Epidemiological study on BSE outbreak in Japan

The aim of this study is to identify, as hypotheses, all feasible sources and routes of infection for the BSE cases in Japan, and to study the probability of each hypothesis. The strategy of this epidemiological study is as follows. 1) BSE risk status in Japan is tentatively divided into 3 stages, i.e., before 1996 April when administrative guidance for feed ban of cattle MBM introduced. After that to 2001 September, the first case of BSE in Japan, then, after 2001 October with real feed ban in the law. 2) Make hypotheses depending on the invasive risk scenarios and propagation risk of BSE in Japan, and they are checked by evidences, case control study or statistics. 3) Grouping of BSE cattle was conducted time sequentially and spatially; that is Group-A (1995-96, born in Hokkaido, Kanto), Group-B (1999 in Kyushu), Group-C (1999-2001 in Hokkaido), Group-D (young cattle born after real feed ban) and Pre-A, Post-D groups. As a result, a milk replacer was considered one of the most probable cause of group-A contamination, and group-C outbreak might be caused by an indigenous BSE propagation of group-A in Hokkaido. If the hypothesis of Holland animal fat as causative material was accepted, however, there are several unexplainable points. Collection of scientific evidences on animal fat impurity and age dependent susceptibility to BSE will be needed to clarify the true causative material.     

Critical Observations on BSE Control in Italy

Eleven native sheep, 1–2 years old, of both sexes were randomly divided into two groups, 6 sheep being allocated to the experimental group and 5 serving as controls. The sheep in the experimental group were fed 80% Tribulus terrestris and 20% alfalfa hay and wheat straw, while the control sheep were given a mixture of 40% alfalfa hay and 60% wheat straw. Clinical signs of hepatogenous photosensitivity were observed from day 11, including reddening and crust formation on the muzzle, nose, ears and eyelids, depression, weight loss, icterus, conjunctivitis, and yellow discoloration of the urine. Laboratory findings on weekly samples indicated significant differences (p<0.05) in white blood cell count, total plasma protein and fibrinogen, total and direct bilirubin, blood urea nitrogen and creatinine concentrations, and aspartate aminotransferase and alkaline phosphatase activities. There were no significant differences in the packed cell volume, in the neutrophil, lymphocyte or eosinophil counts, or in the serum calcium, phosphorus, potassium, sodium or chloride concentrations. At necropsy of the experimental animals, there were various degrees of generalized icterus and the livers were swollen and discolored by bile pigment. Histopathological examination revealed varying amounts of crystalloid material in the bile ducts and renal tubules, hepatocellular degeneration, biliary fibrosis and proliferation, renal tubular necrosis and focal necrosis of cardiac muscle.     

The Role of CEA (Center of Animal Encephalopathies) in the BSE Surveillance: BSE in Italy

Veterinary Research Communications -     

Ten years of BSE surveillance in Italy: neuropathological findings in clinically suspected cases

Between 2001 and 2010, 244 clinically suspected cases of bovine spongiform encephalopathy (BSE) were reported in Italy. This report summarizes the neuropathological findings in cattle displaying clinical signs consistent with a diagnosis of BSE. All animal specimens were submitted for confirmatory testing; samples testing negative underwent neuropathological examination to establish the differential diagnosis. Immunohistochemistry for scrapie prion protein (PrPSc) at the level of frontal cortex was carried out to exclude atypical BSE. Neuropathological changes were detected in 34.9% of cases; no histological lesions were found in 52.3% of subjects; 12.8% of samples were found unsuitable for analysis. BSE was detected in one case, but no cases of atypical BSE were observed. This study identified the diseases most commonly encountered in the differential diagnosis of BSE; furthermore, it demonstrated that the surveillance system is necessary for monitoring neuropathological disease in cattle and for the detection of BSE cases.     

Epidemiological model development using BSE as an example--observations from a statistical viewpoint

Since first BSE cases in cattle born in Germany were recognized, questions have been raised concerning the future development of the disease and the epidemiological dynamics of BSE, and, consequently, modelling approaches that might answer these questions. The database for such modelling efforts is formed by BSE incidence numbers or incidence rates, broken down by age at onset of clinical disease, and by time of onset or time of birth, respectively, from available information gathered for suspect and confirmed BSE cases. To describe such data, statistical age-period-cohort-models and two epidemiologically/biologically oriented modelling approaches are discussed: the so-called three-factor-model used by the Central Veterinary Laboratory of the British Ministry for Agriculture, Fisheries and Food (MAFF) (now Department of the Environment and Rural Affairs (DEFRA)), and a back-calculation-model developed by a working group at the University of Oxford. Resulting model calculations are supposed to serve several purposes, including a prediction of future BSE incidence numbers, and, especially based on the "Oxford"-model, a back-calculation of the epidemic of BSE infections from the epidemic of clinically diseased BSE cases. Analysis of these approaches reveals some problems even to identify unique age, period, or birth cohort effects. An additional estimation of epidemiological components of BSE, for example the frequency distribution of incubation times, has to rely on further assumptions that cannot be validated by the model fit as such. Therefore, modelling results should be interpreted with caution. However, the limitations demonstrated by this discussion emphasize the need for specific studies to investigate certain aspects of the BSE epidemic, for example the distribution of times from infection to disease onset, and for the centralised collection of valid and detailed population data for cattle.     

Epidemiological study of the cystic echinococcosis in Morocco

The objectives of this epidemiological study on cystic echinococcosis (CE) in Morocco (2001-2004) were to update the prevalence of CE in different animal species living in the most important areas of the country and to collect protoscoleces and germinal layers for genetic research purposes. The post mortem inspection concerned 2948 sheep, 2337 goats, 618 cattle, 482 camels and 455 equines (325 horses, 60 mules and 70 donkeys) in five different regions: the Rif (Mediterranean coast and high mountains of the Rif), the Loukkos (Atlantic northwest plain), the center (Rabat and Casablanca regions), the Middle Atlas mountains and the south (arid and semi desert areas). The global CE infection prevalence rates obtained were 22.98% in cattle, 10.58% in sheep, 12.03% in camels, 17.80% in equines and 1.88% in goats. The infection rates were especially high in the Middle Atlas in cattle (48.72%) and in the Loukkos in cattle and sheep (37.61 and 31.65%, respectively). The majority of infected cattle (49.6%) and sheep (52.1%) had hydatid cysts in both liver and lungs. Except for cattle, the liver was more infected than lungs in all the other animal species. Animals more than 5 years old were the most infected in all species. The mean CE infection rates of these animals were about 56% in cattle, 40% in sheep, 20% in camels, 17.80% in equines and 7% in goats. These rates were much higher in the Loukkos (85% of cattle and 59% of sheep) and in the Middle Atlas (68% of cattle and 45% of sheep) than in the other regions. Results showed that Echinococcus granulosus is in an endemic steady state with no evidence of protective immunity in the intermediate hosts. The mean numbers of infections per year are 0.099 for cattle, 0.063 for sheep, 0.03 for camels and 0.010 for goats.     

Effectiveness of the BSE interventions in Japan

Using a stochastic simulation model, we estimated the effectiveness of the three BSE interventions (SRM removal, post-mortem testing and cohort culling) in Japan, in terms of the amount of bovine ID50 that would be prevented from entering the human food supply and the number of life years that would be saved from resulting vCJD cases. The average reduction of the BSE load on the human food supply under SRM removal was 97% over the period from 2002 to 2009. The average reduction of the BSE load under most-mortem testing was 83% over the period from 2002 to 2007. The risk reducing effect of the three interventions combined was 99%. The maximum number of life years saved by the three interventions combined was 40.84 in 2006.     

Estimating the prevalence of BSE in dairy birth cohorts and predicting the incidence of BSE cases in Japan

Following the detection of the first case of BSE in Japan in September 2001, four million cattle were subjected to a rapid test for BSE up to the end of 2004. A further 10 cases were detected in the dairy cattle population and two cases in Holstein steers. We focused on the dairy population and estimated the prevalence of BSE infected animals within each birth cohort for the years 1992–2001 using Bayesian inference. From this we were able to predict historic and future trends in the number of infected animals culled from each cohort and whether or not they could be detected using a rapid test. Assuming that BSE infectivity entered Japan in 1995, 225 (95%CI: 111–418) infected animals were predicted to have been culled from 1995 to 2001, of which 116 (56–219) would have been slaughtered for human consumption, and 33 (12–65) cases would have been detected during this period if a BSE surveillance program as comprehensive as the one in place as of April 2004 was applied. Assuming that BSE infectivity entered Japan in 1992, 905 (366–4633) infected animals were predicted to have been culled from 1992 to 2001, of which 694 (190–2473) would have been slaughtered for human consumption, and 201 (53–693) cases would have been detected during this period. Assuming the April 2004 level of surveillance continues and that the feed ban introduced in 2001 is completely effective, 18 (3–111) BSE cases are likely to be detected in the future. The BSE epidemic in Japan most likely reached a peak between 1998 and 2001 and should be eradicated around 2012.     

Pathogenesis of BSE

Before the emergence of bovine spongiform encephalopathy (BSE) and recognition of its zoonotic potential, the major example of the transmissible spongiform encephalopathies (TSEs) of animals was scrapie of sheep. But there is no evidence that scrapie transmits naturally to any species other than sheep and goats. The pathogenesis of scrapie has been studied most in experimental laboratory rodent species. In most experimental models of scrapie, after peripheral non-neural routes of infection, replication of the agent can first be detected in lymphoreticular system (LRS) tissue. When the route of introduction of agent into the body is localized, initial involvement will be in LRS tissue draining the infection site. Thereafter, there is a striking amplification of the agent in the LRS and spread by lymphatic/haematogenous routes, giving widespread dissemination in the LRS. This precedes replication in the CNS, but is not the means by which infection reaches the CNS. There is now substantial evidence from experimental models of scrapie that involvement of the CNS is by peripheral nervous system (PNS) pathways. In some models employing oral exposure the earliest localized LRS replication is in the gut-associated lymphoid tissue (GALT) and autonomic PNS routing to the CNS has been implicated. However, the relative importance of different routes of spread of TSEs within the body is determined by a number of host- and agent-dependent factors and, therefore, generalizations from an experimental model to a natural disease across a species barrier may not be appropriate. With the occurrence of BSE and recognition of its food-borne route of transmission via meat and bone meal, has come greater awareness of the probable importance of the oral route of infection in ruminant species affected by TSEs. In consequence, studies have increasingly focused on the natural host species to examine pathogenetic events.     

Pathogenesis of BSE

Before the emergence of bovine spongiform encephalopathy (BSE) and recognition of its zoonotic potential, the major example of the transmissible spongiform encephalopathies (TSEs) of animals was scrapie of sheep. But there is no evidence that scrapie transmits naturally to any species other than sheep and goats. The pathogenesis of scrapie has been studied most in experimental laboratory rodent species. In most experimental models of scrapie, after peripheral non-neural routes of infection, replication of the agent can first be detected in lymphoreticular system (LRS) tissue. When the route of introduction of agent into the body is localized, initial involvement will be in LRS tissue draining the infection site. Thereafter, there is a striking amplification of the agent in the LRS and spread by lymphatic/haematogenous routes, giving widespread dissemination in the LRS. This precedes replication in the CNS, but is not the means by which infection reaches the CNS. There is now substantial evidence from experimental models of scrapie that involvement of the CNS is by peripheral nervous system (PNS) pathways. In some models employing oral exposure the earliest localized LRS replication is in the gut-associated lymphoid tissue (GALT) and autonomic PNS routing to the CNS has been implicated. However, the relative importance of different routes of spread of TSEs within the body is determined by a number of host- and agent-dependent factors and, therefore, generalizations from an experimental model to a natural disease across a species barrier may not be appropriate. With the occurrence of BSE and recognition of its food-borne route of transmission via meat and bone meal, has come greater awareness of the probable importance of the oral route of infection in ruminant species affected by TSEs. In consequence, studies have increasingly focused on the natural host species to examine pathogenetic events.     

BSE in the Netherlands: an update

Up to 2006, there have been 82 cases of BSE in cattle born in the Netherlands. This article reviews the current situation regarding BSE in the Netherlands and summarizes the clinical symptoms of the disease. Data from the Netherlands show that a passive surveillance system, by which farmers and veterinarians have to report suspect clinical cases, has a low sensitivity. The epidemiology of, and risk factors for, BSE are discussed. All the Dutch cases of BSE can be attributed to cross-contamination of feed with meat-and-bone meal. On the basis of information about the epidemic and the cases reported to date, it is anticipated that the number of cases of BSE will continue to decline in the Netherlands and Europe. The European Commission has presented a road map that describes how the European BSE policy can be changed in the short and long term if the current favourable trend in BSE cases continues. It is time for a new phase in the management of BSE but with continued protection of the public's health and eradication of BSE.