Innovative review articles by Viggo Bitsch

Review 1    
Epidemiology and Pathogenesis of the
Bovine herpesvirus 2 Infection
Clinical disease in response to initial formation of antibody

Published 2011                 ISBN 978-87-994685-0-8   
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     Bovine herpesvirus 2  (BoHV2) is spread among cattle by the respiratory route.  There are no indications whatsoever of a transmission by insects or milking machines.
     If disease occurs, it appears clinically in two different forms as either pseudo-lumpy skin disease (PLSD) or bovine herpes mammillitis (BHM), but no differences  in pathogenicity of virus strains from PLSD and BHM outbreaks have been found. Both manifestations were recorded in Africa, before the infection was diagnosed in Europe, where it has appeared almost exclusively as BHM. Here, the infection was probably first spread to herds in a region with semen from artificial insemination centres. Later, spread between herds with both acutely and latently infected animals occurred.
     PLSD will be explained as the outcome of a generalized infection, where skin lesions appear as the result of an inflammation process at sites of virus propagation caused  by complement activation, which again is triggered by the action of specific antibody to BoHV2 (complement activation by the classical pathway). This implies that lesions do not appear, until antibody has been produced.
     Naturally occurring clinical cases of BHM have regularly been found antibody-positive in the very early stage of disease when examined by a test of acceptable sensitivity. BHM lesions are accordingly also explained as the outcome of a generalized infection, where inflammatory lesions appear late in the course of the infection at sites of virus propagation immediately after the initial formation of specific antibody. Complement activation by the classical pathwayl explains the sudden appearance of multiple lesions characteristic of PLSD - as well as of BHM, when several lesions develop.
     Tissue damage caused by the inflammatory reactions appears to be aggravated by - or even dependent on - low skin temperature and the associated reduced blood circulation hampering removal of cell-toxic inflammatory substances (and additionally in some cases of BHM probably also by a traumatic influence of milking machines) during the first short period after complement activation. This may explain (1) why udder lesions have developed especially in animals with udder oedema, (2) why clinical outbreaks in Europe have been seen predominantly in the autumn, when the cows were still at pasture during the daytime, and (3) why no skin reactions are observed in most cases of natural infection.
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Review 2

Principal Epidemiological Features of 

Aujeszky's Disease - Suid herpesvirus 1 - 

Infection in Swine and Cattle

Genital infection in swine was common in Europe in the 20th century.

There is evidence that infection in cattle showing 

pruritus on the hindquarters was sexually transmitted 

swine by man.

Published 2015                        ISBN 978-87-994685-1-5

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     Aujeszky's disease – infection with Suid herpesvirus 1 (SuHV1) – is an infection of pigs, which under certain conditions can be spread to several other animal species, usually with a fatal outcome. It has been found world-wide, but has now been eradicated in a number of countries. Denmark is the country, where Aujeszky's disease has been studied most intensively, and the results from investigations of cattle have been of greatest importance for the understanding of the epidemiology of the infection in swine. Denmark was also the first country to initiate eradication  and the first to complete eradication of the indigenous infection. In this review, important features are recapitulated at the end of each section or subsection.
     In cattle, the infection will most often give rise to an intense pruritus of a skin area. In iatrogenic cases the site of virus introduction will determine the site of pruritus, but in natural cases pruritus will appear (1) in the head region or on the chest, which is associated with respiratory infection, or (2) on the hindquarters of females, which is indicative of vaginal infection. In cases of respiratory infection, virus can be found in the mucous membranes of the nasal or pharyngeal cavity of animals with head pruritus, while in cases with chest pruritus virus can be found in lung tissue. In cases with pruritus on the hindquarters, virus can most often be found in the vagina. Pruritus in Aujeszky's disease must be considered a phantom sensation due to stimulation or damage of the central nervous system including sensory ganglia. Practically speaking, respiratory infection of cattle is a dead end infection, as spread among cattle has never been demonstrated. Relatively high virus titres found in mucous membranes in a few cases, however, may be taken to indicate that transmission can not be totally excluded.
     The source of respiratory infection in cattle has always been pigs infected by the respiratory route. Cattle at risk are not necessarily those placed near the infected pigs, as virus in an animal house has been seen transmitted by air currents determined by ventilators over distances of 10-20 meters, in some cases even from pigs in a neighbouring room.
     In swine, the infection was considered to be exclusively respiratory for a long time, and naturally occurring genital infection was not demonstrated until 1981. In herds with outbreaks in cattle characterized by pruritus on the hindquarters (vaginal infection), respiratory infection of pigs was never observed, but a sow had characteristically been served by a foreign boar from 5-14 days earlier. In some such cases investigated, genital infection was confirmed in sows on the same farm, which clearly linked cases in cattle with a posterior localization of pruritus to a concurrent genital infection of swine. Naturally occurring genital infection has later been found also in wild pigs in the USA.
     Respiratory infection of pigs was demonstrated late in the history of the disease. The first outbreak in Denmark was in 1964, and in the preceding 33 years there had been only 3 outbreaks in cattle showing an anterior localization of pruritus indicative of respiratory infection, but close to 60 outbreaks, where the cattle showed a posterior localization of pruritus indicative of genital infection.
     The development of the disease situation in pigs in Denmark has clearly illustrated that SuHV1 has the ability to change in degree of pathogenicity over time. Changes occurred in two steps. In the early 1960's respiratory strains developed, which were spread rapidly between herds due to animal contacts, mainly by trade, and later in the 1970's strains developed, which had an even higher degree of pathogenicity to both cattle and swine. These new strains were found to cause formation of syncytia in tissue cultures  in contrast to earlier isolates from traditional outbreaks. And that the new respiratory strains and the syncytial strains had not been introduced from abroad was confirmed with absolute certainty by restriction fragment pattern analyses of virus DNA. 
     That syncytial virus strains were more virulent to swine than non-syncytial strains was later substantiated by results from examination of isolates from England and Northern Ireland.
     As concluded from the studies of respiratory SuHV1 infection in cattle, the decisive spread of a respiratory infection among swine in a ventilated animal house will be by air currents over many meters determined by the ventilation system and not by close animal-to-animal contacts. This feature also illustrates that during an acute outbreak in a swine herd considerable amounts of virus will be blown out into the surroundings by ventilators, exposing neighbouring herds at a risk of infection. Early observations in Denmark allowed the conclusion that airborne spread between swine herds may occur over several kilometres, but after eradication of the indigenous infection, new virus strains were introduced from abroad, which demonstrated that airborne spread of virus between herds took place over even 10 to 30 kilometres. Syncytial strains of SuHV1 have shown to possess a pronounced tendency to airborne transmission among swine herds, which implies that if a syncytial strain is first introduced into an area, it will be likely to be the prevailing type in that area 
within a few years .

     The special manifestation of Aujeszky's disease in cattle showing pruritus on the hindquarters was regularly associated with use of a boar from a boar centre for natural service of a sow shortly before appearance of the clinical disease. In most cases examined, virus was found in the vagina of the affected bovine animals, although at low titres, and in three outbreaks – the only cases investigated early enough to be successful - virus was demonstrated in the vagina of a sow. It was found that animal sodomy most likely played a role in the transmission of the genital infection from swine to cattle, and this conclusion is further substantiated by comprehensive supplementary information given in this review article. From the fact that genital infection in cattle is closely correlated with contemporary genital infection in swine on the same premises and from the many reports over the years on infection in cattle showing pruritus on the hindquarters, it can additionally be concluded that the SuHV1 infection in a great part of the 20th century was maintained as a porcine genital infection in many countries.