1.1. Vaccines

The history and theory of anthrax vaccines is covered in section 8.6. This annex covers the more practical details on vaccines and lists the names, addresses, telephone and fax numbers and other relevant data that could be traced on available anthrax vaccines.²

1.2. Therapeutic sera

The history and background to therapeutic sera for anthrax are given in sections 7.2.2.3 (for animals) and 7.3.4 (for humans).

2.1. Storage

The vaccines should be stored in a refrigerator but not frozen (repeated freeze-thawing will result in reduced inocula).

2.2. Antibiotics

Since the active ingredient of the livestock vaccines is live (attenuated) B. anthracis, antibiotic treatment may be expected to interfere with vaccine performance. This was demonstrated in one small study in which three guinea-pigs receiving 100 000 U penicillin G intramuscularly in one leg at the same time as the Sterne strain vaccine in the other leg were not protected against challenge 3.5 weeks later with virulent B. anthracis. Three guinea-pigs receiving the vaccine but no penicillin were protected (Webster, 1973).

Animals being vaccinated should not receive antibiotics for several (7–10) days before or after vaccination. The vaccine may be rendered ineffective, for example, in cattle on antibiotics for growth promotion or receiving antimastitis therapy. If there are concerns that antibiotics may have interfered with vaccine efficacy, the animals may be revaccinated after a period of two weeks.

2.3. Movement to other premises or for slaughter or trade

Where animals are scheduled to be moved for local or international livestock and meat trade purposes, it is important to check whether there are advisories in place specifying a withholding period before which animals may be moved to other premises, or sent to slaughter following vaccination (see sections 7.2.1.2 & 8.7). Basically, the vaccines are not recommended for use in animals destined for slaughter for human consumption within 6 weeks of vaccination (OIE, 2008). Local regulations, or the label on the vaccine being used, may specify longer periods, which may vary from 2–6 weeks. The specifications which pertain for the particular situation which exists and in that particular location should be established before any vaccination campaign is initiated.

2.4. Equines

Sterne, while stating in one paper (Sterne, 1939) that his vaccine had been entirely satisfactory during large-scale use on horses, in another paper the same year (Sterne et al., 1939) said that it was necessary to issue separate vaccines for goats and horses. He did not elaborate why this was the case, however. Later he stated (Sterne, 1946) that the same vaccine was now used for all animals and that, while cattle and sheep reacted very mildly, horses reacted more vigorously. He added, however, that no farmer had complained about the reactions. In 1959 he wrote (Sterne, 1959) that horses were slow to develop effective immunity following vaccination, taking a month or more as compared to less than a week in bovines. Lindeque et al. (1996) found that two initial doses approximately 8 weeks apart were necessary for development of dependably measurable antibody titres in zebra (section 8.6.2).

2.5. Goats (and llamas)

Goats are known to be prone to severe reactions to the vaccines. One possible approach to vaccination of goats is an initial schedule of two inoculations one month apart, with the first dose being one quarter of the standard recommended dose (“pre-inoculation dose”), and the second dose being the standard recommended dose. A single annual booster may be administered thereafter. One manufacturer recommends that injection of the vaccine in goats should be done in the tail-fold region (compared with the neck region in most species).

Llamas are frequently cited together with goats as being prone to severe reactions to the livestock vaccine, and this is again stated in section 8.6.2. However, this seems to be based on a single reference (Cartwright et al., 1987). In this, three 3-month-old calves in a herd of 20 llamas became ill three days after subcutaneous inoculation of the Sterne vaccine in the neck. Severe localized oedema developed at the inoculation site. One of the calves responded to penicillin, one died, and one was euthanized due to being moribund. None of the 17 older animals developed a local reaction. The facts may not support the grouping of llamas together with goats as especially prone to severe reactions to the vaccine.

2.6. Injection

Injection should be made through an area of clean dry skin.

2.7. Pregnant and lactating animals

The Sterne strain 34F₂ livestock vaccine has been in use for well over half a century and is frequently administered in response to outbreaks. As outbreaks generally occur in summer or hotter seasons, pregnant animals are frequently among those vaccinated. There are apparently no records of adverse events related to the pregnancies, and the vaccine appears to be safe in pregnant animals (Berrier & Hugh-Jones, personal communication, 2006). A dose level of 10 spores of B. anthracis strain 193 with a mouse LD₅₀ of about 100 spores was used as the “vaccine” in an unspecified number of cows. Excretion of B. anthracis was demonstrated between 1 and 9 days after vaccination with “100% recovery from all the cows tested”. The relevance of this report is doubtful since the legitimacy of referring to inoculation with strain 193 as “vaccination” is questionable. A more relevant study resulted in no evidence that dairy cattle would shed the Sterne strain in milk following immunization. In this, no isolations of B. anthracis were made in milk samples collected from each of 49 vaccinated cows twice daily for 10 days post-vaccination (Tanner et al., 1978).

As mentioned in section 7.2.1.3, the vaccine may be rendered ineffective by antibiotics being used to treat mastitis. It may be necessary to wait until the antibiotic level has fallen before vaccinating. In an outbreak situation, the animals should be carefully monitored (e.g. twice-daily temperature checks) during this waiting period.

2.8. Discard of vaccine and equipment

Being a live spore suspension, leftover vaccine vials, used syringes, needles, gloves, coveralls and other contaminated items should be disinfected, autoclaved or incinerated after completion of the operation (see Annex 3, section 6.5). It should be remembered that the vaccine is also potentially infectious to humans, so contaminated items should be handled with care (see section 2.10 below).

2.9. Milk from vaccinated animals

See section 8.7.

2.10. Accidental operator inoculation

Self-injection by the operator can give rise to infection but few, if any, serious infections from such events are on record. The experience of Ellard (personal communication, 2004) during one of the vaccination campaigns which followed the outbreaks in cattle in western Australia in 1994 (Forshaw et al., 1996) is probably one shared by many veterinarians over the years:

“Vaccination of livestock was routinely undertaken using disposable vaccination guns with both the gun and any residual vaccine incinerated at the end of each day. I should mention that, when using this type of gun, it was not uncommon for the operator to self-inject if the animal struggles at an inopportune moment. This happened to me on at least two occasions without any adverse reaction to the vaccine. On each occasion the incident was reported and monitored, but no treatment was required.”

In one anthrax outbreak in the United States in 1974, at least 12 people were accidentally inoculated with the Sterne strain vaccine. Clinical follow-up was available on seven persons who received small but unmeasurable amounts of the vaccine (probably 0.1 ml or less) at the time of the needle-stick accident. None of the seven developed a cutaneous lesion at the inoculation site. One developed febrile illness, with cervical and right axillary lymphadenopathy and possible aseptic meningitis, several days after he had punctured his right hand with a needle. However, blood or lymph node cultures were not obtained, and the cause of his illness was not determined (Fox et al., 1977).

Three clinical cases associated with “capsule negative” B. anthracis were noted elsewhere. None of these had any association with the Sterne or other vaccine strain; one isolate was from blisters and oedema on the hand and forearms of an immunocompromised individual who had handled 15th century leather in Poland, the second from the faeces of an individual in China with suspected intestinal anthrax, and the third from the blood of a child diagnosed as having endocarditis in Saudi Arabia, though not established as the cause of the condition (Editor’s note, 1996a).

In the event of accidental self-inoculation by the operator, gentle pressure should be applied to the wound to squeeze out any inoculums, followed by thorough washing with soap and water. If saponin is included in the vaccine, there may be a painful local reaction at the site of inoculation. Medical advice should be sought if infection sets in.

2.11. Vaccine failures in livestock

Questions arise from time to time regarding cases of anthrax that occur in herds which have been vaccinated, or about continuing cases after vaccination to control outbreaks. Kaufmann et al. (1973, cited by Salmon & Ferrier, 1992) investigated an outbreak involving more than 4000 cattle, and found that 0.1% died (1.4 % of all deaths) 8–14 days after vaccination, and another 0.1% more than 15 days after vaccination. In the outbreak of 1987 described by Salmon & Ferrier, 5 of 10 deaths occurred 3, 5, 11, 68 and 126 days after vaccination and, in another case, 37 days after revaccination. Deaths continued after vaccination in the 1994 outbreak in cattle in western Australia. In Africa, where livestock owners sometimes do not understand the difference between vaccination and treatment, the knowledge that some of their animals may still die after vaccination may lead to distrust of vaccination and resistance to it being done (see section 9.7, Table 10).

Usually it is not possible to identify the specific reasons for these vaccine failures, but the following points may be helpful.

2.11.3. Interference by maternal antibody

Questions arising following the vaccine campaign in response to the 1994 anthrax outbreak in western Australia (Forshaw et al., 1996) led to a study aimed at determining whether maternal antibody interfered with the response to anthrax vaccine in calves (Ellard, Ellis & Turnbull, unpublished results). Titres to the anthrax protective antigen in 13 calves from vaccinated dams were compared with those in 12 calves from unvaccinated dams. The calves received dose 1 of the live spore 34F₂ vaccine at 5–9 weeks of age, and a second dose 4–5 weeks later (apart from two animals in the vaccinated dam group in which the interval between doses was 9 weeks).

Eight of the vaccinated dams had detectable antibody but only two had substantial titres. The calves of these two had measurable titres at birth, one substantial; the calves of 5 of the other 6 also appeared to be positive but with very low titres, and one calf from a negative dam also had a low titre. In the non-vaccinated group, one dam and her calf at birth and one other calf had evidence of antibody, again at low titre.

Detectable antibody was only present in 13 of the 25 sera at the time of vaccine dose 2 and, analysed by the unpaired Student’s t-test, there was no significant difference between the two groups (P > 0.05). However, 4 and 9 weeks after dose 2, the trend was towards significantly higher titres in the calves from unvaccinated dams (P = 0.034 and 0.002 respectively) and when peak titres were compared, again the means were significantly higher in the calves from unvaccinated dams than in those from vaccinated mothers (P = 0.006). In both groups, however, the titres were not lasting and mostly had fallen close to baseline by 5–6 months after dose 2, with no significance between the two groups from 2 to 3 months after dose 2.

The results indicate that maternal antibody does interfere to some extent with the vaccine response in the calf, and this should perhaps be taken into account when planning vaccination schedules in premises experiencing anthrax. In the calves from vaccinated dams, 5 that received dose 1 at 9 weeks of age did not develop significantly different peak titres from 3 that received dose 1 at 5 weeks. The overall inference is that protection should be left to maternal antibody in calves from vaccinated cows and vaccination of the calves should not commence until at least 3 months of age.

Another consideration is illustrated in the finding that the anthrax attack rate in beef calves < 6 months of age was significantly lower than in older beef cattle during epizootics (Fox et al., 1977; see also section 3.3.7). This lower risk may be related to young beef calves subsisting mainly on their dam’s milk and thus ingesting less contaminated pasture soil and grass. On most affected premises, the cows in these epizootics had not been previously vaccinated, thus eliminating maternal antibody as a factor. This lower risk of disease offsets to some degree the dampening effect of maternal antibody on vaccine response. This again supports the concept that haste to vaccinate calves after birth is not necessary.

It should be added however that the protective effect of maternal antibody against the natural disease has not been studied. In summary, the vaccination status of young calves on infected properties prior to their first vaccination should be considered highly variable and strict paddock management should be considered part of any anthrax control strategy. Cows and calves should be grazed on well-covered pasture with low incidence of disease history wherever possible.

It may be noted that manufacturers in at least Chile, Italy, Romania and Turkey (Table 18) make special recommendations in relation to vaccination of juvenile animals.

TABLE 18

Manufacturers of livestock anthrax vaccine.

2.12. Vaccination of wild animals

Vaccines are not specifically produced for use in wild animals, but some of the vaccines listed in Table 18 are used by regional wildlife veterinarians and staff for vaccinating wild animals (see sections 8.6.2 & 8.7). India and Myanmar include elephants in their schedules (Table 18), albeit referring to domesticated representatives of the species. Although the prescribed method of administration of the vaccine in livestock is, with rare exceptions, the subcutaneous route (Table 18), frequently wildlife vaccination is done using darts, thereby administering the vaccine intramuscularly. Seemingly this is both effective and not dangerous for the animals (de Vos, 1990; de Vos & Scheepers, 1996; Turnbull et al., 2004b).

2.13. Manufacturers of live spore (veterinary) vaccines

Table 18 is based on equivalent tables in previous editions of these guidelines and updated by means of a questionnaire sent to the chief veterinary officers of Member States by the World Organisation for Animal Health (OIE) in October 2002. It should be noted that:

• A number of manufacturers listed in the 1998 guidelines have ceased production and have been removed from the list.
• Replies were not received from a number of countries, so no update was possible (this has been indicated where appropriate).
• One country indicated that it imports its vaccine from Madagascar, but there was no return from Madagascar itself to include in the list.

4.1. For animals

Antiserum (developed in horses) for serum therapy in animals is produced by, or available from:

• Bioplant, Orlov District, Orlov Oblast, 302501, Russian Federation. Tel:/fax: +7 (0) 862 41 37 08.

4.2. For humans

Purified IgG-F(ab)2 antibodies (developed in horses) for human therapy is produced by:

• Lanzhou Institute of Biological Products, 178 Yangchang Road, Lanzhou, China. Tel: +86 931 8340311 8621; fax: +86 931 834 3199.

A heterogeneous anti-anthrax immunoglobulin consisting of gamma and beta globulin fractions of hyperimmune horse serum is produced by:

• The Research Institute of Microbiology, 610024 Kirov, Oktyabrskiy Prospect, 119, Russian Federation. Tel: +7 (0) 8330 38 15 27.