Dolores Gavier-Widén

A cohort study to examine maternally-associated risk factors for bovine spongiform encephalopathy

This long-term cohort study, initiated in July 1989, was designed to examine maternally-associated risk factors for bovine spongiform encephalopathy (BSE), forming part of the epidemiological research programme to assess the risks of non-feedborne transmission of BSE. In this study, the incidence of BSE in offspring of cows which developed clinical signs of BSE is compared with that in offspring, born in the same calving season and herd, of cows which had reached at least six years of age and had not developed BSE. All offspring were allowed to live to seven years of age. The results indicate a statistically significant risk difference between the two cohorts of 9.7 per cent and a relative risk of 3.2 for offspring of cows which developed clinical BSE. However, there is some evidence that this enhanced risk for offspring of BSE cases declined the later the offspring was born, but was increased the later the offspring was born in relation to the stage of the incubation period of the dam. The results presented cannot distinguish between a genetic component and true maternal transmission or a combination of both risks, but they do not indicate either that the BSE epidemic will be unduly prolonged or that the future incidence of BSE in Great Britain will increase significantly.

Recognition of the Nor98 Variant of Scrapie in the Swedish Sheep Population

Within the framework of the active surveillance for transmissible spongiform encephalopathies in sheep in Sweden, 4 cases of the atypical form of scrapie, Nor98, were identified during 2003. Nor98 is a recently recognized and poorly understood variant of scrapie, first described in Norway. The cases were positive by the rapid test (enzyme-linked immunosorbent assay). Immunohistochemical staining showed diffuse thin-granular staining of the cerebellar cortex. Western immunoblotting analysis of specimens of brain stem and cerebellum showed a light band of approximately 12 kDa. Typical scrapie was ruled out based on the confirmatory testing. The affected ewes were from 4 different flocks. They were between 7 and 9 years old. Two were of the ARQ/ARQ genotype, 1 ARR/ARQ, and 1 ARR/AHQ. Two ewes had shown ataxia, and the other 2 had no clinical signs. Whole-flock slaughter was applied, and testing of the flock mates did not reveal additional cases. Nor98 differs from typical scrapie in its epidemiology, frequency of genotypes of sheep affected, clinical signs, microscopic lesions, distribution of scrapie prion protein in the brain, and characteristics of the immunostaining and immunoblotting profiles.

Pathology of natural Mycobacterium bovis infection in European badgers (Meles meles) and its relationship with bacterial excretion

Sixteen European badgers (Meles meles) from three statutory removal operations were studied. Samples of tracheal aspirate, pooled lymph nodes and urine were cultured for mycobacteria. Seven of the badgers were infected with Mycobacterium bovis and had tuberculous pulmonary lesions which varied in severity from extensive granulomatous consolidation to microgranulomas which were not detectable grossly. Tuberculous lesions were also observed in the upper respiratory airways, intestines, kidneys, spleen, liver, thymus, pleura and lymph nodes. One badger had tuberculous bite wounds. The histopathological characteristics of the tuberculous reactions and the associated tissue damage in various organs, together with the gross pathology, indicate that both mildly and severely infected badgers have the potential to excrete M bovis by several routes.

Identification of a Mycobacterium bovis BCG Auxotrophic Mutant That Protects Guinea Pigs against M. bovis and Hematogenous Spread of Mycobacterium tuberculosis without Sensitization to Tuberculin

ABSTRACT Tuberculosis remains one of the most significant diseases of humans and animals. The only currently available vaccine against this disease is a live, attenuated vaccine, bacillus Calmette-Guérin (BCG), which was originally derived from Mycobacterium bovis and despite its variable efficacy is the most widely administered vaccine in the world. With the advent of the human immunodeficiency virus-AIDS pandemic concern has been raised over the safety of BCG. Moreover, since BCG sensitizes vaccinated individuals to the tuberculin test, vaccination with BCG prevents diagnosis of infection in vaccinated individuals. Recently, auxotrophic strains of BCG have been generated by insertional mutagenesis which have been shown to be safer than the parent BCG strain following administration to mice with severe combined immunodeficiency disease. These strains have also been shown to give comparable protection against intravenous and intratracheal challenge of BALB/c mice with M. tuberculosis relative to conventional BCG. Here we report that one of these mutants, a leucine auxotroph of BCG, conferred significant protection of the lungs and spleens of guinea pigs infected with M. bovis and protection of the spleens of guinea pigs infected with M. tuberculosis in the absence of a cutaneous hypersensitivity reaction to tuberculin. Therefore, protective immunity to tuberculosis may, at least in part, be achieved without sensitization to the tuberculin skin test. These results indicate that it may be possible to develop a new generation of vaccines based on BCG that are protective, are safe for use in the immunocompromised, and do not preclude the use of the tuberculin skin test in both humans and animals.

Pathology of bovine tuberculosis in the European wild boar (Sus scrofa)

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Antigen Specificity in Experimental Bovine Tuberculosis

ABSTRACT This report describes the kinetics of T-cell responses to a panel of mycobacterial antigens (PPD-M, PPD-A, ESAT-6, Ag85, 38kD, MPB64, MPB70, MPB83, hsp16.1, hsp65, and hsp70) following experimental infection of cattle with Mycobacterium bovis. Increased antigen-specific lymphocyte proliferation, gamma interferon, and interleukin-2 responses were observed in all calves following infection. Positive lymphocyte proliferation and cytokine responses to PPD-M and ESAT-6 were observed throughout the infection period studied. In contrast, responses to all other antigens were more variable and were not constantly present, suggesting that antigen cocktails rather than individual antigens should be used for immunodiagnosis. The detection of cytokine responses in the absence of lymphocyte proliferation, particularly during the early stages of infection, suggests a role for antigen-specific cytokine readout systems in the early identification of M. bovis infection in cattle.

Vaccination of Guinea Pigs with DNA Encoding the Mycobacterial Antigen MPB83 Influences Pulmonary Pathology but Not Hematogenous Spread following Aerogenic Infection with Mycobacterium bovis

ABSTRACT Protection of cattle against bovine tuberculosis by vaccination could be an important control strategy in countries where there is persistent Mycobacterium bovis infection in wildlife and in developing countries where it is not economical to implement a tuberculin test and slaughter control program. The main aim of such a vaccination strategy would be to reduce transmission of infection by reducing the lung pathology caused by infection and preventing seeding of the organism to organs from which M. bovis could be excreted. Recent reports of successful DNA vaccination against Mycobacterium tuberculosis in small-animal models have suggested that DNA vaccines act by reducing lung pathology without sensitizing animals to tuberculin testing. We therefore evaluated the ability of vaccines consisting of DNA encoding the mycobacterial antigens MPB83 and 85A to reduce lung pathology and prevent hematogenous spread in guinea pigs challenged with a low dose of aerosolized M. bovis. Vaccination with MPB83 DNA reduced the severity of pulmonary lesions, as assessed by histopathology, and resembled M. bovis BCG vaccination in this respect. However, unlike BCG vaccination, MPB83 DNA vaccination did not protect challenged guinea pigs from hematogenous spread of organisms to the spleen. In contrast, vaccination with antigen 85A DNA, a promising DNA vaccine for human tuberculosis, had no measurable protective effect against infection with M. bovis.

The status of tularemia in Europe in a one-health context: a review

The bacterium Francisella tularensis causes the vector-borne zoonotic disease tularemia, and may infect a wide range of hosts including invertebrates, mammals and birds. Transmission to humans occurs through contact with infected animals or contaminated environments, or through arthropod vectors. Tularemia has a broad geographical distribution, and there is evidence which suggests local emergence or re-emergence of this disease in Europe. This review was developed to provide an update on the geographical distribution of F. tularensis in humans, wildlife, domestic animals and vector species, to identify potential public health hazards, and to characterize the epidemiology of tularemia in Europe. Information was collated on cases in humans, domestic animals and wildlife, and on reports of detection of the bacterium in arthropod vectors, from 38 European countries for the period 1992-2012. Multiple international databases on human and animal health were consulted, as well as published reports in the literature. Tularemia is a disease of complex epidemiology that is challenging to understand and therefore to control. Many aspects of this disease remain poorly understood. Better understanding is needed of the epidemiological role of animal hosts, potential vectors, mechanisms of maintenance in the different ecosystems, and routes of transmission of the disease.

A review of infection of wildlife hosts with Mycobacterium bovis and the diagnostic difficulties of the 'no visible lesion' presentation.

Abstract The pathology, frequency and diagnostic implications of ‘no visible lesion’ (NVL) tuberculosis (Tb), i.e. infection with Mycobacterium bovis in the absence of macroscopic lesions, are described in a wide taxonomic range of wildlife hosts. Information collected and evaluated on the definition and occurrence of NVL Tb, histopathological characteristics, post-mortem techniques to detect minimal lesions, and diagnostic difficulties revealed most Tb-infected individuals with NVL had minute tuberculous lesions, which were difficult to see by eye. Acidfast organisms (AFO) were sometimes detected in the lesions. Ideally, mycobacterial culture of pools of lymph nodes and/or oropharyngeal tonsils is necessary for the accurate diagnosis of Tb in the absence of macroscopic lesions. At a very minimum, the diagnostic methods applied for studying the prevalence of Tb in the population should be clearly described, to allow comparison between studies.

Detection of mecC-Positive Staphylococcus aureus (CC130-MRSA-XI) in Diseased European Hedgehogs (Erinaceus europaeus) in Sweden

Recently, a novel mec gene conferring beta-lactam resistance in Staphylococcus aureus has been discovered. This gene, mecC, is situated on a SCCmec XI element that has to date been identified in clonal complexes 49, 130, 425, 599 and 1943. Some of the currently known isolates have been identified from animals. This, and observations of mecA alleles that do not confer beta-lactam resistance, indicate that mec genes might have a reservoir in Staphylococcus species from animals. Thus it is important also to screen wildlife isolates for mec genes. Here, we describe mecC-positive Staphylococcus aureus (ST130-MRSA-XI) and the lesions related to the infection in two diseased free-ranging European hedgehogs (Erinaceus europaeus). One was found dead in 2003 in central Sweden, and suffered from S. aureus septicaemia. The other one, found on the island of Gotland in the Baltic Sea in 2011, showed a severe dermatitis and was euthanised. ST130-MRSA-XI isolates were isolated from lesions from both hedgehogs and were essentially identical to previously described isolates from humans. Both isolates carried the complete SCCmec XI element. They lacked the lukF-PV/lukS-PV and lukM/lukF-P83 genes, but harboured a gene for an exfoliative toxin homologue previously described from Staphylococcus hyicus, Staphylococcus pseudintermedius and other S. aureus of the CC130 lineage. To the best of our knowledge, these are the first reported cases of CC130-MRSA-XI in hedgehogs. Given that one of the samples was taken as early as 2003, this was the earliest detection of this strain and of mecC in Sweden. This and several other recent observations suggest that CC130 might be a zoonotic lineage of S. aureus and that SCCmec XI/mecC may have originated from animal pathogens.