of Veterinary Medicine
Day of lectures at the Friedrich-Loeffler Institute
This was our second day at the world-renowned birth place of virology, the Friedrich-Loeffler Institute. The lectures were held in the beautiful library that has several large stain-glass windows that have a wonderful view of the Baltic sea.
Lecture 1: Transmissible Spongiform Encephalopathy (TSE) strain variability in sheep and cattlePresentor: Dr. Anna Balkema-Buschmann: Deputy director for the Institute for novel and emerging infectious diseasesTSE’s are a group of neurological disease caused by deformed or “mutated” natural occurring proteins known as prions. Some of the diseases that are believed to be caused by these prion proteins are: Bovine Spongiform encephalopathy (BSE) in all ruminants; Scrapie in sheep; Chronic Wasting Disease (CWD) in deer; Creutzfeldt-Jakob’s disease and Kuru in humans. Bovine spongiform encephalopathy (BSE, or AKA “Mad Cow disease”) is a serious , world-wide concern due it’s zoonotic potential. Ingestion of the brain or spinal cord from a BSE infected cattle has been shown to cause a TSE in humans, known as variant Creutzfeldt-Jackob Disease (vCJD) .As a result of these concerns, Germany began to test for BSE in 1998 during slaughter, and detected it’s first case in November 2000. In order to avoid a BSE positive animal entering the food chain there is an approved ELISA rapid test. Every head of cattle that is slaughtered has to be tested if >48 months of age. Presently the numbers of BSE cases are steadily decreasing, and fortunately so are the cases of vCJD.The clinical signs of BSE in cattle are subtle and mainly behavioral, hence the name “mad cow disease”. Clinical signs take a while to develop, and usually present as hypersensitivity to sound, ataxia, hypermetria, that progresses to generalized paresis. Often tremors and muscle fasciculations occur, and occasionally intense pruritis. The route of infection is through ingestion of animal byproducts such as bone meal, brain and spinal cord from cows infected with BSE.Like BSE in Cattle, Scrapie is the most common TSE of sheep and goats. Although not believed to hold the same zoonotic potential as BSE, the clinical signs of scrapie are indistinguishable from those of BSE, and so it is imperative that they be distinguished through testing. Testing for Scrapie in Germany began in 1992; any sheep or goat >18 m must be tested in the EU.The FLI has done research looking into understanding the pathogenesis behind BSE, specially at how the prion protein travels from the GI tract to the brain. Through careful studies involving 56 orally infected cattle, the proposed transmission is ileum Peyer’s patches large ganglia spinal cord brain.In addition, the FLI has also managed to create a transgenic mouse that is is a murine Prp KO and only contains the bovine Prp (prion protein). These KO mice are 10 x more sensitive to BSE than cattle, making them an excellent tool for a bioassay. In addition to learning about classical BSE and Scrapie, we also heard about atypical forms of these diseases. Atypical BSE and Scrapie are believed to be purely spontaneous forms of the disease that occur in older animals (>8 years of age in cattle).Lastly, CWD was discussed to highlight that it is not a problem in Europe like it is in the United sSates. Surveillance is currently being done in deer, however no cases have been reported so far.
Lecture 2: FOOT AND MOUTH DISEASEPresenter: Dr. Bernd Haas: Head of the National research laboratory for Foot and Mouth disease (FMD).FMD is a highly contagious disease that can cause devastating economic impacts wherever it is allowed to spread. Fortunately in the United States, we have been free of FMD since 1929; Canada, Australia, and New Zealand are also free of the disease. The most recent outbreaks (2010-2011) have been in Korea, Japan, and even within the EU (Bulgaria) in a wild boar. In order to highlight the huge economic impact that FMD can have, both Korea and Japan have had outbreaks in the past year, and over 3 million animals were killed resulting in a total loss of $4.8 billion in damages. Countries in South America have fortunately been able to control FMD through intensive vaccinations, however their beef trade with US is severely regulated due to the fact that they are not completely FMD free. Turkey has been trying to become a member of the EU for a long time, however have not been allowed to enter because they still have FMD outbreaks. The case in the wild boar in Bulgaria was discovered because of a well-educated hunter that detected vesicles on the boar’s feet. Fortunately the hunter’s in the EU have to pass a very difficult test in order to have a hunting license and one portion of this test is to recognize potential disease and the lesions associated with them. Clinical signs• Hyper-salivation(due to oral vesicles and ulcers)• dramatic drop in milk production• oral and coronary band vesicles• animals are often non-ambulatoryAlthough FMD is very contagious, and morbidity is 100%, mortality is surprisingly very low. The real impact is that it is severely debilitating to any animal infected, and basically makes their production value drop dramatically. In addition, once an animal is allowed to recover from FMD a carrier state can develop in ruminants that can last for up to 5 years. For these reasons, all animals have to be culled when they are found to be positive for FMD. Fortunately in the EU, they have a mandatory animal identification system which helps to track all movement of cattle. This would prove to be very beneficial in the case of a FMD outbreak, because all potentially infected animals could be quickly identified and tested to limit the spread of the disease.
Lecture 3: ORBIVIRUS DISEASES OF DOMESTIC ANIMALSPresenter: Dr. Michael EschbaumerOrbiviruses are arthropod-vectored and the etiological cause of three very important diseases in the veterinary field: Blue tongue virus(BTV) in sheep , African Horse Sickness (AHS), and Epizootic Hemorrhagic Disease (EHD) in deer.The main vectors are the Culicoides spp. midges; the virus is amplified in the midge’s salivary glands and then transmitted through their bite. While this route of infection does allow for faster transmission of the virus, it also limits the spread based on the life cycle and habitat of the vector. BTV is clinically in-apparent in most hosts, however sheep can be greatly affected. The clinical signs include: fever, nasal discharge, congestion and edema of the muzzle and eventually “cyanosis” of the muzzle and tongue, hence the name “blue tongue”. In addition BTV can cause oral lesions in the mouth of sheep, which could cause it to be treated as a potential FMD case. This can cause 30-70% mortality in sheep.EHD is only really a problem in two areas of the world, North America and Japan. In North America EHD most commonly causes a peracute death in white tail deer; although it can infect cattle, clinical signs are rarely seen. However in Japan, EHD causes Ibaraki disease (Blue tongue-like disease) in cattle.
AHS is an extremely
dangerous disease that can cause up to 95% mortality in naïve populations of horses. It’s clinical signs are swelling of the supraorbital fossa and severe pulmonary edema. Fortunately this virus is only seen in Africa because the vector is not found anywhere else. Midge surveillance is currently being done to constantly monitor for any shift in habitat boundaries for the common vectors of these three diseases, especially that of AHS. Lecture 4: AVIAN INFLUENZAPresenter: Dr. Christian GrundAvian Influenza is a very important topic due to it’s zoonotic potential. It is common knowledge that in 1918 there was a great influenza pandemic that killed approximately 21 million people was an avian influenza virus (H1N1). Influenza viruses have a segmented RNA genome that rely on an error-prone RNA polymerase for transcription. This allows for two routes of genetic change to occur, antigenic drift and antigenic shift. Antigenic drift relies on small mutations to slowly cause genetic variations in the virus; A\antigenic shift allows for rapid mutations following “reassortment” of the virus after two separate influenza strains infect a single cell. Influenza’s genetic variability allows for it to adapt quickly, have a wide range in virulence, and to gives it the ability to infect many potential host species. Unfortunately, Germany had an outbreak of H5N1 a highly pathogenic avian influenza strain (HPAI) in Spring of 2006 and Summer of 2007. Because most of the spread of avian influenza is through water fowl, the FLI was literally at the center of the outbreak. The island of Riems is a the home of 15% of Northern Europe’s waterfowl in the Winter, and was recently declared a European bird sanctuary. During this outbreak, fortunately there was no spread to the poultry industry, however the virus was able to spread into 3 duck farms. As discussed earlier influenza has the potential to infect many host species, and on the neighboring of Rügen in 2006 there were 3 reports of natural infection in domestic cats. Lecture 5: RABIES A GLOBAL PERSPECTIVEPresenter: Dr. Thomas Müller, head of the Rabies laboratory (an OIE lab)Rabies is a fatal zoonotic disease that is of concern everywhere in the world. It is a Lyssavirus that is transmitted through the bite of a wide variety of mammals. For instance, in Europe, the red fox is the main reservoir; in the United States, bats, skunks, coyotes, and raccoons are common carriers. In fact, in the U.S., raccoons are the most commonly infected mammals, however bats are the most likely to transmit rabies to humans. In 2010, Europe began a prevention program that set out oral rabies vaccines targeting the red fox. Many EU countries are involved (Spain, Portugal, Switzerland, Hungary, UK, France, Netherlands, and Sweden), however there is still a need to start vaccine programs in more EU countries, especially those in Eastern Europe. This program was achieved through political commitment, surveillance, diagnostics, and commitments of WHO/OIE. Fortunately, the EU has promised to finance 50% of the cost of the rabies vaccine bait. In most developed countries, rabies is a well-known disease that is not always considered a huge threat due to the low incidence of human cases. However, during the talk we were reminded that in third world countries 1000s of people die due to rabies each year (annual death distribution: Africa: 23,700, Asia: 31,500, India: 19,000). In these third world countries, dogs are the biggest problem; canine rabies is no longer a big problem in US and Europe. Rabies is considered a neglected disease a long with lymphatic filiariasis, GI parasites, leishmaniasis, and schistosomiasis. Out of all the neglected diseases rabies ranks 5th based on disability adjusted life year (DALY) scores; it would rank at the top if it weren’t for the widespread intervention currently in place in many developed countries. In addition to the oral vaccine bait previously discussed, there is also a worldwide rabies initiative known as World Rabies Day. World Rabies Day is an initiative of the Global Alliance for Rabies Control. This event occurs annually on September 28th, the anniversary of Louis Pasteur’s death (developer of the first rabies vaccine). The mission of World Rabies Day is to raise awareness about the impact of human and animal rabies, how easy it is to prevent it, and how to eliminate the main global sources. This initiative has a very informative website: http://www.worldrabiesday.org/Lecture 6: BATS AND RABIESLecturer: Dr. Conrad FreulingBats are reservoirs for many dangerous zoonotic diseases such as: Nipah, Hendra, Sars virus (Corona virus), Ebola, Marburg, and Lyssaviruses. Rabies was the first known bat transmitted zoonotic disease; in the 16th century, it was first seen following vampire bat bites in Panama. The US is the only place were bat rabies is present; everywhere else has Lyssaviruses, just not the strain that causes rabies. OIE rabies free status is NOT altered if bat rabies is present There has been a discovery of a new Lyssavirus (#13!). In 2008 it was first described in a Natter’s bat that was submitted to the University of Hannover. Immunohistochemistry (IHC) confirmed it was Rabies but could not determine the strain. It was then sequenced and has now has been identified as a new strain known as Bokeloh bat Lyssavirus found most often in the Myotis genus (mouse-eared bats)Afternoon session:The afternoon was spent with Dr. Jens Teifke, a board certified veterinary pathologist, who gave us a whirl-wind tour/quiz of gross and microscopic images of common diseases such as foot and mouth disease, classical and African swine fever, malignant catarrhal fever (Ovine Herpes Virus-2), rabbit hemorrhagic disease, avian influenza, etc. The evening was spent in Wieck, a picturesque fishing village on the Baltic Sea.
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