Dangerous Pathogens as a Potential Problem for Public Health.

Pathogens are various organisms, such as viruses, bacteria, fungi, and protozoa, which can cause severe illnesses to their hosts. Throughout history, pathogens have accompanied human populations and caused various epidemics. One of the most significant outbreaks was the Black Death, which occurred in the 14th century and caused the death of one-third of Europe's population. Pathogens have also been studied for their use as biological warfare agents by the former Soviet Union, Japan, and the USA. Among bacteria and viruses, there are high priority agents that have a significant impact on public health. Bacillus anthracis, Francisella tularensis, Yersinia pestis, Variola virus, Filoviruses (Ebola, Marburg), Arenoviruses (Lassa), and influenza viruses are included in this group of agents. Outbreaks and infections caused by them might result in social disruption and panic, which is why special operations are needed for public health preparedness. Antibiotic-resistant bacteria that significantly impede treatment and recovery of patients are also valid threats. Furthermore, recent events related to the massive spread of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an example of how virus-induced diseases cannot be ignored. The impact of outbreaks, such as SARS-CoV-2, have had far-reaching consequences beyond public health. The economic losses due to lockdowns are difficult to estimate, but it would take years to restore countries to pre-outbreak status. For countries affected by the 2019 coronavirus disease (COVID-19), their health systems have been overwhelmed, resulting in an increase in the mortality rate caused by diseases or injuries. Furthermore, outbreaks, such as SARS-CoV-2, will induce serious, wide-ranging (and possibly long-lasting) psychological problems among, not only health workers, but ordinary citizens (this is due to isolation, quarantine, etc.). The aim of this paper is to present the most dangerous pathogens, as well as general characterizations, mechanisms of action, and treatments.

Therapeutic Antibodies for Biodefense.

Diseases can be caused naturally by biological agents such as bacteria, viruses and toxins (natural risk). However, such biological agents can be intentionally disseminated in the environment by a State (military context) or terrorists to cause diseases in a population or livestock, to destabilize a nation by creating a climate of terror, destabilizing the economy and undermining institutions. Biological agents can be classified according to the severity of illness they cause, its mortality and how easily the agent can be spread. The Centers for Diseases Control and Prevention (CDC) classify biological agents in three categories (A, B and C); Category A consists of the six pathogens most suitable for use as bioweapons (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox and viral hemorrhagic fevers). Antibodies represent a perfect biomedical countermeasure as they present both prophylactic and therapeutic properties, act fast and are highly specific to the target. This review focuses on the main biological agents that could be used as bioweapons, the history of biowarfare and antibodies that have been developed to neutralize these agents.

Biological Warfare Plan in the 17th Century­the Siege of Candia, 1648­1669.

A little-known effort to conduct biological warfare occurred during the 17th century. The incident transpired during the Venetian­Ottoman War, when the city of Candia (now Heraklion, Greece) was under siege by the Ottomans (1648­1669). The data we describe, obtained from the Archives of the Venetian State, are related to an operation organized by the Venetian Intelligence Services, which aimed at lifting the siege by infecting the Ottoman soldiers with plague by attacking them with a liquid made from the spleens and buboes of plague victims. Although the plan was perfectly organized, and the deadly mixture was ready to use, the attack was ultimately never carried out. The conception and the detailed cynical planning of the attack on Candia illustrate a dangerous way of thinking about the use of biological weapons and the absence of reservations when potential users, within their religious framework, cast their enemies as undeserving of humanitarian consideration.

Neurochemical and Neurobiological Weapons.

Nerve agents and neurobiological weapons are among the most devastating and lethal of weapons. Acetylcholinesterase inhibitors act by increasing the amount of acetylcholine in the neuromuscular junction, resulting in flaccid paralysis. Tabun, VX, soman, and sarin are the major agents in this category. Exposure to nerve agents can be inhalational or through dermal contact. Neurotoxins may have peripheral and central effects on the nervous system. Atropine is an effective antidote to nerve agents. Neurobiological weapons entail using whole organisms or organism-synthesized toxins as agents. Some organisms that can be used as biological weapons include smallpox virus.

Dynamics of positional warfare malaria: Finland and Korea compared.

BACKGROUND: A sudden outbreak of vivax malaria among Finnish troops in SE-Finland and along the front line in Hanko peninsula in the southwest occurred in 1941 during World War II. The common explanation has been an invasion of infective Anopheles mosquitoes from the Russian troops crossing the front line between Finland and Soviet Union. A revised explanation is presented based on recent studies of Finnish malaria. METHODS: The exact start of the epidemic and the phenology of malaria cases among the Finnish soldiers were reanalyzed. The results were compared with the declining malaria in Finland. A comparison with a corresponding situation starting in the 1990's in Korea was performed. RESULTS AND DISCUSSION: The malaria cases occurred in July in 1941 when it was by far too early for infective mosquitoes to be present. The first Anopheles mosquitoes hatched at about the same time as the first malaria cases were observed among the Finnish soldiers. It takes about 3-6 weeks for the completion of the sporogony in Finland. The new explanation is that soldiers in war conditions were suddenly exposed to uninfected mosquitoes and those who still were carriers of hypnozoites developed relapses triggered by these mosquitoes. It is estimated that about 0.5% of the Finnish population still were carriers of hypnozoites in the 1940's. A corresponding outbreak of vivax malaria in Korea in the 1990's is similarly interpreted as relapses from activated hypnozoites among Korean soldiers. The significance of the mosquito induced relapses is emphasized by two benefits for the Plasmodium. There is a synchronous increase of gametocytes when new mosquitoes emerge. It also enables meiotic recombination between different strains of the Plasmodium. CONCLUSION: The malaria peak during the positional warfare in the 1940's was a short outbreak during the last phase of declining indigenous malaria in Finland. The activation of hypnozoites among a large number of soldiers and subsequent medication contributed to diminishing the reservoir of malaria and speeded up the eradication of the Finnish malaria. A corresponding evolution of Korean malaria is anticipated with relaxed tensions and decreasing troop concentrations along the border between South and North Korea.

Plant-pathogenic bacteria as biological weapons - real threats?

At present, much attention is being given to the potential of plant pathogens, including plant-pathogenic bacteria, as biological weapons/bioterror weapons. These two terms are sometimes used interchangeably and there is need for care in their application. It has been claimed that clandestine introduction of certain plant-pathogenic bacteria could cause such crop losses as to impact so significantly on a national economy and thus constitute a threat to national security. As a separate outcome, it is suggested that they could cause serious public alarm, perhaps constituting a source of terror. Legislation is now in place to regulate selected plant-pathogenic bacteria as potential weapons. However, we consider it highly doubtful that any plant-pathogenic bacterium has the requisite capabilities to justify such a classification. Even if they were so capable, the differentiation of pathogens into a special category with regulations that are even more restrictive than those currently applied in quarantine legislation of most jurisdictions offers no obvious benefit. Moreover, we believe that such regulations are disadvantageous insofar as they limit research on precisely those pathogens most in need of study. Whereas some human and animal pathogens may have potential as biological or bioterror weapons, we conclude that it is unlikely that any plant-pathogenic bacterium realistically falls into this category.

Detection of indoor biological hazards using the man-portable laser induced breakdown spectrometer.

The performance of a man-portable laser induced breakdown spectrometer was evaluated for the detection of biological powders on indoor office surfaces and wipe materials. Identification of pure unknown powders was performed by comparing against a library of spectra containing biological agent surrogates and confusant materials, such as dusts, diesel soot, natural and artificial sweeteners, and drink powders, using linear correlation analysis. Simple models constructed using a second technique, partial least squares discriminant analysis, successfully identified Bacillus subtilis (BG) spores on wipe materials and office surfaces. Furthermore, these models were able to identify BG on materials not used in the training of the model.

Angels and Devils: Dilemmas in Dual-Use Biotechnology.

Dual-use research, which results in knowledge that can be used for both good and ill, has become increasingly accessible in the internet age to both scientists and the general public. Here, we outline some major milestones for dual-use policy and present three vignettes that highlight contemporary dual-use issues in biotechnology.

Dual-Use Nano-Neurotechnology: An assessment of the implications of trends in science and technology.

The chemical and biological nonproliferation regime stands at a watershed moment, when failure seems a real possibility. After the unsuccessful outcome of the 2016 Eighth Review Conference, the future of the Biological and Toxin Weapons Convention is uncertain. As the Chemical Weapons Convention (CWC) approaches its Fourth Review Conference in 2018, it has almost completed removing the huge stocks of chemical weapons, but it now faces the difficult organizational task of moving its focus to preventing the reemergence of chemical weapons at a time when the international security situation appears to be increasingly more difficult and dangerous. In this article, we assess the current and near-term state (5-10 years) and impact of three related areas of science and technology that could be of dual-use concern: targeted delivery of agents to the central nervous system (CNS), particularly by means of nanotechnology; direct impact of nanomaterials on synaptic functions in the CNS; and neuronal circuits in the brain that might be targeted by those with hostile intent. We attempt to assess the implications of our findings, particularly for the consideration of the problem of state-level interest in so-called nonlethal incapacitating chemical agents for law enforcement at the CWC Review Conference in 2018, but also more generally for the longer-term future of the chemical and biological nonproliferation regime.

Forensic Approaches to Detect Possible Agents of Bioterror.

Many biological agents have been strategic pathogenic agents throughout history. Some have even changed history as a consequence of early discoveries of their use as weapons of war. Many of these bioagents can be easily isolated from the environment, and some have recently been genetically manipulated to become more pathogenic for biowarfare. However, it is difficult to determine accidental outbreaks of disease from intentional exposures. In this review, we examine how molecular tools have been used in combination with forensic research to resolve cases of unusual outbreaks and trace the source of the biocrime. New technologies are also discussed in terms of their crucial role impacting forensic science. The anthrax event of 2001 serves as an example of the real threat of bioterrorism and the employment of bioagents as weapons against a population. The Amerithrax investigation has given us lessons of the highest resolution possible with new technologies capable of distinguishing isolates at the base-pair level of sensitivity. In addition, we discuss the implications of proper sanitation to avoid waterborne diseases. The use of new methods in forensic science and health-related surveillance will be invaluable in determining the source of any new disease outbreak, and these data will allow for a quick response to any type of public health threat, whether accidental or purposely initiated.

Classification of chemical and biological warfare agent simulants by surface-enhanced Raman spectroscopy and multivariate statistical techniques.

Initial results demonstrating the ability to classify surface-enhanced Raman (SERS) spectra of chemical and biological warfare agent simulants are presented. The spectra of two endospores (B. subtilis and B. atrophaeus), two chemical agent simulants (dimethyl methylphosphonate (DMMP) and diethyl methylphosphonate (DEMP)), and two toxin simulants (ovalbumin and horseradish peroxidase) were studied on multiple substrates fabricated from colloidal gold adsorbed onto a silanized quartz surface. The use of principal component analysis (PCA) and hierarchical clustering were used to evaluate the efficacy of identifying potential threat agents from their spectra collected on a single substrate. The use of partial least squares-discriminate analysis (PLS-DA) and soft independent modeling of class analogies (SIMCA) on a compilation of data from separate substrates, fabricated under identical conditions, demonstrates both the feasibility and the limitations of this technique for the identification of known but previously unclassified spectra.

The command of biotechnology and merciful conquest in military opposition.

Biotechnology has an increasingly extensive use for military purposes. With the upcoming age of biotechnology, military operations are depending more on biotechnical methods. Judging from the evolving law of the theory of command, the command of biotechnology is feasible and inevitable. The report discusses some basic characteristics of modern theories of command, as well as the mature possibility of the command theory of military biotechnology. The evolution of the command theory is closely associated with the development of military medicine. This theory is expected to achieve successes in wars in an ultramicro, nonlethal, reversible, and merciful way and will play an important role in biotechnological identification and orientation, defense and attack, and the maintenance of fighting powers and biological monitoring. The command of military biotechnology has not become a part of the virtual military power yet, but it is an exigent strategic task to construct and perfect this theory.

Neurobiological weapons.

Biological warfare is a potential threat on the battlefield and in daily life. It is vital for neurologists and other health care practitioners to be familiar with biological and toxic agents that target the nervous system. most illnesses caused by biological warfare agents are not commonly considered neurologic disease, however. Many of these agents (such as anthrax) may present with headache, meningitis, or mental status changes in addition to fever and other symptoms and signs (Tables 2 and 3). Thus, a neurologist may be consulted acutely to aid in diagnosis. Because of the incubation time of many biological agents and their protean manifestations, it is likely that health care workers will be on the front lines in the event of a bioterrorist attack. We must be prepared.

[Viruses as biological weapons]. / Biyolojik silah olarak viruslar.

The destruction made by nuclear, biological and chemical weapons used by governments and terrorist groups in the near history is posing anxiety and fear for human being. Rumour about the possible use of these agents leads to the development of serious negative effects on populations. Since there are no vaccine and therapy for most viral agents and cost of production as biological weapons is low, interest rate is rising for viruses. In this review, general characteristics, diagnosis, therapy and protective measures for viral agents such as variola virus, hemorrhagic fever viruses, encephalitis viruses, Hantaviruses and Nipah viruses, those can be used as biological weapon, have been summarized.

Armies of pestilence: CNS infections as potential weapons of mass destruction.

Infectious agents have been investigated, developed, and used by both governments and terrorist groups as weapons of mass destruction. CNS infections, though traditionally considered less often than respiratory diseases in this scenario, may be very important. Viruses responsible for encephalitides can be highly infectious in aerosol form. CNS involvement in anthrax is ominous but should change treatment. Brucellosis, plague, Q fever, and other bacteria can uncommonly manifest with meningoencephalitis and other findings. Emerging diseases may also pose threats. We review infectious agents of particular concern for purposes of biowarfare with respect to CNS manifestations and imaging features.

What can spores do for us?

Many organisms have the ability to form spores, a remarkable phase in their life cycles. Compared with vegetative cells, spores have several advantages (e.g. resistance to toxic compounds, temperature, desiccation and radiation) making them well suited to various applications. The applications of spores that first spring to mind are bio-warfare and the related, but more positive, field of biological control. Although they are often considered metabolically inert, spores can also be used as biocatalysts. Other uses for spores are found in the fields of probiotics, tumour detection and treatment, biosensing and in the "war against drugs".

The next target of bioterrorism: your food.

One of the many forms that biological warfare may take is the targeting of major food crops. In a poor country where millions of citizens depend on staple crops such as rice, an act of bioterrorism that destroys the crop would create a famine, resulting not only in malnutrition and starvation but also in reduced immune resistance to a range of common illnesses. To reduce the potential of deliberate introductions of crop pathogens as acts of terrorism, researchers must be able to "fingerprint" pathogens at the molecular level and discriminate between naturally occurring and deliberately introduced outbreaks. Several domestic and international surveillance, tracking, and reporting efforts are under way.

Current therapy and the development of therapeutic options for the treatment of diseases due to bacterial agents of potential biowarfare and bioterrorism.

An important part of biodefense is the optimization of current therapy and the development of new therapeutic options for the treatment of the diseases most likely encountered in the form of biological weapons. Guidelines for the prevention and treatment of anthrax, plague, tularemia and botulinum toxin intoxication are reviewed. The strategies in development for the prevention of anthrax focus primarily on active and passive immunization against protective antigen, because of its central role as a toxin delivery module. Novel vaccine strategies for plague, tularemia and botulism are also reviewed.