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National Research Council (US). Trends in Science and Technology Relevant to the Biological and Toxin Weapons Convention: Summary of an International Workshop. Washington (DC): National Academies Press (US); 2011.

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Trends in Science and Technology Relevant to the Biological and Toxin Weapons Convention: Summary of an International Workshop.

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DEFENSE AND COUNTERMEASURES

Vaccines and Medical Countermeasures – Nancy Connell, University of Medicine and Dentistry of New Jersey, USA

Dr. Nancy Connell opened the session by providing an overview of research developments relevant to vaccines and medical countermeasures. Dr. Connell noted that there has been a transition from empirical to rational design of antibiotic and antiviral drugs along with the use of techniques such as combinatorial chemistry. She pointed out that traditional antibiotics targeted nucleic acids and protein and cell wall synthesis, but that newer approaches have targeted additional aspects of virulence such as the production and secretion of toxins. Approaches to modulate host immune functions have also been explored, including stimulation of innate immunity or targeting of the CD45 antigen on macrophages, an antigen shown to be susceptible to attack by some pathogens.

Dr. Connell also discussed developments in vaccines, and again noted that research has moved toward rational design based on increased understanding of the immune system and of host-pathogen interactions. Dr. Connell noted approaches to jump-start components of the immune response such as antigen delivery to dendritic cells to stimulate lymph-node homing and the delivery of engineered MHC Class I single-chain trimers to stimulate T and B cell activation. She pointed out that the first line of exposure to microorganisms is most commonly at mucosal surfaces such as the respiratory and gastrointestinal tracts. As a result, researchers continue to explore ways to generate protective mucosal immunity although challenges remain in understating the biology and interactions with commensal bacteria at these surfaces. Researchers continue to explore new adjuvants as well, to boost the overall immune response or to direct it down cell-mediated or humoral pathways.

Dr. Connell commented on a convergence of multiple technologies with regard to vaccine delivery and future research directions. She highlighted the role of nanotechnology in creating new delivery systems, as well as advances in aerosolization, encapsulation, and techniques such as DNA shuffling. Dr. Connell identified personalized vaccines, vaccines directed against non-communicable diseases such as cancer and cardiovascular disease, and “lifestyle vaccines” against anything from weight gain to tooth decay as future trends, although it is not yet clear whether all of these will be feasible.

Dr. Connell concluded by noting possible misuses of vaccine and countermeasure knowledge Researchers seek ways to block or reduce the emergence of drug-resistant microbial strains and Dr. Connell commented that some of the knowledge acquired during drug development and testing could potentially be misused, such as information on drug toxicity, drug targets and virulence factors, and drug-resistant strains. Exploration of immune system modulation also raises the possibility of disrupting the balance of biological control systems and affecting interactions among the nervous, endocrine, and immune systems.

Monitoring and Molecular Diagnosis of Emerging Infections – Raymond Lin, National Public Health Laboratory, Singapore

Dr. Raymond Lin spoke to the workshop on monitoring and diagnosis of emerging infections. Dr. Lin emphasized that having an effective public health system to respond to naturally-occurring disease outbreaks also enables preparedness for a biothreat event and noted that a collaborative effort between disciplines such as epidemiology, laboratory microbiology, and clinical practice in responding to new public health concerns is essential.

Dr. Lin discussed several methods of disease monitoring and surveillance–traditional clinical surveillance, seroepidemiology, and predictive modeling–using Singapore’s response to H1N1 influenza as an example (Chen et al., 2010; Lee et al., 2010; Ong et al., 2010). Through clinical surveillance, samples were collected daily from sentinel sites among general practitioners and hospitals and combined with laboratory confirmation of influenza and the collection of virus samples for further analysis. These samples were collected not only from symptomatic patients, but from those who were treated for any reason. These data enabled strain typing as well as estimates of the time and number of the population infection peak. In comparison, Singapore tested a serosurvey approach that measured antibodies to influenza. Tested cohorts included military, community, hospitals, and long-term care facilities. Dr. Lin also reported evaluation of a modeling approach, in which symptoms at sentinel clinics were used without confirmatory lab tests. These data generated a range of probabilities for the timing of the population infection peak, with the peak narrowing as more data were collected. The estimates of community infection at the end of September 2009 were compared from the three monitoring methods, resulting in 5 percent community infection by clinical surveillance, 13 percent by seroconversion data, and 13 percent by predictive modeling. Dr. Lin observed that clinical surveillance with laboratory confirmation can provide relatively real-time information but requires a high volume of testing to achieve accurate statistics. Seroepidemiology is accurate for retrospective infections and can be used to analyze particular subgroups, but can be difficult to organize. Modeling is predictive and easy to organize, but disagreement remains about how useful modeling approaches are to predicting disease and such models need to be verified by other surveillance methods. Countries are also exploring the use of Google search data or social media such as twitter as alternate disease monitoring strategies. So far, however, there is limited data on whether such methods are useful and results may be affected by news-driven peaks (Cook et al., 2010).

Dr. Lin next noted that the 2009 H1N1 outbreak was unprecedented for the speed with which the genomes from viral isolates were sequenced in many countries. He described several ways in which observed or constructed mutations in H1N1 isolates were studied for potential effects on virulence, including D222G in the receptor-binding region and E627K in polymerase basic protein 2, a mutation which had been observed in previous pandemic influenza strains (Maurer-Stroh et al., 2010). However, Dr. Lin noted that study results varied with regard to the effects of these mutations, revealing the limits of our knowledge of the flu. In epidemiology, effective tools for accessing and mining massive amounts of digitized data are needed to draw out significant clusters and alerts. Dr. Lin briefly discussed one such framework, the Care Quest Infection Surveillance and Management (CQ/ISaM) for multi-drug resistant staphylococcus aureus (MRSA), in which clinical data streams are compiled in a central point and can be queried using natural language to generate real-time charts. However, Dr. Lin concluded by emphasizing the important role for front-line physicians to identify outbreaks at the local scale while they remain below the threshold observable through national surveillance systems.

Agricultural Biosecurity: Threats to Crop Production – Michael Jeger, Imperial College London, UK

Dr. Michael Jeger spoke to the workshop about crop security issues. He began by drawing comparisons between traditional and modern methods of crop production, noting that traditional methods often feature small, irregular fields with mixed crops and low use of inorganic fertilizers, herbicides and pesticides, while modern methods feature large, single-crop fields with specially bred cultivars and routine use of chemical products. Dr. Jeger also noted the extensive biodiversity of plant pathogens, which include viruses, bacteria, fungi, and nematodes.

Dr. Jeger commented that there are several epidemiological scales of disease spread – field level affecting farmers, nationally and regionally affecting national economies, and globally due to both natural and anthropogenic influences. He pointed to the increasing scale of international trade and the potential movement of pathogens through shipping and questioned whether national agricultural health systems are fully prepared to respond to potential outbreaks. He also presented several examples of significant agricultural diseases including the regional and global spread of wheat yellow rust (Brown and Hovmøller, 2002), and noted that devastating banana disease has spread to all of the major growing regions in the world. Dr. Jeger presented data documenting a four-fold increase in identified geminiviruses from 1991–2005 (Rodoni, 2009), and noted that this increase does not appear to be an artifact of increases in sequencing. He highlighted the potentially large economic costs from crop disease outbreaks, suggesting that these diseases may have a major impact whether from accidental or deliberate disease spread.

Dr. Jeger also raised several questions to consider with regard to invasive plant diseases and biosecurity, including the nature of the threat, whether pathogen eradication is feasible, what safeguards should be built into national plant health systems, whether there will be impacts from global trade or climate changes, whether it is possible to predict upcoming concerns, and whether the pathogen that first arrives in a new region or the one that follows is likely to be the most serious problem. With regard to this last point, Dr. Jeger presented a model for how new pathogen strains evolve when introduced into a reservoir (adapted from Antia et al., 2003). He noted that there will be frequent failures of the pathogen to cross over into a new crop species; however a strain will eventually evolve with properties that enable it to emerge as a new pathogen. He also noted that formal plant health regulations may take months or years to be developed, which may not be adequate to respond to accidental or deliberate plant disease outbreaks. Dr. Jeger concluded that improved biosurveillance is needed, along with properly validated methods for collecting and analyzing the information.

Discussion

The discussion following the presentations touched on surveillance systems and ways for the public and agricultural health communities to achieve increased lead time in recognizing emerging disease outbreaks. Among the points noted during the discussion was that current surveillance systems largely rely on passive surveillance, rather than on the use of active surveillance of sentinel groups. It was also suggested that advances in biotechnology can contribute to the generation of new, pathogen-resistant plant varieties.

Copyright © 2011, National Academy of Sciences.
Bookshelf ID: NBK56619

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