Equine Influenza and Herpes Virus – Current Disease Situation
Prof. Dr. Klaus Osterrieder, head of department of veterinary virology in the Freie Universitaet Berlin, and PhD students, enrolled at the Freie Universitaet’s international network university “Dahlem Research School” DRS as well as the GRAKO/IMPRS, organized the symposium “Equine Influenza and Herpes Virus – Current Disease Situation” in Berlin on October 16th 2009.
The meeting gave international experts in the field of equine infectious diseases, researchers, administrative authorities, representatives of pharmaceutical industry and interested guests a platform to discuss and evaluate the current situation and threat as well as future perspectives concerning Equine Influenza (EIV) and Equine Herpesviruses type 1 and 4 (EHV-1 and -4) in different countries. The variety of information ranged from sampling and diagnostic procedures over molecular virology and modelling systems to prophylaxis via vaccination and therapeutics. All participants lauded the idea of bringing together people struggling with the same topic but on different levels of interaction . This attempt did not only succeed at unifying an enormous body of information, different views and valuations, but also offered, based on this knowledge and a better understanding of the situation, the opportunity for new collaborations, new and innovative attempts and solutions in the collective fight against two major problems of equine infectious medicine.
Timo Schippers, first year PhD student in K. Osterrieder’s project group, opened the meeting with a short introduction of the recently founded DRS. The DRS, evaluated and awarded by the excellence initiative, provides an international framework for the academic career development of young researchers. Six students of the Institut für Virologie are enrolled in the PhD program “Biomedical Sciences” within the Natural & Life Sciences branch bringing together veterinarians, pharmacists and biologists. Compared with classical doctoral programs at the Freie Universität, within the PhD program a mentoring team accompanies the students during at least three years of independent research complemented by lectures, specific courses and training in transferable skills.
The first session gave an introduction in current research projects and results.
Jenny Mumford, member of the Cambridge Infectious Disease Centre (CIDC) and director of equine influenza research (Cambridge, UK) gave an overview on Equine Influenza outbreaks, surveillance and the role of the OIE (Office International des Epizooties, World Organization for Animal Health) in disease control. Presenting outbreaks from the past years, she pointed out that mainly poor epidemiological data, small sample numbers and regional variation in vaccination programs, management, sample collection and analysis, are leading to protracted and retrospective information that usually is, unfortunately, not shared on time. Therefore, WHO, OIE experts and active EIV researchers are lacking basic data to give founded recommendations that are necessary for attempts of an international concept of prevention and intervention.
Richard Newton from the Animal Health Trust in Newmarket, UK, addressed the explosive problem of acquisition of new hosts in EIV, within the species as well as across species borders. Case reports and retrospective investigations from the USA and the UK show that dogs are not only susceptible to EIV but that the virus can also, in the case of outbreaks reported from Florida since 2004, be transmitted from dog to dog. Concerning an equine H3N8 strain isolated earlier in 2009 in China , the expert raised questions about laboratory escape, the possibility of pigs as a reservoir and the obviously “frozen evolution” of this infectious agent, Furthermore, he gave a very interesting insight into mathematical models that can be used to estimate effects of vaccination policies, population sizes and other factors as well as to investigate vaccine failures. EIV models so far reveal that small outbreaks are most common and that vaccination reduces the average outbreak size significantly, concluding that one should continue vaccinations in outbreak areas as recently conducted in Australia, where a major outbreak occurred in 2007 in a naïve and, hence, completely susceptible population.
Talking about intra-host variation of EIV, James Wood, also from the CIDC, underlined that an understanding of intra-host variation is not only important per se but also the fundamental basis of investigations of cross-species jumps. Dynamics within the reservoir species differ between pathogens and can be accompanied by occasional spill-over to other species. The frequency of these spill-overs as well as a possible establishment of stuttering transmission within the next species is dependent on the speed of mutation and therefore replication rate and of the extend of change. A cross-species jump is finally implemented when outbreaks and on-going dynamics of the pathogen are seen in the next species. Presenting experiments conducted in horses and dogs, he showed how the three important questions for 1) the overall rate of mutation, 2) the width of the transmission bottleneck and 3) the relevance of prior immunity can be answered. He emphasized the importance of studying natural pathogen dynamics in normal natural hosts in multidisciplinary approaches to understand the emergence of epidemics. Importantly, in the case of equine influenza, cross-species jumps seem to be “prepared” in the donor host (horse) by the presence of a number of variants that apparently manifest themselves in the recipient (host) dog and where purifying selection ultimately results in a pathogen that is readily maintained and transmissible in the recipient species.
An introduction in the field of herpesviruses was given by Klaus Osterrieder, Freie Universitaet Berlin. He pointed out similarities and differences between influenza- and herpesviruses, both under the necessity of replication with their evolutionary process accelerated through human intervention but one – EIV - maximizing replication to magnify mutation rate and damage, the other one – EHV - en route to commensalism. The expert in the field of equine herpesviruses presented studies of a single point mutation driving neuropathogenicity in EHV-1 ORF30 coding for the DNA polymerase. The N to D mutation at aa position 752, giving the virus an about 10-fold replicative advantage, does not change its capacity to shed in the population which raises the question for evolutionary advantages, giving an other example of how little we still understand pathogen dynamics.
The second and third sessions gave the panel of experts the opportunity to get an overview of the current disease situation in different countries in Europe and Asia.
Neil Bryant (Animal Health Trust, Newmarket, UK) presented the disease situation in Great Britain and attempts of free diagnostic testing in order to increase the sample number. The report showed that outbreaks within the last years were mainly associated with problems in the vaccination and/or quarantine management and the introduction of horses from abroad.
Ann Cullinane, Irish Equestrian Centre, Kildare, Irelandd, a country largely involved in the export of horses, pointed out problems and concerns regarding the disruption of training and performances due to endemic situations. A targeted EIV vaccination program since 1980 and active surveillance of EIV and EHV including free testing during outbreaks present a rather sophisticated situation but still keep a need for funding and further investigations.
Belgium, represented by Annick C. Gryspeerdt, University of Gent, has a horse population of 275000 horses and is facing the same struggles most countries do: Horses not involved in FEI regulations are often not vaccinated and keep a reservoir and therefore potential for outbreaks for both diseases, shown by a recent neuropathogenic outbreak of EHV-1.
The situation in Bavaria, representing southern Germany, was demonstrated by Antonie Neubauer-Juric. The expert from the Bavarian Health and Food Safety Authority presented a new established EHV-1 and -4 multiplex real time PCR diagnostic method and pointed out the lack of a surveillance system and, as known for other countries, therefore a lack of sampling and adequate sample numbers for an evaluation of the infection rate.
The same problems were described by Norbert Nowotny of the veterinary school in Vienna, Austria. The absence of a surveillance system does not allow an up to date assessment of the situation in the country and the few notified cases per year are very likely just the tip of the iceberg as veterinarians send samples only on a very rare basis.
Gittan Groendahl from the SVA in Uppsala, Sweden, presented the situation of EHV and EIV in Sweden, a country with a large horse density of about 1 horse/30 persons. A campaign of training veterinarians in sampling and a system of diagnostics in a “packages-formate” (airway-, abortion- package testing for several viruses according to symptomatics) reveal exemplary large sampling numbers per year although a surveillance system is not established here either. Vaccination management is, according to Dr. Groendahl’s report, still a problem in trotting horses but recently got announced to be mandatory for EIV after an epidemic spreading rapidly over the whole country in 2007.
Gianluca Autorino gave an insight in the situation of the two diseases, which are notifiable in Italy. He described an EIV surveillance program lasting from 2002 to 2005 that took place on six different racetracks and reported an overall prevalence of 30% for EIV and around 90% of EHV-1 and EHV-4. As heard from other countries, vaccination management for EIV improved only after an influenza storm in 2003 and small sample numbers are problematic.
Prof. Rysbek Nurgaziev from Bishkek, Kyrgyzstan, reported on an abortion storm in April and March 2009 that first was thought to be related to Salmonella but investigations revealed negative results for the agent and a possible correlation to EHV-1 is currently examined. A cooperation with countries like Kyrgyzstan or Mongolia, homing large horse populations and connecting the western and central European continent with Asia is very interesting and it is the explicit hope of all the experts to gain a much better understanding of the diseases by getting an insight intopathogen dynamics within those horse populations.
The last session, “Vaccinal control”, started with an introduction of Jenny Mumford. She underlined the issue, that vaccine candidates are usually only tested against unvaccinated controls, certainly leading to a statistically significant reduction of clinical signs and virus excretion with animal experiments mainly focussed on safety and not on efficacy testing. The expert opened the session by posing critical questions about strain selection and continuous excretion upon vaccination and called for a manual of standard and restrictions concerning efficacy centrally coordinated by the OIE.
Jules Minke, a veterinarian/PhD representing Merial, presented the two products FluAvert, a cold adapted modified life vaccine marketed by the Intervet-ScheringPlough company and ProteqFlu, a recombinant Canarypox virus marketed by Merial. He discussed both products regarding the five main goals of 1) a quick onset of immunity, 2) a improvement of closing the immunity gap between the second and third shot as most weak point, 3) long term protection, 4) efficacy in the presence of maternal antibodies and 6) the prove of efficacy in old horses. Furthermore he mentioned the problem of ambivalent needs for an efficient and safe vaccine on the one hand and field needs, convenience of use in particular, on the other hand.
Saskia van de Zande from Intervet-ScheringPlough first listed and compared different EIV vaccines available on the European and U.S. market today. Moreover she critically questioned whether the currently used animal models are comparable to the population and conditions targeted later on.
Fort Dodge-Pfizer and its inactivated EHV vaccines were presented by Sabrina Krug, summarizing the advantages of an active immunization to reduce clinical signs of respiratory disease due to infection with EHV-1 and-4 as well as to reduce abortion caused by EHV-1.
In summary, both participants and organizers were pleased and enthusiastic about the course of the meeting and enjoyed the lively interchange of ideas. It was noted that the exchange should continue in regular intervals.