@prefix vivo: . @prefix edm: . @prefix ns0: . @prefix dcterms: . @prefix skos: . vivo:departmentOrSchool "Land and Food Systems, Faculty of"@en ; edm:dataProvider "DSpace"@en ; ns0:degreeCampus "UBCV"@en ; dcterms:creator "Whiting, Richard John"@en ; dcterms:issued "2010-03-31T23:07:11Z"@en, "1982"@en ; vivo:relatedDegree "Master of Science - MSc"@en ; ns0:degreeGrantor "University of British Columbia"@en ; dcterms:description """Four experiments were conducted to evaluate a crude immunoglobulin preparation fractionated from abattoir porcine serum with ammonium sulphate. The preparation was used as an additive to milk replacer for colostrum deprived, low birth-weight pigs reared in a non-isolated environment. Six pigs per treatment were used in experiments 1 and 3. Eight pigs per treatment were used in experiments 2 and 4. In the first experiment, members of the negative control group did not survive and mortality of the other three groups which received some immunity was high. In the second experiment, the negative control group was eliminated from the trial, so those receiving only colostrum for 12 hours died, but the two groups receiving immunoglobulin treatment showed improved survival (63, 50%). In the third experiment, higher levels of immunoglobulin (15g./kg. body weight, initially followed by 5g./kg/day) did not show a significant effect on survival in comparison with the previous levels of 10g./kg. to 2g./kg.. However, rate of gain in body weight was significantly higher in the high dose level of immunoglobulin. In the fourth experiment the pigs were maintained on immunoglobulin for 10, 15, and 21 days and it was found that 21 day treatment eliminated deaths. The highest rate of gain was achieved with those on 21 day treatment in experiment 4. However, these rates of gain were considerably below those achieved with Digs on the sow. The causes of mortality were predominately E. coli scours, septicaemia due to E. coli and other bacteria, pneumonia, and in the last two experiments, Salmonellosis. The prevention of death in experiment 4 by the immunoglobulin extract, indicated the success of the preparation against the Salmonella species encountered."""@en ; edm:aggregatedCHO "https://circle.library.ubc.ca/rest/handle/2429/23216?expand=metadata"@en ; skos:note "ARTIFICIAL REARING OF LOW BIRTH-WEIGHT PIGS by RICHARD JOHN WHITING Sc. Ag., The Univ e r s i t y of B r i t i s h Columbia, 1970 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Department of Animal Science) We accept t h i s t hesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA May 1982 © Richard John Whiting, 1982 In presenting t h i s thesis i n p a r t i a l f u l f i l m e n t of the requirements for an advanced degree at the University of B r i t i s h Columbia, I agree that the Library s h a l l make i t f r e e l y available for reference and study. I further agree that permission for extensive copying of t h i s thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. I t i s understood that copying or publication of t h i s thesis for f i n a n c i a l gain s h a l l not be allowed without my written permission. Department of A/\"Wy*»( ^ Cooper et al_., (1978) found runts at gestational ages of 44, 53, 56 and 75 days of gestation. Obviously these data do not pin-point a conclusive stage of gestation at which f e t a l growth retardation occurs. However, since 99 per cent of f e t a l growth (by weight) occurs a f t e r day 40 of gestation (Marrable, 1971), the occurrence of runting t h i s early suggests that i n t r a - u t e r i n e retardation may be determined before i t becomes recognizable and may occur throughout f e t a l development i n some cases. Widdowson (1971) compared the development of organs in the runt with that of a fetus taken at an equal si z e and with that of a l i t t e r -mate of normal s i z e . Two outstanding differences were noted: f i r s t l y , muscle development, as measured by quadriceps s i z e was s i g n i f i c a n t l y less in the runt than in e i t h e r the fetus of equal weight or the normal l i t t e r -mate; secondly, the l i v e r s of the fetus and runt were comparable in size yet very much smaller than the l i v e r of the normal lit t e r m a t e with the added c h a r a c t e r i s t i c of a very low carbohydrate content in the runt. Heart, spleen and stomach of the runt were intermediate i n weight between those 25 o f the f e tus and normal l i t t e r m a t e . The b ra i n o f the run t was nearer to normal weight than any o the r pa r t o f the body. G e n e r a l l y , Widdowson (1971) found tha t the decrease i n organ s i z e o f the run t was due to both hypop las ia (decreased c e l l s i z e ) and hypotrophy (decreased c e l l number). Widdowson (1971) went on to compare the growths o f a run t and a normal l i t t e r m a t e f o r th ree years and found tha t the runt was 60 kg . l i g h t e r a t the end o f t h i s term. S ince there were no r e s t r i c t i o n s i n d i e t o r as a r e s u l t o f envi ronmental e f f e c t s a f t e r weaning, i t may i n d i c a t e tha t i n t r a -u t e r i n e growth r e t a r d a t i o n may p rov ide a permanent s e t - b a c k . 26 2.5 Mechanisms o f A c t i o n o f B a c t e r i a i n the I n t e s t i n e Wi th in the i n t e s t i n e there are th ree major ways tha t b a c t e r i a may a s s o c i a t e w i th the i n t e s t i n a l mucosa to produce d i s e a s e . F i r s t l y , they can a t t ach to the mucosa w i thout pene t ra t i on and induce d i s e a s e by m u l t i -3 p l y i n g and producing exo tox in . Th i s occurs i n E. c o l i e n t e r i t i s o f the smal l i n t e s t i n e and i s caused by e n t e r o t o x i n producing E. c o l i . Second ly , b a c t e r i a can a t t ach to and penet ra te the mucosa but not the s u b e p i t h i l i a l t i s s u e s and induce d i sease by damaging e p i t h i l i a l c e l l s and a l s o produce e x o t o x i n . Th is can occur i n E. c o l i e n t e r i t i s o f the l a rge i n t e s t i n e and i s caused by i n v a s i v e s t r a i n s o f E . c o l i . T h i r d l y , b a c t e r i a can a t t ach t o , and penet ra te the mucosa to reach the s u b e p i t h e l i a l t i s s u e s , m u l t i p l y i n the submucosa, and spread s y s t e m a t i c a l l y a l s o growing i n t r a c e l l u l a r ^ i n phagocytes. Th is mode o f a c t i o n occurs w i th Sa lmone l la e n t e r i t i s caused by S . t y p h i . ( M c C l e l l a n d , 1979) . A major phenomenon i n v o l v e d i n b a c t e r i a l i n vas i on o f e p i -t h e l i a l su r faces i s b a c t e r i a l adherence. S ince p e r i s t a l s i s and f l u s h i n g w i th s e c r e t i o n s tends to remove b a c t e r i a and ma in ta in a con t i nuous l y lower l e v e l o f growth and prevent invaders from p r o l i f e r a t i n g , attachment to the gut e p i t h e l i u m by adherence i s a major mechanism a f f e c t i n g the a b i l i t y o f a pathogen to p r o l i f e r a t e . Bes t known i n t h i s connect ion i s E. c o l i w i th i t s va ry ing adhesion f i m b r i a e . The most s t ud ied i s the K88 an t igen which has n o n - f l a g e l l a r f i l amentous su r face p i l l i c a r r i e d on the genome o f a p l asm id . (Smith and L inggood, 1971) . Other adherence f a c t o r s o f E. c o l i i n the neonatal po rc ine i n t e s t i n e are the an t igens K99, s t r a i n 987 t y p e , and type 1 common p i l l i o f which each has a d i f f e r e n t r ecep to r s i t e on the i n t e s t i n a l e p i t h e l i u m (Dupond and P i c k e r i n g , 1980) . A l l o f these su r face 27 s t r u c t u r e s are a n t i g e n i c and e l i c i t ant ibody responses where the ant ibody ac t s as an an t i -adherence f a c t o r p o s s i b l y by masking the adherence s i t e o f the bac te r ium. In re fe rence to the K88 a n t i g e n , the po rc ine recep to r s i t e f o r i t i s c o n t r o l l e d by a dominant gene and t he re fo re animals which are double r e c e s s i v e are immune to K88 s t r a i n s o f b a c t e r i a un less o ther f a c t o r s are present de termin ing v i r u l e n c e . ( R u t t e r , 1975; Ru t te r e t a l _ . , 1976) . The mechanism o f en te ro tox i ns i s not f u l l y unders tood. However two en te ro tox i ns have been shown to be produced by s t r a i n s o f E. c o l i patho-gen ic f o r sw ine : one i s a n t i g e n i c and heat l a b i l e (LT) and the o ther i s non -an t i gen i c and heat s t a b l e (ST) (Dupont and P i c k e r i n g 1980). Both t o x i n s are t r ansm i t t ed by a p lasmid and both may be produced by the same s t r a i n o f E. c o l i . I t has been suggested t ha t the non -an t i gen i c ST was impor tant i n the d i a r r h e a o f swine ( G y l e s , 1971) . 28 2.6 Diarrhea in P i g l e t s In a normal, healthy i n t e s t i n a l mucosa, s a l t s and water are absorbed by an energy requiring mechanism. The d r i v i n g force of water absorption i s an active transport of e l e c t r o l y t e s , p a r t i c u l a r l y sodium and chlorine. Acute enteritis,which causes diarrhea i n newborn animals^produced watery stools from fecal f l u i d p r i m a r i l y o r i g i n a t i n g in the small i n t e s t i n e (Tennant and Hornbuckle, 1980). The rapid de-hydration causes hemoconcentration and along with the movement of ions, leads to metabolic acidosis caused by renal f a i l u r e to excrete hydrogen ions and by increased production of organic acids r e s u l t i n g from decreased tiss u e oxygenation. Hyperkalemia (hiigh potassium) also r e s u l t s as does hypoglycemia due to decreased gluconeogenesis and increased anaerobic g l y c o l y s i s (Tennant and Hornbuckle, 1980). In the s p e c i f i c case of the enterotoxic mechanism of E. c o l i , the toxin (LT only) acts by binding to receptors on the mucosal c e l l membranes to ac t i v a t e adenyl cyclase which converts ATP to c y c l i c AMP. The cAMP acts as a second messenger to influence permeability of the membrane. The net r e s u l t i s that sodium absorption i s blocked and chlorine i s secreted. The chlorine ion p u l l s water and cations with i t into the gut lumen to maintain osmotic equilibrium. This i s the cause of f l u i d loss (Dupont and Pickering, 1980). E. c o l i heat stable toxin (ST) does not activa t e adenyl cyclase however, as has been discovered recently, i n mice and rabbi t s , i t s action may be mediated through the build-up of guanyl cyclase which produces cGMP (Hughes et al_., 1978). In the case of Salmonella i n f e c t i o n , s i m i l a r dehydration and hydrogen ion and e l e c t r o l y t e disturbances are the r e s u l t . Salmonella 29 i s an i n v a s i v e organism and penet ra tes the mucosa and p r o l i f e r a t e s i n the gut a s s o c i a t e d lymphoid t i s s u e (Dupont and P i c k e r i n g , 1980) . I t s e f f e c t can occur throughout the i n t e s t i n e a l though i t u s u a l l y invades the lower gut mucosa more r e a d i l y . Using the r a t , Powell e t a l _ . , (1971) showed d i a r r h e a inc reased e s p e c i a l l y the i l e a l s e c r e t i o n o f wa te r , sodium and c h l o r i n e and po tass ium. They found an i nc reased h y d r o s t a t i c pressure i n the lamina p r o p r i a , perhaps caused by venous or l ymphat ic o b s t r u c t i o n , w i th r e s u l t a n t i nc reased membrane p e r m e a b i l i t y . 30 2.7 N o n - S p e c i f i c G a s t r o - i n t e s t i n a l Immune Mechanisms There i s a s e r i e s o f mechanisms which opera te i n defense a g a i n s t pathogenic b a c t e r i a and i n some c a s e s , v i r u s e s and p a r a s i t e s . 2 .7 .1 The G a s t r i c Trap A g a s t r i c t rap i s p rov ided by the HCl which i s a n t i - b a c t e r i a l and i s h i g h l y e f f e c t i v e aga ins t a lmost a l l b a c t e r i a . However, i f the g a s t r i c mucosa i s not f u n c t i o n a l , a s , p o s s i b l y , i n the neonate, o r i f the cha l l enge dose i s l a r g e enough, o r i f b a c t e r i a are not reached by the a c i d i t y o f the stomach, b a c t e r i a may pass t h i s t rap to p r o l i f e r a t e l a t e r i n the g a s t r o - i n t e s t i n a l t r a c t ( G i a n n e l l a e t a l _ . , 1971) . In neonates , the work on g a s t r i c a c i d s e c r e t i o n seems q u i t e incomplete and c o n t r a d i c t o r y . Cranwel l e t a l _ . , (1968) found tha t p i g l e t s i n a c l ean environment had a c i d s e c r e t i o n a t one week o f age, wh i l e those r a i s e d i n a convent iona l environment d i d n ' t sec re te u n t i l 30 days o f age. L a t e r , Cranwel l and T i t chen (1974) d i scove red tha t s e c r e t i o n cou ld begin from 2 days o f age us ing a s u r g i c a l l y separated pouch from the stomach and t ha t the s e c r e t i o n was s i g n i f i c a n t . H i l l (1970) s t a ted tha t a c i d s e c r e t i o n was very minimal dur ing the f i r s t 2 weeks. Jones (1972) r e f e r r e d to work which s ta ted t ha t HCl s e c r e t i o n does not begin u n t i l 20 days o f age o f m i l k f ed or 14 days i f g i ven c e r e a l s . The l i k e l y e x p l a n a t i o n o f d i s c r e p a n c i e s i s t ha t the p i g l e t has a competent g a s t r i c mucosa a t l e a s t w i t h i n a few days o f b i r t h , but environmental o r n u t r i t i o n a l f a c t o r s c o n t r o l i t s development (Cranwel l and T i t c h e n , 1974) . 2 . 7 . 2 I n t e s t i n a l M o t i l i t y The ra te o f passage o f chyme w i l l determine to a l a rge ex ten t whether l o c a l propagat ion w i l l o c c u r . There i s ev idence tha t the t ime o f 31 con tac t between the e p i t h i l i a l l i n i n g o f the gut and an i n v a s i v e pathogen such as a Sa lmone l la s t r a i n o f b a c t e r i a determines the development o f d i sease ( S p r i n z , 1969) . I t has been shown by the use o f a gang l ion b l o c k i n g drug which slowed the ra te o f p e r i s t a l s i s i n r a t s t ha t there was a s u b s t a n t i a l i n c r e a s e i n the number o f c o l i f o r m s i n the smal l i n t e s t i n e . (Dixon and P a u l l e y , 1963) . D ia r rhea i s a s s o c i a t e d w i th decreased m o t i l i t y ( C h r i s t i a n s e n e t a l . , 1972) and gut s t a s i s ( R u t t e r , 1975; White e t . a l . , 1972; K o h l e r , 1972) . Re la ted to i n t e s t i n a l m o t i l i t y i s the l e v e l o f s e c r e t i o n o f l a r g e amounts o f s t e r i l e f l u i d by the duodenum which washes out b a c t e r i a (N ie l son e_t aj_-, 1968) . 2 . 7 . 3 I n t e s t i n a l M i c r o f l o r a In the deve lop ing p i g l e t r a i s e d c o n v e n t i o n a l l y , wh i l e g a s t r i c a c t i v i t y i s low, b a c t e r i a are inges ted from the environment and s u c c e s s -f u l l y adapted s t r a i n s p r o l i f e r a t e . P r o b a b l y , the es tab l i shment o f a hea l thy and na tu ra l m i c r o f l o r a occurs here and evo lves as the d i e t changes from m i l k to s o l i d f o o d . In a hea l thy young p i g the eco logy o f the gut ma in ta ins a homeostasis which i s f u r t h e r ensconced i n a more mature a n i m a l . In the nurs ing p i g l e t l a c t o b a c i l l i p r o l i f e r a t e producing l a c t i c a c i d which i n i t s a c i d i t y i n h i b i t s o ther b a c t e r i a . L a t e r , the r e s i d e n t b a c t e r i a c rea te a n t i b a c t e r i a l c a t a b o l i t e s i n c l u d i n g l a c t i c a c i d and sho r t cha in v o l a t i l e f a t t y a c i d s to lower the pH. In a d d i t i o n , the r e s i d e n t f l o r a dominate the demand f o r space and n u t r i e n t s to prevent o ther forms from ga in i ng access to grow ( F r e t e r and Abrams, 1972; F r e t e r , 1974) . Working w i th cont inuous f low c u l t u r e s , Ozawa and F r e t e r (1964) found tha t r e s i d e n t s t a i n s used nea r l y a l l energy sources and any invader s t r a i n c o u l d n ' t p r o l i f e r a t e un less a source not used by the r e s i d e n t s was s u p p l i e d . 32 Another f a c t o r o f the environment o f the lumen i s t ha t i t has a low redox p o t e n t i a l which a l l o w s on l y c e r t a i n s t r a i n s o f b a c t e r i a to s u r v i v e ( M c C l e l l a n d , 1979) . A f u r t h e r f a c t o r i n f l u e n c i n g b a c t e r i a l eco logy i n the gut i s t ha t some b a c t e r i a can produce s p e c i f i c a n t i m i c r o b i a l s o f l i m i t e d spectrum which appear to i n f l u e n c e the a b i l i t y o f a p a r t i c u l a r s t r a i n to s u r v i v e (Branche e t a K , 1963) . In t r e a t i n g w i th a n t i b i o t i c s a g a i n s t an i n f e c t i o n ( e . g . Sa lmone l la ) the magnitude o f the cha l l enge dose may be reduced and the i n f e c t i o n may be pro longed by reduc ing the t o t a l i n t e s t i n a l f l o r a and a l l o w i n g the i n f e c t i v e s t r a i n to p r o l i f e r a t e (Ase rko f f and Benne t t , 1969) . The s t a b i l i t y o f the m i c r o f l o r a suggests t ha t immunity i s o p e r a t i v e a g a i n s t the e f f e c t s o f i n v a s i v e or mucosal a s s o c i a t e d b a c t e r i a and tha t low grade pathogens ( i . e . the i n t e s t i n a l f l o r a ) e i t h e r are r e s t r i c t e d to the gut lumen where immunological i n t e r -a c t i o n s are prevented or d i s p l a y a low degree o f a n t i g e n i c i t y . (Shed lo fsky and F r e t e r , 1974) . 2 . 7 . 4 Non-Immunological Fac to rs i n the S e c r e t i o n s o f the G . I . T r a c t Severa l n o n - s p e c i f i c i n h i b i t o r s o f b a c t e r i a l growth are present i n the duodenal s e c r e t i o n s and i n m i l k o f the nu rs ing i n d i v i d u a l . B i l e s a l t s are metabo l i zed by the r e s i d e n t b a c t e r i a and may form a n t i -me tabo l i t es to c e r t a i n b a c t e r i a ( M c C l e l l a n d , 1979) . L a c t o f e r r i n and lysozyme are both present i n i n t e s t i n a l s e c r e t i o n s and m i l k and , w i th s e c r e t o r y IgA, are b a c t e r i c i d a l ( H i l l and P o r t e r , 1974; Knopf e t a l . , 1971) . L a c t o f e r r i n , which i s commonly present i n m i l k c h e l a t e s i r o n which r e s t r i c t s b a c t e r i a l growth (Orson and R e i t e r , 1981; B u l l e n e t a l . , 1972) . Complement may be i n v o l v e d i n r e a c t i o n s i n o r near the mucosa. The a l t e r n a t e o r p roperd in pathway o f complement a c t i v a t i o n i s accepted 33 as important in the defense against gram negative bacteria of the gut (Hood et a l . , 1978). This is supported by the discovery that some complement components are synthesized by the intestinal mucosa (Lai A Fat et a i . , 1976). 34 2.8 Humoral and C e l l u l a r Immunity i n Po rc i ne Mammary S e c r e t i o n s Colost rum i s the f l u i d sec re ted by the mammary g land dur ing the f i r s t 24 hours ( K a r l s s o n , 1966) and m i l k i s sec re ted du r ing the remainder o f l a c t a t i o n . IgG i s the pr imary immunoglobul in component o f serum and c o l o s t r u m ; IgA i s the pr imary component o f m i l k ; and IgM i s a minor component o f bo th . In the f i r s t 24 hours IgG decreases f i v e -f o l d and w i t h i n the f i r s t week i t decreases t h i r t y - f o l d . Thus i t drops from forming 80% o f t o t a l c o l o s t r a l immunoglobul in to 25% o f t o t a l m i l k immunoglobul in ( C u r t i s and Bourne, 1971) . IgA on l y decreases t h r e e - f o l d dur ing the f i r s t week and hence emerges as the major immunoglobul in i n sow m i l k , accoun t ing f o r 50 to 60% o f m i l k immunoglobul in ( C u r t i s and Bourne, 1971) . Co los t rum f u n c t i o n s ma in ly i n p r o t e c t i o n a g a i n s t sys temic i n f e c t i o n because the immunoglobul ins i t con ta ins are absorbed through the gut mucosa i n t o the c i r c u l a t i o n . Th i s occurs i n a pe r i od o f t ime du r ing which the p i g l e t i n t e s t i n e absorbs macromolecules i n t a c t before gut c l o s u r e a f t e r 24 to 36 hours (Payne and Marsh , 1962) . M i l k p rov ides c o p r a - a n t i b o d i e s which f u n c t i o n w i t h i n the i n t e s t i n a l lumen dur ing the pre-weaning pe r iod ( W i l s o n , 1974; B rand tzaeg , 1973) . 125 Bourne and C u r t i s (1973) us ing I l a b e l l e d immunoglobul in determined the p ropo r t i ons o f serum d e r i v e d and l o c a l l y produced immuno-g l o b u l i n i n mammary s e c r e t i o n s . They found tha t a l l c o l o s t r a l IgG came from the serum and tha t 60% o f c o l o s t r a l IgA was syn thes i zed by the mammary g land (a sma l l p o r t i o n o f t o t a l c o l o s t r a l immunog lobu l ins ) , and , conse-q u e n t l y , cons ide red tha t co los t rum was a serum t ransudate (Bourne, 1973). They found t ha t m i l k , on the o the r hand, was a t r ue mammary s e c r e t i o n s ince 35 more than 90% o f the IgA and IgM and 70% o f IgG was produced l o c a l l y . In con junc t i on w i t h immunoglobul ins, po rc ine m i l k con ta ins a t r y p s i n i n h i b i t o r which occurs f i r s t l y a t h igh l e v e l s and f a l l s to a very low l e v e l by the f i f t h day (Laskowski e t a l _ . , 1957) . T h i s probably f u n c t i o n s to prevent degradat ion o f c o l o s t r a l immunoglobul ins before they can be absorbed i n the i n t e s t i n e ( S c o o t , 1972) . A l though no i n fo rma t i on e x i s t s f o r po rc ine c o l o s t r u m , human co los t rum shows a r e l a t i v e l y h igh l e v e l o f T lymphocytes and macrophages (Parmely and B e e r , 1977) . Parmely and Beer suggested t h a t i t was p o s s i b l e , but not p roven , tha t these c e l l s cou ld s u r v i v e i n the g a s t r o - i n t e s t i n a l t r a c t . They f u r t h e r suggested tha t the mammary t i s s u e may \"package\" s p e c i f i c c e l l u l a r components i n the co los t rum to c o n t r i b u t e to immuno-competency i n the neonate and tha t t h i s c e l l mediated immunity (CMI) from the mammary g land depended upon i n d u c t i v e events a t d i s t a n t mucosal sur face (b ronch ia l a s s o c i a t e d and gut a s s o c i a t e d lymphoid t i s s u e s ) . 36 2.9 Preweaning M o r t a l i t y In a survey o f the l i t e r a t u r e from 1937 to 1976 McCallum (1977) found t h a t l e v e l s o f preweaning m o r t a l i t y have c o n s i s t e n t l y ranged between 18 and 30 per cent o f p igs born ( i n c l u d i n g s t i l l b i r t h s ) . Two s t u d i e s (Fahmy and B e r n a r d , 1971; E n g l i s h and S m i t h , 1974) recorded t h a t 50 per cent o f the t o t a l preweaning m o r t a l i t y occur red be fore 3 days o f age. Pomeroy (1960) noted t ha t 70.2 per cent o f t o t a l preweaning m o r t a l i t y occur red be fore 3 days of age , and Jones (1972) recorded 63.1 per c e n t . Thus , any at tempt to reduce m o r t a l i t y must a f f e c t the e a r l i e s t days o f pos t na ta l e x i s t e n c e . 2.9.1 Causes o f Preweaning M o r t a l i t y The causes were f a i r l y c o n s i s t e n t among the authors c i t e d and are summarized i n Tab le 2 .3 These are t rauma, s t a r v a t i o n , general weakness, d i s e a s e , congen i t a l a b n o r m a l i t i e s , and o ther causes . Trauma i n v o l v e s c rush ing o r t ramp l ing o f p igs by the sow. Some o f the data may r e f l e c t the e f f e c t o f o ther pr imary causes p red i spos ing trauma such as m a l n u t r i t i o n , genera l weakness, or c h i l l i n g . S t a r v a t i o n , a major pr imary cause o f d e a t h , cou ld r e s u l t from two d i f f e r e n t c o n t r i b u t i n g f a c t o r s . The f i r s t i s a g a l a c t i a o f the sow w h i c h , i n the s t u d i e s o f E n g l i s h and Smith (1974) c o n t r i b u t e d to 27 per cent o f the s t a r v a t i o n . The o ther f a c t o r , c o n t r i b u t i n g 73 per c e n t , i s severe compe t i t i on w i t h i n l i t t e r s due e i t h e r to supernumary p i gs i n r e l a t i o n to a v a i l a b l e t e a t s or to d i s -p a r i t y i n b i r t h w e i g h t s which r e s u l t s i n unequal compe t i t i ve advantage f o r heav ie r p igs ( E n g l i s h and S m i t h , 1974) . The common r e s u l t o f s t a r v a t i o n i s hypoglycaemia (Sharpe, 1966; Edwards, 1972) which may be aggravated by c h i l l i n g ( C u r t i s , 1974) . General weakness, which c o n t r i b u t e s to h igh Table 2 . 4 A Summary of Major Causes C o n t r i b u t i n g to Death i n Baby P igs (per cent c o n t r i b u t i o n ) Reference Trauma S t a r v a t i o n R e l a t i v e Disease Congen i ta l Other Weakness Abnormal i ty Sharpe (1966) 21.2 17.1 9.6 9.6 2.1 40 .4 Fahmy and Bernard 19.2 — 26.9 17.5 14.2 22.2 (1971) E n g l i s h and Smith 18.2 42.8 14.9 — 12.3 11.8 (1974) Rodef fe r e t a l . , 30.9 17.6 14.7 18.2 — 13.1 (1975F 38 losses, is most clearly associated with parturition aberrations of which the most common result is prenatal anoxia or hypoxia (English and Smith, 1974). \"Parturition aberrations\" include premature umbilical cord rupture and a prolonged farrowing interval between births (Rodeffer e_t aJL. 1975) Disease, as a cause of death, includes different diseases depending on the study. Sharpe (1966) listed the major causes as gastroenteritis and septicaemia. Fahmy and Bernard (1971) listed scours and pneumonia as major disease factors. Rodeffer et al_., (1975) listed transmissable gastroenteritis (T.G.E.) , other diarrheas, and pneumonia. Congenital abnormalities varied among the studies. English and Smith (1974) listed the major traits including atresi ani, cardiac abnormality, congenital splay-leg, cleft palate, and hypoplasia kidney. 2.9.2 Effect of Low Birthweight on Survival \"The effect of birth weight on survival is essentially linear within a wide range of values\" (Bereskin et al_.» 1973). Thus, low birth-weight is a major contributing factor to reducing survival (Sharpe, 1966;; Fahmy and Bernard, 1971; Bereskin_et al_., 1973). Table 2.4 l ists mortality values found for low birthweight pigs by several researchers. These high mortality rates may vary with strain of pig or environment which, in turn, may include temperature and milking ability of the sow (Pomeroy, 1960). These high mortality rates reflect a greater susceptibility to the major causes of death. There was a higher incidence of trauma in low birthweight pigs (Sharpe, 1966); a markedly higher incidence of starvation (Sharpe, 1966; English and Smith, 1974); and low birthweight had some effect on the incidence of septicaemia (Sharpe, 1966). Also, low birth-weight pigs are much more susceptible to chilling. Newland et al_., (1952) Table 2 . 5 E f f e c t o f B i r t h Weight on M o r t a l i t y Reference Weight Range Per Cent M o r t a l i t y Pomeroy (1960) <900g 83 .0 (before 3 days) Sharpe (1966) <800g 82.1 Fahmy and Bernard <910g 60 .0 (1971) ( E n g l i s h and Smith <907g 74.6 (1974) VO 40 found that the drop in body temperature after chilling was inversely related to body weight. Pomeroy (1960) cited three factors contributing to higher mortality in low birth weight pigs: 1. they may be less vigorous and active, and less competitive at the teats during nursing. 2. they have a larger surface area in relation to body weight. Therefore there is a relatively greater heat loss per unit of body weight. 3. they may be physiologically immature. 41 Foot-Notes 1. Immunocytes include all cells of the immune system. 2. The failure of the immune system, as a result of previous contact with antigen, to respond to the same antigen, although capable of responding to tohers. Tolerance is best established by neonatal injection of an antigen (Benaceraf and Unanue, 1979). 3. An exotoxin is a soluble poisonous substance passing into the medium during growth of a microorganism. An endotoxin is a poisonous substance present in bacteria but separable from the cell body only on its disintegration. An enterotoxin is a toxin of bacteria produced within and affecting the intestine. (Websters 7th New Collegiate dictionary, 1965) 42 3 . Exper imenta l 3.1 I n t r o d u c t i o n Co los t rum-depr i ved p igs have been s u c c e s s f u l l y rea red i n a n o n - i s o l a t e d environment s i n c e 1961 (Owen e t a l _ . , 1961) . A f t e r work by Owen and B e l l (1964) , Scoot (1972) , and McCallum (1977) , McCallum (1977) conc luded tha t i t was p o s s i b l e \" t o r a i s e co los t rum-depr i ved neonata l p igs i n an o r d i n a r y swine barn environment and ach ieve s u r v i v a l r a t es comparable to those p r e s e n t l y t o l e r a t e d under na tu ra l c o n d i t i o n s \" us ing a b a t t o i r serum-der ived immunoglobul ins i n m i l k r e p l a c e r s . Both Scoot (1972) and McCallum (1977) concluded tha t o r a l a d m i n i s t r a t i o n o f 10 grams per k i l og ram o f body weight o f immunoglobul ins on the f i r s t day f o l l o w e d by 2 grams per k i l og ram on succeed ing days cou ld con fe r adequate pass i ve immunity on co los t rum-depr i ved p i g s . Scoot (1972) found tha t a d m i n i s t r a t i o n o f immunoglobul ins over 21 days i n c r e a s e d s u r v i v a l compared to 10 day t reatment ( from 75 per cent to 88 per cent ) and McCallum (1977) observed a sharp i n c r e a s e i n m o r t a l i t y f o l l o w i n g removal o f immunoglobul in a f t e r 10 days compared to those cont inued on t reatment f o r 20 days . The purpose o f exper iments repor ted he re in was to eva lua te the e f f e c t o f o r a l l y admin is te red immunoglobul ins on co los t rum-depr i ved p igs o f low b i r t h w e i g h t . Exper iments o f Lodge and E l l i o t (1979) , us ing the a r t i f i c i a l r e a r i n g techn ique o f McCallum e t a l . , (1977) , found tha t 21 day w e i g h t , 56 day weight and age a t 90kg. were h i g h l y c o r r e l a t e d w i t h b i r t h w e i g h t , but t ha t low b i r t h w e i g h t was l e s s i n h i b i t i n g under a r t i f i c i a l r e a r i n g than under na tu ra l r e a r i n g . Lodge and E l l i o t (1979) a l s o found t ha t a r t i f i c i a l r e a r i n g reduced m o r t a l i t y o f low b i r t h w e i g h t p i g s . 43 The t r i a l s described herein were c a r r i e d out in a barn environment on a commercial farm 1 in an environmentally c o n t r o l l e d room adjacent to the farrowing rooms. A series of 4 experiments was car r i e d out to determine e f f e c t s of low b i r t h weight on surviv a l and growth. 44 3 .2 Exper iment I 3.2.1 O b j e c t i v e The o b j e c t i v e o f t h i s exper iment .was t o assess the e f f i c a c y o f a b a t t o i r d e r i v e d po rc ine immunoglobul in e x t r a c t from serum as a m i l k r e p l a c e r a d d i t i v e f o r r e a r i n g low b i r t h w e i g h t p i g s . 3 . 2 . 2 M a t e r i a l s and Methods 3 .2 .2 .1 Exper imenta l Animals Twenty- four low b i r t h weight p igs weigh ing l e s s than lOOOg o f Y o r k s h i r e X Landrace breed ing were a l l o t t e d w i t h i n a ten day p e r i o d . Farrowings were at tended and exper imenta l p igs were removed from the sow a t b i r t h o r 12 hours l a t e r . P igs were weighed a t b i r t h , ea r tagged , and i n d i v i d u a l l y penned i n a nursery room. P igs were randomly ass igned to t rea tmen ts . Cages were a d j o i n i n g w i r e mesh 46cm x 25cm x 20cm i n two t i e r s . P r i o r to the t r i a l the room and cages were thorough ly c leaned and d i s -i n f e c t e d . Cages were washed p e r i o d i c a l l y du r i ng the t r i a l . Temperature i n the nursery room was main ta ined between 30°C and 33°C. A l l p igs rece i ved i r o n dext ran i n j e c t i o n s and had t h e i r needle tee th and t a i l s c l i p p e d a t two days o f age. A second i r o n dex t ran i n j e c t i o n was g iven a t 10 days o f age. 3 . 2 . 2 . 2 P r e p a r a t i o n o f Po rc i ne Immunoglobulins Immunoglobulins used i n a l l t r i a l s were prepared by Canada Packers L t d . , To ron to , O n t a r i o . The immunoglobul in - f r a c t i o n de r i ved a t 40 per cent s a t u r a t i o n w i t h ( N H 4 ) 2 SO^ was washed, d i a l y z e d , mixed w i th condensed whole m i l k and spray d r i e d (Owen, personal communication). 3 . 2 . 2 . 3 D i e t a r y Treatments In a l l t r ea tmen ts , p igs r e c e i v e d a non-medicated commercial 2 m i l k r e p l a c e r . Feed i n t a k e was ad jus ted to 7 .5 per cen t o f t h e i r body 45 weight i n a i r dry mat ter which was d i l u t e d 1 : 4 w i t h wa te r . For the f i r s t 3 days d i e t s were formula ted w i th a 10 per cent dex t rose s o l u t i o n . P igs were weighed every o the r day and feed a l lowances were ad jus ted a c c o r d i n g l y . Immunoglobulin was mixed w i t h the m i l k r e p l a c e r and fed a t l e v e l s s e t out i n the f o l l o w i n g schedu le : 1. No c o l o s t r u m , m i l k r e p l a c e r o n l y . 2 . Colost rum f o r 12 hou rs , f o l l owed by m i l k r e p l a c e r o n l y . 3 . Co los t rum f o r 12 h o u r s , p lus immunoglobul in a t 2g/kg body we igh t /day f o r 9 .5 days . 4 . Immunoglobulin e x t r a c t on f i r s t day ( lOg /kg body w e i g h t ) , p lus immunoglobul in (2g/kg body we igh t /day) f o r 9 days . Scour ing an imals were t r e a t e d , as necessa ry , on an i n d i v i d u a l 3 p i g b a s i s w i t h Furoxone . The t r i a l was o f 21 days d u r a t i o n . 3 . 2 . 2 . 4 Feeding Regimen S i n c e the p igs would not feed from sha l l ow bowls immediate ly a f t e r b i r t h , they were f o r c e fed w i th sy r i nges u n t i l they would n i p p l e f e e d . In l a t e r t r i a l s n i p p l e feed ing was s u c c e s s f u l from b i r t h but dur ing t h i s t r i a l some d i f f i c u l t y was encountered. At 10 days o f age a l l p igs were swi tched to sha l l ow bowls . Feeding was every 2 hours f o r the f i r s t 4 days , every 4 hours on days 5 to 8 and every 6 hours from days 9 to 21 . Fresh water was made a v a i l a b l e from day 5 and creep feed was o f f e r e d f r e s h d a i l y a f t e r 10 days o f age. 3 . 2 . 3 Measurements and Observa t ions P i g s were weighed every 2 days . M o r t a l i t y was recorded and post mortems were c a r r i e d out on a l l dead p igs by the P r o v i n c i a l Ve te r i na r y L a b o r a t o r y , A b b o t s f o r d , B . C . I n f e c t i o u s agents and c a u s a t i v e f a c t o r s were 46 i d e n t i f i e d whenever possible. Mortality was analyzed s t a t i s t i c a l l y by giving a survivor a zero value and a dead pig a 1 value. The analysis used was analysis of variance (ANOVA) with the design model being: Y^j = p + T- + e^j where T.. = Treatment E f f e c t s y = Population Mean £.. = Experimental Error Rate of gain was also analyzed with t h i s model. The mean birth-weights of survivors and dead pigs were compared with a \" t \" t e s t (Choi, 1978). 3.2.4 Results and Discussion Mortality was high (Table 3.1.b) with a l l pigs in the negative control group dying before 10 days of age. Those which received colostrum plus supplemental immunoglobulin extract f o r 10 days showed the highest s u r v i v a l . The differences between treatments were not s i g n i f i c a n t (P 0.05). The mean birth-weight of the s u r v i v i o r s was s i g n i f i c a n t l y higher than that of the dead pigs (P 0.01). This difference suggests that higher birth-weight pigs had an advantage in th i s t r i a l . The cause of death was predominantly a s p i r a t i o n pneumonia complicated by E. c o l i septicaemia. The pneumonia was in v a r i a b l y caused by the presence of foreign material in the bronchi and lungs introduced while force feeding with syringes. A major c h a r a c t e r i s t i c of dead pigs, regardless of treatment, was a f l a c c i d , d i l a t e d i n t e s t i n e or distended stomach. The cause of th i s state could have been over-feeding and could have involved E. c o l i e n t e r i t i s . A l l pigs were d i a r r h e t i c befor death. Most pigs which died showed a marked lack of depot f a t in d i c a t i n g no energetic reserves f o r s u r v i v a l , and 47 Tab le 3.1a Experiment 1: Exper imenta l Animals Treatment Number i n Treatment Mean B i r t h -We igh t Group t S . D . No c o l o s t r u m ; no immuno- 6 765 ± 157 g g l o b u l i n Co los t rum; no immuno- 6 854 + 121 g g l o b u l i n Colost rum + immunoglobul in 6 843 + 190 g (2g /kg /day) Immunoglobulin ( lOg /kg /day 6 752 + 190 g to 2g /kg /day) Tab le 3.1b Experiment 1: Resu l t s Treatment % S u r v i v a l % S u r v i v a l Rate o f Gain to Day 10 to Day 21 ( q/day ) No c o l o s t r u m ; no immuno- 0 g l o b u l i n Co los t rum; no immuno-g l o b u l i n 33 33 46 .5 + 24.2 Colos t rum + immunoglobul in 50 50 42.1 + 23.5 (2g /kg /day) Immunoglobulin ( lOg /kg /day 16 16 7.5 (1 p i g ) -to 2g /kg /day) 48 dehydration, no doubt a result of the diarrhea. A higher level of disease carrying microbes in the environ-ment might have been present due to the reservoir of infection carried by the negative control animals which were all i l l from the beginning of the t r i a l . Sanitation and high moisture levels were difficult to control by washing the cages. The resulting moist, humid, and non-sterile conditions may have been ideal for the growth of microbes. It was assumed that a 12 hour nursing period was adequate for attaining sufficient immunoglobulin levels in the plasma. This is supported by work of Scoot (1972) and Carlson and Lecce (1973). 49 3 .3 Exper iment I I 3.3.1 Ob jec t i ve The o b j e c t i v e o f t h i s experiment was to f u r t h e r assess the e f f i c a c y o f a b b a t o i r d e r i v e d po rc i ne serum immunoglobul in e x t r a c t as a m i l k r e p l a c e r a d d i t i v e f o r r e a r i n g low b i r t h weight p i g s . To reduce the pool o f i n f e c t i o n , nega t i ve c o n t r o l s r e c e i v i n g no immunoglobul ins ( a r t i f i c i a l o r co los t rum de r i ved ) were not i nc luded i n t h i s t r i a l . 3 . 3 . 2 M a t e r i a l s and Methods 3 .3 .2 .1 Exper imenta l Animals Twenty- four low b i r t h weight p igs weigh ing l e s s than lOOOg o f Y o r k s h i r e X Landrace breeding were a l l o t t e d w i t h i n a ten day p e r i o d . Farrowings were a t tended and exper imenta l an imals were removed a t b i r t h o r 12 hours l a t e r . P igs were weighed a t b i r t h , ear tagged , and i n d i v i d u a l l y penned i n a nursery room. P i g s were randomly ass igned to t rea tmen ts . Cages were a d j o i n i n g w i re mesh 46cm x 25cm x 20cm i n two t i e r s . P r i o r to the t r i a l the room and cages were thorough ly c leaned and d i s i n f e c t e d . Cages were l e f t unwashed throughout the t r i a l p e r i o d . Temperature i n the nursery room was main ta ined between 30°C and 33°C. A l l p igs r e c e i v e d i r o n dext ran i n j e c t i o n s and had t h e i r needle t ee th and t a i l s c l i p p e d a t two days o f age. A second i r o n dex t ran i n j e c t i o n was g i ven a t 10 days o f age. 3 . 3 . 2 . 2 D i e t a r y Treatments 2 P i g s r e c e i v e d a non-medicated commercial m i l k r e p l a c e r . Feed i n t ake was reduced from the l e v e l i n exper iment I to 6 per cent o f body weight i n a i r dry mat ter which was d i l u t e d 1 : 4 w i th wate r . For the f i r s t 3 days d i e t s were fo rmu la ted w i t h a 10 per cent dex t rose s o l u t i o n . P igs were weighed every o the r day and feed a l lowances were ad jus ted acco rd -50 ingly. Immunoglobulin extract was mixed with the milk replacer and fed at l e v e l s set out in the following schedule of treatments: 1. Colostrum f o r 12 hours, followed by milk replacer only. 2. Colostrum f o r 12 hours, followed by immunoglobulin at 2g/kg body weight/day f o r 9.5 days. 3. Immunoglobulin (lOg/kg body weight) on the f i r s t day followed by immunoglobulin at 2g/kg body weight/day f o r 9.5 days. Scouring animals were treated, as necessary, on an 4 individual pig basis with Anistat , a broad spectrum a n t i b i o t i c . The t r i a l was of 21 days duration. 3.3.2.3 Feeding Regimen Pigs were nipple fed dor one week then changed to bowl feeding f o r the remainder of the t r i a l . Feeding was every 2 hours f o r the f i r s t 4 days, every 4 hours on days 5 to 8, and every 6 hours from days 9 to 21. Fresh water was ava i l a b l e to them from day 5 and creep feed was offered fresh d a i l y a f t e r 10 days of age. 3.3.3 Measurements and Observations Pigs were weighed every 2 days. M o r t a l i t y was recorded and post mortems were conducted on a l l dead pigs by the Provincial Veterinary Laboratory, Abbotsford, B.C.. Infectious agents and causative factors were i d e n t i f i e d whenever possible. Mortality and rate of gain were analysed as in Experiment 1, using analysis of variance. The mean b i r t h weights of survivors and dead pigs were compared with a \" t \" t e s t (Choi, 1978). 51 3.3.4 Results and Discussion Mortality (Table 3.2.b) decreased from the level achieved in Experiment 1. This may be attributed to improved technique, elimination of the negative control group (as a pool of i n f e c t i o n ) , and improved environmental conditions. The group receiving only colostrum f o r 12 hours showed a mortality rate at 21 days s i g n i f i c a n t l y higher than the other two groups (P 0.05). There was no s i g n i f i c a n t difference in mortality between thos receiving colostrum with immunoglobulin and those receiving immunoglobulin extract instead of colostrum. Since i t was observed in Experiment 1 that feeding at 7.5 per cent of body weight led to a distended stomach and possible g a s t r i c s t a s i s producing scours, the level of feeding was reduced to 6 per cent of body weight in a i r dry matter, and t h i s problem was consequently reduced. White et al_., (1969) found in t h e i r t r i a l s , that scour was always preceded by g a s t r i c s t a s i s . They found that a d i r e c t r e l a t i o n s h i p existed between pH and growth of bacteria in the stomach. A lack of l a c t i c acid producing organisms in the stomach of the achlorhydric pig , with resultant high pH in the stomach, might lead to rapid growth conditions for coliforms which could then pass to the i n t e s t i n e and cause a scour syndrome. Endotoxin release in the stomach by coliform bacteria could also lead to reduced g a s t r i c acid secretion exacerbating the conditions. There was no s i g n i f i c a n t difference between b i r t h weights of surviving versus dead pigs. 52 Table 3.2a Experiment 2; Experimental Animals Treatment Number in Treatment Mean Birth-weight Group ± S.D. Colostrum; no immuno- 8 677 ± 111 g globulin Colostrum + immunoglobulin 8 707 ± 170 g (2g/kg/day) Immunoglobulin (lOg/kg/day 8 736 ± 143 g to 2g/kg/day) Table 3.2b Experiment 2: Results Treatment % Survival % Survival Rate of Gain to Day 10 to Day 21 ( g/day ) Colostrum; no immuno- 37 0 globulin Colostrum + immunoglobulin 75 63^ 35.2 + 15.4 g (2g/kg/day) Immunoglobulin (lOg/kg/day 63 50 b 39.8 ± 16.9 g to 2g/kg/day) (differing superscripts denote s t a t i s t i c a l l y different values at P= .05 ) 53 Causes o f m o r t a l i t y were genera l sep t i caemia f o r 6 p igs probably due to c o l i f o r m i n f e c t i o n , d e f i n i t e c o l i f o r m sep t i caemia f o r 3 p i g s , and c o l i f o r m e n t e r i t i s w i t h sep t i caemia f o r 7 p i g s . A l l dead p igs showed c h a r a c t e r i s t i c s o f emac ia t ion and dehydra t ion which may be a r e s u l t o f the d i a r r h e a which occu r red i n a l l an imals which d i e d . Rate o f ga in d i d not d i f f e r s i g n i f i c a n t l y between the two groups o f s u r v i v i n g p igs (Table 3.2 b ) and o v e r a l l remained a t a very low l e v e l . Consumption o f c reep feed and water s u p p l i e d ad l i b i t u m cou ld not be weighed a c c u r a t e l y because o f wastage. 54 3.4 Exper iment I I I 3 .4 .1 O b j e c t i v e The o b j e c t i v e o f t h i s exper iment was to compare a lower l e v e l o f immunoglobul in e x t r a c t a d m i n i s t r a t i o n , ( lOg /kg body weight f o r the f i r s t day fo l l owed by 2g/kg body we ight /day f o r 9 days) w i th a hioher immunoglobul in l e v e l (15g/kg body weight f o r the f i r s t day f o l l owed by 5g/kg body w e i g h t / d a y ) . Treatment groups o f p igs nu rs ing co los t rum f o r 12 hours i n s t e a d o f h igh i n i t i a l doses o f immuno-g l o b u l i n were a l s o i nc l uded f o r compar ison. 3 . 4 . 2 M a t e r i a l s and Methods 3 .4 .2 .1 Exper imenta l Animals Two consecu t i ve r e p l i c a t e s were c a r r i e d o u t . To each r e p l i c a t e 24 low b i r t h w e i g h t p igs o f l e s s than lOOOg o f Y o r k s h i r e X Landrace breed ing were a l l o t t e d w i t h i n a 10 day p e r i o d . Farrowings were a t tended and exper imenta l p igs were removed a t b i r t h o r 12 hours l a t e r . P igs were weighed a t b i r t h , ear tagged, and i n d i v i d u a l l y penned i n a nursery room. P igs were randomly ass igned to t rea tments . Cages were a d j o i n i n g w i re mesh 46cm x 25cm x 20cm i n two t i e r s . P r i o r to the t r i a l the room and cages were thorough ly c leaned and d i s i n f e c t e d . Cages were l e f t unwashed throughout the t r i a l p e r i o d . Temperature i n the nursery was main ta ined between 30°C and 33°C. A l l p igs r e c e i v e d i r o n dex t ran i n j e c t i o n s and had t h e i r needle tee th and t a i l s c l i p p e d a t two days o f age. A second i r o n dex t ran i n j e c t i o n was g iven a t 10 days o f age. 3 . 4 . 2 . 2 D i e t a r y Treatments 2 P i g s r e c e i v e d a non-medicated commercial m i l k r e p l a c e r . Feed i n t ake was se t a t 6% o f body weight of a i r dry mat ter which was d i l u t e d 55 1 : 4 with water. For the f i r s t 3 days diets were formulated with a 10 per cent dextrose sol u t i o n . Pigs were weighed every other day and fed accordingly. Immunoglobulin extract was mixed with the milk replacer and fed at le v e l s set out in the following schedule of treatments: 1. 15g/kg bodyweight immunoglobulin on the f i r s t day followed by 5g/kg body weight/day f o r 9 days. 2. lOg/kg body weight immunoglobulin on the f i r s t day followed by 2g/kg body weight/day f o r 9 days. 3. 12 hours of colostrum nursing followed by 9.5 days of immunoglobulin at 5g/kg body weight/day. 4. 12 hours of colostrum nursing followed by 9.5 days of immunoglobulin at 2g/kg/day. 4 In r e p l i c a t e 1 the a n t i b i o t i c A n i stat was used. In 3 r e p l i c a t e 2 the a n t i b a c t e r i a l Furoxone was used. 3.4.2.3 Feeding Regimen Pigs were nipple fed for one week then changed to bowl feeding f o r the remainder of the t r i a l . Feeding was every 2 hours f o r the f i r s t 4 days, every 4 hours on days 5 to 8, and every 6 hours from days 9 to 21. Fresh water was ava i l a b l e from day 5 and creep feed was offered fresh d a i l y a f t e r 10 days of age. 3.4.3 Measurments and Observations Measurments and s t a t i s t i c a l analyses were the same as in the two previous experiments except that another dependant variable was included, frequency of scouring. The design was a randomized block design since two r e p l i c a t e s were ca r r i e d out. 56 3.4.4 Results and Discussion Mortality (Table 3.3..b) was s i m i l a r to that in Experiment 2 where i t was approximately 50 per cent in the treated groups. There was no s i g n i f i c a n t difference between treatments f o r mortality. Thus, the r e s u l t s indicated no s i g n i f i c a n t difference between those receiving colostrum and those receiving immunoglobulin extract, or between those receiving a higher level of immunoglobulin and thowe receiving a lower l e v e l . The assumption that 12 hours of nursing was adequate was based on the findings of Scoot (1972) and Carlson and Lecce (1973). This assumption r e l i e s on the pig receiving adequate colostrum during nursing. However, low b i r t h weight pigs are frequently disadvantaged in t h i s respect, not being as competitive or not being able to reach a teat. Thus, in some cases within t h i s t r i a l , i n d i v i d u a l s may not receive an adequate level of systemic passive immunity which may lead to s u s c e p t i b i l i t y to i n f e c t i o n a f f e c t i n g the mortality rate. As was the case, those receiving a r t i f i c i a l immunoglobulin extract instead of colostrum, showed a high survival before day 10, but the difference was not s i g n i f i c a n t . The difference between mean b i r t h weights of survivors and dead pigs was not s i g n i f i c a n t . I t was observed that Table 3.3a Experiment 3: Experimental Animals 57 Replicate Treatment Number i n Treat- Mean Birth-Weight ment Group ± S.D. Immunoglobulin (15g/kg 6 761 ± 166 g /day to 5g/kg/day) Immunoglobulin (lOg/kg 6 729 ± 227 g /day to 2g/kg/day) Colostrum + immuno- 6 835 + 99 g glo b u l i n (5g/kg/day) Colostrum + immuno- 6 746 ± 192 g glo b u l i n (2g/kg/day) 2 Immunoglobulin (15 to 6 814 ± 83 g 5 g/kg/day) Immunoglobulin (10 to 6 671 + 96 g 2 g/kg/day) Colostrum + immuno- 6 704 ± 218 g glo b u l i n (5g/kg/day) Colostrum + immuno- 6 gl o b u l i n (2g/kg/day) 834 i 59 g Table 3.3b Experiment 3: Experimental Results Replicate Treatments % Survival % Survival Rate of Gain Scouring Frequency - to Day 10~~~ to Day 21 (g/day) days scouring/survivor) Mean Scouring • Frequency 1 15 g/kg for Day 1 then 50 46.3 + 4.0 a 7 5 g/kg/day for 9 days 10 g/kg for Day 1 the 2 g/kg/day for 9 days Colostrum for 12 hrs. 5g/kg/day for 9.5 days Colostrum for 12 hrs. ; 2g/kg/day for 9.5 days 15 g/kg for Day 1 then 50 55.7 + 3.5 a 9 5 g/kg/day for 9 days 10 g/kg for Day.1 then 83 55.7 ± 3.5 a 8.8 n 50 39.7 ± 1.2b 5.3 . ; 33 51.5 ± 0.7 a 5 66 55.3 + 8.8 a 3.3 5.0 + 2.6C 2 g/kg/day for 9 days Colostrum for 12 hrs. ; 17 59.0(1 only)\" 15 5 g/kg/day for 9.5 days Colostrum for 12 hrs. ; 50 60.0 ± 8.7 a 7 8.9 + 3.5 d 2 g/kg/day for 9.5 days Combined 15 g/kg for Day 1 then 84 50 51.0 ± 6 . l a 5 g/kg/day for 9 days 10 g/kg for Day 1 ther 2 g/kg/day for 9 days Colostrum for 12 hrs.; 5 g/kg/day for 9.5 days Colostrum for 12 hrs.; 2 g/kg/day for 9.5 days n 84 66 41.0 ± 6.5 b 75 25 54.0 + 4.4 a 75 58 57.3 ± 8.4 a c o 59 under500g b i r t h weight there was no s u r v i v a l , however the number o f obse rva t i ons was few. Cause o f death dur ing the f i r s t r e p l i c a t e , i n 11 cases was S a l m o n e l l o s i s caus ing d i a r r h e a and s e p t i c a e m i a . The ac tua l sero type was i d e n t i f i e d as Group B Sa lmone l l a i n 4 cases w h i l e i n the remaining cases sero type was u n i d e n t i f i e d . In one case death was due to E. c o l i e n t e r i t i s . Dur ing the second r e p l i c a t e , Sa lmone l la were h e a v i l y i m p l i c a t e d , bu t , due to the i n t e r f e r e n c e o f a n t i b i o t i c s g iven dur ing t rea tment , cou ld not be i s o l a t e d i n a l l c a s e s . K l e b s i e l l a was a l s o i s o l a t e d from two p i g s . Rate o f ga in (Table 3 .3 .b ) was i nc reased over t ha t found i n Exper iment I I . Those r e c e i v i n g immunoglobul in a t the lower l e v e l showed a s i g n i f i c a n t l y lower r a t e o f ga in i n both r e p l i c a t e s (P = 0.05) (F igu res 3 . 1 . a and 3 . 1 . b ) . S ince the p igs r e c e i v i n g 2g/kg body we igh t / day o f immunoglobul in a f t e r r e c e i v i n g co los t rum showed a s i g n i f i c a n t l y h igher (P = 0.05) growth r a t e than those which r e c e i v e d a r t i f i c i a l immuno-g l o b u l i n ( lOg /kg body weight on the f i r s t day) i n s t e a d o f c o l o s t r u m , the e f f e c t may be due to an i n s u f f i c i e n t i n i t i a t i n g dose o f lOg /kg body weight f o r pass i ve sys temic immunity. However, even i f t h i s t reatment a f f e c t e d growth r a t e , i t d i d not show any s i g n i f i c a n t a f f e c t on m o r t a l i t y r a t e . Both Scoot (1972) and McCallum (1977) found tha t the h igher dosage o f immunoglobul ins (15 and 5g/kg body we igh t /day) i nc reased ra te o f ga in s l i g h t l y . Scoot (1972) i n d i c a t e s t ha t b lood g l o b u l i n l e v e l s were not as h igh w i th a r t i f i c i a l l y supplemented as w i th sow nursed p i g s . Frequency o f scou r i ng o f the s u r v i v o r s showed no s i g n i f i c a n t d i f f e r e n c e s between the scheduled t rea tmen ts , however, the f requency o f scou r ing was s i g n i f i c a n t l y d i f f e r e n t between the two r e p l i c a t e s (Table F i g u r e 3.1.a Growth i n E x p e r i m e n t 3, R e p l i c a t e 1 Fiqure 3.1.b Growth in Experiment 3, Rep 2000 1500 A -Colostrum + m - \" + 2g/kg/day Ig 5g/kg/day Ig • -10 to 2 g/kg/day Ig O -15 to 5 g/kg/day Ig 1000 U If IB 20 62 3 . 3 . b ) . The obv ious reason f o r t h i s d i f f e r e n c e seems to have been tha t d i f f e r e n t a n t i - s c o u r drugs were used i n each r e p l i c a t e sugges t ing t ha t 4 the a n t i b i o t i c A n i s t a t was more e f f e c t i v e i n c o n t r o l l i n g scours than 3 the a n t i b a c t e r i a l Furoxone . In both r e p l i c a t e s , the scou r i ng f requency o f s u r v i v o r s i nc reased the h ighes t l e v e l a f t e r removal o f p igs from immunoglobul in supplementat ion a t 10 days o f age (F igu re 3 . 2 ) . Th i s suggests t ha t the p igs r equ i r ed f u r t h e r pass i ve p r o t e c t i o n w i th immuno-g l o b u l i n s beyond the ten th day. Figure 3 .2 . Scour ing Frequency (per cent o f s u r v i v o r s scou r i nq ) 100 A Experiment 3 ; R e p l i c a t e 1 A Experiment 3 ; R e p l i c a t e 2 ° Experiment 4 A A A O A A 2 _L_ A A A A A 8 JL A A L_ o o J 1 L_ A A O A J I 1 3 5 Days on T r i a l 11 13 15 17 19 21 64 3 .5 Exper iment IV 3.5.1 O b j e c t i v e The o b j e c t i v e o f t h i s exper iment was to compare per iods o f immunoglobul in f e e d i n g . The pe r iods s e l e c t e d f o r comparison were 10 , 15 and 21 days on immunoglobul in e x t r a c t a t a l e v e l o f lOg /kg body weight f o r the f i r s t day f o l l owed by 2g/kg body we igh t /day f o r 9 days . 3 . 5 . 2 M a t e r i a l s and Methods 3 .5 .2 .1 Exper imenta l Animals Twenty- four low b i r t hwe igh t p igs o f l e s s than lOOOg o f Y o r k s h i r e X Landrace breed ing were a l l o t t e d w i t h i n a ten day p e r i o d . Farrowings were at tended and exper imenta l p igs were removed a t b i r t h . P i g s were weighed a t b i r t h , ea r tagged , and i n d i v i d u a l l y penned i n a nursery room. P igs were randomly ass igned to t rea tments . Cages were a d j o i n i n g w i r e mesh 46cm x 25cm x 20cm i n two t i e r s . P r i o r to the t r i a l the room and cages were thorough ly c leaned and d i s i n f e c t e d . Cages were l e f t unwashed throughout the t r i a l p e r i o d . Temperature i n the nursery room was main ta ined between 30°C and 33°C. A l l p igs r e c e i v e d i r o n dext ran i n j e c t i o n s and had t h e i r needle tee th and t a i l s c l i p p e d a t two days o f age. A second i r o n dex t ran i n j e c t i o n was g iven a t 10 days o f age. 3 . 5 . 2 . 2 D i e t a r y Treatments 2 P i g s r e c e i v e d a non-medicated commercial m i l k r e p l a c e r . Feed i n take was ad jus ted to 6 per cent o f body weight i n a i r dry mat ter which was d i l u t e d 1 : 4 w i th wate r . For the f i r s t 3 days d i e t s were fo rmula ted w i th a 10 per cent dex t rose s o l u t i o n . P igs were weighed every o the r day and feed a l lowances were ad jus ted a c c o r d i n g l y . Immunoglobulin was mixed w i th the m i l k r e p l a c e r and fed a t one l e v e l : lOg /kg body weight 65 on the f i r s t day followed by 2g/kg body weight/day for succeeding days. Three periods of immunoglobulin feeding were applied: 10 days, 15 days, and 21 days. Scouring was treated, as necessary, on an in d i v i d u a l pig 3 basis, with Furoxone . 3.5.2.3 Feeding Regimen Pigs were nipple-fed throughout the 21 day t r i a l period. Creep feed was offered from day 10 but water was offered p e r i o d i c a l l y , only, by b o t t l e , to prevent s p i l l a g e . Feeding was every 2 hours for the f i r s t 4 days, every 4 hours on days 5 to 8 and every 6 hours from days 9 to 21. 3.5.3 Measurements and Observations Pigs were weighed every 2 days. Mortality was recorded and post mortems were conducted on a l l dead pigs by the Provincial Veterinary Laboratory, Abbotsford, B.C. Infectious agents and causative factors were i d e n t i f i e d whenever possible. M o r t a l i t y , rate of gain, and frequency of scouring (for survivors) were s t a t i s t i c a l l y analysed with analysis of variance using the same model as in Experiment 1. Also the mean b i r t h weights of ; survivors and dead pigs were compared with a \" t \" t e s t . 3.5.4 Results and Discussion Mortality rate (Table 3.4.b) improved compared to previous 66 Tab le 3.4a Experiment 4 : Exper imenta l Animals Treatment Number i n Treatment Mean B i r t h - w e i g h t Group t S .D . 10 days on immunoglobul in 8 674 + 148 g . 15 days on immunoglobul in 8 708 + 111 g . 21 days on immunoglobul in 8 749 + 116 g . Tab le 3.4b Experiment 4 : Resu l t s Treatment % S u r v i v a l % S u r v i v a l Rate o f Gain Frequency o f to Day 10 to Day 21 (g/day) Scour ing (Days s c o u r i n g / s u r v i v o r ) 10 days 63 5 0 a 40.8 + 2 3 . 2 c d 1.0 15 days 100 8 R a b 37.4 + 1 4 . 5 C 1.1 21 days 100 100 b 60.3 i 1 0 . 6 d 0.3 67 t r i a l s . M o r t a l i t y was s i g n i f i c a n t l y h igher (P = 0.05) on the 10 day t reatment compared to the 21 day t rea tment . However, 3 out o f 4 which d i e d i n the 10 day t reatment group d i d so w h i l e r e c e i v i n g immunoglobul in be fo re 10 days o f age. T h e r e f o r e , the r e s u l t i s s p u r i o u s . The e f f e c t o f pro longed feed ing o f immunoglobul in d e f i n i t e l y reduced m o r t a l i t y by m a i n t a i n i n g b e t t e r hea l t h and p reven t ing scours i n those p igs r e c e i v i n g immunoglobul in a f t e r 10 days . Death was due to b a c t e r i a l i n f e c t i o n caus ing d i a r r h e a i n 4 cases and pneumonia i n 1 case . Sa lmone l la was i s o l a t e d from 4 o f the 5 dead and presumed present a l s o i n the f i f t h . Thus the i n f e c t i o n caus ing death was d iagnosed as S a l m o n e l l o s i s i n a l l c a s e s . There was no s i g n i f i c a n t d i f f e r e n c e between mean b i r t h weights o f s u r v i v o r s and dead P i g s . Rate o f ga in (Tab le 3 .4 .b and F igu re 3.3) was h ighes t i n the group r e c e i v i n g immunoglobul ins f o r 21 d a y s , but o n l y s i g n i f i c a n t l y h igher (P = 0.05) than the group r e c e i v i n g immunoglobul ins f o r 15 days . The 21 day group had the h i ghes t mean r a t e o f ga in o f a l l groups i n the f o u r exper iments c a r r i e d o u t . Frequency o f scou r i ng (Tab le 3 .4 .b ) was very markedly reduced du r i ng t h i s t r i a l compared to Experiment I I I where i t was a l s o r eco rded . The group r e c e i v i n g immunoglobul in f o r 21 days showed no d i a r r h e a a f t e r 4 days o f age and the o the r two groups showed a much reduced f requency between 13 and 20 days o f age (F i gu re 3 . 2 ) . S i nce bowl f eed ing was e l i m i n a t e d and n i p p l e - f e e d i n g was cont inued throughout , chances o f sp read ing contamina t ion i n the feed were l i k e l y markedly reduced. Water p r o v i s i o n was l i m i t e d to p e r i o d i c b o t t l e f eed ing s i n c e i t c o u l d n ' t be prov ided ad l i b i t u m w i thou t s p i l l i n g l e a d i n g to a wet Figure 3.3. Cumulative Weight Gain. Experiment 4 1400 f 1200 1000 800 600 400 200 A - 10 days on Immunoglobulin O - 15 days on Immunoglobulin • - 21 days on Immunoglobulin 11 13 15 Days of Age 69 environment which seemed to be deterimental to the pigs from experience in the preceding t r i a l s . 70 3.6 General D i s c u s s i o n The approach o f t h i s s tudy was t w o - f o l d . F i r s t l y , a r t i -f i c i a l r e a r i n g was seen as a mean f o r i n c r e a s i n g s u r v i v a l o f low b i r t h -we igh t p i g s . S e c o n d l y , t h i s a r t i f i c i a l r e a r i n g techn ique w i t h immuno-g l o b u l i n e x t r a c t was a p p l i e d i n a n o n - i s o l a t e d envi ronment . Thus , the r e s u l t s can be d i s c u s s e d from both p e r s p e c t i v e s . An impor tant obse rva t i on i n these t r i a l s was a lower ra te o f ga in than p r e v i o u s l y found by McCallum (1977) us ing a very s i m i l a r d i e t , and by o the r workers (F igu re 3 . 4 ) . The ra te was h ighes t w i th the 21 day t reatment i n Exper iment IV where scou r i ng was markedly reduced but was s t i l l w e l l below ra tes found w i t h sow reared p igs o f low b i r t h weight w i t h i n the same herd (60g/day vs 125g/day) . Two ou ts tand ing reasons f o r t h i s are e v i d e n t . F i r s t l y , the p i gs on t r i a l may have been r e s t r i c t e d i n t h e i r food i n t a k e too much f o r optimum growth. Cons ide r i ng the d i e t to be adequate, the main c o n t r i b u t i n g f a c t o r cou ld be too i n f r equen t feed ing s i n c e t h e i r i n t a k e a t each feed ing was l i m i t e d by t h e i r c a p a c i t y . However, w i thou t automat ic f e e d i n g , more f requen t feed ing would be d i f f i c u l t . Second l y , the lower r a t e o f ga in may have been due to t h e i r low b i r t h we igh t s . Low b i r t h w e i g h t seems to have a d e f i n i t e e f f e c t on r a t e o f g a i n . However, Lodge and E l l i o t (1979) i n d i c a t e d t ha t a lower b i r t h -weight was l e s s i n h i b i t i n g on growth under a r t i f i c i a l r e a r i n g than under na tu ra l r e a r i n g . Widdowson (1971) , i n a t r i a l , showed t ha t run t p igs never reach the p o t e n t i a l o f l a r g e l i t t e r mates. One must d i s t i n g u i s h between low b i r t h w e i g h t p igs which are normal a n a t o m i c a l l y , but s m a l l , and t rue r u n t s . Not a l l p igs under lOOOg are n e c e s s a r i l y r u n t s . The Figure 3.4 Comparative Growth Curves A -A -o -: Perry and Lecce (1968); a r t i f i c i a l rearing » \" \" \" ; sow rearing Siers et a l . (1977); a r t i f i c i a l rearing ; sow rearing O - This t r i a l : Experiment IV (21 days on Ig) 10 12 14 16 18 20 22 Days of Age 72 m a n i f e s t a t i o n o f run t c h a r a c t e r i s t i c s i s l a r g e l y i n d i c a t e d by s i z e , however p igs above 600g d o n ' t seem to show any r u n t i n g appearance. True run ts seem underdeve loped, p o s s i b l y due to p rena ta l undernour ishment. T h e i r p h y s i c a l appearance o f very smal l s i z e and d i s p r o p o r t i o n a t e l y l a r g e domed heads suggests t h i s . S m a l l , but non-runt p igs may not be as d isadvantaged as t rue run ts when prov ided adequate n u t r i t i o n and hence may show adequate compensatory growth to make up f o r low b i r t h w e i g h t . Indeed, i n a l l but the f i r s t t r i a l , b i r t h w e i g h t d i d not a f f e c t s u r v i v a l . However, a l l those below 500g a t b i r t h , d i e d . I t i s p o s s i b l e t ha t the s u r v i v a l o f ve ry smal l t r ue run ts ( e . g . below 500g b i r t h w e i g h t ) r e q u i r e s more e x t r a o r d i n a r y a t t e n t i o n to hygiene and envi ronment . Dur ing sampl ing o f the sow-reared low b i r t h w e i g h t p i g s , v a r i a b i l i t y on growth r a t e was found to be high ( c o e f f i c i e n t o f v a r i a t i o n = 30.4 per c e n t ) . Th i s i s unders tandable i f the o p e r a t i v e f a c t o r s d e t e r -min ing growth a t t h i s pre-weaning age are c o n s i d e r e d . Such f a c t o r s i n c l u d e : 1. Nurs ing success which i s determined by a g g r e s s i v e n e s s , m i l k p roduc t ion o f the sow, and access to a p roduc t i ve t e a t . 2. Freedom from scours or o ther d i sease m a l a d i e s . 3 . Genet ic p o t e n t i a l o f the i n d i v i d u a l . S ince low b i r t h w e i g h t p igs a re l e s s compe t i t i ve du r ing nu rs ing and are more s u s c e p t i b l e to c h i l l i n g (as exp la i ned by the r e l a t i o n s h i p between we igh t , su r f ace a r e a , and heat l o s s (Monte i th and Mount, 1974 ) ) , a r t i f i c i a l r e a r i n g i n a c o n t r o l l e d environment would e l i m i n a t e many o f the s t r e s s -f u l f a c t o r s and a l l o w a more e q u i t a b l e s i t u a t i o n . Runts may be even 73 f u r t h e r d isadvantaged f o r s u r v i v a l because o f a low rese rve o f carbohydrate i n the l i v e r and muscles a t b i r t h f o r energy (Widdowson, 1971) . The high s u r v i v a l l e v e l s i n Exper iment IV p rov ide support f o r the advantage o f a r t i f i c i a l r e a r i n g o f low b i r t h w e i g h t p i g s . The f a c t o r s c o n t r i b u t i n g to the e f f i c a c y o f the immuno-g l o b u l i n e x t r a c t can be a n a l y s e d . Th i s e x t r a c t , which i s a p r e c i p i t a t e \" s a l t e d out \" w i t h a 40 per cent ( N H 4 ) 2 SO^ s o l u t i o n , con ta ins a l l o f the gamma-globul in and much o f the b e t a - g l o b u l i n f r a c t i o n s o f serum (Owen, 1961). L i k e c o l o s t r u m , which i s cons ide red a serum t ransudate (Bourne, 1973) , i t would c o n t a i n over 80 per cent IgG, l e s s IgA then co los t rum (8 vs 13 per c e n t ) , and more IgM than co los t rum (10 vs 4 per cent ) (Bourne, 1973) . A l s o , u n l i k e c o l o s t r u m , serum d e r i v e d immungolobul in con ta ins no sec re to r y IgA ( S - I g A ) . One cou ld presume tha t the e f f i c a c y o f the e x t r a c t was predom-i n a t e l y due to IgG. However, the presence o f IgM and non -sec re to ry IgA cannot be i g n o r e d . M i l e r e t a l _ . , (1975) found tha t the minimum e f f e c t i v e concen t ra t i ons f o r l o c a l p r o t e c t i v e e f f e c t i n l i g a t e d loop t e s t s w i th p igs were 0 . 5 , 0 . 0 5 , and 0.005 mg/ml o f IgG, IgM, and IgA r e s p e c t i v e l y . There-f o r e , even lower l e v e l s o f IgM and IgA may have a s i g n i f i c a n t p r o t e c t i v e e f f e c t . IgG i t s e l f , has been found to be o f s i g n i f i c a n t p r o t e c t i o n aga ins t e n t e r i c c o l i b a c i l l o s i s (Brandenburg and W i l s o n , 1972) . How IgG func t i ons w i t h i n the gut lumen i s open to ques t i on but i t has a n t i t o x i n and a g g l u -t i n a t i n g p r o p e r t i e s (Beneceraf and Unanue, 1979) . A l though i t may not be ab le to adhere to the gut l i n i n g as S-IgA does , a g g l u t i n a t i o n o f b a c t e r i a would f a c i l i a t e t h e i r p e r i s t a l t i c remova l . F i n a l l y , the e f f i c a c y o f t h i s e x t r a c t a g a i n s t Sa lmone l la b a c t e r i a i s o f c o n s i d e r a b l e i n t e r e s t . To d a t e , t h i s techn ique has been 74 used to prevent m o r t a l i t y due to E. c o l i e n t e r i t i s (Owen e_t aj_., 1961; Scoot, 1972; McCallum, 1977; and Kenelley et_ al_., 1979). Since i t protects against Salmonella, as shown i n the present study, many of the herds from which the blood f o r immunoglobulin extraction was taken must have antigenic quantities of Salmonella i n f e s t i n g them. The contribution of these herds must have been great enough to provide a s u f f i c i e n t l y high antibody t i t r e against Salmonella to be preventive in these experiments. 75 Conclusions 1. The a r t i f i c i a l r earing technique with a r t i f i c i a l immunoglobulins used i n these t r i a l s w i l l save low birthweight pigs i f weaned at b i r t h . However, growth rate i s r e s t r a i n e d , possibly by r e s t r i c t i v e feeding or by t h e i r low b i r t h weight. 2. The l e v e l of immunoglobulin of 10 g/kg./body weight on the f i r s t day followed by 2 g/kg/day on succeeding days seems to be e f f e c t i v e as a dosing l e v e l . 3. Longer periods of immunoglobulin administration may be necessary i n a non-isolated environment. Whether t h i s i s a r e s u l t of low birthweight i s not known. 4. This immunoglobulin extract used was e f f e c t i v e protectio against the Salmonella bacteria encountered in these t r i a l s . Certain types of Salmonella may be present at endemic l e v e l s i n many swine herds. 5. An increased understanding of the causes of runting i s necessary i n order to j u s t i f y the e f f o r t of attempting to save the smallest ones. 76 Foot -Notes 1. R and H Farms, A l d e r g r o v e , B .C . 2 . Federated Coopera t i ves L t d . M i l k Rep lacer - 30 . ( f o r p igs and lambs) . 3 . Furoxone i s manufactured by the A u s t i n Company, C l e v e l a n d , Oh io . I t con ta ins the a c t i v e i n g r e d i e n t f u r a z o l i d o n e , a n i t r o f u r a n , and i t i s a broad spec t rum, s y n t h e t i c a n t i -b a c t e r i a l compound. 4 . A n i s t a t i s a broad spectrum a n t i b i o t i c c o n t a i n i n g Ch lo ramphen ica l , Neomycin S u l f a t e , S u l f a t h i a z o l e , and Su l fame thaz ine . The manufacturer i s not known. \\ 77 BIBLIOGRAPHY A l l e n , W.D. and P o r t e r , P. 1973. The r e l a t i v e d i s t r i b u t i o n o f IgM and IgA c e l l s i n i n t e s t i n a l mucosa and lymphoid t i s s u e s o f the young unweaned p i g and t h e i r s i g n i f i c a n c e i n on togenes is o f s e c r e t o r y immunity. Bach , J . F . 1976. An t igen and Ant ibody R e a c t i o n s ; pp .248 -288 , i n \"Immunology\", e d i t e d by Bach , J . F . , John W i l e t and Sons , Toron to . 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Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use."@en ; ns0:scholarLevel "Graduate"@en ; dcterms:title "Artificial rearing of low birth-weight pigs"@en ; dcterms:type "Text"@en ; ns0:identifierURI "http://hdl.handle.net/2429/23216"@en .