Med. Weter. 2013, 69 (9) 568
Opis przypadku Case report
Side effects of drugs are reported in veterinary
medicine. In Switzerland, where system for the
moni-toring of side effects in animals had been introduced,
only 134 notifications were registered in 2009. Most
frequently, that is in 30% of cases, side effects were
caused by antihelminthic preparations, more seldom
by anti-infectious and hormonal drugs in 19% and
13% of cases, respectively. Side effects of vaccination
are reported even more seldom. Most of the reports
concern the most popular vaccine against the blue
tongue disease. Alarming symptoms have been noted
in one out of 1393 vaccinations. Other vaccines reported
to induce side effects are antifungal and circovirus
vaccines in swine, but these reports have been
extre-mely rare (10). In a mild form, oedema, abscesses, or
lymphadenoma occur most commonly at the injection
site. More seldom are general signs, including nervous
system disturbances, such as encephalopathy,
ence-phalitis, meningitis, or polimielitis. Sporadically, side
effects include septicaemia, thrombocytopenia or
pancytopenia, abortions, and arthropathy, or, in extreme
cases, anaphylactic shock or death (3-5, 7, 9, 10).
In the present article three cases of adverse effects in
cattle are presented, following the administration of
vaccines against 1) IBR/IPV and BVD/MD, 2) BRSV
and PI3 and/or 3) Carofertin injections.
Case reports
Case 1. Herd of 150 Polish Friesian cows were vaccinated intramuscularly with a deletion vaccine against IBR/IPV (Bovilis-IBR, Intervet-Schering) containing an inactivated antigen BHV-1 (gE) strain GK/D (60 units in 1 ml) and with an inactivated vaccine against BVD-MD (Bovilis BVD/Bovilis, Intervet Shering) containing an inactivated antigen of cytophatic strain C-86. Within one to four hours after vaccination, 12 (8%) cows developed conjunctival hyperaemia, as well as oedema of the eyes, neck, and dewlap. Urticaria was observed on the skin of the head and neck. In four cows, severe oedema affected the entire head giving it a hippopotamus-like appearance. The animals were
Sides effects of vaccination and Carofertin injections
in cattle: Case reports
JÊDRZEJ M. JAKOWSKI, W£ODZIMIERZ GRZELAK*, JACEK ZIÊTARA**, JAN W£ODAREK
Institute of Veterinary Medicine, Faculty of Animal Breeding and Biology, Poznañ University of Life Sciences, Wo³yñska 35, 60-637 Poznañ, Poland
*Clinic for Animals, Kardyna³a Wyszyñskiego 23, 88-220 Osiêciny **Veterinary Clinic Centrum s.c., Witosa 29, 89-240 Kcynia
Jakowski J. M., Grzelak W., Ziêtara J., W³odarek J.
Sides effects of vaccination and Carofertin injections in cattle: Case reports
SummaryThe paper presents three cases of side effects of the following veterinary drugs in cattle: 1) inactivated vaccines against IBR/IPV and BVD/MD, 2) a live vaccine against BRSV and/or 3) â-carotene in Carofertin. In the first case, as an effect of a simultaneous intramuscular vaccination of 150 cows with inactivated vaccines against IBR/IPV and BVD/MD, classical allergy sings with urticaria, strong oedema at the injection site and head swelling occurred in 12 (8%) animals. Shortly after anti-inflammatory treatment, all sings disappeared. In the second case, an intranasal inoculation of newly purchased calves with a vaccine against BRSV caused a severe immune depression manifesting itself in a sudden strong diarrhea and death of 18 out of 20 calves (90%) within a few days after vaccination. This may have resulted from the fact that the animals had been vaccinated shortly after transportation, during the adaptation time. In the third case, an intramuscular administration of Carofertin to one cow caused hypersensitivity in the form of urticaria, the swelling of the eyelids and the udder, as well as vulval oedema of the vulvae. Treatment was successful, and all alarming signs subsided. Possible reasons for these rapid reactions are widely discussed.
Keywords: side effects, vaccination against IBR/BVD, vaccination against BRSV and PI3, Carofertin application, cattle
Med. Weter. 2013, 69 (9) 569 treated symptomatically with Dependin Veyx (Veyx) 50 ml
in 10 ml doses, containing 7.5 mg prednisolone and 2.5 mg dexametazone in 1 ml, as well as with Calciphos (Biowet Drwalew) 250 ml in intravascular infusion. There was a total remission of signs within 2-9 days. It is worth adding that this was the seventh vaccination against IBR/IPV and BVD/MD in the herd. Each vaccination was repeated at intervals of 5.5-6 months. This vaccination was conducted at the end of August 2001 on a hot day at about eleven a.m. Each cow received 2 ml of each vaccine in the neck muscles (on both sides of the neck).Vaccines were injected with disposable syringes and needles.
Case 2. The application of a vaccine against BRSV and PI3V caused a rapid reaction in newly purchased calves, manifesting itself in sudden, severe diarrhoea and high mortality within several days after vaccination. Twenty calves were bought in late September 2012 from a large--scale trader in animals. The buyer personally selected calves from a bigger group of animals purchased by the trader in domestic farms. At the time of being delivered to the buyers farm, at the beginning of October 2012, the calves were 5-8 weeks old, and their body mass was 80-120 kg. Their general condition was very good. They were placed in a separate, light and dry pen on straw. All received milk, good quality hay, and water. Upon arrival, the calves were given Rispoval IntraNasal Rs+Pi3 (Pfizer), containing a live modified syncytial respiratory virus, strain 375, and a live bovine parainfluenza virus (PI3), strain RLB103. Additionally, they received a s.c. genthamycin injection (Zactran® (Merial) at a dose of 6 mg/kg b.w. The
first alarming clinical signs in the form of watery diarrhoea appeared in three calves within 5 days after the purchase. All the calves were taken off powdered milk and given Diakur Plus (Boehringer Ingelheim Vetmedica GmbH). The sick calves were additionally administered Potencil®
(Virbac Animal Health) at a dose of 1 ml/10 kg body weight, Buscopan compositum (Boehringer IngelheimVetmedica GmbH) at a dose of 1ml/10kg body weight, and per os Biomox 100 (Vetoquinol) at a dose of 6 g twice a day. All the calves received an i.m. injection of Vit. E 50 + Se pro inj. 100 ml (Novartis) at a dose of 2 ml/10 kg body weight. After two days, signs from the respiratory system occured: faster wheezing breath, mucopurulent discharge from the nose, lacrimation and abundant salivation. In spite of the therapy, the animals almost completely lost appetite, they did not drink, and their internal temperature rose to 40.5--41°C. The first two calves died 7 days after the purchase, and they were the animals that had not shown any alarming signs of disease on the previous day. The autopsy revealed no significant changes. The remaining animals were given intra muscular Oxytet XLA (ScanVet) at a dose of 1 ml/10 kg b.w., Metacam 20 mg (Boehringer IngelheimVetmedica GmbH) at a dose of 2.5 ml/100 kg b.w., DOXYMED 50 (Dopharma) at a dose of 2 g/100 kg b.w. twice a day, Vita-mine C 10% inj. (Biowet Pulawy) at a dose of 1 ml/10 kg b.w., and Prolyt Pack (Biochem). The calves were hydra-ted intravenously or intraperitoneally and watered with an abomasal tube. This treatment did not have any effect after 11 days another eight calves died. The autopsy
revealed oedema and hyperaemia of the lungs, as well as small amounts of serum liquid in the pleura cavity. The surviving animals were administered intravenously PA-180 at a dose of 1.5 ml/30 kg b.w. and/or Metacam (Boehringer Ingelheim Vetmedica GmbH) and Calfoset (KRKA Poland). This treatment was unsuccessful, either. Recovered animals relapsed. After 20 days from the purchase, the number of dead calves increased to 14, and after 25 and 30 days, to 17 and 18, respectively. Ultimately, only two calves survived. In the meantime, a BVD examination of the blood revealed the presence of PI individuals, but owing to high laboratory costs, the calves belonging to the pool were not examined individally.
Case 3. In late May 2008, a Holstein-Friesian cow was given an intramuscular 20 ml injection of Carofertin (Werfft--Chemie, GmbH), containing 10 mg beta carotene in 1 ml of solution. Several minutes after the injection, urticaria appeared on the sides of the neck (Fig. 1). Simultaneously, swelling of the eyelids and/or chemosis (Fig. 2), as well as a considerable swelling around the ears (Quinckes oedema) were observed. Moreover, vulvul oedema (Fig. 3) occur-red, as well as hyperaemia and cyanosis of the udder skin. The cow received intravenously Calcium borogluconatum
Fig. 1. Urticaria
Med. Weter. 2013, 69 (9) 570
25% (Biowet Drwalew SA) at a dose of 0.5 ml/kg b.w. and intramuscularly 15 ml Rapidexon (Novartis), containing 2 mg/1 ml dexamethasone in the form of natrium phospho-ricum. After about 30 minutes, the signs disappeared. As it resulted from the anamnesis, in the years 2008 and 2009 several dozen similar cases were observed on a smaller farm. In two cases the animals died.
Discussion
Local reactions are usually the mildest
postinocula-tion complicapostinocula-tions. Most frequently they appear in the
form of oedema, hyperaemia, and pain at the site of
the injection. Local postinoculation reactions occur
particularly often after the administration of a live
vaccine, and their sings usually disappear after 2-3
days. In the case of reactions to adjuvants added to
the vaccine, the signs may persist much longer. Side
effects may sometimes be more severe and require
treatment. The most frequent reactions to inactivated
vaccines in cows are a short-term loss of production,
a temporary somatic cells increase, and a moderate
increase in internal temperature (1, 2). These have been
confirmed by reports. In cows vaccinated twice with
an inactivated deleted vaccine against IBR, a
signifi-cant decrease in production was observed within 14
days (2). This effect was more pronounced after the
vaccine had been administered for the second time. In
cows vaccinated against IBR/BVD, abortions have
been reported, whereas in cows vaccinated with
a modified live vaccine against IBR, severe infections
of keratoconjunctivitis have beeb observed (6, 8).
Moreover, among cows vaccinated against IBR/IPV,
there have been cases of encephalomeningitis (3).
In the above case, cows developed typical allergic
sings including urticaria, strong swelling at the
injec-tion site, and head oedema. Less informainjec-tion is
avail-able on the side effects of vaccines against BVD/MD.
According to the producers, such vaccines may trigger
mild local reactions disappearing without treatment.
These reactions usually depend on the kind of
adju-vants used in the vaccine. Inactivated vaccines may
have a fragmentary infectivity if vaccination is
per-formed improperly (11). In the case of live vaccines,
the appearance of MD was reported in cows shortly
after vaccination in the 1960s. Live antigens of the
vaccine against BVDV have been known to penetrate
the placenta barrier, infecting the foetus and causing
sings of disease in newborn calves or malformations
of the central nervous system (13). There have also
been reports about the immunosuppressive influence
of vaccines and about negative effects of their
conta-mination with other viruses (11). Lately, pancytopenia
dangerous to the lives of calves has been reported
after the vaccination of their mothers against BVD with
a live attenuated vaccine BVD (4, 5).
It seems that in the first case presented here, a strong
allergic reaction after the vaccination against IBR/IPV
and BVD/MD may have been be related to highly
unfavourable environmental conditions (high ambient
temperature) during vaccination. This hypothesis seems
to be confirmed by the fact that a similar booster
vac-cination of a neighbouring herd, conducted several days
later in a lower temperature with the same vaccine did
not result in any side effects.
Data on the side effects of vaccination against BRSV
in cows are scarce. Such cases have been reported in
the Blue Belgian breed vaccinated with an inactivated
monovalent vaccine against BRS Vacores
®(Rhone--Merieux, Lyon, France) containing strain BRSV 220/69
inactivated with â-priopriolacton (12). One-month-old
calves were vaccinated twice at an inteval of 21 days.
In accordance with the producers instructions, the
calves received another injection at the age of four
months. Both clinical sings and the macroscopic
lesions of the lungs were similar to those
characteri-stic of BRSV infections. The outbreak of the disease
took place in calves aged 204 ± 29 days, 30% of which
died because of the respiratory distress syndrome
within 6 days after the first clinical signs. It seems that
in the second case presented above, the sudden acute
course of the post-inoculation reaction was caused by
administering the vaccine shortly after transport in the
adaptation stress period. It is known that vaccination
should preferably be performed 2-3 weeks before the
transport or a potentially stressful situation, which in
the case described above was impossible. The
reac-tion may also have been related to the presence of
calves permanently infected with BVDV, which was
confirmed in the group of purchased animals.
Immuno-suppressive activity of this virus is commonly known.
The application of the live vaccine may have
deepened the immunological deficit and trigger an
extreme reaction of the organism, leading to death.
The absence of a sufficient protective reaction to the
vaccine is puzzling. This may have been caused by
the simultaneous administration of a long-lasting
Med. Weter. 2013, 69 (9) 571
biotic (which is not fully legitimate) with known
immunosuppressive properties.
It seems that in both cases presented above, the side
effects were additionally caused by the wrong timing
of vaccination (ignoring the high ambient temperature
and transport stress). Such mistakes are relatively
frequent. For example, in humans they are responsible
for about 41% of side effects occurring directly after
drug administration (The Office for Registration of
Medicinal Products, Medical Devices and Biocidal
Products. Biuletyn Leków nr 4, 2009).
Carofertin contains â-carotin, the most active isomer
of carotene. It actively influences the development of
ovarian folliceles and secretions from the uterus glands
of, as well as stimulates secretion from the corpus
luteum. In cows, it is commonly used for the therapy
and prevention of reproductive disturbances. The
producer of Carofertin actually warns about the
possi-bility of occasional hyperresponsiveness to the
com-ponents of the medicine manifesting itself in a
tempo-rary irritation or oedema at the site of injection, but
a dangerous general allergic reaction has not been
described so far.
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Corresponding author: prof. dr hab. Jêdrzej M. Jakowski, ul. Aza-liowa 23, 62-002 Z³otniki; e-mail: jasko@up.poznan.pl
