Quantification of the Effects of Age on the Dose Response of Variola major in Suckling Mice

Dose-response data for Variola major (V. major), the causative agent of smallpox, were obtained from the open literature, summarized, and fitted with three dose-response models. It is known from prior outbreak experience that there is generally a difference in infectivity of the agent and its subsequent mortality depending on the age of the patient. A source of animal dose-response data were found with age delineation for the exposure group (suckling mice, intraperitoneal exposure). This delineation was used to adapt current dose-response models to include an age dependency parameter. The degree of the models' fit to the data was ascertained using maximum likelihood estimation (MLE). The effect of host age could be described quantitatively using modifications to the beta Poisson and exponential dose-response models. The modifications improvement in the accuracy of risk prediction by 72% for the beta Poisson model and 7% for the exponential model, compared to the original (unmodified) models.     

Prevention of bioterrorism by vaccines

Prevention against the weapons of bioterrorists is limited by the multiplicity of agents that could be used. Against smallpox, stocks of the classical vaccine must be prepared, but this vaccine is dangerous and we must look for a new and safer vaccine. A vaccine against anthrax is probably possible relatively soon. One may be less optimistic concerning plague, since it is not sure that we could protect against the pulmonary plague, but research in this field is an emergency. The large number of viruses capable of inducing haemorrhagic fevers makes especially difficult the preparation of vaccines against these infections. We must also make available monoclonal antibodies that could be used as therapies against toxin, notably botulism, or against antibiotic-resistant bacteria.     

Detection limit of negative staining electron microscopy for the diagnosis of bioterrorism‐related micro‐organisms

Aims: To determine the detection limit of diagnostic negative staining electron microscopy for the diagnosis of pathogens that could be used for bioterrorism. Methods and Results: Suspensions of vaccinia poxvirus and endospores of Bacillus subtilis were used at defined concentrations as a model for poxviruses and spores of anthrax (Bacillus anthracis), both of which are pathogens that could be used for bioterrorist attacks. Negative staining electron microscopy was performed directly or after sedimentation of these suspensions on to the sample supports using airfuge ultracentrifugation. For both virus and spores, the detection limit using direct adsorption of a 10‐μl sample volume onto the sample support was 10⁶ particles per ml. Using airfuge ultracentrifugation with a sample volume of 80 μl, the detection limit could be reduced to 10⁵ particles per ml for spores and to 5 × 10⁴ particles per ml for poxviruses. The influence on particle detection of incubation time, washing and adsorption procedures was investigated. Conclusions: The reproducibility and sensitivity of the method were acceptable, particularly considering the small sample volume and low particle number applied onto the sample support. Significance and Impact of the Study: Diagnostic negative staining electron microscopy is used for the diagnosis of pathogens in emergency situations because it allows a rapid examination of all particulate matter down to the nanometre scale. This study provides precise detection limit for the method, an important factor for the validation and improvement of the technique.     

Arboviruses and epizootic viruses

Some viral diseases are transmitted to human by arthropods (arboviroses), or by animals (zoonoses). Among more than 500 arboviruses and epizootic viruses that are classified into seven families, only a few are responsible for zoonoses or cause severe human diseases. Infected patients may show an acute disease associated with different symptoms, ranging from high fever to encephalitis, pulmonary distress, and haemorrhages. Some diseases show one or more of these symptoms and the factors responsible for severe outcomes, either linked to the virus, or to the host, or to the vector, remain poorly understood. Arboviroses and zoonoses are emerging or re-emerging diseases that need a multidisciplinary effort to control the propagation of the infectious agent and the pathogenesis in infected patients. Some viruses could be used for bioterrorism attacks. In virology, studies on the interactions of the viruses with their vectors and vertebrate hosts and on the pathophysiology of the infections will allow a better prevention of these diseases.     

The threat of smallpox

Smallpox is a highly contagious disease mainly transmitted by aerosols with a high case-fatality. The smallpox virus has evolved from a long adaptation to humans during Evolution, explaining that the virus is highly specific for humans and nonpathogenic for animals. Smallpox was eradicated in 1977 and vaccination was abandoned in the 1980's. This virus is a dreadful potential biological weapon since the reemergence of smallpox on the planet might be expected to be devastating, due to its high 'contagiosity', which would rapidly spread in naive populations, especially those living in urban areas, and worldwide through air travels. There is no anti-viral treatment and vaccine is active in the first four days post-exposure. Today, the stocks of smallpox virus constitute one of the most dangerous threats for humanity. There is a need for improving the safety of the vaccine and to reconsider the preventive strategy to face a possible attack by smallpox virus.     

Bacteriological risks: detection and tracing

Advances in molecular taxonomy of bacteria have generated many tools allowing identification of any bacteria, whether culturable or not. In addition to taxonomic identification, growing knowledge on pathogenicity mechanisms allows the detection of bacteria with given virulence genes. The problem is in asking the proper questions so that the most appropriate tools can be chosen. Some rapid identification tools (gene amplification, in situ hybridisation) require a starting hypothesis. Other tools (rrs gene amplification and sequencing) can be used without prior hypothesis, but take longer. To face the bioterrorist threat, particular attention should be given to laboratory and strain dispatch (within- and between-laboratory) organisation.     

刍议重症急性呼吸综合征带来的启示

重症急性呼吸综合征(SARS)自暴发至今,已经造成数百人死亡、数百亿美元的经济损失。在同SARS斗争的同时,应该想到生物技术发展对人类产生的双重效应,以及如何防止生物科学新突破被误用和滥用;也应该想到生物恐怖对人类可能的威胁,因此应积极保护我们的基因资源。SARS除了带给人类灾难以外,也带给我们更多的思考,并可能会促成我们建立相应的机制,以应对未来可能出现的更大灾难。     

Risk Assessment of Potential Bio-Terrorism Agents for Laboratory Workers

In the wake of recent national and global events, biological weapons have become an increasingly urgent issue. Preparedness and defense are now the topic of numerous conferences and funding opportunities. Due to this increasing activity researchers must now focus more intently on their own safety and security. Bio-safety measures are analyzed by means of risk assessments. In this paper we will explore qualitative risk assessments and the risks associated with six specific pathogens and toxins that are potential bio-terrorism agents: Bacillus anthracis, Yersinia pestis, Francisella tularemia, Smallpox virus, and the two toxins, ricin and botulinum.