We recently reported on the toxicity of chemical weapons. In this article, we take a look at the toxic nature of biological weapons.
What are we talking about?
Biological weapons [1] can be used for biological warfare (at state level), bioterrorism (for restricted groups) and bio-crimes. They may contain bacteria, viruses, fungi or toxins. Some of these agents are lethal, while others only cause disease and/or incapacitation.
Biological weapons can be directed against populations, crops and livestock. They are often dispersed in aerosol form, as this is one of the most effective means of spreading them.
Sometimes the agents are disseminated to come into direct contact with people or equipment, and sometimes even ingested.
In this article, we’ll look at which agents are most commonly used, and why we need to identify them so we can act quickly.
Objectives
It is necessary to identify clinical syndromes that may be caused by biological agents, – differentiate natural diseases [2] from those that may be caused by biological weapons, using standard diagnostics and epidemiological patterns, – select appropriate therapies with suitable antimicrobial agents, – collaborate with caregivers, first-aiders and public health agencies to develop drills and their appropriate responses in the field.
More than 180 pathogens and biotoxins have been studied for potential use as biological weapons.
The use of biological weapons offers a number of advantages over chemical agents: microbial agents are often considered easier to produce in large quantities, to transport, and to spread through air and water. The ability to be transmitted from person to person can also be an advantage in terms of wider dissemination.
Biological agent classification
Biological agents are classified into different categories depending on their ability to cause disease and their impact on public health. The Atlanta CDC categorizes them into 3 groups:
Category A
A category A strain is an absolute priority. It is easily disseminated or transmitted with a high mortality rate, and has a major impact on public health. It can cause major panic and social disruption. It calls for specific public health preparedness actions. Examples include Bacillus anthracis [3] (anthrax), Clostridium botulinum toxin (botulism), Yersinia pestis (plague [4]), Variola major (smallpox), Francisella tularensis (tularemia) and hemorrhagic fever viruses such as Ebola, Marburg and Lassa.
Category B
A category B strain represents the second priority. It is moderately easy to spread, with moderate morbidity and low mortality. It requires specific improvements in CDC’s diagnostic and disease surveillance capabilities.
Examples include Brucella sp. (brucellosis), Chlamydia psittaci (psittacosis), Coxiella burnetti (Q fever), ricin (toxin), enteric pathogens (Salmonella, E.coli O157H7), Shigella, staphylococcal enterotoxins B and encephalopathy viruses.
Category C
It is potentially designed for mass distribution, with the potential for high morbidity and mortality. The impact on health can be significant. In category C, pathogenic viruses such as Nipah virus and Hantavirus are emerging.
How to react?
In the absence of any declared or observed biological attack, the first pathological signs are generally non-specific. This issue has been the subject of a special chapter in our blog. Healthcare personnel need to be alert to unusual or unexpected illnesses or general patterns of disease. CDC guidelines provide diagnostic clues that can be useful for the early identification of a potential release of biological agents (1).
For example, a large number of sick people presenting with similar symptoms at the same time, or after large gatherings of people in the same place (e.g. a large concert), or even abnormally high morbidity or mortality associated with common diseases, may alert to the deliberate nature of the disease spread.
When a biological attack is suspected, the type of disease must be taken into account to prevent possible person-to-person transmission. Post-exposure vaccinations or prophylactic medication can prevent certain toxicities. The use of agents capable of causing serious illness and death can rapidly saturate health resources with patients requiring intensive care and life-saving interventions. This was our experience at the start of the Covid 19 outbreak, even though it was not a voluntary act.
Once the voluntary nature of the attack has been confirmed, identifying the agent and determining the population at risk are essential elements of patient management.
The different agents
We’ve already dealt with most of the microbes mentioned above, so we’ll only mention their main characteristics here.
Anthrax: B. anthracis [3] (category A)
A Gram-positive bacillus, it is found in the environment in the form of resistant spores. When animals that have died of anthrax are buried, earthworms bring the spores to the surface, enabling them to re-infect other healthy animals (cursed fields). Of the 4 existing forms of anthrax – cutaneous, gastrointestinal, by inhalation or injection – only the gastrointestinal (by ingestion) or inhalation forms can be used for terrorism. Mortality in the first form is between 25 and 60%, and 45% in the case of inhalation.
Plague [4]: Y. pestis (category A)
This Gram-negative bacillus killed over 25 million people during the Black Death of the Middle Ages. It is transmitted to humans by contaminated rat fleas. Bubonic plague is fatal in over 40% of sufferers, while septicemic plague and pulmonary plague are consistently fatal without treatment. Attack trials using contaminated fleas have been carried out (successfully!) by the Japanese members of Unit U731.
Brucellosis: Brucella sp. (category B)
Transmission occurs through contact with infected animals, consumption of undercooked meat or unpasteurized milk. This bacterium is highly aerosolizable and must be handled in the laboratory under special conditions. The disease appears flu-like, with headaches, fever and arthralgia. Patients may develop hepatomegaly, orchitis, epididymitis, endocarditis and anemia. The neurofibrosis that follows causes death in around 2% of cases.
Tularemia [4]: F. tularensis (category A)
It is an intracellular Gram-negative coccobacillus, transmitted by ticks. There is no human-to-human transmission.
Symptoms include fever, headache and fatigue, with others depending on the route of exposure. Aerosolization of F. tularensis for malicious purposes can result in pneumonic, oropharyngeal, ulceroglandular and oculoglandular tularemia. Pneumonic tularemia is the most severe and results from inhalation exposure; patients present respiratory symptoms and chest pain, and may develop pleural effusions and mediastinitis.
Q fever: C. burnetti (category B)
The disease is spread by ingestion, aerolization and tick vectors.
Symptoms include fever, chills, malaise, sweating, arthralgia, myalgia, cough, pleurisy, nausea, vomiting and diarrhea. Around half of all people infected with C. Burnetti are asymptomatic. Acute Q fever is generally more disabling than lethal, but pneumonia and myocarditis can be fatal. The disease is fatal if left untreated.
[5]Glanders : Burkholderia (category C)
Burkholderia mallei causes glanders, a disease that mainly affects horses. It is extremely rare for humans to contract the disease through inhalation or contact with mucous surfaces or skin lesions. Symptoms include fever, chills, night sweats, lymphadenopathy, headache, myalgias, tachypnea, nausea, vomiting and diarrhea. Disseminated infections are generally fatal if left untreated for 7-10 days. Even with treatment, mortality can be as high as 50%.
Smallpox virus (group A)
This orthopoxvirus is responsible for smallpox. This disease was eradicated in 1980 thanks to a concerted worldwide vaccination campaign and is now officially restricted to laboratories in the USA and Russia; however, there are probably unauthorized stockpiles. The smallpox virus is an ideal biological weapon because it is easily aerosolized, highly infectious and transmissible from person to person.
Ricin [6] (category B)
It is extracted from the seeds of Ricinus communis, a plant that produces castor oil.
Ricin inactivates ribosomes and causes toxicity by inhibiting protein synthesis. Both the A and B protein chains are required to cause toxicity; once ricin has entered the body, the B chain enables the A chain to enter cells. The A chain then inhibits the 28S subunit of the 60S ribosome, inhibiting translation and protein production.
The median lethal dose (LD50) of ricin by inhalation in humans is 5 to 10 μg/kg. Symptoms of ricin toxicity include nausea, diarrhea, tachycardia, hypotension and convulsions.
Clinical criteria are available to help diagnose botulism, as this condition is often misdiagnosed as myasthenia gravis.
Botulinum [7] toxin (category A)
Clostridium botulinum is a Gram-positive, spore-forming, anaerobic bacterium that produces botulinum toxin, also known as botulinum neurotoxin.
It consists of a light chain and a heavy chain; the heavy chain is responsible for transporting the light chain into the neuron, while the light chain contains the enzyme that cleaves target proteins.
The toxin acts by inhibiting acetylcholine release at the neuromuscular junction.
Once absorbed by the neuron, the light chain targets components of the SNARE complex (soluble Nethylmaleimide-sensitive fusion factor attachment protein receptor), responsible for vesicular trafficking and neurotransmitter release.
Le botulisme provoque une paralysie flasque descendante, affectant d’abord les muscles bulbaires, avec une progression vers les muscles squelettiques et respiratoires. Les premiers symptômes apparaissent dans les quelques heures suivant l’empoisonnement et comprennent la dysphagie, une vision floue et des difficultés d’élocution. La mort peut survenir en raison d’un arrêt respiratoire dû à la paralysie des muscles respiratoires. La toxine a une DL50 de 1 ng/kg chez la souris. En cas d’inhalation, la dose létale chez un humain de 70 kg est de 0,7 à 0,9 ug ou de 70 ug en cas d’ingestion.
Improve healthcare team results
Once a patient has been diagnosed as suffering from an illness potentially caused by a biological weapon, the inter-professional healthcare team should be contacted, including clinicians, nurses, pharmacists and public health officials. Proper decontamination of the patient and appropriate precautions for first responders and hospital staff to avoid further casualties or the spread of contagious diseases are priorities. In the event of large-scale attacks, it is necessary to communicate with hospital management and government officials to access stocks of medical supplies and mobilize human and other resources to treat large numbers of patients.
Training and education prior to biological warfare events, when emotions are calm and resources sufficient, are more effective than training just in time after an event. Healthcare personnel must have a clear understanding of the resources available and the anticipated demands on those resources during large-scale events.
The relatively recent use of ricin and anthrax as bioterrorism agents shows that even small-scale attacks quickly become international news. Care providers may need to communicate with law enforcement agencies, the media and elected representatives (2).
Conclusion
We’re talking about chemical weapons, biological weapons, nuclear weapons, radiological weapons grouped together under the name NRBCe. But there are also conventional weapons… All these weapons are evolving, becoming more sophisticated… Companies are working to protect populations, and we scientists are dissecting, analyzing, comparing, classifying… hoping never to move on to the practical application of our work…
References
(1)- M.1.Hayoun, R.J.Chen, K.C. Kin, National Library of Medicine, 1 janvier 2024
(2) Oliveira M, Mason-Buck G, Ballard D, Branicki W, Amorim A. Biowarfare, bioterrorism and biocrime: A historical overview on microbial harmful applications. Forensic Sci Int. 2020 Sep;314:110366. [PMC free article: PMC7305902] [PubMed: 32683271]
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