Different ideas on the pathogenesis and treatment of swine edema-disease

ACTA AGRARIA DEBRECENIENSIS 2021-2 DOI: 10.34101/ACTAAGRAR/2/10038 45 Di e en ideas on he pa hogenesis and ea men o swine edema-disease Gab iella No o ni Dankó1* – Gyula Dankó2 † 1Uni e si y o Deb ecen, Facul y o Ag icul u al and Food Sciences and En i onmen al Managemen , Depa men o Animal B eeding H-4032, Deb ecen, Böszö ményi u. 138 2Doc o o Ve e ina y Medicine, Hunga y, Deb ecen; *Co espondence: no o nine@ag .unideb.hu SUMMARY Al hough li e a u e da a associa e he eason o swine edema-disease wi h ce ain se o ypes o Esche ichia coli bac e ia, he au ho s assume ha he p ima y cause o edema is mo e di e en . Suscep ible agen s and ac o s, mos ly o eed compound a e in ol ed. Du ing he diges ion o some eed-o igin p o ein opia e-like me aboli es, exo phins a ise, simul aneously a es he elease o ace ylcholine. Consequences o ace ylcholine sho age a e spasm o sphinc e s (mos ly pylo us), in es ine-dila a ion, con ac ion o bladde -sphinc e , and u ine e en ion. The endo phins and exo phins in ensi y he insulin elease om he panc eas, hypoglycemia e ol es, which is associa ed wi h loss o balance. Acco ding o he au ho s in edema-disease pigle dies because o hypoglycemia. Keywo ds: E.coli , hypoglycemia, exo phins, pig s ess INTRODUCTION Edema disease was i s desc ibed in I eland in 1938 as an "unusual condi ion a ec ing he diges i e o gans o he pig." (Moxley, 2000). S udies in 1955 we e he i s o iden i y an associa ion be ween hemoly ic Esche ichia coli (E.coli) and edema disease (G ego y, 1955; Scho ield and Da is, 1955). Pig-edema disease (ED) is mainly obse ed in ecen ly weaned pigle s, al hough i can also appea in he g owing and inishing phases. ED appea ance 1 o 4 weeks a e weaning is associa ed wi h as g ow h (Nabuu s e al., 2001), abou 70% o a ec ed pigs die, and su i ing pigs may g ow slowly. The clinical his o y o pe acu e dea h: heal hy, well-condi ioned, ecen ly weaned pigs, along wi h isual obse a ion o pe iocula edema and ex ensi e edema o he s omach and mesocolon, a e help ul in diagnosis. The e may be a cha ac e is ic squeal due o edema o he la ynx. Dia hea may p ecede he signs o edema disease i he E.Coli esponsible also possesses genes o en e o oxins. En e o oxins a e ex acellula p o eins o pep ides (exo oxins) which a e able o exe hei ac ions on he in es inal epi helium (Nagy and Feke e, 1999). These oxins damage he walls o small blood essels including hose in he b ain and cause luid o oedema o accumula e in he issues o he s omach and he la ge bowel. Cha ac e is ically, he s omach is ull o d y eed. Diagnosis is easy o make in an ou b eak in which he ull ange o clinical signs and pa hologic ea u es a e likely o occu . I is mo e di icul when only a ew animals a e a ec ed o when he disease occu s in an a ypical age g oup. E.coli isola ion and cha ac e iza ion a e necessa y o a de ini i e diagnosis. Cul u e o he small in es ine and colon ypically yields a hea y g ow h o hemoly ic E.coli, bu in some cases, he o ganism may no longe be p esen in he in es ine a he ime o dea h (The Me ck Ve .Man., 2010). This disease is a ibu ed o a hea -labile oxin om he Shiga oxin amily (also called e o oxins o Shiga-like oxins) p oduced by ce ain se o ypes o E.coli (Alexa e al., 2004; Nabuu s, 2001; Souza e al., 2001). E.coli colonizing he small in es ine and p oduce e o oxin 2e. This oxin abso bs om he in es ine in o he bloods eam, damages he endo helial cells in a ge issues. The endo helial cell damage induces an inc ease in ascula endo helium pe meabili y esul ing in edema (Pe ozo and Mallo qui, 2019). The same E.coli s ains we e also ound in non-a lic ed pigs a lowe o a compa able equencies. I sugges ed ha he weaned pig is a ese oi o pa hogenic bac e ia (Imbe ech s e al., 1992). I is unclea how he en e o oxins can pass he in es inal ba ie . Nabuu s e al. (2001) ound pigs wi h acu e edema disease show acidosis o he gu wall and me abolic acidosis. The in es inal pH 7.0 causes mucosal hype -pe meabili y, co esponds wi h a h ee- old inc ease in mac omolecula (e.g. oxins) pe meabili y. P obable he endo oxin p oduced by Coli bac e ia causes opioid sec e ion (Ca e al., 1982). The e iology o he disease is complex since changes in ood composi ion and empe a u e, loss o passi e p o ec ion om he sow, and gene ic suscep ibili y o he pigs a e in ol ed in he pa hogenesis (Imbe ech s e al., 1992). Responsi eness o pigs is di e en and seems o be ansmi ed he edi a ily since some he ds seem o be na u ally esis an o edema disease (Souza e al., 2001). Con ol o bac e ial p oli e a ion in ED is di icul as he oxin has al eady been abso bed in o he ci cula ion and bound o ecep o s when clinical is clea . An imic obial he apy o en used o p o ec una ec ed animals, may inc ease an ibio ic- esis an isola es o heal hy pigs o wi h clinical signs non- compa ible wi h dia hea. Mo eo e , due o he apid cou se o he illness, ea men comes oo la e o pigle s wi h clinical symp oms (Casano a e al., 2018). Misuse and o e use o an imic obials a e he main d i e s in he de elopmen o d ug- esis an pa hogens. An imic obial esis ance is a global heal h and de elopmen h ea . I equi es u gen mul isec o al ac ion in o de o achie e he Sus ainable De elopmen Goals (WHO, 2021). NOVOTNI DANKÓ, G. – DANKÓ, GY. ACTA AGRARIA DEBRECENIENSIS 2021-2 DOI: 10.34101/ACTAAGRAR/2/10038 46 MATERIALS AND METHODS Own obse a ions, expe iences, and aising ques ions The p ac ical obse a ions we e in he 1980s and 1990s, on small-scale pig a ms, in Hunga y (Szabolcs- Sza má coun y). Typical clinical signs o pigs su e ed om edema disease in ou p ac ice: Sudden appea ance o disease a e weaning, he oice o he ill animal was aucous, he e was an abno mal high pi ched squeak, pu y eyelids, he unde -skin connec i e issue o head edema-like pu ed-up. Incoo dina ion, lameness, s agge ing in he la e s ages, became pa ially pa alyzed and wen o hei legs. The e we e b ea hing di icul ies. The pig s opped ea ing, canno omi (e en canno make him omi ), and didn’ u ina e. The empe a u e was igh , in gene al. Pos -mo em examina ions showed edema ( luid in issues) o he g ea e cu a u e o he s omach wall, coiled colon, and eyelids. The s omach was ma kedly igh and s e ched a , he con en o which is d ie han in gene al. The s omach wall some imes was wide and in il a ed, he mucosa gela inous on some a eas. The small gu was uns ung, dis ended, and ull o dilu ed ma e . The mesen e ic lymph nodes swollen, some imes we e da k- ed. The u ina y bladde was ull. The colonic mesen e y was edema ous and gela inous oo. Acco ding o he p ac ical obse a ions, la ge whi e- ype pigle s in good condi ion died. The medical ea men o sick animals was a ely success ul. Reco e y o hose pigs which did no die ook up o 2 o 3 weeks. Ce ain b eeds o pigs migh be associa ed wi h disease, sugges ing a gene ic p edisposi ion. Based on ou obse a ions and expe iences we assume, ha edema-disease p ima ily is no caused by Coli bac e ia, bu di e en suscep ible agen s and ac o s, mos ly o eed-compound, among o he s. The p ac ical obse a ions showed ha he edema disease de eloped mainly a e some s ess, o example, change o ood, accina ion, emascula ion, anspo , weaning, o e eeding, ooping, e c. We assume ha edema disease happened in he case o ecep i e pigs. Some sow li e s we e mo e endange ed han o he s, he p oblem applied in hese sow li e s one a e he o he . P esumably, hese pigs we e s ess- sensi i e, so we assume ha edema-disease is gene ically de e mined, connec wi h s ess sensi i i y. Based on ou p ac ical expe ience edema disease mo e o en e ol ed when ye and pumpkin seeds we e in he eed. Mainly he c ude - no comple ely ma u ed- ye was dange ous in his ega d. The glu en o ce eal seeds is pa icula ly ich in glu amic acid. Glu amic acid was sepa a ed i s om he suga bee exuda es and o pumpkin seed-ge m. – The ques ion a ises: is he e any ole o glu amic acid in he de elopmen o edema-disease? The dange o hese eeds is in hei high glu amic-acid concen a ion? Once, a a me mowed poppy seed (Papa e hoeas), and his pigs ea om his. The nex day, one o he gil s’ mo ed unce ainly, swaying. La e he animal eco e ed. P obably, he e a e opium-like subs ances in he plan wild poppy, which could esul in mo emen diso de s. – The ques ion a ises: is i possible ha he pa hogenesis o his disease is due o he ac ual ole o opioids, opioid pep ides? In he case o he human acu e mo phine-poisoning, small pupil, slow pulse, dis u bance o consciousness obse ed. Glandula sec e ion ceases, he bowel mo emen s a e s opped, and in he end, espi a ion pa alysis occu s. The pylo us spasms p e en s omach con en ’s mo emen . The s omach o pigle s ha died in edema disease is ull and s ained oo. The side e ec s o opia es a e he u e h al sphinc e (sphinc e esicae) con ac ion, u ina y e en ion, and swollen eyelids. The edema ous pigle s we e cha ac e ized by swollen eyelids, hea y ullness o he bladde , and u ina y e en ion. – The ques ion a ises: whe he he edema disease can be an acu e mo phine-poison o simila o, o whe he i is possible pa hogenesis o his disease he ac ual ole o opioids, opioid pep ides, espec i ely? Pep ides, which unc ions a e simila o mo phine o o he opioids, we e isola ed om he b ain and o he sou ces as he pi ui a y. Pep ides wi h opioid ac i i y can be poin s ou in pepsin hyd olysa es o whea glu en and α-casein. These pep ides a e called exo phins because o hei exogenous o igin and mo phine-like ac i i ies. Some s omach-p oduced exo phines a e esis an o he in es inal p o einases. They abso b om he gas oin es inal ac in o he bloods eam (Zioud ou e al., 1979). Howe e , pep ic diges ion some ood p o eins, such as casein and whea glu en same ma e ials so o med, which ha e opia e-like ac i i y. So he eed, which con ains hese p o eins, p oduces opia e-like ma e ials du ing hei diges ion. These me aboli es could include ye, pumpkin seeds, and glu en. Assuming he e ec o edema disease caused by exo phines, he p ima y cause is ha kind o oods ( o example ye) which diges ion elease glu en, consequen ly opioid-like e ec exo phins. As men ioned abo e, he s ess-sensi i i y is a causing e ec in pig edema pa hogenesis. In s ess ul ci cums ances, he animal p oduces mo e acid in he s omach. Du ing he diges i e p ocess, eeds ich in glu en (e.g. ye g ains) elease exo phins. Exo phins each he synap ical esiculums p e en ing he elease o ace ylcholine neu o ansmi e s, ace ylcholine de ici occu s. Ace ylcholine a ec s in es ine mo ion. Consequences o ace ylcholine sho age a e spasm o sphinc e s (mos ly pylo us), in es ine-dila a ion, con ac ion o bladde -sphinc e , and u ine e en ion. Because o hese phenomenon’s he ill animal is no u ina e and canno omi . This physiological e ec is aceable as he s omach o dead pigs in edema disease was always ull and canno make hem omi . The exo phins and endo phins enhance he insulin elease om he panc eas, so insulin su plus and hypoglycemia o med, espec i ely (Schusdzia a e al., 1981). The hypoglycemia mani es ed i s in mo emen diso de s a e hen comple e pa alysis ACTA AGRARIA DEBRECENIENSIS 2021-2 DOI: 10.34101/ACTAAGRAR/2/10038 47 occu s esul s in e aplegia. A he same ime, a coma de elops, which in u n causes he dea h o he animal. The pig dies because o hypoglycaemic coma in edema disease, consequen ly. The cause o dea h is espi a o y-cen e dep ession. CONCLUSIONS Li e a u e da a assign he eason o pos -weaning dia hea and swine edema-disease caused by ce ain se o ypes o Esche ichia coli bac e ia (F ydendahl, 2002; Luppi e al., 2016). No p oduc has been de eloped ha is cu en ly e ec i e o ea edema disease (Moxley, 2000). One an imic obial agen ha may be e ec i e is en o loxacin (Ky iakis, 1997). Al hough an ibac e ial agen s may be use ul, he e a e wo se ious p oblems wi h hei use. One is ha hey may in e e e wi h ac i e immuniza ion, he eby allowing clinical signs and mo ali y o de elop a e wi hd awal o he an imic obial d ugs om he eed. The second is ha selec ion o s ains wi h an imic obial esis ance may occu . Inc easing an imic obial esis ance can easily become a p oblem in he ds wi h enzoo ic edema disease (Moxley, 2000). Based on au ho ’s obse a ions and expe iences edema-disease p ima ily is no caused by Coli bac e ia, bu di e en suscep ible agen s and ac o s. The p ac ical obse a ions showed ha he edema disease de eloped mainly a e some s ess and happened in he case o ecep i e pigs. P esumably, he disease is gene ically de e mined, connec wi h s ess sensi i i y. O he issues ha a ose: is he e any ole o glu amic acid in he de elopmen o edema-disease and is i possible pa hogenesis o his disease he ac ual ole o opioids, opioid pep ides. Pep ides wi h opioid ac i i y can be poin s ou in pepsin hyd olysa es o whea glu en and α-casein. Assuming he e ec o edema disease caused by exo phines, he p ima y cause is ha kind o oods ( o example ye) which diges ion elease glu en, consequen ly opioid-like e ec exo phins. In s ess ul ci cums ances, he animal p oduces mo e acid in he s omach. Du ing he diges i e p ocess, eeds ich in glu en elease exo phins which block he synap ical esiculums p e en ing he elease o ace ylcholine neu o ansmi e s. Ace ylcholine de ici a ec s in es ine mo ion. The exo phins and endo phins enhance he insulin elease om he panc eas, so insulin su plus and hypoglycemia o med, espec i ely. Based on he au ho ’s obse a ions, ans e ing o glucose was e icien , symp oms disappea ed. Mos app op ia e was he 40% glucose solu ion in a enous adminis a ion. O al adminis a ion o honey was e ec i e oo, 2–3 imes pe day, 2–3 easpoons o he sick animals. Healing began wi h he slow no maliza ion o mo emen diso de s. Fi s ly, he pa ien s eps on hind legs slowly s ood up, collapsed some imes, and hen ook a ew s eps. I was s iking ha he animals a he beginning o healing u ina ed a lo , hen de eca ed hickened aces. A ew days la e , hey we e ed alone and hen eco e ed spon aneously wi h almos no symp oms. A e all, he au ho s hope ha hese ideas will se e as a basis o u he esea ch on a ious aspec s o swine edema disease. ACKNOWLEDGEMENTS In memo y o my belo ed a he , Gyula Dankó (1935–2016), esea che and p ac icing e e ina ian. 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