Ma.au.re Pathogu.s: Rul Issues and Real Risks
`
`Ih\i ght D. Bowm3n
`Depamuent of ?,,!icrobiology and lmmUDology
`Com.ell University
`Itbaca, NY 14853-6401
`
`Jeftr.y C. Bwubru>I,
`The J.C. Bum!wn Compmy
`274 1 Ardisia L:w.e
`Naples, n34109
`
`ABSTRAC T
`
`The pathogens of the major domestic animal;, i.e., c.hkke.ns, cattle, and pigs, posing a threat to people through
`m:mw-e are considered. The discussio:1 is limited to those pathogens ~ t are a threat from ell\iro:anwu:al
`contanllll3rion, suc.b u through w:i.tersbed co::1:ru:nm3tioo or vegetable contamination, m!w- than from those
`pathogem that are co:1Side1ed to c:i.use disease mainly though food-borne ombxeas of disease. Tbe p:i.per lists tbe
`major signs a:od disease as.socia:ed \\ith tbe 3 major p:i.thogem in c.hkke.ns and the six major pathogens associated
`with pigs 300 c:ml.e. Mentioo is also tmde oftbe role of tile domestic cat in the potemial contaminatio::1 of
`w:i.tersh@d witb oocyns of Toxoplasma go11dii. Finally, attention is called to the need to care.full}' ide.ntify the
`patbogem of fflle impommce, to de::en:nine bow these pathogens pose a threat to people, and to develop a be.:::er
`UDdmt:md:ing of what is required to cause tbe.ir routin.e des.ructioo by dismfectio:1.
`
`Exhibit 1045
`Bazooka v. Nuhn - IPR2024-00098
`Page 1 of 9
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`.~ manures are coming Wlde.r more aud more scrutiny relati,-e to their e.n,iro::we.ntal impact For years,
`farmers were doing what was considered responsible :md "gree~" i.e., they \\"ere recycling their :mim3l wa,,·te
`through land application of applic:ufo3 to crops. Proble.m; v.i th this sce~o b3, -e denloped as the res.ult of farms
`tad.mg to become larger and brger (as in me USDA 's recognition of Animal Feeding Operatio::,s, AFO•s) and me
`ba tb31 the public i; funber and funbe.rremovedpsychologic:tlly and socfall}' from :uiliual waste (It was only 100
`years ago that New Yo?k City, like most cities, was removing tom of horse ID3nure from its streets 03 a daily basis.).
`Al the same time, me public bas raised its e.'q)Ka.tio:1S as to wh:u it v.ilJ 3ccept relaln:e to its food :ind drinking
`water, this is indicated by the oeed to measw-e con.:uninants in le,-e.ls of pans per million or billion and the EPAs
`applica!io3 of uro oo!.e,rance for certain pathogens. It is for this reason, tb31 a d ry like New YOO: bas bee.n forced to
`consider mnos of providing patboge.n•free water by pro: ecting its watw.bed or by spe.uding large sums to put a
`filtration sys::em in place. (see: http://www.epa.go\·fregioo2/epd/97043.hmi). Although effluents from w:w.ewater
`treatment plants in watersheds are koo\\U 10 contain potential hwmn patbogens, concem is also being d:r:awo 10 the
`po:ential pathogE-:1S in anim31 \\':l.Ste and their abilit)' to enter drinking water.
`
`There are o::ily three species of domestic animals (other tb3.n hou;ehold pe,; dogs and cau ) that are &roted in tbe
`Uni::ed States 03 a large scale (See: "USDA's Nariooal Agriculrural Statistics Service (NASS);
`bup://l't·ww.D3S-s.usda.gov/ces.Ui/census97/atlas97/sunuuru-yl .ban.) Tbe---~ a:nim:tls are chickens (uoWld 7 bilJio3
`broilers and 400 million layers), 65 million pig_s, aud 100 million canle (beef cow-s being 35 million :md dairy cows
`being 10 million; remaining 56% are bulls, heifers, steers, e::c.). The numbers of horses in tbe United States is
`cw:re.mly about 2 million. There is a declining number of sbeep, Clll'remi}' around 7 millio:a. For compariso3
`pw-poses, there are arOUDd 275 million people in the United States. Thus, i1 i; ,-e.ry easy to understand that the waste
`produced by these animals is subs.anti.a~ :md that th~s-e i; coocem for pote.nrial co3.:uniuation of hod and water with
`pathogens that these animals migb.: harbor.
`
`Many of tbe pathogens found in :mim:tl manure really pose no threat to htt!llatlS as wa::erbome age.ots, although they
`do pose threats to animal baodlers or via mea1 tb31 is contamina:ed during processing_. Ullfortuoa:ely, tables listing
`the infectious age.ors from animals often combine the food-bome and water-borne pathogens tnn'.ing i1 difficult to
`detenuioe which are cone.ems that need to be assess from the point of \iew of was::e m:tll3gemen:i . • ~ so, the nrious
`lists of patbogens often ioclude large numbers of organisms that could be considered potential patbogens
`trommissible from these animal; to hwn:m, but ofl:eo ma:ay of the ory.nism; 03 the list are oot of trul}' significant
`cone em. For e.-::unple, Chlamydia aud ,\fycobac;qrfum arium are pote:a!ial hwmn patbogens tb31 can be transmitted
`to people from birds, but tbESe pattaogens do not occur io commercial ope.nuious io the United States. Similarl}\ the
`~'"""'·onu producing fungi may be capable of soil suni\·:tl, but they :u-e not t)'pically present in nwnue . . ~ so,
`\iruses appear 03 many lists of animal pathogens that are in manure and cros-s-mumnissible 10 ~ but there
`acru:tlly is little e\ide ce that such mumnission occurs or that infection in htmWlS would denlop if U't.OSlllissiou
`did take place.
`
`The reality i; that there are onl}' set·eral patbogens associa::ed with each farmed domestic animal species that are of
`significant cone em relati,-e ;o waste conaol and m:tll3gem.e:a;. Ho\\-e\-e.r, some of these patbogens pose a real and
`present threa1 to people through environmental cow~tion. One of the best examples is the & chrricllia coli
`Ol 57:H7 which bas caused several wa:aboroe outbreaks rela:ed to the contunimtion of drinking water with
`organisms from cattle nwnue. Tbe most rece:al case was described by me CDC (Morbidity and Monaliry Weeki}'
`Repon, 1999) mi occurred in Sep:em.ber 1999 at a fair in Albaoy, NY. Approx:iw.tel}' 108,000 persons attended
`the fair . Of the--~, 921 reported diarrhea. Positive stool cultures tor E. co# 0 157:H7 were ob;ained from 116
`persons. SL'a y•five persons were hospitalized. Eleveo cbildre.o de,-etoped hemolytic u.s-emic syndrome. Two
`persons died,. a 3-)-ear-old girl and a 79-yeu-old man. The som:e of the infection was a contaminated shallow well
`The water from. the well was not chlorimted or otbe.rwise m ated. In outbreaks such as this it is possible that the
`infectious age.m is not specific and infections would be expected from other fecal :m ociated mkroorgru:ii.s.ms. This
`was e.ucdy me case in this Albany. NY, incident \\ith o,w 32 indl\'lduals having been demonstrated to ban
`positive Campy lobau "1' jefWli culru.s-es.
`
`l1 i; impon.uit to remember that the.re may h•n:e been a rime when these zoonotic aud water-borne mfec.tions we.re
`more coounon amongst people in the United Sta::es tb3.n they u e today. lnfatu diarrhea is one of the major causes of
`death of c.hildre.o in developing oarions and bas been ooe of tbe driving forces bebiod the de---..ire to pro\ide clean
`water to all me child:ren of tbe world. Tbe infant monality r.ue in the United S1ates was much bigbe.r in me past, and
`it is highly likely that some of these deattas were due to such diseases, but it "ill oever be kno\\u to what e.mn:i they
`
`Exhibit 1045
`Bazooka v. Nuhn - IPR2024-00098
`Page 2 of 9
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`impacted cbiJdbood sw-,..ival in the p3Sl. Ho\\-en r, i; is impomnt to point out dut one of the reasons that
`epidemiologists today can rapidly pinpoin: the cause and sou.TCe of infections, sucb as th31 occurring in Wa~o
`County NY, is because of me tremendous ad\·ance.m.e~us tha1 b3,-e been made in the use of moleculu biological
`memods tba: allow tbe fulge.rprinting of the specific se.rorype implicated in the infection. Thu;, as these me1hods
`increa;e in sensitivity and specificity, the possibility of being better able to identify soW'tes of contrunill3tion will
`continue to increase .
`
`• ~ ,iruses are for the most pm oot cousidered :u this rime to pose a threat to hwmn bealth. Tbe ooe possible
`exception is me a,ian influenza , irus W t could possibly persist in nwmre or efflue:a:s. The ch:mc.e of such a ,irus
`coming from cooun.erci:tl chic.ken producers is practically infinitesimal. The.re are al.most oo co:nuuercid chickens
`tba: are infected v.itb this Yirus, and if i1 did occur in commercial cbicke:a resid:uals, it would probably ban to be
`amplified by due.ks and theo by pi~ be.fore it could be U\UlSfe.md to btmWlS as a respir:uo:y infection.
`
`Commercial chic.kens present three patbogeos that are potential threats to people through fecal oral co:a.1:Unlll3tion
`(see ''Table J. Major p.atbog_em io comruerdal chk ke.o maoure that pose a threat of hum.aD infection."). For the
`most pan, the o::ily people wbo b3\-e become infected with a:ay of these chicken patboge.ns ban bee eitbe.r through
`direo: co::>.tao: with the chickens, i.e., handlers or processors, or through couwnina:ed meat, eggs, or oilier poultry
`products. Salmonella tinifriridi: is capable of tmdergoing a::msovarial transmissioo in tbe chic.ken. The
`tnll1$1llissio::>. takes place only ra:rel}' and the number of eggs W t are coot:uui:aated in this DW1Der is ,·ery s.mal~ 1 in
`10,000 ew or less tbrougbom the United States.
`
`Pi~ have a larger :a.umber of ory.nism; Wll chickens W t pose a threat to human bealth tbrougb their waste
`products (see "Tabte 2. ?v!ajor pathoge:ns in commercial swiue nl3llure tbst pose a threat of bttru.10 infection.'').
`Again,. as with cbickeos, most cases of E. coli and Salmonella that are related to swine are actually due ;o foodbome
`infections and have very little to do with manw-e co:a.!J'OL Swine urine is a po::eutially importaot source of
`L~p,ospira, maybe an eveo more important source tb3.D catde, which bas been implicated in wambome infections
`(Jackson e.t :tl, 1993; ~0..!V.l'R, 1998). S\\iue are ID3jor hosts of Hvlicobactc.r pylori which bas recentlybeeo
`implicated in b\t!ll:lll stomach ulcers, bowt\'el, there is uo iDdicatioo that mnsmissioo from swine occurs. There is
`also :tbuost uo i:afomution on the swvl\,ai of Helicobacte.r in the en,iromueut, howet·er, it appears tha1 in tap wuer
`it v.ilJ stlJ'\in oo more du.ti a &:w days ((Fan-Xue et al., 1998) Balann·dium c--0/i is commonly fotmd in fre---.,,b swine
`feces, but i1 does oot appear W t it SW'\ives well in nwmre. It probably does do well in wa::er, bu: this bas never
`beeo examined in detail relati, -e to cyst viability . .Ascan.·s :uum is still commonly present in some small perc.emage
`of comme.rciall}' reued S\\iue, and the ew that are shed in the manure are highly resistant co most disinfection
`processes.
`
`Cattle have an may of pathogens tbst are 001 too much differe::u from those seeo in S\\iue (See "Tabte 3. ?v!ajor
`pathoge:ns in comm~rci:tl cattle m.anu.Tt tha1 pose a threa1 of human infection."). The.re b.:n:e bee:a sen ral
`waterbome omb:reaks of E. co!i 0 15 7:H? that most likely come from cattle m3:a.ure (See abo, -e aud M:MWR,. 1999).
`This same report also shows the possibility of Campyl-Obactc.r also causing wateibome iofec.tio::u in people. The
`cases of lep~ospirosis are the same as for pigs, :tltbougb it is possible that in some areas of the United States there is
`a much better chance of cattle waste getting to rec:re:uio?W waters dim swine was:e. Campylobacif1' also seems
`capable of SUJ'\i,ing smprisi:agly well in aooerobic digesters (Kearney e:i al., 1993). 0,ptosporidium parrum from
`cattle is considered a ID3jor source of potential infection to humans as e,,..ide.nced by the outbreak that occw:red in
`?,,filw:ull;.ee (M.ac.Kem.ie et al., 1994). h is CU.Tffiltly becoming: possible to perhaps recogni:u whicb infections are
`animal de.ri\-ed using n .. TLOus molecular typing methodologies (Ho1D3n e:i al., 1999). Cattle u e also considered to be
`a major source of potential hum.an infection with Giardia lambh·a, bo\\-e, -e.r, the fact W t giardiasis is oo:i life
`threatening and relativel}' easy to treat bas reduced concerns relative to this disease significantly.
`
`Do~ and cats produce a bioma.s.s of wa,,""te material that is proportiooa:e to that tmde by fumed domestic: aoilmls.
`The.re are uoWld 50 millioo dogs and 60 millioo cats in households in the United States. For the mos, pan, the
`parasites of these pe:rs b3\-e oot beeo co:1sidered of coocem rel:ui\-e co water and wastewa::er. Tbe dog roundworm,
`Toxoazra ctmis, bas lo::,.g bffo co::isidered a cause of cbildbood blindness, but in spite of tbe cases that occur e1cb
`ye31', the disease ce.uds to be focally located within the confines ofindi,idual backyard siruatio::u. Howet-e.r, me
`rec em outbrcl of coxoplasmosis in Vm:ouver, British Columbia,. Camda, bas emphasized that domestic :mmal
`waste may play a significant role in watershed coutaminatio::>. (Bov.ie et al., 1997). The habits oftbe---...e pe:zs,
`
`Exhibit 1045
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`Page 3 of 9
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`bown·er, make them m.ucb more difficult to coOJJ'ol or for their V.\tste to be treated tbsn the large oumber of funned
`animal; iD the Ullited States.
`
`Thus, in the manure of chic..kem, cattle, and pigs that are regularly funned iD the Ullited States, tbere are only a few
`pathogens tha1 b3,-e been identified as posing a tbre:u 10 people. Some ofdlese pattaogeos, such as E. co!i0 157:H7,
`pose a truly significant threat that is v:onby of concem and interveniion. ."J the same time, disease; suc.b u
`C1)J)tosporidiosis for wbicb th6e is oo treaanen: are also v:onby of significant in:en-ention due to the large amounts
`of morbidity they are capable of causing the populatioo. On the other band, ceru.in pathogens sucb as Giardia
`/.amb!ia ~y be considered more of a ouisauce than a sipific:u.t disease; of course, the ,iew would be diffemn if
`you were the iDdi,idual affected. Finally, certain of the pattaoge.ns, e.g., Salmonella, are more importun a; threats
`from coota~ted food items tlu.o from a waste co:urol pe.rspectn:e.
`
`C'u:rreod)\ nrious laws are being ~cted that deal witb f:u:ming and the regulatioo of the farming indusay. This bas
`led to requirements fur AFOs and will possibly lead to addirion:d requiremems for no::i--point source pathogen
`control. For tbe---~ t)pes of laws and regula!io::is to be meaningful it is critical that the most imponam pa tho gem be
`identified,. that their respectin roles in disea;e relarin to the cype of tra:asmissioo,. and the effects of diffemn
`disin!ectioo methods oo tbe.ir ,iability be det~'1lU.ll.@d.
`
`REFERENCES
`
`Bowie WR, King AS, Welker DH, lsaac•Ren:oo JL, Bell A, Eng SB, M.arion SA. 1997. Ou:bre:'l. of toxoplasmosis
`associa:ed \\itb municipal d.rinlting water. L:u.cet, 350, pp 173-177.
`
`Fan•Xue G, Chua A, Liu• Tia G, Zeng Qing S. 1998. SUJ'\i\·al of Hclic.obac;fr pylon· in milk and tap wa:er. Journal
`of Gastroenterology mi Hepatology, 13. pp 1096· 1098.
`
`Homan \V. \'UI God.om T, Kao \ 'Y, Hepeoer J. 1999. Clw::merization of Cr)ptospqridium pan.11111 iD btmW:1 and
`animal feces by single-rube nested pol)mmse ch:rio reaction and resuiction ao:tlysis. Parasitology Reseuc:h. 85. pp
`707-7 12.
`
`Jackson L~ Kaufma:a::i AF, Ad.ams WG, Pl:ae.lps ~fB, Ad:reasen C. Laogkop CW, Fr.mci.sBJ, Weoga JD. 1993.
`Ou,bre~ ofleptoSpitosis associated witb S\\immiog. Pedialric lofectiou; Disease Joum:tl., 12, pp48-54.
`
`Kea.'lley TE. Larltin MJ, Frost JP, Le, -en PN. 1993. SUJ'\inl ofpa,bogeoic bacteria during mesopbilic anaerobic
`digestion of :l!limal v.\tste. Joa"ll3l of Applied&cteriology, 75, pp2 15-2 19.
`
`Mac.Ke.nzie WR, Hoxie NJ, Proctor ME, Gradus MS, Blair K.~ Pete.rso::i D~ Kazmierczak 11, Addiss DG, Fox KR,
`Rose JB, Da,i.s JP. 1994. A m.1Ssi\-e outbrW in Milwaukee of Cryp;osporidium infection tra:asmitted through the
`public water supply. New Engl.and Joum.al of Medic:ioe, 33 1, pp. 161· 167.
`
`Morbidity and Mortality Weekly Report. 1998. Update: leptospirosis and une.-q,l:rined acute febrile ilhless among
`athletes psnicipatiog in triathlons - IDiDois and Wisconsin. 1998. ~O.!WR 4 7(32), pp 673-676. CDC, Atlanta, GA.
`
`Morbidity and Mortality Weekly Report. 1999. Public W ltb dispatch: Outbreak of Estk~nChia c.oli 0 157:H7 and
`Campyk>bactc.ramoog attendee; oftbe Wasbm@:oo Couory Fair - New Yo!k, 1999. ?-,0.!WR 48(36); 803. CDC,
`Ad:uita, GA.
`
`USDA 's Nation.al Agrirulrural Statistics S~T\ic e (NASS); http://wv,-w .ll3Ss. usda.g0\"/ce.nsus.fce.nsus97/adas97/(cid:173)
`sw:nma.'"}' l.htm.
`
`USEP.~ Region 2. 1997. EPA issues in: erim filtration a\"Oidaoce de::ennimrion to NYC for its Catskill•Delaware
`water system_ blfP://v,·ww.ep3.gO\·hegioo2/epd/97043.btm
`
`Exhibit 1045
`Bazooka v. Nuhn - IPR2024-00098
`Page 4 of 9
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`Table l. M.ajor pathogens in commercial chic.ken m.1.llure tb:tt pose a threat of human inf@ctio:1.
`
`E tchtrichia CVJli
`Site of infection in pN>ple
`
`Transmission
`
`Hu.man dis.ease
`Major resen •oirs
`Site of infection in chid tens
`Suni n l in e.n,ironmeat
`
`Chic.ken manure bas net-a bee.n implicated in atl)' human infections \\ith mis
`pathoge
`lnf@ctio11S in people ban t)'pically occurred through con.:unin.ated food, but
`inf@ctio::i could be mnsfe.ned ,ia contuniu.ated water
`Enteritis
`£. c--0li is fairly omnipresen: in the intestinal mtm of a:aimals
`Snw.l intestine
`Sunfres we.U in the envirownttlt
`
`Transmission
`
`Hu.man dis.ease
`Major resen •oirs
`
`Sollflonr/Jo 1yphhnuriJlm and Sabnontlla enmiddi.t
`Site of infection in pN>ple
`Snw.l intestine. The chicken specific seronr of Salmon"l la, S. pullonun, bas
`not been found to produce di;ea;e in people
`lnf@ctio11S in people ban t)'pically been ,ia uncooked or pmially cooked
`foods ~ t have sm:ed as growth media for the baaeria. It bas been
`U"allSlllltted in contuuinated wa:a . 1n the ca;e of Salmon"!la tmifriridi:,
`there is mnsot'3.rial tratm:nis-sion, so it is possible for eggs to be infeaed
`when ptU'C.h3sed.
`Dy!.entery
`Salmonella pullorum is found m.ainl}' in chicke11S, but c.hicke.ns and many
`other bosu can serve as tbe resm:oirs for tbe many sero,:us of
`Sahnom>lla
`Snw.l intestine
`Can survit·e ·wffk-s to months in m.ana-re or manure slurries
`
`Site of infection in chickens
`Suni n l in e.n,ironmeat
`
`Hu.man dis.ease
`Major resen •oirs
`Site of infection in chickens
`Suni n l in e.n,ironmeat
`
`Conjuncri\·a and respiratory uaci
`T)pk all}' by direa contact witb oocysts in chicken feces or by breathing au,,--.
`containmg oocysts
`T)pk ally ocular int"Oh'e..men:i oni}'
`Chicke11S mi otbe.r birds
`In:e-sti?w mto: :wt respiratory epithelium
`Oocysts probably SW'\'lt-e re-latit -e..l}' we-lJ in tbe environment in a fa.sbion
`-simil.ar to tbose of en, tos
`ridium on·wn
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`Exhibit 1045
`Bazooka v. Nuhn - IPR2024-00098
`Page 5 of 9
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`Table 2. M.ajor patbogeos in commercial swine m.1.llure that pose a threat ofhwuat:1 infection.
`
`Etchtrichia CVJli
`Site of infection in pN>ple
`Transmission
`
`Hu.man dis.ease
`Major resen •oirs
`Site of infection in pigs
`Sonin l in f'.D\ironmeot
`
`ln:esti?w O'aCt
`lnf@ctions in people are usutlly O'atlSlllltted ,ia comamin.3::ed food. but
`infectio::i could be mnsfe.ned ,ia contunul.3::ed water
`Enteritis
`Widespread in animals
`Snw.l Ultestine
`The mnn survl\,ai of£. coU in mesophllic 3ll.3erobic dige,,---iers is ru'OWld 3
`mon:hs.
`
`Sollflone/Jo e.Ju,le.ro.ruis and Salmontlla muriridis
`Site of infection in pN>ple
`Snw.l UltesriDe, leading to sustained baaeremias and meta.static spread
`.~st al-ways due to UDCooked or pania.lly cooked foods th.31 b.3,-e been
`Transmission
`contaminated in processing, also oo occasion ,ia coot:Unlll3ted water.
`Due to improvements in tile tn3J13ge.ment of tbe poll indusuy, m.any few
`cases caused by porcine sero\'3.f'S in recent years.
`Salmonella eliolVJ'Osuis h.as the ability to colo:::aize exmintesrinal sites a:od
`establish persis::ent infecrio::is in people tha: are related to susta.in.ed
`t»:o:eremias and se,we disease.
`Pigs (Sahnonc!la cho!c.msui:)
`ln:e-stinal mtct, and cause eteriris
`Cm sUJ'\'lve "'-eeks to months in m:uwre or aw:uue slurries
`
`Major resen •oirs
`Site of infection in pigs
`Sonin l in H \ironmeat
`
`Lep,orpira polflona (11.so Ltptorpira eanieolo, Ltptotpira zrippotJphosa, Leptospira kttrohoe1r1orrhogioe) and
`Le to
`ira bro.iit14l'O
`Site of infection in pN>ple
`Transmission
`
`Hu.man dis.ease
`
`Major r esen •oirs
`
`Site of infection in pigs
`Soni n l in f'.D\irODmtOt
`
`Htlieobartor pylori
`Site of infection in pN>ple
`Transmission
`
`Hu.man dis.ease
`Major r esen •oirs
`Site of infection in pigs
`Sonin l in H \ironmeat
`
`83:cteremia \\ith spread to tbe cerebrospiml fluid
`Usually ,ia tbe ingw.io::i of water contaminated \\ith the u."lll.e of a:aimals;
`ombruks ban beeo associautd f)pk all)• \\i th recreatiolllll expos.ure of
`people to wa::er recei\:ing b.nuland dr::rinage in sumnw- months.
`An influeuza-like febrile illness (fent, chills, held.ache, mtl$Cle pain)
`followed la:a by me.ningitis. May :t.lso have a bemonbagk ras.b. 1n
`seveM cases ge,; e.x::ensive n sculitis, jaUDdice, aud re~ dalmge.
`Pigs serve a.s reservoirs, some 2% (O 4% of pigs are se.roposiffl:e; pig_s
`e.liminat e orp.nis.ms in urine o,-e1 a long period of time
`Kidneys
`Most Jeptospir:te are saprophytic aquatic org:uiis:ms, so tbey sw-,.,ive wen in
`contaminated waters wbe.n the pH is bern-een 7 to JO. These organisms
`.e.n m ision
`nfer sn ~robic eavironmew with reduced o
`
`Stomxb mucosa
`Belie-, -ed dut mnsmissioo is by direct fecal~r:tl or oral-oral co::i.act,. bu:
`waterborne transmission h.as not bee excluded
`UJceration of the gaslric mucosa
`Pigs, also apparently common in cats
`s~omxb
`Sun in tor days to "'-eeks in \\-a,a , may su.T\fre longer in m:1!1UTe
`
`Exhibit 1045
`Bazooka v. Nuhn - IPR2024-00098
`Page 6 of 9
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`Bolo.nlidi1'1t1 e.qli
`Site of infection in pe-ople
`Transmission
`
`Hu.man dis.ease
`Major n sen•oirs
`Site of infection in pigs
`Suninl in e.n,ironmeat
`
`A.team su,un
`Site of infection in pe-ople
`
`Transmission
`
`Hu.man dis.ease
`Major n sen•oirs
`
`Site of infection in pigs
`Suninl in e.n,ironmeat
`
`C«um and coloo
`Probably most cypically by direct fecal-oral co:1.act; tbeoretic:t.lly, it could be
`a " -a::erborue disease
`Dy!.entery with some mucosal dul!age
`Pigs, guinea pigs, people
`C«um and coloo
`Probabl · does 'i\o'tll in water
`
`orlv in manure or seu':le:e
`
`L.m·ae of this oetmtode migrate through the liver :ind lungs; the worms
`seldom de\·elop to tile 3dult stage in people
`lngestioo of eggs oo food items contamin3,ed \\i tb rn'Ule !ll3llure or soil th31
`bas rece1':ed S\\ine waste. Tbe eggs t3ke set·er:tl weeks to become
`infectious after lea\ing the swine bost. Tbe eggs are relam:ely bea\'Y, so
`waterborne tra:asmissioo is Wlmu.al
`Could came allergic pn.ewuo::iitis
`Pigs. People ban tbeir own species, Ascaris lwnbricoides, that is m :asmitted
`in hwmn waste. Tbe eggs of the ,wo species are Uldistingui;h3:ble
`morpbologically
`Snw.l intestine, following a liver mi hu..g migration of l:tn·ae
`The eggs are \ 'tlj' resistant ,o enviroomental e.o:a-emes, .uid for this re:lSOll, are
`used as an indicator of treatment effecti,uess
`
`Exhibit 1045
`Bazooka v. Nuhn - IPR2024-00098
`Page 7 of 9
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`Table 3. M.ajor patbogeos in commercial cattle manure tb3t pose a threat of hUDW:1 infection.
`
`Etchtrichia CVJli 0 157:H?
`Site of infection in pN>ple
`Transmission
`
`Hu.man dis.ease
`Major resen •oirs
`
`Site of infection in u.ttle
`Suninl in H \ironmeat
`
`Cecum and colon (also Hewn)
`Most often in contaminated uncooked foods or raw vegetable;, also
`sometimes via COIU3~ted wa:e.r
`Dimbea tb:u ID3Y progress to bemorrb:tgic colitis and dysentery
`Cah:e; \\-itb dianbH; adult c:mJe may be infected but sbow no signs. Found
`io. about 5% of cattle fecal sample;.
`fn:e-sti?w O'aCt
`Sunfre; well for \\-eeks (O months in contamina: ed water., soil., and manure
`
`VariousSobr1onr/Ja sttova.rs, Sabr1onr/Ja 1yphiltu,rimn aad Salmontlla dublin
`Site of infection in pN>ple
`Snw.l intestine
`Most often in uncooked or pani:tlly cooked foods th.31 b:lt-e sen-ed as growth
`Transmission
`media for tbe bacteria, also t'la coo.tamiluted wa:a
`Dysentery to eo.:eric fet·a
`can!,
`Snw.l intestine
`Cao. sun'l\·e weeks to months io. m.anas-e or manure slurries
`
`Hu.man dis.ease
`Major r esen•oirs
`Site of infection in u.ttle
`Sunin l in H\ironmeat
`
`Hu.man dis.ease
`
`Ltprorpiro Pomona, LtplO$J)irO luudjo, Lrptorpira icttroharmorrllagiae
`Site of infection in pN>ple
`& cteremia \\ith spread to tbe cerebrospiml fluid
`Transmission
`Usu:tlly ,ia tbe io.ge-srio::i of water contaminated \\ith tbe wine of animals;
`ombruks ban been assoc:La.ed f)pk all}' \\i th recreatiolllll expos.ure of
`people to water recei\ing f:.muland dr::rinage iD sumnw- moo.tbs.
`An illflueuz.iAike febrile illness (fent, chills, Wdacbe, mw.cle pain)
`followed la:a by meningitis. May also b:lve a bemorrll3gk rash. lo.
`seveM cases ge,; e.xtensive n sculitis, jaUDdice, and re~ damage.
`Cattle (3% to 11% are saopositive, be.lien 2% to 4% activel}' infected); also
`many ottaer ID3~ e.g., rm and dogs
`Kidneys
`Most Jeptospir:te are saprophytic aqw.tic organisms, so tbey sw-,.,ive wen in
`contaminated waters wbe.n me pH is be.-v.-een 7 to JO. These organism;
`refer ru:i aerobic eaviroum.eo.: with reduced o
`.e.n tension
`
`Major r esen•oirs
`
`Site of iafe-ction in u.ttle
`Sunin l in H\ironmeat
`
`·
`Como •lobocttr · ·
`Site of infection m pN> e
`Transmission
`Hu.man dis.ease
`
`Major r esen•oirs
`
`Site of infe-ction in u.ttle
`Sunin l in H\ironmeat
`
`fn:e-sti?w O'aCt
`Oo. a few occasions assoc:i.ated with contunin.ated wa::er or unpas::eurized milk
`Dimbea to dyseo.::ery, usually self4 liming in 3 to 5 days. Campylobaaw /Mi :
`causes a we fonn of sepsis iD people - usually infected after colU3ct with
`aborting cows.
`Cattle, bo\\-et-er, C.Ompylobacifr Jfjunibas a wide bost r:mge that includes
`do~ people, cats, and birds
`fn:e-sti?w O'aCt
`SW'\ives rather pootl}' in the e:iviroo.mew, cypiall}' die in bours to day.
`Lit-es a lo:ag time in mesophilic 31:l:lerobic digestm with ioactivarioo.
`n tes tbat
`est c able of li,'lD .. a1 least one
`
`Exhibit 1045
`Bazooka v. Nuhn - IPR2024-00098
`Page 8 of 9
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`Oyptosporidnlm pan'"U.,,1
`Site of infection in pe-ople
`Transmission
`Human dis.ease
`Major resen•oirs
`Site of infection in cattle
`Sonin l ill e.D\iroameot
`
`Cio.rdio. IAmblio
`Site of infection in pe-ople
`Transmission
`Human dis.ease
`Major resen•oirs
`Site of infection in cattle
`Sonin l ill e.a\iroameot
`
`Snw.l intesrillal mucosa
`Oocysts in wa:er, direct fecal-or:tl contm:
`Dimbea
`People, cattle, other m:uwmls
`Snw.l intestinal mucosa
`Oocysts sw-,..ive weeks to months in ·wuer, soil, or manure depending oo the
`eoviromuenul conditioos
`
`Snw.l intestinal mucosa
`C)'StS in v:a::er, direct !ecal--oral contact
`Dimbea
`People, cattle, other m:uwmls
`Snw.l intestinal mucosa
`,m sw,.i,-e \\-ell in cokl cleao l\"-:lte.r: sUJ'\'l\·e
`
`rl 1 in matU11e or soil
`
`Exhibit 1045
`Bazooka v. Nuhn - IPR2024-00098
`Page 9 of 9
`
`