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Frank S. Hsu, T. P. Yeh and C. T. Lee

in the Presence of Mycoplasmal Pneumonia in SwineTiamulin Feed Medication for the Maintenance of Weight Gains

1983. 57:1474-1478.J Anim Sci

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T I A M U L I N F E E D M E D I C A T I O N F O R T H EM A I N T E N A N C E O F W E I G H T G A I N S I N

T H E P R E S E N C E O F M Y C O P L A S M A LP N E U M O N I A I N S W I N E l

Fra n k S . Hsu , T . P . Yeh an d C . T . LeeAn ima l In d u s t ry Resea rch In s t i t u t e , TSC. , Ch u -n an

Miao l i Na t i o n a l C h u n g Sh in g Un iv e rs i ty , Ta iwan , R ep u b l i c o f Ch in a

S u m m a r yTiamu l in , a semi sy n th e t i c an t i b io t i c , was fed

to growing p igs and i t s va lue in main ta in ingwe ig h t g a in ~md feed e f f i c i en cy i n t h e face o fm y c o p l a s m a l p n e u m o n i a w a s d e te r m i n ed . F o u rt rea tmen t s d iv id ed amo n g 6 4 g ro win g p ig s f ro ma co n v en t i o n a l p ig fa rm w ere u sed t o t e s tt h e e f fec t s o f t i amu l in ad min i s t e red i n feed a tlevels o f 10 , 20 and 30 ppm. Al l p igs werea r t i f ic i a l l y i n fec t ed wi th My co p la sm a h y o -p n e u m o n i a e . M e d i c a t io n w a s s t a r t e d o n t h e1 4 th d ay a f t e r i n fec t i o n (d O) an d co n t i n u edfo r 2 8 d (d 0 t o 2 8 ) . P ig s were co n t i n u ed o nt e s t fo r an ad d i t i o n a l 1 4 -d p e r io d fo r fu r t h e ro b se rv a t i o n (d 2 8 t o 4 2 ) a f t e r t h e me d ica t edfeed was wi th d rawn . T i amu l in fed a t 1 0 , 2 0 an d3 0 p p m f o r 2 8 d d i d n o t c u r e t h e m y c o p l a s m a lp n e u m o n i a . T h e e f f e c t o f t i a m u l i n o n g r o w t hp e r f o r m a n c e w a s n o t t h e s a m e f o r a ll p e r i o d s.Du r in g t h e med ica t i o n p e r io d (d 0 t o 2 8 ) , b o thd a i l y g a in an d feed co n v e rs io n were n o t s i g n i f i -c a n t l y a f f e c t e d b y d i e t a r y t i a m u l i n c o n c e n t r a -t i o n s . F o r t h e p o s t - t r e a t m e n t p e r i o d ( d 2 8 t o4 2 ) , t i am u l in im p ro v ed d a i ly g a in (P< .0 5 ) an df e e d c o n v e r s io n ( P < . 0 5 ) o v e r t h o s e o f n o n m e d i -ca t ed co n t ro l s , an d t h e re sp o n ses o f b o th d a i l yg a in an d feed e f f i c i en cy i n c reased l i n ea r ly(P< .0 5 ) a s d i e t a ry t i am u l in l ev e ls i n c reased .(Key Wo rd s : T i amu l in , Gro win g P ig s , My co -p l a sma l Pn eu mo n ia , We ig h t Ga in s , Feed Ef f i -c i en cy . )

I T h e a u t h o r s a c k n o w l e d g e D r . J. J . O ' C o n n o r ,m a n a g e r o f E . R . S q u i b b a n d S o n s , In c ., P r i n c e t o n , N Jf o r g e n e r o u s l y p r o v i d i n g T i a m u l i n f u m a r a t e ; M r . H . L .Tso u fo r s t a t i s t i c a l a n a ly se s , a n d M r . C . N. W e n s fo ri s o l a t i o n o f M y c o p l a s m a s p p .R e c e i v e d M a r c h 1 9 , 1 9 8 1 .A c c e p t e d M a y 2 , 1 9 8 3 .

I n t r o d u c t i o nM y c o p l a s m a l p n e u m o n i a ( M P ) i s p r o b a b l y

t h e m o s t w i d e s p re a d a n d e c o n o m i c a l l y d a m a g in gd i sease i n swin e i n t h e wo r ld (Swi t ze r an d Ro ss ,1 9 7 5 ) . M y c o p l a s m a h y o p n e u m o n i a e ( M . s u i -p n e u m o n i a e ) w a s f o u n d t o b e t h e e t i o l o g i c a lag en t p ro d u c in g MP in s t u d i e s co n d u c t ed b yMare an d Sw i t ze r (1 9 6 5 ) i n Io w a , an d b yG o o d w in e t a l. (1 9 6 5 ) i n En g l an d . Gro ss l e s io n sa re ch a rac t e r i zed b y we l l -d e f i n ed , d a rk p u rp l eo r g rey i sh a reas p r im ar i l y in v o lv in g t h e o u t e red g es o f t h e ap i ca l an d ca rd i ac l o b es o f t h elu n g. Th e o rg an i sm cau ses mic ro sco p i c p u l -mo n ary l e s io n s d esc r i b ed a s p e r i b ro n ch i a l an dp e r iv a s c u la r l y m p h o c y t i c p r o l i f e r a ti o n s ( L iv i ng -s ton e t a l . , 1972; McKean e t a l . , 1979) .T i a m u l i n [ 1 4 - d e o x y - 1 4 ( 2 - d i e t h y l a m i n o e t h y lm e r c a p t o c e t o x y l ) m u t i li n h y d r o g e n f u m a r a t e ] ,a semi sy n th e t i c d e r i v a t i v e o f t h e an t i b io t i cp l eu ro m u l in , i s ac t i v e ag a in s t n u m ero u s Gram -p o s i ti v e a n d G r a m - n e g a t i v e p a t h o g e n s t h a tcause d isease in l ives tock (Drews e t a l . , 1975) ,b u t i s p a r t i cu l a r l y ac t i v e ag a in s t M. h y o p n eu -m o n iae i n v i tro (Bro w n e t a l. , 1 9 7 6 ) an d i n v iv o(Glawischnig and Ste in inger , 1976; Schul ler ,1 9 7 6 ; Jo h n so n e t a l. , 1 9 7 8 ; Go o d w in , 1 9 7 9 )a n d T r e p o n e m a h y o d y s e n t e r ia e ( T a y l o r, 1 9 8 0 ),t h e p r i n c ip a l cau sa t iv e ag en t o f sw in e d y sen t e ry .In f i e l d t e s t s , Len sch (1 9 8 0 ) fo u n d t h a t t h e u seo f t i amu l in i n feed a t l ev e l s o f 2 0 an d 3 0 p p mwas e f fec t i v e i n imp ro v in g g ro wth ra t e an dfeed e f f i c i en cy i n t h e p re sen ce o f swin e d y -s e n t e r y a n d p n e u m o n i a . T h e p r e s e n t s t u d yassessed t h e v a lu e o f t i amu l in fed a t l o w l ev e l st o g ro win g p ig s in ma in t a in in g we ig h t g a in s an dfeed e f f i c i en cy i n t h e p re sen ce o f an a r t i f i c i a l l yi n d u c e d i n f e c t i o n o f M P .

M a t e r i a l s a n d M e t h o d sExperimental Anirnals and Design. S i x t y - f o u r

1474J O U R N A L O F A N I M A L S C I E N C E , V o l . 57 , N o . 6, 1 9 8 3

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TI AM ULIN AND WEI GHT GAI NS OF P IGS 147 5L a n d r a c e x L a r g e W h i t e c r o s s b r e d b a r r o w s , a p -p r o x i m a t e l y 8 w k o f a g e, w e r e o b t a i n e d f ro mt h e s w i n e h e r d o f t h e A n i m a l I n d u s t r y R e s e a r c hI n s t i t u t e ( A I R I ) o f t h e T a i w a n S u g a r C o r p o r a -t i o n . F e c a l s w a b s w e r e c o l l e c t e d f r o m a l l p i g sp r i o r t o e x p o s u r e a n d n o a s c a r d is a n d T r e p o -n e m a h y o d y s e n t e r i a e w e r e f o u n d . T h e a n i m a l sw e r e a s s ig n e d r a n d o m l y t o fo u r t r e a t m e n tg r o u p s o n t h e b a s i s o f w e i g h t a n d l i t t e r o ri g i n .C o m p a r i s o n s w e r e m a d e a m o n g f o u r t e stg r o u p s , e a c h o f w h i c h h a d f o u r r e p l i c a t e s .T r e a t m e n t s w e r e g r a d e d l e v e ls o f 0 , 1 0 , 2 0 a n d3 0 p p m t i a m u l i n i n t h e d i e t f o r 2 8 d . A l la n i m a l s w e r e a r t i f i c i a l l y i n f e c t e d w i t h M P a t 9w k o f a g e . Pi g s w e r e h o u s e d i n a s e m i - o p e n e db u i l d i n g a n d w e r e p e n n e d i n g r o u p s o f fo u r i np e n s t h a t p r o v i d e d f l o o r s p a c e o f a p p r o x i -m a t e l y 1 .6 m z / p i g . F e e d a n d f r e s h w a t e r w e r es u p p l i e d a d l i b i t u m a n d w a s t e f r o m e a c h p e nw a s f lu s h e d d a i l y t h r o u g h a f lo o r d r a i n .

Art i f i c ia l In f ec t i on Procedure . M y c o p l a s m a Ip n e u m o n i a s t ra i n N o . 1 1 , o b t a i n e d f r o m I o w aS t a t e U n i v e r s i ty , w a s i n o c u l a t e d i n t r a t r a c h e a l l yi n t o s p e c i f i c - p a t h o g e n - f r e e (S P F ) p i g s a t a d o s eo f 5 m l. T h e p i g s s u b s e q u e n t l y d e v e l o p e dc l i n ic a l s i g n s t y p i c a l o f M P a n d w e r e n e c r o p s i e do n d 1 4 . T h e l u n g s s h o w e d l e s i o n s c h a r a c t e r i s t i co f M P . T h e p n e u m o n i c l u n gs w e r e h o m o g e n i z e di n p h o s p h a t e b u f f e r a t a r a ti o o f 1 : 1 0 w / v( W h i t t l e s t o n e , 1 9 7 8 ) , a n d t h e r e s u l t in g s u s p en -s i on w a s u s e d t o i n o c u l a t e f o u r 8 - w k - o l d S P Fp i g s, e a c h o f w h i c h r e c e i v e d a 5 - m l a l i q u o ti n t r a t r a c h e a l l y . S u b s e q u e n t l y , t h e s e f o u r p i g sw e r e n e c r o p s i e d a n d a h o m o g e n i z e d s u s p e n s i o no f t h e i r l u n g l e s i o n s w a s u s e d t o i n o c u l a t et h e 6 4 e x p e r i m e n t a l p ig s , e a c h o f w h i c h r e c ei v e d5 m l i n t r a t r a c h e a l l y . T h e i n o c u l u m w a s c u l t u r e da n d e x a m i n e d , a n d i t w a s c o n f ir m e d t h a tM . h y o r h i n i s , P a s t e u r e U a s p p a n d B o r d e t e l l ab r o n c h i s e p t i c a w e r e a b s e n t . T h e p r e s e n c e o f M .h y o p n e u m o n i a e w a s c o n fi r m e d b y e x a m i n a t io no f c u l t u r e s o f d i s e a s e d l u n g s ( F r i i s , 1 9 7 5 ) a n db y a n i m m u n o f l u o r e s c e n t t e c h n i q u e ( W e n g ,1 9 7 9 ) .Basal Diet and Medicat ion . A b a s a l d i e t w a sp r e p a r e d a c c o r d i n g t o s t a n d a r d s p e c i f ic a t i o n sf o r g r o w i n g p i g s , e x c e p t t h a t i t w a s d e v o i d o fa n t i b i o t i c s o r c h e m o t h e r a p e u t i c a g e n t s . T h ec o m p o s i t i o n o f t h e b a s a l d i e t i s g i v en i n t a b l e 1 .T i a m u l i n 2 w a s p r o v i d e d a s a p r e m i x c o n t a i n i n g

2Dynamutilin; E. R. Squibb and Sons, Inc. , Prince-ton, N ,

TABLE 1. COMPOSITION OFTHE B A S AL DIETIngredient %Soyb ean mea l, solvent (IFN 5-04-604) 22.0Yeast, toru la (IFN 7-05-527) 1.0Corn, yello w (IFN 4-02-935) 69.5Molasses, cane (IFN 4-04-646) 2.5Napie r grass , deh ydra ted ( IFN 1-00-023) 2 .0Dica lc ium phosp ha te ( IFN 6-01-080) 1 .5Limestone , ground ( IFN 6-02-632) .5Salt .5Vi t a m in p r e m ixa .1Trace minera l prem ixb .5Calcula ted nutr ien t Composit ionCrude prote in , % 16.53Crude fa t , % 3 .27

Crude f iber , % 3.53Ca, % .71P, % .62Digestible energy, Kc al/kg 3,350a v i t a m in p r e m ix p r ov ide d pe r k i log r a m o f d i e t :v i tamin A, 8 ,000 IU; v i tamin D, 800 IU ; v i tamin E, 10rag; vitamin K3, 1 mg; thiamine, 1 rag; r iboflavin, 5rag; Ca-pantothenate, 15 rag; niacin, 20 rag; vitaminB 6 .75 mg and vitamin B12 32/lg .bTr a c e m ine ra l p r e m ix p r ov ide d pe r k i log ra m o fdiet: Fe, 40 rag, Mn, 20 rag; Cu, 225 mg and Zn, 80m g.

2 5 % a c t i v e m a t e r i a l .T i a m u l i n w a s a d m i n i s t e r e d i n t h e f e e d a t

c o n c e n t r a t i o n s o f 1 0 , 2 0 a n d 3 0 p p m . M e d i c a -t i o n w a s s ta r t e d o n t h e 1 4 t h d fo l l o w i n gi n s t i l la t i o n ( d O ) o f t h e i n f e c t io u s i n o c u l u m .T r e a t m e n t w a s c o n t i n u o u s f o r 2 8 d ( d 0 t o 2 8 ) ,a n d s w i n e w e r e c o n t i n u e d o n t e s t f o r 1 4 d (d2 8 t o 4 2 ) f o r f u r t h e r o b s e r v a t i o n a f t e r t h em e d i c a t e d f e e d w a s w i t h d r a w n .

Growth S tud i e s . T h e e f f e ct s o f t i a m u l i n o ng r o w t h a n d f e e d e f f i c i e n c y o f s w i n e d u r i n g t h e4 2 - d t r i a l p e r i o d ( d 0 t o 4 2 ) w e r e e v a l u a t e d .T h e w e i g h t o f e a c h p i g w a s r e c o r d e d o n d 0 , 2 8a n d 4 2 . F e e d c o n s u m p t i o n w a s r e c o r d e d o n ap e n b a s i s f o r d 0 t o 2 8 a n d 2 8 t o 4 2 .

Clinical Observations. P i g s w e r e e x a m i n e dd a i l y f o r e v i d e n c e o f d i s e a s e , i n c l u d i n g g e n e r a la p p e a r a n c e , r e s p i r a t o r y r a t e s a n d n a s a l / o c u l a rd i s c h a r g e s .

Bacterio logical and Pathological Examina-tions. N e c r o p s i e s w e r e p e r f o r m e d o n o n e - h a l fo f t h e p i g s i n e a c h g r o u p o n d 4 2 p o s t i n f e c t i o n .D e g r e e s o f M P w e r e r e c o r d e d a c c o r d i n g t o a ne i g h t p o i n t s c al e r e c o m m e n d e d b y B r a s s in e a n dD e w a e l e ( 1 9 7 6 ) . G r a d e s 0 , 1 , 2 , 3 , 4 , 5 , 6 a n d

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1476 HSU ET A/-.7 represent the severi W of MP lesions fromnormal t o most severe.

At necropsy, cultures were made from lungsand pulmonary lymph nodes for M. hyopneu-moniae, Pasteurella spp, Salmonella spp, Hemo-philus pleuropneumoniae, Bordetella bron-chiseptica and other pathogenic organisms, M.hyopneumoniae was isolated by the proceduresproposed by FilLs (1975), Pasteurella multocida,H. pleuropneumoniae, Salmonella spp., B.bronchiseptica and other microorganisms wereisolated by methods given by Halt (1977).

Portions of the pneumonic lungs werestudied by the immunofluorescent antibodytechnique for identification of M, hyopneumo-niae; the procedure proposed by Weng (1979)was used.Samples of pneumonic lungs were fixed inneutral, buffered formaldehyde (10%) solution,dehydrated and embedded with paraffin. Sec-tions were cut 6 tam thick, stained with hema-toxylin and eosin and subjected to histopatho-logical examinations.S ta t i s t i ca l Ana lys i s . Body weight gains andfeed conversion .were evaluated by one-wayanalysis of variance (Steel and Torrie, 1980)and linear and quadratic regression analyses(Snedecor and Cochran, 1980). The scores forpneumonic lesions were analyzed statisticaUyby the chi square method (Steel and Torrie,1980).

Re s u l t sCl in ica l O bs er va t ions and Pa tbo log ica l F ind -ings . All 64 artificially infected pigs begancoughing and developed increased respiration

rates to varying (milk to moderate) degrees bythe 10th d postinoculation. These symptomspersisted to some degree throughout the trial.The results of the gross and histologicalexaminat ion are listed in table 2. AU of the pigsnecropsied showed evidence of mycoplasmapneumonia. Of the 24 pigs from the threemedicated groups, 22 (91.7%) had gross lesionsconsistent with MP, whereas all eight pigs frorfinonmedicated groups had MP lesions. Micro-scopically, all 32 experimental pigs examined,including medicated and nonmedicated pigs,had histopathological lesions compatible withMP, but no other pneumonic lesions wereobserved, There were no statistical differencesin lesion scores between medicated and non-medicated pigs.Bac ter io log ica l F ind ings . Of the 32 pneu-monic lungs submitted for isolation of micro-organisms, 17 (53.1%) had M. hyopneumoniae,11 (35.3%) had P. multoc ida , 7 (23.5%) had H.pleuropneumoniae, 7 (23.5%) had Salmonellaspp and 2 (6.3%) had B. bronchiseptica. Of the32 lungs examined by the immunofluorescentantibody technique, 26 (81.3%) were positivefor M. hyopneumoniae.G r o w t h S t u d i e s. Daily gain and feed conver-sion data are presented in table 3. The effect oftiamulin on growth performance was not thesame in all periods. During the medicationperiod (d 0 to 28), bo th daily gain and feedconversion were not significantly affected bydietary tiamulin concentrations. For thepost-treatment period (d 28 to 42), tiamulinimproved daily gain (P


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TIAMULIN AND WEIGHT GAINS OF PIGSTABLE 3. EFFECT OF TIAMULIN ON WEIGHT GAINS AND FEED EFFICIENCYIN GROWING PIGS EXPOSED TO MYCOPLASMAL PNEUMONIA

1477

ItemTreatment, ppm tiamulin

0 10 20 30 SE aD 0 to 28

Avg initial weight, kg 18.9 18.8 19.3 19.7 .94Avg final weight, kg 35.4 35.9 35.2 36.4 1.61Avg daily gain, kg .59 .61 .57 .60 .03Feed/gain 2.38 2.32 2.40 2.39 .11D 28 to 42

Avg initial weight, kg 35.4 35.9 35.2 36.4 1.61Avg final weight, kg 41.6 42.7 42.4 44.0 1.67Avg daily gain, kgb .44 .48 .51 .54 .03Feed/gain c 3.66 3.30 3.25 3.01 .16D 0 to 42

Avg initial weight, kg 18.9 18.8 19.3 19.7 .94Avg final weight, kg 41.6 42.7 42.4 44.0 1.67Avg daily gain, kg .54 .57 .55 .58 .03Feed/gain 2.73 2.59 2.63 2.58 .11astandard error of the mean.bLinear response (P


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