICIENCY IN PIGS

Plate

2

Fig. 13. R e-growing hair-stubble on a stunted pig, 6 weeks old, recovering from almost total baldness. Alopecia was first observed at 4 weeks of age ; thereafter, the hair could be pulled out easily. Figs. 14 to 17. Gastritis and intestinal changes in pigs dying in the second feeding experiment a t Cambridge. (These pigs were removed as weaners from the farm when the disease in herd Q was at its height. Although they suffered from a febri le condition before d eath, no other explanation could be found for the alimentary changes. The febrile nature of the disease is incompatible with virus transmissible gastro-en teritis, and pooled faeces from 2 cases produced no ill-effects when fed to a colostrum-depri ved pig that had been reared in isolation. Gastritis and similar bowel changes were seen in pigs removed straight from herd Q ).