Global & Disaster Medicine

Archive for the ‘Bioterrorism’ Category

An enhanced-delivery anthrax vaccine formulation

Weir GM, MacDonald LD, Rajagopalan R, et al. Single dose of DPX-rPA,
an enhanced-delivery anthrax vaccine formulation, protects against a
lethal _Bacillus anthracis_ spore inhalation challenge. npj Vaccines,
Abstract
——–
Anthrax is a serious biological threat caused by pulmonary exposure to
aerosolized spores of _Bacillus anthracis_. Biothrax® (anthrax
vaccine adsorbed (AVA)) is the only Food and Drug
Administration-licensed vaccine and requires 5 administrations over 12
months with annual boosting to maintain pre-exposure prophylaxis. Here
we report the evaluation of a single intramuscular injection of
recombinant _B. anthracis_-protective antigen (rPA) formulated in the
DPX delivery platform. Immune responses were compared to an alum-based
formulation in mice and rabbits. Serological analysis of anti-rPA
immunoglobulin G and toxin neutralization activity demonstrated higher
responses induced by DPX-rPA when compared to rPA in alum. DPX-rPA was
compared to AVA in rabbits and non-human primates (NHPs). In both
species, DPX-rPA generated responses after a single immunization,
whereas AVA required two immunizations. In rabbits, single injection
of DPX-rPA or two injections of AVA conferred 100% protection from
anthrax challenge. In NHPs, single-dose DPX-rPA was 100% protective
against challenge, whereas one animal in the 2-dose AVA group and all
saline administered animals succumbed to infection. DPX-rPA was
minimally reactogenic in all species tested. These data indicate that
DPX-rPA may offer improvement over AVA by reducing the doses needed
for protective immune responses and is a promising candidate as a
new-generation anthrax vaccine.

North Korea: “advanced, underestimated and highly lethal” bioweapons program.

NYT

“…..But today, analysts say, the gene revolution could be making germ weapons more attractive. They see the possibility of designer pathogens that spread faster, infect more people, resist treatment, and offer better targeting and containment. If so, North Korea may be in the forefront.

South Korean military white papers have identified at least ten facilities in the North that could be involved in the research and production of more than a dozen biological agents, including those that cause the plague and hemorrhagic fevers…..”

North Korea Biological Weapons Program


Emergent BioSolutions Inc. announced that Health Canada has approved the company’s New Drug Submission (NDS) for its anthrax vaccine, BioThrax® (Anthrax Vaccine Adsorbed).

Emergent BioSolutions

  • BioThrax is indicated for active immunization for the prevention of disease caused by Bacillus anthracis, in individuals 18 through 65 years of age, whose occupation or other activities place them at risk of exposure, regardless of the route of exposure.
  • BioThrax is administered in a three-dose primary schedule (0, 1 and 6 months) with boosters at three-year intervals recommended thereafter.

 


Summary of Process for Emergency Use Authorization (EUA) Issuance

The flow chart below provides a summary of the process for Emergency Use Authorization (EUA) issuance.

Flow chart providing a summary of the process for Emergency Use Authorization (EUA)

 

Description of chart:

Issuance of an EUA by the FDA Commissioner requires several steps under section 564 of the FD&C Act. First, one of the four following determinations must be in place:

  1. The Department of Defense (DoD) Secretary issues a determination of military emergency or significant potential for military emergency
  2. The Department of Homeland Security (DHS) Secretary issues a determination of domestic emergency or significant potential for domestic emergency.
  3. The Department of Health and Human Services (HHS) Secretary issues a determination of public health emergency or significant potential for public health emergency
  4. The DHS Secretary issues a material threat determination

After one of the above four determinations is in place, the HHS Secretary can issue a declaration that circumstances exist to justify issuing the EUA.  This declaration is specific to EUAs and is not linked to other types of emergency declarations.

The FDA Commissioner, in consultation with the HHS Assistant Secretary for Preparedness and Response (ASPR), Centers for Disease Control and Prevention (CDC), and the National Institutes of Health (NIH), can then issue the EUA, if criteria for issuance under the statute are met.  FDA publishes public notice of each EUA that is issued in the Federal Register.

The last step in the process is termination of declaration and EUA, if appropriate and needed.


Current Emergency Use Authorizations

Emergency Use Authorization, with Emergency sign

FDA

The Emergency Use Authorization (EUA) authority allows FDA to help strengthen the nation’s public health protections against CBRN threats by facilitating the availability and use of MCMs needed during public health emergencies.

Under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the FDA Commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when there are no adequate, approved, and available alternatives.

Section 564 of the FD&C Act was amended by the Project Bioshield Act of 2004 and the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), which was enacted in March 2013

Current EUAs

The tables below provide information on current EUAs:


An alleged ricin terror plot in Cologne, Germany

Ricin

 

The CTC Sentinel

The June 2018 Cologne Ricin Plot: A New Threshold in Jihadi Bio Terror

August 2018, Volume 11, Issue 7
Authors:  Florian Flade
  • “…..German intelligence had learned that Sief Allah H. had bought various materials via the internet, including more than a thousand castor beans and an electronic coffee grinder.
  • During the police raid, a powdery substance was found, which subsequently tested positive for ricin……
  • Investigators found 84.3 milligrams of already-produced ricin and 3,150 castor beans……..”

See the source image


Synthetic Bioterrorism: New genetic tools are making it easier and cheaper to engineer viruses and bacteria in the lab and potentially making them more contagious and lethal.

NPR

Biodefense in the Age of Synthetic Biology:  http://nap.edu/24890

ISBN 978-0-309-46518-2 | DOI 10.17226/24890
Committee on Strategies for Identifying and Addressing Potential Biodefense
Vulnerabilities Posed by Synthetic Biology; Board on Chemical Sciences and
Technology; Board on Life Sciences; Division on Earth and Life Studies;
National Academies of Sciences, Engineering, and Medicine

One danger is making existing bacteria or viruses more dangerous by giving them antibiotic resistance or altering them so that they produce toxins or evade vaccines.

“…..in a table-top exercise conducted last month by the Johns Hopkins Center for Health Security…..experts in pandemic response and national security grappled with a fictional virus called “Clade X” that was created by a terrorist group that inserted genetic elements of deadly Nipah virus into a normally-mild human parainfluenza virus.

The terrorist group in this scenario wanted to depopulate the Earth, and deliberately released the contagious virus at multiple spots around the globe. The resulting pandemic killed 150 million people within a year as officials struggled to contain the social and economic chaos until a vaccine could be made…….”


The tricky tularemia bacterium

NIH

NIH scientists show how tularemia bacteria trick cells to cause disease

What

Francisella tularensis is the bacterium that causes tularemia, a life-threatening disease spread to humans via contact with an infected animal or through mosquito, tick or deer fly bites.  As few as 10 viable bacteria can cause the disease, which has a death rate of up to 60 percent. Scientists from the National Institute of Allergy and Infectious Diseases — part of the National Institutes of Health — have unraveled the process by which the bacteria cause disease. They found that F. tularensis tricks host cell mitochondria, which produce energy for the cell, in two different phases of infection. In the first eight hours of infection, the bacteria increase mitochondria function, which inhibits cell death and prevents the cell from mounting an inflammatory response to avoid an immune system attack. In the 24 hours after, the bacteria impair mitochondrial function, undergo explosive replication and spread. These basic science findings could play a role in developing effective treatment strategies, according to the researchers.

Previously, researchers discovered that F. tularensis could inhibit inflammation following infection of immune system cells called macrophages, but they did not understand how it occurred. The new study, published in Infection and Immunity, illuminates that process, confirming that the bacterium’s manipulation of the mitochondrial machinery in the host cell is required to block strong inflammatory responses. Also, the researchers show that the timing of the manipulation of the mitochondria machinery during infection is important to how the bacteria control host cell death. The researchers also said this could be the first study to show that a bacterium’s sugar-like protective outer capsule, or polysaccharide, can increase mitochondria function, in this case, during early infection.

The researchers believe that better antimicrobial treatment strategies — against F. tularensis and possibly other pathogens — could result from further study of the role the capsule polysaccharide plays in manipulating mitochondria. For example, learning how to block the increased mitochondrial function in phase one could limit infection, they say. In their study, they also treated F. tularensis-infected macrophages in the laboratory with two types of drugs that protect mitochondria.  The treatment reduced cell death and limited bacterial replication. The group plans to extend that work to mice.

Article

F Jessop et al. Temporal manipulation of mitochondrial function by virulent Francisella tularensis to limit inflammation and control cell death. Infection and Immunity DOI: 10.1128/IAI.00044-18 (2018).


FDA issues final guidance for drug companies to use for developing pre-exposure prophylaxis for inhalational anthrax.

FDA

FDA In Brief: As part of a longstanding program encouraging the development of medical countermeasures; new FDA policy promotes innovation to thwart inhalational anthrax

May 23, 2018

Media Inquiries

  Tara Rabin
  240-402-3157

“The FDA has long played an important role preparing our nation for potential bioterrorism threats, providing guidance and support around the development of medical countermeasures that can be used safely, effectively and reliably during public health emergencies,” said FDA Commissioner Scott Gottlieb, M.D. “Since the 2001 anthrax attacks, the U.S. government’s efforts to protect the nation from bioterrorism threats have continued to evolve. We now know that a comprehensive preparedness plan for potential anthrax threats must account for both pre- and post-exposure scenarios. That’s why the FDA has taken steps to modernize its guidance on inhalational anthrax to advance the development of new drugs for prophylaxis, prior to exposure. This builds upon the treatments that are currently available for inhalational anthrax and advances the agency’s longstanding commitment to the development of a full suite of medical countermeasures as part of its established programs.”

The U.S. Food and Drug Administration today issued final guidance, Anthrax: Developing Drugs for Prophylaxis of Inhalational Anthrax, which is designed to assist in the development of drugs for prophylaxis (prevention) of inhalational anthrax for individuals who may be potentially exposed to or have inhaled aerosolized Bacillus anthracis (B. anthracis) spores, but who have not yet displayed related signs and symptoms.

While there are FDA-approved drugs for treatment of anthrax and for post-exposure prophylaxis of inhalational anthrax, situations can arise where starting therapy immediately before the anticipated or potential exposure can reduce the risk of illness and death (for example, first responders who anticipate an imminent risk of exposure to B. anthracis spores).

The FDA’s final guidance is the result of a multi-year effort to advance its policy framework for the development of treatments targeting inhalational anthrax. The final guidance revises the indication to “prophylaxis of inhalational anthrax” for the reduction of disease risk in those who have inhaled, or are likely to inhale, aerosolized B. anthracis spores, but who do not yet have established disease.

Clinical trials in humans cannot be conducted since naturally occurring inhalational anthrax is extremely rare and it would be unethical to deliberately expose healthy human volunteers to B. anthracis spores. Therefore, the final guidance clarifies that drugs developed for the prophylaxis of inhalational anthrax can rely on evidence from animal studies (known as the Animal Rule) to support approval when the criteria under the Animal Rule have been met.

The FDA encourages drug developers to reference the final guidance issued today when designing studies to appropriately establish the safety and effectiveness of drugs for prophylaxis of inhalational anthrax.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.


US experts sound off: The USA ‘….is “woefully unprepared for these biological threats” in an increasingly interdependent world……’

Homeland Security Today

  • James Lawler is “…a retired Navy commander whose experience includes serving as director for medical preparedness policy on the National Security Council and director for biodefense policy on the White House’s Homeland Security Council…”
  • “….Kenneth Luongo, president and founder of the Partnership for Global Security, echoed that the U.S. “remains woefully underprepared” for a biological attack or a “new intensity level” of pathogens…..”
  • “….Former USAID Director Andrew Natsios, director of the Scowcroft Institute of International Affairs, told the panel that the country is “a lot more fragile than we realize” when it comes to emergency response….”

 


Categories

Recent Posts

Archives

Admin