Lesions in sheep following administration of a vaccine of a Freund's complete adjuvant nature used in the control of ovine paratuberculosis

CASE HISTORIES: Occurrences of adverse reactions in seven sheep flocks in Australia following vaccination against paratuberculosis where veterinary attention was requested are reviewed. All cases occurred within the 3-year period following commencement of use of a vaccine of a Freund's complete adjuvant nature, at a time when approximately six million doses of vaccine had been administered.

CLINICAL FINDINGS: In the first case, 26/58 (45%) Merino sheep vaccinated as adults had palpable tissue reactions at or near the site of vaccination; enlarged prescapular lymph nodes were palpated in 17 (29%), and nine (16%) sheep had both palpable lesions at the site of vaccination and enlarged prescapular lymph nodes. The reactions included caseous nodules up to 5.5 cm in diameter. In the other cases, fistulating or granulomatous wounds were occasionally found at the recommended site of injection behind the ear, and myiasis was rare. Occurrences of inappropriate choice of injection site were recorded, including injection into the axilla of two Merino rams, and lesions in the tissues of the maxilla and nose of almost 50% of 350 Border Leicester lambs. Four outbreaks of progressive paralysis due to injection into cervical musculature were reported, described as ‘OJD staggers’ by producers.

DIAGNOSIS: Granulomatous cellulitis and lymphadenitis associated with oil droplets typical of ‘oil granulomata’. Injection of vaccine into the dorsal cervical area resulted in progressive paralysis due to myonecrosis and suspected granulomatous leptomeningitis.

CLINICAL RELEVANCE AND CONCLUSIONS: Although lesions at and near the site of injection are common, adverse reactions to vaccination were rare and included mortality from cervical spinal injection, production losses from injection in the maxilla or axilla or if myiasis resulted, and potential marketing losses if animals or carcasses are discounted as a result of the lesions. Risk factors for adverse reactions included inadequate restraint of sheep, breed of sheep, experience of the operator, poor injection technique, and inappropriate placement of vaccine. Increasing attention to the proper restraint of animals, restricting vaccination to the recommended site behind the ear, careful placement of the vaccine into subcutaneous tissue to avoid drainage of vaccine material into tissues such as the spinal cord, and post-vaccination supervision to address welfare concerns should adverse reactions occur are recommended.     

Injection site lesions of footrot vaccines in sheep

Three trials were conducted to assess the size and frequency of lesions induced by an oil-based and an alum-precipitated aqueous B. nodosus commercial footrot vaccine at two injection sites (neck and brisket) with or without prior skin swabbing with methanol. Animals used were previously unvaccinated and clean and dry at time of vaccination. Trial 1 contained 57 2-tooth Booroola Merino x Coopworth ewes, trial 2 contained 60 mixed-age Corriedale ewes, and trial 3 contained 39 rams of mixed age and sex. Firm nodules or plaques with indurated edges and with a maximum dimension of 1cm or more appeared soon after vaccination and were still very common (50-100% of sheep vaccinated) 5-6 weeks after injection. A variable proportion exhibited a liquefied central area of necrosis and later discharged necrotic material. The oil-based vaccine produced significantly larger lesions than the alum-precipitated aqueous vaccine. Lesion size at the brisket site was significantly larger than the neck site in ewes but not in rams. Skin preparation with methanol had no effect on lesion frequency or size.     

Field trials of a formulation containing moxidectin and 6 in 1 vaccines for sheep

Objective: To assess the efficacy and safety of a formulation containing moxidectin and 6 in 1 vaccine in sheep under field conditions.
Design: Efficacy and safety study.
Animals: Two hundred and five crossbred Merino lambs and two hundred and eight Merino ewes were used in the studies.
Procedure: A formulation was made for the simultaneous treatment of sheep with moxidectin and immunisation against clostridial diseases and caseous lymphadenitis. The efficacy against nematodes, vaccine response and safety were assessed.
Results: Effective control of nematodes and responses to antigens were achieved following subcutaneous administration. The formulation was safe to administer; occasional minor tissue reactions were evident, but no other adverse effects of treatment were observed in either pregnant ewes or lambs, using either the recommended dose, or an overdose of the formulation.
Conclusion: Administration of a formulation containing moxidectin, five clostridial antigens and caseous lymphadenitis antigen proved safe and efficacious under field conditions.     

Differences between breeds of sheep in their responses to Bacteroides nodosus vaccines

In a field experiment on irrigated pasture, sheep of several breeds were vaccinated twice, subcutaneously, in the upper neck, with Bacteroides nodosus vaccine containing either depiliated cells (DC vaccine), or whole, piliated cells (WC vaccine) and the responses were measured over the following 14 weeks. DC vaccine was as effective as WC vaccine in protecting against the development of foot-rot under conditions of moderate challenge, although the WC vaccine induced significantly higher pilus agglutinating antibody titres. Foot-rot developed in significantly more vaccinated Merinos (Peppin and Saxon strains) than in Romney Marsh, Dorset Horn or Border Leicester breeds. Agglutinating antibody titres after WC vaccination were significantly lower in the Peppin Merino than in the other sheep for the first 6 weeks, while after DC vaccination the titres remained elevated longer in the Border Leicester and Saxon Merino and were significantly higher from 6 weeks onwards. Reactions at the inoculation sites were generally larger in the British breeds than in the Merinos and among the former the reactions were largest, most numerous and most frequently discharged their contents in the Dorset Horn. Bodyweight gains in all vaccinated sheep were initially reduced, compared with controls, but the differences were no longer significant after the eighth week.     

Incidence of adverse events in ferrets vaccinated with distemper or rabies vaccine: 143 cases (1995-2001)

OBJECTIVE: To determine the incidence of adverse events in ferrets vaccinated with a modified-live avian cell culture canine distemper virus vaccine licensed for use in ferrets, an inactivated rabies vaccine licensed for use in ferrets, or both. DESIGN: Retrospective study. ANIMALS: 143 ferrets. PROCEDURE: Medical records were reviewed to identify ferrets that had an adverse event after vaccination. RESULTS: Adverse events developed within 25 minutes after vaccination in 13 ferrets. One ferret developed an adverse event after receiving a distemper and a rabies vaccine simultaneously and developed a second adverse event the following year after receiving the rabies vaccine alone. Therefore, a total of 14 adverse events were identified. All adverse events were an anaphylactic reaction characterized by generalized hyperemia, hypersalivation, and vomiting. Ten of the 14 anaphylactic reactions occurred after ferrets received both vaccines, 3 occurred after ferrets received the distemper vaccine alone, and 1 occurred after a ferret received the rabies vaccine alone. Incidences of adverse events after administration of both vaccines, the distemper vaccine alone, and the rabies vaccine alone were 5.6, 5.9, and 5.6%, respectively. Ferrets that had an anaphylactic reaction were significantly older at the time of vaccination than were ferrets that did not. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that there may be a high incidence of anaphylactic reactions after vaccination of domestic ferrets. Ferrets should be observed for at least 25 minutes after vaccination, and veterinarians who vaccinate ferrets should be prepared to treat anaphylactic reactions.     

Lesions attributed to vaccination of sheep with Gudair for the control of ovine paratuberculosis: post farm economic impacts at slaughter

OBJECTIVE: To determine i) the prevalence of lesions at the site of vaccination with Gudair, and ii) the incidence of discounting of slaughtered sheep carcasses due to the presence of these lesions. DESIGN: A survey of the prevalence of injection lesions and actual discounts applied to 20 consignments of vaccinates slaughtered in abattoirs in New South Wales. PROCEDURE: Consignments of sheep previously vaccinated against ovine Johne's disease (OJD) were assessed on the slaughter chain for the prevalence of vaccination site lesions and any costs associated with carcass trimming were estimated. In addition a telephone survey was conducted to determine the experiences and risk attitudes of 8 abattoirs in south east New South Wales likely to have previously processed vaccinates. RESULTS: The prevalence of lesions observed was 18% for adult (mutton) and 65% for lamb carcasses. The value of the trim removed was insignificant, the labour cost of its removal was nil and no carcass was downgraded to a lower value grade. CONCLUSION: Under the market conditions existing at the time the study was conducted, in sheep vaccinated at the recommended site high on the neck, it is unlikely that OJD vaccination site lesions will be a significant cost to producers or the processing industry and will represent only a very small proportion of the total cost of OJD control by vaccination.     

Effect of liquid paraffin on antibody responses and local adverse reactions of bivalent oil adjuvanted vaccines containing newcastle disease virus and infectious bronchitis virus

Effects of liquid paraffin on antibody responses and local adverse reactions after intramuscular injection of oil adjuvanted vaccines containing Newcastle disease (ND) and infectious bronchitis (IB) virus were investigated in chickens. Each vaccine was prepared with a liquid paraffin such as Carnation, Crystol 52 and Lytol. These vaccines induced sustained antibody responses against ND and IB. Among local adverse reactions, Lytol induced granulomatous reactions and abscesses, but Carnation and Crystol 52 did not. The residual weight of liquid paraffin at the injection site decreased in the order Carnation, Crystol 52, Lytol. Crystol 52 was composed of relatively few short-chain hydrocarbons (i.e., n-C20H42). The vaccine with liquid paraffin mainly composed of n-C16H34-n-C20H42 was suggested to induce fewer adverse reactions.     

A field trial with a commercial vaccine against foot-rot in sheep

A commercial, polyvalent, alum-oil adjuvanted vaccine against foot-rot was tested under conditions where climatic and management circumstances have traditionally made foot-rot difficult to control or eradicate. The vaccine had a protection effectiveness of 84.4% 120 days after the completion of vaccination. Although 93.5% of ewes developed lesions at inoculation sites, they caused no management problems. A negative correlation between foot-rot status and the development of lesions at inoculation sites was considered to show that a sheep factor exists which is related to susceptibility to both foot-rot and reactions at the site of inoculation. The nature of this factor was not determined. Vaccination was considered the easiest and most effective way of controlling the spread of foot-rot among ewes with lambs at foot in the test district.     

Field evaluation of a commercial M-protein vaccine against Streptococcus equi infection in foals

A double-blind randomized clinical trial was undertaken to determine the value of parenterally administered Streptococcus equi M-protein vaccine in foals during an epizootic of strangles. Weaned mixed-breed foals (n = 664) housed on 2 adjacent feed-lots (A and B) arrived over a 5-day period, 2 weeks before primary vaccination. Foals in lot B (n = 114) were randomly administered vaccine (n = 59) or saline solution (placebo; n = 55) on 3 occasions at biweekly intervals. Foals in lot A (n = 450) were given 1 dose of vaccine (n = 225) or placebo. The following clinical observations were scored blindly by a single observer for all foals in lot B and for 120 (randomly sampled) foals in lot A on a single day, 2 (Lot B) and 6 (lot A) weeks after final vaccination: cervical lymphadenopathy, type of bilateral nasal discharge, and palpable swelling at injection site(s). Bacteriologic culture of nasal swab specimens or lymph node aspirates from selected foals with clinical disease yielded S equi. Cervical lymphadenopathy was observed in 17 of 59 (29%) vaccinates and 39 of 55 (71%) nonvaccinated controls in lot B and in 32 of 60 (53%) vaccinates and 29 of 60 (48%) controls in lot A. Contingency chi 2 analysis confirmed significantly lower cervical lymphadenopathy rate (chi 2 = 18.5; P less than 0.001) and prevalence of mucopurulent nasal discharge (chi 2 = 11.4; P less than 0.01) for vaccinates in lot B only. Swelling(s) at the vaccine injection site were palpated in 44% of lot B and 29% of lot A vaccinates vs less than 2% of placebo controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

An inactivated vaccine for the control of bluetongue virus serotype 16 infection in sheep in Italy

Because no suitable products are at the moment available to safely control the spread of BTV-16 in Europe, an inactivated vaccine was produced from the reference field isolate of bluetongue virus serotype 16. One group of six sheep was vaccinated subcutaneously with the inactivated vaccine twice, on days 0 and 28, whereas a second group of eight sheep was inoculated with saline solution and used as mock-vaccinated control animals. Seventy-eight days after the first vaccination, all sheep were inoculated subcutaneously with a suspension containing 10(6.3) TCID(50) of a virulent reference BTV-16 isolate. Apart from a transient inflammatory reaction at the injection site, no adverse effects were reported following vaccination. All vaccinated animals developed high titres (7.3-9.3log(2)(ED50%/50 microl)) of virus-specific neutralising antibodies and were resistant to challenge with BTV-16. Conversely, following challenge, control animals developed hyperthermia and long lasting high-titre viraemia.     

Myositis, lameness, and recumbency after use of water-in-oil adjuvanted vaccines in near-term beef cattle.

A producer administered 2 US Department of Agriculture-licensed adjuvanted veterinary vaccines (inactivated bovine rotavirus-coronavirus vaccine; Clostridium perfringens type C-Escherichia coli bacterin-toxoid) into muscles of the left and right hips of 469 pregnant beef cows. Within 24 hours, 5 cattle were recumbent, and another 2 had non-weight bearing pelvic limb lameness (1.5% affected; 7/469). During the next 10 days, 50% of the herd developed firm swellings up to 24 cm in vaccination sites in muscles of the hip. Histological samples revealed granulomatous myositis with intralesional oil. Lesions resolved slowly during the next 6 months. Six cattle were injected experimentally with the vaccines. None became lame, but all developed foreign body granulomatous myositis similar to those in the affected herd. The maximum diameter of experimentally induced lesions in muscle at necropsy 60 days after injection with the recommended dose of the bacterin-toxoid vaccines was 12 cm. Histological examination revealed pyogranulomatous myositis, fibrosis, and myonecrosis. The inactivated viral vaccine induced milder granulomatous myositis with intralesional lipid and scant fibrosis. Acute transient lameness on the ranch was attributed to use of 2 irritating biological vaccines in the hip muscles of cows that were close to parturition.     

Saponin Adjuvants. IV. Evaluation of The Adjuvant Quil a in the Vaccination of Cattle Against Foot-And-Mouth Disease

The saponin adjuvant Quil A has been investigated in the vaccination of cattle against foot-and-mouth disease. Using a Frenkel type vaccine a dose-response relationship has been established between Quil A and neutralizing antibody titres. Ten ml of vaccine was combined with 0, 50, 200, 800, and 3200 µg of Quil A. The combinations were each injected into 4 animals. The local reaction on the site of injection produced by injection of the vaccine alone and in combination with different doses of Quil A has been estimated. On this basis a therapeutical dose at 1 mg of Quil A has been estimated to combine maximum adjuvant effect with a minimum of adverse reactions. This dose has been tested in the vaccination of cattle with FMD vaccines derived from BHK suspension cell virus of type O and A respectively. The vaccines were tested in 10 ml and 5 ml doses with or without Quil A, and each in 4 animals. It is concluded that Quil A is a valuable adjuvant for use in the induction of neutralizing antibodies against foot-and-mouth disease in cattle.     

Safety and immunologic effects after inoculation of inactivated and combined live-inactivated dermatophytosis vaccines in cats

OBJECTIVE: To determine antidermatophyte immunologic effects of an experimental combined live-inactivated dermatophytosis vaccine (CLIDV) and a commercial inactivated dermatophytosis vaccine (IDV) in cats and to evaluate adverse effects associated with administration of these vaccines. ANIMALS: 20 healthy juvenile domestic shorthair cats. PROCEDURE: Cats were injected with 2 doses of CLIDV at the standard dosage or 1 dose of CLIDV at 10 times the standard dosage; IDV was administered at the manufacturer-recommended dosage. Cats were observed for illness and reactions at inoculation sites. Periodically, samples were obtained for fungal culture, lymphocyte blastogenesis test (LBT) as an indicator of cell-mediated immunity against dermatophyte antigens, and antidermatophyte IgG titers. Following vaccination, cats were challenge-exposed by topical application of Microsporum canis macroconidia and examined weekly for clinical signs of dermatophytosis. RESULTS: of 10 cats given CLIDV developed focal crusts at the injection site that resolved without treatment; these were areas of dermatophyte infection with the vaccine strain. Antidermatophyte IgG titers increased significantly with all vaccination protocols. Cellular immunity against M canis increased slightly and variably during the vaccination period and did not differ significantly between vaccinated and control cats. All cats developed dermatophyte infection after challenge exposure. Vaccination with CLIDV or IDV was associated with slightly reduced severity of initial infection. CONCLUSIONS AND CLINICAL RELEVANCE: Noculation with IDV or CLIDV did not provide prophylactic immunity against topical challenge exposure with M canis. Inoculation with either vaccine did not provide a more rapid cure of an established infection.     

Safety of a non-adjuvanted therapeutic vaccine for the treatment of feline dermatophytosis

The safety of a non-adjuvanted inactivated fungal vaccine for the treatment of dermatophytosis in cats was investigated in two studies: a controlled laboratory study, and a placebo-controlled double-blind field study with a cross-over design in Europe. In the laboratory study, two groups of 10 cats each were administered an intramuscular twofold overdose, followed by five single 1 ml doses, of either vaccine or control product at 14-day intervals. In the field study, cats were treated with three intramuscular injections of 1 ml vaccine administered at 14-day intervals, as recommended by the manufacturer. A total of 89 cats were enrolled in the field study and divided into two groups to receive either vaccine or placebo for the first three treatments, followed by the opposite product for the final three treatments. The cats enrolled in the two studies were 12 weeks of age or older, as recommended by the manufacturer. All the cats were monitored closely for possible injection site reactions, systemic reactions (including changes in rectal body temperature) and adverse events. The results from both studies showed no significant differences between the vaccinated cats and the control or placebo-treated cats with regard to local or systemic reactions. A few mild to moderate local reactions were noted, but these were evenly distributed between the vaccinated and placebo-treated cats and resolved within a few days. No severe or serious adverse events related to the vaccinations were observed.     

Efficacy of a killed vaccine for the control of paratuberculosis in Australian sheep flocks

A field trial was undertaken from 1999 until 2004 to determine the efficacy of a killed M. a. paratuberculosis vaccine, Gudair, for the control of ovine Johne's disease (OJD) in merino sheep run under Australian pastoral conditions. On each of three farms experiencing significant OJD losses (5-15% per annum), 200 merino lambs (age 1-4 months) were vaccinated, and 200 lambs were left unvaccinated. Animal assessments and sample collections were conducted twice yearly until 4 or 5 years of age. The impact of vaccination on mortality rate, faecal shedding of M. a. paratuberculosis (by pooled and individual faecal culture), liveweight, wool productivity, vaccine injection site lesions and cellular (BOVIGAM) and humoral (PARACHEK) immunity was examined. Vaccination stimulated cell-mediated and humoral immune responses, reduced mortalities due to OJD by 90% and delayed faecal shedding for the first year post-vaccination. Thereafter, the prevalence of shedders among vaccinates was reduced by 90%. The numbers of M. a. paratuberculosis excreted by the vaccinated groups were also reduced by at least 90% at most sampling times. However, high levels of excretion by vaccinates occurred on some occasions, and although only 7 of 600 vaccinates died from OJD, all 7 had multibacillary lesions. Thus there remains a risk that some vaccinated sheep will transfer the disease. Small reductions in liveweight were found in vaccinated lambs in the first year, but there was little effect on wool production. Vaccine injection site lesions were detected in almost 50% of sheep after 2 months, and these persisted for at least 4 years in 20-25% of vaccinates. Data from this trial enabled the registration of Gudair in Australia in 2002 and underpins the pivotal role of vaccination in the current management of OJD.     

Immunisation against infections caused by Listeria monocytogenes in sheep

Immunisation against listeriosis in sheep using a live, attenuated vaccine was introduced in Norway in 1984. Since then 65,000 to 80,000 animals have been vaccinated annually. Information obtained by a questionnaire showed that the incidence of listeriosis decreased from approximately 4.0 per cent before the introduction of the vaccine to 1.5 per cent after vaccination started. The incidence of abortions was 0.7 per cent in vaccinated flocks compared to 1.1 per cent in unvaccinated flocks. There were a few adverse reactions in the vaccinated sheep.     

The use of an autogenous Dichelobacter nodosus vaccine to eliminate clinical signs of virulent footrot in a sheep flock in Bhutan

An outbreak of virulent footrot was investigated in a flock of 605 Merino cross-bred sheep in Bhutan. Conventional control methods in the preceding eight years had reduced its prevalence from 36-79% in different components of the flock to about 15% overall. Only one serogroup (B) of Dichelobacter nodosus was identified among 40 isolates cultured from affected sheep. A vaccine prepared from this strain was used in a pilot trial to compare the response of 14 treated and 14 untreated sheep. All affected, vaccinated animals in this trial healed quickly and were protected against re-infection while additional cases developed among untreated sheep during a period favourable for the spread of footrot. The serogroup B vaccine was administered to the whole flock for two successive years. No other footrot treatment was given during these or subsequent years. The whole flock was examined three times, foot by foot, for two years and twice yearly for another two years. When vaccination began there were 88 affected sheep in the flock, an affected sheep being defined as an animal with a foot-score of 2 or greater in one or more feet. There were neither affected sheep in the flock 30 days after the first dose of vaccine nor were any identified in later inspections. Virulent footrot, originating from the farm under investigation, persisted in neighbouring village flocks during this period. It was concluded that whole flock specific D. nodosus vaccination made a major contribution to the elimination of all clinical signs of footrot from the flock of 605 sheep where the condition had previously persisted for 10 years.     

Rabies and brucellosis immunization status and adverse reactions to rabies vaccines in veterinary students.

Rabies pre-immunization has been recommended for high risk professions, including veterinarians. Cell-cultured rabies vaccines have considerably reduced the risk of post-vaccination neurological reactions found in earlier vaccines. However, some adverse reactions have been reported with Human Diploid Cell Vaccines. 329 French veterinary students were surveyed about their rabies and brucellosis vaccination status, the occurrence of adverse reactions to rabies vaccine, and their antibody titer monitoring practices. Questions also were asked to determine if mandatory rabies pre-exposure immunization upon entry to veterinary school motivated students to maintain their rabies pre-exposure vaccination. The overall vaccination rate was 98.5% for rabies and 17% for brucellosis. 19% of the rabies vaccinated students reported some form of adverse reaction, whatever the vaccine brand used, but not experienced systemic allergic reaction. Adverse reactions were twice more frequent in female than male students and were more frequent after primary series than revaccination series (Relative Risk = 1.76). Despite the mild reactions encountered, rabies pre-exposure vaccination has been well-accepted by French veterinary students. In contrast, vaccination against brucellosis was not as well-accepted for prophylaxis.     

Effect of Quil A,a saponin derivative,on the response of sheep to alum precipitatedBacteroides nodosus vaccines

Alum precipitatedBacteroides nodosus vaccines prepared from two antigens with and without the saponin derivative, Quil A, did not induce adverse tissue reactions in sheep injected subcutaneously. Vaccinated, non-infected Merino sheep had higher agglutinin antibody titres when the vaccines included Quil A. Moreover, the recovery rates in vaccinated sheep affected with foot-rot were higher when the vaccines included Quil A.     

Fatal adverse pulmonary reaction in calves after inadvertent intravenous vaccination

Fatal adverse reactions to vaccination are uncommon and poorly documented. To our knowledge, this is the first case report of fatal adverse reaction to an inadvertent intravenous vaccination in three calves vaccinated against respiratory (Somnustar Ph) and clostridial (Tasvax 8) diseases. All three calves had severe acute interstitial pneumonia with multifocal pulmonary hemorrhages that resulted in fatal respiratory failure. Qualitatively, the pulmonary lesions in these calves were similar to those in septicemic/endotoxemic calves; however, the severity and extensity of pulmonary hemorrhages were of a higher degree than those usually observed in clinical septicemia/endotoxemia. In addition, approximately 30% of the arterioles and small arteries were surrounded by hemorrhages, which occasionally extended around adjacent bronchioles. A unilateral peri-jugular hematoma with recent transmural perforation of jugular vein found in all three calves was believed to have been caused by the injection needle during vaccination, and the fatal pulmonary changes were believed to have been secondary to the intravenous injection of vaccine.