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Introduction

Bovine spongiform encepholopathy (BSE), caused by an abnormal prion protein  was first diagnosed in the United Kingdom in 1986, and by December, 2002, a total of 183,132 British cattle were affected (1,2,3,4). BSE belongs to the transmissible spongiform encephalopathy (TSE) group, which affects humans and animals. In humans, the syndromes include Creutzfeldt-Jacob Disease (CJD), Gerstmann-Straussler-Scheinker Syndrome (GSS), Kuru, Fatal Familiar Insomnia (FFI), and in  animals: sheep (scrapie), mink (transmissible mink encephalopathy), deer and elk (chronic wasting disease) (5). The diseases in cats (feline spongiform encephalopathy) and captive ungulates in the UK are also associated with the BSE agent.

Epidemiological studies in the UK have shown that BSE was caused by contamination of cattle feed with a scrapie-like agent that was  found in meat and bone meal (MBM)  used as a protein additive in cattle feed (6).

BSE became extremely important as a zoonosis because of its apparent link with a new variant (nvCJD) of CJD, of which the first 10 cases were reported in 1996 (7). The most likely explanation for the emergence of nvCJD in humans was exposure to an apparently new variant of CJD, homologous to that causing   BSE, and believed to be an abnormal form of the scrapie prion protein (PrPres) (8).

The origins of BSE

The origin of BSE continues to intrigue neurologists, scientists and the general public. After an exhaustive examination, Wilesmith et al. (2) proposed in 1988 that the most plausible explanation of its origin was a change in the rendering process used to produce meat and bone meals for livestock feeds during the late 1970's. This change involved the phasing out of the hydrocarbon solvent/steam process for extraction of tallow residues from the greaves, which were used in the production of meat and bone meal. In the absence of solvent/steam treatment it seems possible that the scrapie agent present in some of the processed sheep carcasses and contaminated the final product. The new product was widely marketed throughout the UK infecting cattle and other animals such as domestic cats, zoo felines and ungulates (12,13,14,15,16). A second hypothesis for the BSE epizootic was its triggering by the inclusion of carcasses or organs from cattle with undiagnosed TSE in rendered meat and bone meal, and third explanation was the introduction of carcasses of BSE - infected wild animals imported from Africa. These explanations still reflect the same change in the rendering process because spontaneous cases could presumably have occurred regularly or sporadically for decades if not centuries. Until   December 31, 2002, 121 cases of vCJD were diagnosed in the UK, 6 cases in France (1+1+4: 96/ 99/ 02), 1 case in Ireland (1999), 1 in Italy (2002) and 1 in the USA (2002), which was considered to be a British case because the patient had resided in the UK during the time of infection. (Table 1).

Table 1: Human CJD cases diagnosed by the CJD surveillance unit, Edinburgh, Scotland (1990 - 2002).

At December 31,  2002

Cases of BSE have also been diagnosed exclusively in cattle imported from the UK, and not in local/ autochtonic cattle in the following countries: Canada, 1 case (11/93); Falkland Islands, 1 case (1989); Oman, 2 cases (1998). BSE cases have been diagnosed and continue to appear with the introduction of the new diagnostic tests in various European countries and two non-European countries (Table 2).

Table 2: Number of reported cases worldwide from 1989 to 2002.

At 31 December 2002

Cattle are continually monitored for BSE and BSE is decreasing in the UK. The decrease in numbers of BSE in the UK is shown in Table 3

Table 3: Number of cases of bovine spongiform encephalopathy (BSE) reported in the United Kingdom from 1987 to 2002.

At 31 December 2002

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Materials and Methods

Animals

A 10 year old dairy cow (Delhi) from a Kibbutz herd located on the Golan Heights, died on 20 May 2002 following a two- day illness, characterized by a drop in milk and nervous symptoms including ataxia, teeth grinding and involuntary chewing movements. The cow had calved twins on May 15, 2002 that were subsequently euthanised. Because rabies is endemic in this region and in view of the presented nervous signs, a rabies FA test was performed. Samples from the medulla (Fig.1) at the obex region were taken for immunoblotting using the Prionics-check test, and a relevant sample was placed in 10% neutral buffered formalin for histopathology and immunohistochemistry.

Fig. 1 Sampling the medulla for BSE testing.

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Results

The rabies FA test was negative and the Prionics check test was positive (Fig. 2).

A paraffin section of the medulla oblongata of the obex region was performed and stained by HE. Marked spongiform changes in the neuropil of the nucleus of the solitary tact were seen (Fig. 3); and minimal vacuolation in the vagal and olivary nucleus was observed.

Immunohistochemistry for PrPsc using the monoclonal antibody F89/160.1.5, showed marked accumulation of PrPsc in the vagus nuclear complex, the nucleus of the solitary tract and other nuclei of the medulla oblongata (Fig. 4). Paraffin sections and a paraffin block were submitted to the OIE Reference Laboratory, University of Bern (Switzerland) and to the Veterinary Laboratories Agency, Weybridge (UK) for confirmation of our diagnosis of BSE. Both OIE reference laboratories confirmed BSE.

Fig. 2 Immunoblotting Prionics-Check test positive

Fig. 3:   Solitary tract nucleus, spongiform changes conistent with BSE

Fig. 4 Immunohistochemistry , positive staining with the Mab F89/160.1.5.

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Discussion

Epidemiological investigation and discussion

The cow "Delhi" belonged to a herd of 1,300 dairy heifers and cows. The cow had been bought by a kibbutz on the Golan Heights as a two-year-old heifer from another kibbutz in the Jordan Valley. The affected cow had two living cohort mates (both born within twelve months of the affected cow in the herd of origin). The cow had one living female calf and one male calf. All these animals were euthanized, and examined for BSE and were negative. An immediate standstill ban was placed on both herds. Compulsory testing of all slaughtered bovines over thirty months old was initiated on July 1 2002. Since this date, each slaughtered bovine in this age group is compulsorily examined before release for human consumption. Within this testing scheme, 7952 animals have been tested until December 31, 2002. Since January 1 2002, a total of 8706 bovine brains have been examined, of which 7952 were from slaughterhouses prior to release for human consumption. The specific risk materials (SRM) are removed from all cattle older than 12 months and incinerated. The active surveillance for BSE in all fallen stock continues. The flowing table is updated weekly and posted on the WEB http://agri3.huji.ac.il/~yakobson/bse/      

Until July 29,2002 Israel was considered free of BSE (19) based on measures taken by†the Veterinary Services and Animal Health (VSAH) (OIE-BSE, risk analysis, Assessment and Management in Israel, November 1998). To prevent BSE from entering Israel, VSAH have taken the following measures (17):

1. A ban on the importation of ruminant meat and bone meal (MBM) from the United Kingdom (UK) is in force since December 1988. In fact no ruminant MBM from the UK had been imported to Israel for at least 5 years prior to the ban.

2. A ban on the importation of MBMs of mammalian origin from all countries effective since July 1990.

3. State regulations, banning the feeding to all farm animals, including poultry and   fish with meat and bone meals (MBMs) derived from mammalian food animals, are in force since August 1996. Consequently, recycling of local mammal material has been discontinued since 1996, meaning that local rendering plants do not process animal waste from mammalian origin. Since 1996, rendering plants exclusively for poultry exist in Israel.

There is, so far, no clear explanation for the first BSE case in Israel.

The importation of MBMs of mammalian origin was banned since December 1988 from UK and from all countries since July 1990 but the importation of feather and poultry meal from the UK has been permitted since 1989. The permit was issued after receiving the assurance of the UK authorities that these meals were produced in officially inspected plants that deal exclusively with poultry material. Each consignment was accompanied with a confirmatory official certificate. These consignments continued until 2001, but the possibility of cross-contamination of these meals seems remote.

In a recently published opinion of the Scientific Steering Committee (SSC) of the EU, a more plausible source was indicated, namely imports of MBM, from 1986 to (June) 1990, from five continental European countries, which are regarded in retrospect to have been “risk countries” during this period.

Another possible source of BSE could have been tallow of European origin that is included in calf- milk substitutes.

If none of those possibilities is confirmed, and provided no additional BSE cases are found, the first and only case in Israel will be classified as “sporadic”.

Table 4: Bovine brains examined for BSE in Israel in 1991 - 2002.

As of December 31, 2002

Table 5: Israel: BSE testing according to source of cattle and age group, 2002

 [1] Fallen cattle: Central incinerator

[2] €Slaughtered healthy cattle >30 months, tested††in abattoirs prior to release (initially at random ; compulsory since 1.7. 2002)

[3] Cadavers sent to KVI for PM (CNS signs)

N.A. = not available

At 31 December 2002

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