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Developmental Milestones/Developments to Date:

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Benjamin, Georges C. “Chemical and Biological Terrorism: Planning for the WorstPhysician Executive Volume 26 Issue 1. 80. January/February 2000.

  1. Chemical or biological terrorism is the use of pathogenic microbes or toxins derived from plants, animals, microbes, or chemical agents to achieve terror.” – page 80
  2. ”Chemical and biological weapons, like nuclear weapons, are categorized as weapons of mass destruction (WMD) because of the high number of potential victims that can result from their use.” – page 80 *
  3. ”While any chemical can be weaponized, the chemical agents traditionally of concern fall into four categories: nerve agents like sarin, which create an anticholinergic-like syndrome; vesicants like mustard gas, that cause a blistering or burn-like syndrome; cyanide, which interrupts aerobic metabolism; and riot control agents such as mace, which generally cause incapacitation.” – page 80
  4. ”Biological agents act like chemical agents but have a slower onset of action. Agents of concern include Ricin.” – page 81
  5. ”The ideal bioweapon is hard to detect from the usual microbial flora, has person-to-person spread, and is easy to aerosolize. There are two groups of organisms of public health concern: those that cause a high morbidity or a high mortality.” – page 81
  6. ”Examples of high morbidity organisms include salmonella, cholera, or E. coli. The number of highly toxic organisms is fortunately quite low and includes anthrax, smallpox, and the viruses that cause hemorrhagic fevers, plague, brucellosis, and tularemia.” – page 81
  7. “Clues that biological terrorist events have occurred include an unexplained increase in respiratory cases or deaths, or dead and dying animals. Epidemiological clues include diseases with the wrong mode of transmission, which occur in an inappropriate geographic distribution or infect a new or novel population.” – page 81
  8. “Components of a biological/chemical terrorism disaster plan: plan how to identify the threat; develop an effective public health disease surveillance system; link the public health system and the traditional medical care delivery system; develop command and control systems; determine hospital bed availability; define disease containment, isolation, and quarantine procedures; plan how to obtain extra life support equipment such as respirators; plan how to train clinical staff to identify high-risk unusual diseases; ensure non-clinical staff are trained on the management of suspicious packages and mail; identify experts; plan simple handling and transport; plan how to communicate high risk information; manage medical examiner cases; and maintain a crime scene.” – page 81
  9. ”Effective disease control strategies such as case finding, decontamination, prophylaxis and vaccination, and quarantine must be defined.” – page 82

Chemical, WMD, Bioterrorism, Public Health, Military, Sarin, Japan, Ricin, E. coli, Cholera, Salmonella, Anthrax, Smallpox, Hemorrhagic fever, Plague, Brucellosis, Tularemia, Prophylaxis, Vaccination, Quarantine


Glass, Thomas A. and Monica Schoch-Spana, “Bioterrorism and the People: How To Vaccinate a City against Panic,” Clinical Infectious Diseases, 34:217-23 (Jan 15, 2002)

  1.  [Glass and Schoch-Spana propose a five point model for community participation in response bioterror attacks, especially epidemics]: 1. “treat the public as a capable ally,” 2. “enlist civic organizations,” 3. “anticipate the need for home-based patient care and infection control,” 4. “invest in public outreach and communication strategies,” and 5. “ensure that planning reflects the values and priorities of affected populations.”
  2. The public has generally been discounted as an effective means of defense against bioterrorism; this attitude is not based on experience, as the authors claims “natural and technological disasters and disease outbreaks indicate a pattern of generally effective and adaptive collective actions.”
  3. “Collective behavior changes over time and in relation to external events.  This suggests that, in times of disaster, panic may be ‘iatrogenic’: that is, the actions of emergency managers may determine the extent and duration of he panic, to the extent that it exists.”

Emergency Response, Public Health, Prophylaxis, Anthrax, Ethics


Sasaki, Asami, et al., “Evidence-based Tool for Triggering School Closures during Influenza Outbreaks, Japan,” Emerging Infectious Diseases, Vol. 15, No. 11, November 2009.

  1. ”Using empirical data on absentee rates of elementary school students in Japan, we developed a simple and practical algorithm for determining the optimal timing of school closures for control of influenza outbreaks.”
  2. ”Influenza pandemic preparedness and seasonal influenza control programs have focused on vaccine development and antiviral drugs, which are only partially effective and not always available to all persons at risk (1–3). Nonpharmaceutical interventions, such as social distancing, represent additional key tools for mitigating the impact of outbreaks.”
  3. ”Because children are a major factor in the transmission of influenza within communities and among households, school closure may be a valuable social distancing method (4,5).”
  4. ”We evaluated the optimal influenza-related absentee rate for predicting outbreaks of influenza.”
  5. ”Our analysis suggests that a single-day at a threshold influenza-related absentee rate of 5%, double-days >4%, or triple-days >3% are optimal levels for alerting school administrators to consider school closure. The double- and triple-day scenarios performed similarly, and gave better results than the singleday. Thus, the double-day scenario might be the preferred early warning trigger.”
  6. ”We used the Youden index for calculating optimal thresholds (7). The Youden index = (sensitivity) + (specificity) – 1. A perfect test result would have a Youden index of 1. For the single-day scenario, the optimal threshold was 5%, with a sensitivity of 0.77 and specificity of 0.73.”

Flu, Public Health, Prophylaxis, Biosurveillance, Japan


McNeill, Donald, G., “Flu Shots in Children Can Help All Ages, Study Says,NYT p. A16, March 10, 2010.

  1. “Although previous studies have demonstrated what scientists call ‘herd immunity,’ none have been so incontrovertable, because they were done in less isolated places with more sources of flu passing through.”
  2. “Dr. Anthony Fauci … added that its results validated the American government’s decision to vaccinate children first during the recent swine flu epidemic.”
  3. “In 25 of the colonies that joined, all children ages 3 to 15 received flu shots in late 2008; in 24 others, they received hepatitus A vaccine instead.”
  4. “There was a 60 percent ‘protective effect’ for the whole community, the study concluded.”
  5. “It implies, Dr. Bridges said, that giving flu shots only to school children would protect the elderly just as well as giving flu shots to the elderly themselves.”

Vaccination, Prophylaxis, Flu, Canada


Ramasamy, S., et al., “Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents,” Review, British Journal of Pharmacology, Defence Science & Technology Organisation, Human Protection and Performance Division, Fishermans Bend, Vic., Australia; April 20, 2010.

  1. “Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis.”
  2. “There are two licensed anthrax vaccines available (Little, 2005; Wang and Roehrl, 2005). The US anthrax vaccine adsorbed is extracted from a cell-free culture filtrate of an unencapsulated, toxin-producing strain of Bacillus anthracis (V770-NP1R). The UK vaccine (Health Protection Agency) is prepared from a similar strain called Sterne 34F2. Both vaccines contain the protective antigen (PA) adsorbed to aluminium hydroxide and contain small amounts of lethal factor (LF) and oedema factor (EF). The vaccines are both effective against anthrax infection when administered prophylactically, although the vaccination protocols differ.”
  3. “Although current human anthrax vaccines are effective against anthrax, they still suffer from batch-to-batch variation in composition, require multiple doses and yearly booster injections and have been associated with occasional adverse reactions.”
  4. “Protection against anthrax via current anthrax vaccines is mediated largely by antibody (humoral) responses to the protective antigen (PA); however, cellular immunity has been shown to also play an important role.”
  5. “Previous studies have shown that whole spore-based vaccines are more effective against virulent strains of B. anthracis than the current PA-based vaccines.”
  6. “The FDA recommends that ciprofloxacin, doxycycline or amoxicillin be used for a period of 60 days post exposure to B. anthracis (”
  7. “The most significant novel therapy has been the development of antibody-based passive immuno-therapy against anthrax toxin components, primarily PA and to a lesser extent LF. This has been made possible through significant funding from the US government to support the development and commercialization of antibody-based therapy.”

Anthrax, Prophylaxis


Pharmaceutical Research and Manufacturers of America, “Medicines in Development for Infectious Diseases,” Report, Biopharmaceutical Research Continues Against Infectious Diseases with 395 Medicines and Vaccines in Testing,, September 10, 2010.

  1. “America’s biopharmaceutical research companies are developing 395 medicines and vaccines to combat the many threats posed by infectious diseases. Each of these medicines in development is either in clinical trials or under review by the Food and Drug Administration.”
  2. “Among the medicines now being tested are 88 antibiotics/antibacterials for treating bacterial infections such as pneumonia and tuberculosis; 96 antivirals for treating such viruses as hepatitis, herpes and influenza; and 145 vaccines to prevent or treat diseases such as staph infections and pneumococcal infections. Not included in this report are medicines in development for HIV infection.”
  3. “Two combined monoclonal antibodies that bind to, neutralize, and destroy toxins caused by Escherichia coli infections.”
  4. “A medicine for the most common and difficult-to-treat form of hepatitis C that inhibits the enzyme essential for viral replication.”
  5. “An anti-malarial drug that has shown activity against Plasmodium falciparum malaria that is resistant to current treatments.”
  6. “A potential new class of antibiotics to treat methicillin-resistant Staphylococcus aureus (MRSA).”
  7. “A novel treatment that works by blocking the ability of the smallpox virus to spread to other cells, thus preventing it from causing disease.”
  8. “‘Included are several developments for anthrax vaccines.'”

Anthrax, Prophylaxis, Vaccination, Drug Resistance, Pharma


Wu, Gaobing, et. al., “A Chimeric Protein that Functions as both an Anthrax Dual-Target Antitoxin and a Trivalent Vaccine,Journal, Antimicrobial Agents and Chemotherapy, Volume 54, No. 1, p. 4750-4757, November 2010, American Society for Microbiology.

  1. “Effective measures for the prophylaxis and treatment of anthrax are still required for counteracting the threat posed by inhalation anthrax.”
  2. “In this study, we first demonstrated that the chimeric protein LFn-PA, created by fusing the protective antigen binding domain of lethal factor (LFn) to PA, retained the functions of the respective molecules.”
  3. “In animal models, LFn-DPA exhibited strong potency in rescuing mice from lethal challenge with LeTx.  We also evaluated the immunogenicity and immunoprotective efficacy of LFn-DPA as an anthrax vaccine candidate.”
  4. “Mice immunized with LFn-DPA tolerated a LeTx challenge that was 5 times its 50% lethal does.  Thus, LFn-DPA represents a highly effective trivalent vaccine candidate for both pre-exposure and post-exposure vaccination.”
  5. “Overall, we have developed a novel and dually functional reagent for the prophylaxis and treatment of anthrax.”

Anthrax, Prophylaxis, Vaccination, Biodevelopment


Pollack Andrew, “Antibiotics Research Subsidies Weighed by U.S.New York Times Last accessed November 11, 2010.

  1. “Worried about an impending public health crisis, government officials are considering offering financial incentives to the pharmaceutical industry, like tax breaks and patent extensions, to spur the development of vitally needed antibiotics.”
  2. “While the proposals are still nascent, they have taken on more urgency as bacteria steadily become resistant to virtually all existing drugs at the same time that a considerable number of pharmaceutical giants have abandoned this field in search of more lucrative medicines.”
  3. “The number of new antibiotics in development is “distressingly low,” Dr. Margaret A. Hamburg, commissioner of the Food and Drug Administration, said at a news conference last month. The world’s weakening arsenal against “superbugs” has prompted scientists to warn that everyday infections could again become a major cause of death just as they were before the advent of penicillin around 1940.”
  4. “For example, scientists have become alarmed by the spread from India of a newly discovered mutation called NDM-1, which renders certain germs like E. coli invulnerable to nearly all modern antibiotics. About 100,000 Americans a year are killed by infections acquired in hospitals, many resistant to multiple antibiotics. Methicillin-resistant staphylococcus aureus, or MRSA, the best known superbug, now kills more Americans each year than AIDS.”
  5. “Besides tax breaks and extra protection from competition, other ideas policy makers are considering include additional federal funding of research and guaranteed purchases by the government of new antibiotics. Measures like these are already used to encourage the development of drugs for rare diseases, through the Orphan Drug Act, and for illnesses like malaria that primarily afflict poor countries.”
  6. “The Obama administration is also taking some steps. The federal agency that oversees development of treatments for bioterrorism agents like anthrax is broadening its scope to encompass more common infections. In August, the agency, known as the Biomedical Advanced Research and Development Authority, awarded its first such “multi-use” contract, giving an initial $27 million to a company called Achaogen to develop an antibiotic that could be used for plague and tularemia as well as antibiotic-resistant infections.”
  7. “The Department of Health and Human Services is considering creating an independent fund that would invest in small bio-defense companies. Antibiotic-resistant germs would be one priority, according to a report that the department issued in August.”
  8. “The European Union is also working on a plan, based on proposals from the London School of Economics. A year ago, the United States and the European Union formed a task force on antibiotic resistance.”
  9. “Ramanan Laxminarayan, who directs the Extending the Cure project on antibiotic resistance at Resources for the Future, a policy organization, said the government should focus on conserving the effectiveness of existing antibiotics. That could be done by preventing unnecessary use in people and farm animals and requiring better infection control measures in hospitals.”
  10. “Only five of the 13 biggest pharmaceutical companies still try to discover new antibiotics, said Dr. David M. Shlaes, a consultant to the industry and the author of a new book “Antibiotics: The Perfect Storm.””
  11. “One reason is that antibiotics are typically taken for a week or two and usually cure the patient. While that makes them cost-effective for the health system, it also makes them less lucrative to drug companies than medicines for diseases like cancer or diabetes, which might be taken for months, or even for life, because they do not cure the patient.”
  12. “Another factor is that new antibiotics are likely to be used only sparingly at first, to stave off the emergence of resistance. While that might be medically appropriate, it reduces the ability of a drug company to recoup its investment, said Dr. Barry I. Eisenstein, a senior vice president at the antibiotic maker Cubist Pharmaceuticals. Another factor discouraging investment, some experts say, is that the F.D.A. recently made it harder for new antibacterial drugs to win approval.”

NDM-1, Public Health, Prophylaxis, Pharma


Rowe, Aaron, “Molecules To Protect The Brain From Nerve Gas“, 6 January 2012,,, Last Checked 16 January 2012.

  1. “A new family of oxime compounds can cross the blood-brain barrier in mice and protect the animals from nerve gas poisoning. The researchers who developed them hope the molecules could serve as antidotes for exposure to the gases or certain pesticides.”
  2. “One of the most common antidotes for nerve gas exposure is pralidoxime. (Soldiers carry syringes filled with the compound in case of a chemical weapons attack.) It reactivates cholinesterases when the molecule’s oxime group breaks the bond formed between the organophosphate and the enzyme.”
  3. “But pralidoxime has a problem: It contains a positively charged quaternary amine, which prevents it from slipping through the blood-brain barrier. So although pralidoxime can undo paralysis in respiratory tissue, it can’t alleviate problems within the central nervous system.”
  4. “To overcome this problem, John Cashman and his team at the Human BioMolecular Research Institute, a nonprofit organization in San Diego, designed a set of oximes that replace the quaternary amine with an amidine. This group can be neutral in charge, allowing the molecule to pass into the brain.”
  5. “In a test of the new molecules’ efficacies, several of them protected mice from a lethal dose of a sarin mimic when researchers injected the compounds into the animals. None of the treated mice succumbed to the poison, but half of the mice that received no treatment died. The researchers found high levels of the amidine-oximes in the treated animals’ brains. Next Cashman and his colleagues want to test their compounds to see if they can protect the brain from pesticide poisoning.”

Chemical, Prophylaxis, Vaccination