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
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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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