Sintidsbehandling

Mastit, juverinflammation, hos mjölkkor är en multifaktoriell sjukdom. För det mesta orsakas den av bakterier. Vissa mastiter kan vara juverbundna och smittar mellan kor via t.ex. mjölkningsutrustning, andra är miljöbundna och smittar kon från dess närmiljö. Mastit är den vanligaste orsaken till utslagning inom mjölkproduktion Den kan delas upp i klinisk mastit, med synliga symptom, och subklinisk mastit, utan synliga symtom. Akuta kliniska mastiter brukar allmänbehandlas med antibiotika under pågående laktation. För subkliniska mastiter finns olika strategier, bland annat beroende på vilken bakterie som orsakat mastiten. Eftersom majoriteten av bakterierna som orsakar subklinisk mastit är penicillinkänsliga rekommenderas idag att behandla kon lokalt i alla fyra juverdelarna med långtidsverkande penicillinbaserat preparat i samband med sinläggning. I andra länder är det vanligt att kor sinläggs rutinmässigt med antibiotika, även bredspektrumantibiotika kan vara ett alternativ då. Syftet med uppsatsen var att göra en litteraturstudie för att undersöka bakgrunden till dagens rekommendationer från Sveriges Veterinärmedicinska Sällskap (SVS) om antibiotikabehandling vid sinläggning med huvudfokus på urvalet av kor som erbjuds sintidsbehandling. Idag rekommenderas att kor med subklinisk mastit ska behandlas i samband med sinläggning. Urvalet av kor som får antibiotikabehandling är selektivt, det vill säga kor med god prognos ska behandlas. Kor i juverhälsoklass, JHKL, 3-4 ska få behandling efter positiv bakterieodling, kor med JHKL 5-8 skall alltid behandlas och kor i JHKL 9 ska inte behandlas p.g.a. dålig prognos. På den svenska marknaden erbjuds enbart långtidsverkande bensylpenicillinbaserat antibiotikum, som administreras lokalt i alla juverdelar. Om patogenen inte skulle svara på penicillin, är rekommendationen att inte behandla alls, sådana kor ska helst gallras ut. I min slutsats har jag kommit fram till att dagens rekommendationer, med selektiv antibiotikabehandling vid sinläggning, fortfarande är ytterst adekvata och grundade på relevanta studier. Att behandla vid sintiden är bra då det går åt en mindre mängd antibiotika jämfört med att behandla under laktation och att behandla alla juverdelar är bra, då dessa är beroende av varandra och smitta mellan dem skulle kunna ske. Sverige anammar ett restriktivt antibiotikaföreskrivande vid sinläggning som rimmar väl med svensk lag och bidrar till att minska antibiotikaresistensen. Jag har inte hittat några stöd för att rutinmässig sintidsbehandling med bredspektrumantibiotika skulle ha några fördelar. Tvärtom, finns ett behov av ännu smalare sintidspreparat än de som finns i Sverige idag, eftersom det preparat som erbjuds idag innehåller även aminoglykosider. Rekommendationerna skulle kunna skärpas ännu mer genom att man även skulle begära att ta bakterieodling på kor i juverhälsoklasser 58, så att ingen av dessa bär på en resistent bakterie och därmed får penicillin. På så vis skulle antibiotikaförbrukningen kunna minskas ytterligare.Mastitis within dairy cows is a multifactorial disease, often caused by bacteria. Some bacteria could be udder borne and contagious, from cow to cow, via milking equipment, for instance. Other bacteria are environmental borne and infect the cow from its environment. Mastitis is the most common disease that eliminate dairy cows. The disease can be divided into clinical mastitis, with visible symptoms, and subclinical mastitis, without visible symptoms. Acute clinical mastitis is treated with antibiotics during lactation, whereas there are different strategies to cope with subclinical mastitis. It depends on what bacteria causes the mastitis. Because the majority of the bacteria causing subclinical mastitis are sensitive to penicillin, the recommendation today is to treat the cow locally in all four quarters of the udder with long term effect penicillin at dry off. In other countries blanked dry cow treatment with broad spectrum antibiotics is administrated. The aim of this literature study was to investigate the rational behind the Swedish recommendations on dry cow treatment with main focus on the selection of cows that are to be given dry cow therapy. Today the recommendation is to treat cows with subclinical mastitis at dry off. The selection of cow to treat with antibiotics is selective. That is, only cows with a good prognosis should be treated, cows with an udder health class (Swedish classification, mainly based on somatic cell count) 3-5 should be treated after positive bacteria cultivation, cows in udder health class 5-8 should always receive treatment and those in class 9 should not, as the prognosis isn’t good. In the Swedish market only bensylpenicillin based antibiotics with long term effect, administrated in all quarters, is offered. If the pathogen isn’t sensitive to penicillin, the recommendation is not to treat her, but to cull the cow. The conclusion is that the recommendations regarding selective dry cow treatment still are adequate and based on facts and studies. To treat cow during dry period is good as little antibiotics is used compared to treat cows during lactation, also treat all four quarters is important as they are dependent and could infect each other. In Sweden antibiotics are prescribed prudently when it comes to dry off cows. This is in accordance to Swedish law and contributes to maintain a stable development in antibiotic resistance. In this study I have not found any support for blanket dry cow treatment with broad spectrum antibiotics. On the contrary, there is a need for an even narrower antibiotic to dry off cows in Sweden as the antibiotics used today also contains aminoglycosides. The recommendation could be even more prudent when it comes to prescribe antibiotics at drying off, by also demand that cows in udder health class 5-8 also were tested for bacteria, so that cows carrying resistant bacteria weren’t given penicillin. In this way the use of antibiotics could be even more reduced

Immunitet mot bovint respiratoriskt syncytialt virus efter naturlig infektion

Bovint respiratoriskt syncytialt virus (BRSV) kan orsaka allvarlig luftvägssjukdom hos nötkreatur och är vanligt förekommande i svenska nötkreatursbesättningar. Sjukdomsförloppet kan vara subkliniskt, ge milda symptom eller orsaka svår sjukdom med dödlig utgång. En genomgången naturlig infektion verkar skydda mot allvarlig sjukdom, men exakt hur länge en individ är skyddad och vilken typ av immunitet som ger skydd har forskare ännu inte kartlagt fullständigt. Det är dessutom oklart i vilken utsträckning nötkreatur återinfekteras och om dessa utgör symptomlösa smittbärare med en viktig roll i virusets epidemiologi. Syftet med detta examensarbete var att kartlägga antikroppssvar efter naturlig infektion med BRSV, samt att fastställa exempel på efter hur lång tid och vid vilken antikroppstiter nötkreatur kan bli återinfekterade med BRSV. Examensarbetet fokuserade på att beskriva kinetiken av BRSVspecifika IgG1-antikroppstitrar i serum hos nötkreatur under 2–4 år efter naturlig infektion. Därtill jämfördes titrar av BRSV-specifika IgG1-antikroppar med virusneutraliserande (VN) antikroppar i serum samt BRSV-specifika IgG1-antikroppstitrar i mjölk och serum på individnivå. Återinfektioner beskrevs i en besättning och individuella BRSV-specifika serum IgG1-antikroppstitrar vid återinfektion av enstaka djur fastställdes. Resultaten indikerade att nötkreatur har serumantikroppar, både BRSV-specifika IgG1 och VNantikroppar, i minst fyra år efter naturlig infektion av BRSV. En relativt god korrelation mellan IgG1 och VN-antikroppar fastställdes. Antikropparna verkar bidra till skydd mot allvarlig sjukdom, men inte mot infektion och virusutsöndring. Ett visst immunologiskt minne verkar kvarstå i minst fyra år, då antikroppstitrarna, såväl IgG1 som VN-antikroppar, blev högre vid återinfektion av BRSV än vid primärinfektion. Vid primärinfektion var den individuella variationen av antikroppstitrar stor, men mängden antikroppar verkade inte ha betydelse för antikroppssvarets duration, då samtliga analyserade prover innehöll antikroppar (IgG1) fyra år efter infektion. Mjölkproverna som analyserades visade exempel på att det även gick att påvisa IgG1 i outspädd mjölk i minst fyra år efter en primärinfektion, men mängden IgG1 kunde inte kvantifieras och således gick det inte visa på någon korrelation mellan IgG1 i serum och mjölk. Kunskapen kan bidra till förståelse om infektionsdynamiken i stora populationer, t.ex. när besättningsimmuniteteten avtar efter ett utbrott, vilket kan påverka framtida vaccinationsstrategier. Sammantaget kan dessa data indikera immunitetens duration och användbarheten för ELISA samt analys av serum och mjölk för att förutspå skydd på individnivå.Bovine Respiratory Syncytial Virus (BRSV) can cause severe airway disease in cattle and is very common in Swedish cattle farms. The disease can be subclinical, mild or severe with lethal outcome. Natural disease seems to protect from severe clinical signs upon reinfection. Exactly for how long an individual is protected and what type of immunity is protective is not completely understood. It is also unclear to which extent animals become re-infected and if these are asymptomatic carriers, with an important role in virus epidemiology. The purpose of this thesis was to quantify and map IgG antibody responses after a natural infection with BRSV and give examples of after how long time and at which antibody titre cattle can be reinfected with BRSV. This thesis focused on describing the kinetics of BRSV-specific serum IgG1- antibody titres in cattle during 2-4 years after a natural infection. In addition, titres of BRSV-specific IgG1 antibodies and virus neutralising antibodies (VN-antibodies) in serum were compared. Finally, BRSV-specific IgG1 antibodies in milk and serum were compared at the individual level. Reinfections in a herd and individual BRSV-specific serum IgG1 antibodies before and after reinfection of a few animals was also described. The results showed that cattle have serum antibodies, both IgG1 and VN-antibodies, at least four years after natural infection with BRSV and that the titres of these antibodies covary fairly well. These antibodies seem to have contributed to protection against severe disease but did not protect from being infected and neither from shedding virus. A certain level of specific immunological memory seems to have persisted, as the antibody titres of both IgG1 and VN-antibodies increased more after re-infection with BRSV compared to after primary infection. After a primary infection the magnitude of antibody responses varied greatly between different animals, but the level of antibodies seems to be of less significance for the duration of responses, as all samples analyzed were positive for antibodies (IgG1) four years after primary infection. In this work, some examples have been given, that it is possible to use ELISA to detect IgG1 in undiluted milk at least four years after a primary infection, but it was not possible to quantify the IgG1 by sample dilution. Hence, no covariation of IgG1 in serum and milk could be demonstrated. The knowledge will contribute to the understanding about infection dynamics in large cattle populations, for example when herd immunity declines after an outbreak, which may influence future vaccination strategies. Altogether these data indicate the duration of humoral immunity and the utility of ELISA and milk analysis to predict protection against BRSV on an individual level

Longitudinal study of the immune response and memory following natural bovine respiratory syncytial virus infections in cattle of different age

Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, a multitude of BRSV vaccines are used to reduce clinical signs. To enable the design of vaccination protocols to entirely stop virus circulation, we aimed to investigate the duration, character and efficacy of the immune responses induced by natural infections. The systemic humoral immunity was monitored every two months during two years in 33 dairy cattle in different age cohorts following a natural BRSV outbreak, and again in selected individuals before and after a second outbreak, four years later. Local humoral and systemic cellular responses were also monitored, although less extensively. Based on clinical observations and economic losses linked to decreased milk production, the outbreaks were classified as moderate. Following the first outbreak, most but not all animals developed neutralising antibody responses, BRSV-specific IgG1, IgG2 and HRSV F- and HRSV N-reactive responses that lasted at least two years, and in some cases at least four years. In contrast, no systemic T cell responses were detected and only weak IgA responses were detected in some animals. Seronegative sentinels remained negative, inferring that no new infections occurred between the outbreaks. During the second outbreak, reinfections with clinical signs and virus shedding occurred, but the signs were milder, and the virus shedding was significantly lower than in naïve animals. Whereas the primary infection induced similar antibody titres against the prefusion and the post fusion form of the BRSV F protein, memory responses were significantly stronger against prefusion F. In conclusion, even if natural infections induce a long-lasting immunity, it would probably be necessary to boost memory responses between outbreaks, to stop the circulation of the virus and limit the potential role of previously infected adult cattle in the chain of BRSV transmission

Longitudinal study of the immune response and memory following natural bovine respiratory syncytial virus infections in cattle of different age

International audienceHuman and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, a multitude of BRSV vaccines are used to reduce clinical signs. To enable the design of vaccination protocols to entirely stop virus circulation, we aimed to investigate the duration, character and efficacy of the immune responses induced by natural infections. The systemic humoral immunity was monitored every two months during two years in 33 dairy cattle in different age cohorts following a natural BRSV outbreak, and again in selected individuals before and after a second outbreak, four years later. Local humoral and systemic cellular responses were also monitored, although less extensively. Based on clinical observations and economic losses linked to decreased milk production, the outbreaks were classified as moderate. Following the first outbreak, most but not all animals developed neutralising antibody responses, BRSV-specific IgG1, IgG2 and HRSV F- and HRSV N-reactive responses that lasted at least two years, and in some cases at least four years. In contrast, no systemic T cell responses were detected and only weak IgA responses were detected in some animals. Seronegative sentinels remained negative, inferring that no new infections occurred between the outbreaks. During the second outbreak, reinfections with clinical signs and virus shedding occurred, but the signs were milder, and the virus shedding was significantly lower than in naïve animals. Whereas the primary infection induced similar antibody titres against the prefusion and the post fusion form of the BRSV F protein, memory responses were significantly stronger against prefusion F. In conclusion, even if natural infections induce a long-lasting immunity, it would probably be necessary to boost memory responses between outbreaks, to stop the circulation of the virus and limit the potential role of previously infected adult cattle in the chain of BRSV transmission

Kinetics of BRSV-neutralising serum antibody titres in cattle of different age and production status.

Cattle were (A) 23–30 months old (6.5 months gestation), (C) 7–11 months old, (D) 4–5 months old, (E) 2–3 months old, not analysed (N.A), or (F) born during or just after a BRSV outbreak in January 2016 (month 0). Limit of detection in the virus neturalising assay: titre 20.</p

Kinetics of HRSV-F-reactive serum antibodies in cattle of different age and production status.

At the time of a BRSV outbreak the cattle were (A) 23–30 months old (6.5 months gestation), (C) 7–11 months old, (D) 4–5 months old, (E) 2–3 months old, or (F) born during or just after the outbreak in January 2016 (month 0). Data are presented as competition percentage. The limit of detection is presented as a dotted line.</p

Kinetics of BRSV-specific total IgG1 in milk from cattle of different age and production status.

At the time of a BRSV outbreak (in January 2016, month 0) the cattle were (A) 23–30 months old (6.5 months gestation), or (C) 7–11 months old. Corrected optical density (COD) values are presented as percentage of a positive control serum. Broken lines represent dry periods and red circles are timepoints for calving.</p

Kinetics of BRSV-specific serum IgG1 in cattle of different age and production status.

At the time of a BRSV outbreak the cattle were (A) 23–30 months old (6.5 months gestation), (C) 7–11 months old, (D) 4–5 months old, (E) 2–3 months old, or (F) born during or just after the outbreak in January 2016 (month 0). Corrected optical density (COD) values are presented as percentage of a positive control serum.</p

Least Square Means of milk production, roughage and non-roughage intake of 272, 163 and 272 cows, respectively, that remained in production for commercialisation, before, during and after a BRSV outbreak in 2016.

(DOCX)</p

Kinetics of HRSV N-specific serum IgG1 antibodies in cattle of different age and production status.

At the time of a BRSV outbreak the cattle were (A) 23–30 months old (6.5 months gestation), (C) 7–11 months old, (D) 4–5 months old, (E) 2–3 months old, or (F) born during or just after the outbreak in January 2016 (month 0). For each serum sample, the optical density (OD) against a control antigen was subtracted from the OD value against the N protein (Corrected OD, COD) and the COD was transformed into a sample-to-positive value (SP) by using the formula SP = CODsample/(CODpos—CODneg).</p