Developments in biologicals最新文献

Q fever is a zoonosis caused by the bacterium Coxiella burnetii, a highly infectious agent that can survive in the environment. Therefore, Q fever has a major public health impact when outbreaks occur. Small ruminants are identified as the source in the majority of outbreaks in humans. Accurate diagnosis and effective control strategies are necessary to limit the zoonotic and veterinary impact of Q fever. For this, knowledge of the pathogenesis of Q fever and excretion routes of C. burnetii from infected animals is crucial. Abortions as well as normal parturitions in infected small ruminants are the most important excretion routes of C. burnetii. Excretion of C. burnetii via faeces and vaginal mucus has also been suggested. However, contamination of these samples by bacteria present in the environment may influence the results. This hampers the accurate identification of infected animals by these samples; however, the detection of C. burnetii in milk samples seems not to be influenced by environmental contamination. Q fever in animals can be detected by direct (immunohistochemistry and PCR) and indirect (complement fixation test (CFT), enzyme- linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA) methods. A combination of both direct and indirect methods is recommended in current protocols to detect Q fever on herd level. For the control of Q fever in domestic animals, vaccination with a phase 1 C. burnetii whole cell inactivated vaccine is reported to be effective in preventing abortion and reducing bacterial shedding, especially after several years of administration. Vaccination might not be effective in already infected animals nor in pregnant animals. Furthermore, the complicated vaccine production process, requiring biosafety level 3 facilities, could hamper vaccine availability. Future challenges include the development of improved, easier to produce Q fever vaccines.

The USDA Center for Veterinary Biologics (CVB) has the regulatory authority to issue licenses and permits that allow the marketing of pure, safe, potent, and effective veterinary biological products. Under the standard licensing or permitting process, a manufacturer develops, characterizes, and evaluates a product prior to licensure. The CVB evaluates the submitted information, inspects the manufacturing facilities and methods of production and testing, and confirms key product test results through independent testing. This complete and comprehensive evaluation may not be possible during the emergence of a new animal disease or in response to an introduction of a significant transboundary animal disease agent. Processes are in place in the US that allow for more rapid availability of veterinary products in an emerging or emergency animal health situation. But, it can be advantageous to attain preapproval of products prior to their anticipated need. In this article, issues associated with obtaining approval for use of a biological product under emerging or emergency conditions are discussed.

Hendra virus (HeV) and Nipah virus (NiV) are the causative agents of emerging transboundary animal disease in pigs and horses. They also cause fatal disease in humans. NiV has a case fatality rate of 40 - 100%. In the initial NiV outbreak in Malaysia in 1999, about 1.1 million pigs had to be culled. The economic impact was estimated to be approximately US$450 million. Worldwide, HeV has caused more than 60 deaths in horses with 7 human cases and 4 deaths. Since the initial outbreak, HeV spillovers from Pteropus bats to horses and humans continue. This article presents a brief review on the currently available diagnostic methods for henipavirus infections, including advances achieved since the initial outbreak, and a gap analysis of areas needing improvement.

Heartwater, caused by the Rickettsiales Ehrlichia ruminantium (ER), is a tropical tick-borne disease of wild and domestic ruminants, transmitted by Amblyomma ticks. It causes significant economic losses due to high mortality and the high cost of antibiotic treatment of affected animals, limiting herd productivity. It is present in sub-Saharan Africa, islands in the Indian Ocean and two Caribbean islands (Guadeloupe and Antigua) from where it threatens the American mainland due to risk of the spread of infected A. variegatum by migratory birds or by uncontrolled movement of animals. If an accidental introduction of a tick-free ER carrier animal occurs, autochthonous A. maculatum has proven to be a good experimental vector for heartwater. Modeling A. variegatum population dynamics has been developed, but further work is needed to predict favourable habitats and allow targeted surveillance. We overview here the advances in diagnostics, vaccines and epidemiology of heartwater and analyze the research gaps and needs to mitigate potential ER introduction and spread on the American mainland. Effective serologic ELISA tests allow prevalence studies, and several PCR-based diagnostic tests are currently available to detect ER in sick animals. However, the development of rapid assays, including multi-pathogen tests, would enhance the efficacy and cost-effectiveness of heartwater diagnosis. Several experimental vaccines (inactivated, attenuated and recombinant) are under development. Attenuated and inactivated vaccines are effective against homologous strains but their efficacy in the field is decreased due to broad antigenic diversity of ER. New molecular typing assays are now being used to study the genetic structure of ER populations worldwide, but the linking of genotyping to cross-protection is still not straightforward. Currently an inactivated vaccine would be the most appropriate vaccine for the American mainland due to its safety, the availability of a fully controlled bioprocess allowing ER mass production and the possibility to design "regional cocktail vaccines". This would require the selection and isolation of Caribbean ER strains supported by data of molecular epidemiology studies in this region. Development of an universal recombinant vaccine requires increased knowledge of ERbiology, including virulence mechanisms. Comparison of virulent and attenuated strains using"omic approaches" is on-going and will be crucial to understand these mechanisms and to develop improved vaccines.

Hendra virus and Nipah virus are viral zoonoses first recognized in the mid and late 1990's and are now categorized as the type species of the genus Henipavirus within the family Paramyxoviridae. Their broad species tropism together with their capacity to cause severe and often fatal disease in both humans and animals make Hendra and Nipah "overlap agents" and significant biosecurity threats. The development of effective vaccination strategies to prevent or treat henipavirus infection and disease has been an important area of research. Here, henipavirus active and passive vaccination strategies that have been examined in animal challenge models of Hendra and Nipah virus disease are summarized and discussed.

Classical swine fever is a serious and economically important transboundary disease threatening pig production globally. The infection may occur in backyard pigs, feral pig populations and domestic pigs. Whereas there are proven control strategies for the latter pig population, control in backyard pigs with poor biosecurity settings or in wild boar populations of high density still poses a problem in some parts of the world. Laboratory diagnostic methods, efficacious vaccines and contingency plans are in place in most industrialised countries. So far modified live vaccines (MLV) are still the first choice for rapid and reliable immune protection. Since antibodies elicited by conventional MLV cannot be distinguished from antibodies after natural infection, considerable efforts are put into the development of a live marker vaccine accompanied by a serological test. Nevertheless, some remaining gaps with respect to the diagnosis of and vaccination against classical swine fever have been identified.

Ebola viruses are zoonotic pathogens with the potential of causing severe viral hemorrhagic fever in humans and nonhuman primates. Bats have been identified as a reservoir for Ebola viruses but it remains unclear if transmission to an end host involves intermediate hosts. Recently, one of the Ebola species has been found in Philippine pigs raising concerns regarding animal health and food safety. Diagnostics have so far focused on human application, but enhanced pig surveillance and diagnostics, particularly in Asia, for Ebola virus infections seem to be needed to establish reasonable guidelines for public and animal health and food safety. Livestock vaccination against Ebola seems currently not justified but proper preparedness may include experimental vaccine approaches.

The United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) Veterinary Services (VS) is charged with monitoring, controlling, and responding to select reportable diseases and all foreign animal diseases. Emergency Management and Diagnostics (EM&D) oversees Foreign Animal Disease (FAD) preparedness and response. In order to effectively prepare for and respond to FADs, such as highly pathogenic avian influenza and foot-and-mouth disease, VS develops plans, strategies, and policies to effectively combat an intrusion. USDA APHIS VS has made significant gains in preparedness and response planning. However, much remains to be done especially in surveillance, diagnostic tools, and vaccines. There are significant needs for novel medical technologies to improve diagnostic capabilities and offer additional approaches for FAD response.

In late 2011 a novel virus of the Simbu serogroup, family Bunyaviridae, genus Orthobunyavirus, was discovered at the German-Dutch border and named "Schmallenberg virus" (SBV). Since then, the virus has spread rapidly to other European countries, and the involvement of biting midges has been demonstrated. Affected adult ruminants show none or only mild clinical signs including fever, reduced milk production or diarrhoea. However, in keeping with related viruses, an infection of SBV-naive cows and ewes during a critical period of pregnancy can lead to severe foetal malformations summarized as "arthrogryposis- hydranencephaly syndrome." Diagnostic assays like real-time RT-PCR and antibody ELISA are now available; and substantial knowledge of this virus has been gathered quickly. However, further research and exchange of information are essential.

Newcastle disease (ND) is a contagious disease of birds that can have severe economic consequences for poultry producers, including a serious impact on the international trade of poultry and eggs. Newcastle disease virus (NDV) isolates are also called avian paramyxovirus serotype-1 isolates, but only infection with virulent NDV (vNDV) causes the disease. Virulent Newcastle disease virus (vNDV) isolates are distributed worldwide and have a high capacity to mutate, allowing the development of multiple vNDV genotypes evolving simultaneously at different locations. Large gaps in existing knowledge in the areas of epidemiology and evolution limit the possibilities to control the disease. Recurrent infection of poultry and wild birds allows the maintenance of a reservoir for the viruses; however, the role of wild birds and poultry in vNDV evolution is largely unknown. In the area of diagnostics, the performance of fast and accurate diagnostics methods is often affected by the evolution of viral genomes. Therefore, there is a need for the validation of multiple recently developed experimental tests and a need to develop additional fast and inexpensive diagnostic tests to be used in the field. In the area of vaccination, the development of inexpensive thermostable NDV vaccines and the development of vaccines capable of preventing viral replication are the highest priorities for endemic countries. In countries considered free of vNDV the development of low- cost vaccines that produce minimal vaccine reactions to prevent decreased productivity are higher priorities. Worldwide, better strategies that replace the culling of infected birds are needed to control outbreaks.