MICR 4000 Unit 4

What details regarding the spores were investigators quickly able to determine? (what strain was used? Were they weaponized?). What did this tell investigators?

- "Ames" strain of Bacillus anthracis stored at USAMRIID - Highly purified spore preparations - Not weaponized - Particular envelopes only sold in MD and VA - Mailbox used to mail letters was in NJ - Told them it was someone who had experience working in the lab (researcher), had good technical skills, and lived or had access to the northeastern US

Briefly describe the 2001 anthrax attacks.

- 5 envelopes mailed - Two US senators - Several media organizations - Speculation of 6th envelope - 22 victims - 11 inhalational - 11 cutaneous

How do the types of influenza viruses (A and B) differ? (in terms of characteristics that we discussed in class)

- A has various subtypes and strains, B has different strains not subtypes - A can experience antigenic drift or shift, while B really only has the possibility of drift - A has multiple different hosts (pigs, birds) while B only has humans as the hosts (seals are a questioned source)

Explain the two methods of antigenic variation for influenza viruses.

- Antigenic drift: regular, random, small changes that occur like mutations (mistakes in replication). A single mutation does not cause problems, drift causes problems slowly over time as mutations accumulate. Commonly causes epidemics. - Antigenic shift: sudden or abrupt changes that are also random. These tend to be big changes, so these can have major impacts in terms of brand-new versions of surface proteins or something similar. Causes pandemics and epidemics.

What sort of information is included in the "name" for a flu virus?

- Antigenic type: A, B, C or D - Host of origin: spillover from chickens, pigs, and no host of origin if humans - Geographical origin - Strain number - Year of isolation - If type A, subtype: H1N1 or some other type

How is B. pertussis thought to cause the disease symptoms associated with Whooping cough? How does this impact the effectiveness of antibiotics if given three weeks after infection?

- B. pertussis gets into the respiratory tract, attaches to the ciliated cells, and produces toxins that paralyze the cilia (destroys them) and cause inflammation in the respiratory tract - After 3 weeks, antibiotics no longer effective because bacteria are no longer present

What problems exist in regards to the ban set in place by the Biological and Toxin Weapons Convention?

- Banned development, production, stockpiling and acquisition of biological weapons as of 1975 - No way to back up this statement - Had no way to implement punishment - The number of countries engaging in bioweapons research doubled over the next decade despite ban

Why are the vaccination rates for the MMR vaccine low? What role has Andrew Wakefield's paper played in this? What were some of the problems with his paper?

- Biggest problem is misinformation - Fed through coincidence of when kids get their first MMR shot (12-15 months) and when they show the first signs of autism (12-18 months) - Wakefield's paper inaccurately suggested a link between vaccines and autism though now retracted - Inaccurate tests and conclusions - Had lawyers involved that needed the evidence for their anti-vaxx cases - Evidence also he was working with individuals who were developing new measles vaccine

What is cocooning?

- Can't vaccinate the baby, so vaccinate everyone who is going to be in close contact with the baby - Cocoon of vaccinated relatives - Not effective because not enough people are covered, babies come in contact with people that aren't relatives

What factors are important in preparation for a possible biological weapons attack?

- Detect - Diagnose - Differentiate - Defend - Disperse - BioShield Act (2004)

What are some reasons for "vaccine hesitancy"?

- False information - Parents feel they should have more input - Distrust of big pharma and the government - Physicians not spending enough time discussing with parents who are on the fence - Vaccines are a victim of their own success

What are the symptoms associated with measles infections? What complications are possible? (include the possible longer-term complications)

- Fever - The 3 C's: cough, coryza, and conjunctivitis - Koplik spots - Rash - Short-term complications: secondary infections like ear infections, pneumonia, GI symptoms - Long-term: not a risk with vaccination, Subacute sclerosing panencephalitis (SSPE), long term immune suppression and problems

Why must an individual be vaccinated each year?

- Genetic diversity means there needs to be a vaccine every year - There are constantly new viruses and new strains undergoing shift or drift - The current vaccine design only gives immunity for 3-6 months, so need to rebuild the immune response

What is herd immunity? How does it work?

- Herd immunity is immunity where a large enough population of people are immune to a certain disease, and it effectively shuts down transmission to those who are not immune - High levels of vaccination means sick people and unvaccinated people are less likely to come into contact with one another to spread disease because there are so many immune people

Know some desirable traits of organisms or toxins that might be used as biological weapons.

- High morbidity and mortality - Person to person transmission - Low infectious dose - Ability to cause large outbreaks - Lack of treatment, preventatives, and vaccines - Access - Ability to cause panic, anxiety, and disruptions that stop normalcy - Stable - Aerosol - Release is undetectable

From an immunology standpoint, what is the point of immunization?

- Immune response without damage - Repeated exposure creates a better immune response

How has Yersinia pestis been used negatively in the past?

- In WWII at least two separate times Japanese army tried to deliver mixtures of rice and wheat along with some plague infected fleas to china in an effort to spread two plague outbreaks - Evidence US and Soviet Union worked on efforts to be able to directly aerosolize plague

What are the two types of flu vaccine?

- Inactivated vaccines: injectable form, variations in terms of what viruses are present so protect varies against different types of flu, potency is varied as well - Nasal spray: live, attenuated

How has Clostridium botulinum toxin been used negatively in the past?

- Inhalation route - Japanese army fed certain toxins to some of their prisoners, and a cult attempted aerosolized dispersal at multiple bases - 1991 Iraq produced thousands of liters of concentrated toxin, more than they would need to kill every single person on earth 3x over

Explain the controversy surrounding the H5N1 mortality rate.

- It is considered the be ~60% (seasonal flu is 0.1% and the 1918 influenza pandemic was ~2.5%) - Argued against and debated in the literature because of the possibility of subclinical cases and research has been questionable - This mortality rate is concerning because if there was a pandemic, it would be terrifying

How has Bacillus anthracis been used negatively in the past?

- Japanese army stockpiled 2kg of anthrax spores that they were going to try to incorporate into bombs - US and Soviet Union accidental release from soviet weapons facility - Terrorist cult released spores from top of a building in Tokyo, but released nonpathogenic strain

Why is Whooping cough re-emerging?

- Lower vaccination rates - Acellular vaccine: studies suggest immunity is fading faster - Acellular has 3-5 antigens while whole cell vaccine had 100s - So bacteria can mutate and the vaccine cannot protect

Why is maternal vaccination important?

- Mothers getting Tdap in their third trimester, around 36 weeks - Important because majority of maternal antibodies are passed to the baby between 36-40 weeks

How is Bacillus anthracis infected spread?

- Not person to person - Animals - As a weapon - Can come from soil in certain circumstances

What are some general concerns regarding vaccine safety?

- Reversion being possible in attenuated live vaccines - Immunocompromised individuals cannot get some vaccines - People can have allergic reactions to vaccine components

Why is there interest in developing a universal flu vaccine?

- Something that could protect against any and all influenza viruses - Necessary because of the genetic diversity and because of the fact that new viruses are constantly emerging without us knowing which ones will be prominent every year - If designed correctly, could protect against strains we have not even thought about yet and can provide significant protection against a pandemic - Also, there is the possibility for longer immunity

How were Viral hemorrhagic fevers used negatively in the past?

- Soviet Union tried to weaponize Ebola, Marburg, Lassa fever - US wanted to weaponize yellow fever and rift valley fever - Circumstantial evidence that North Korea weaponized yellow fever

Explain the concerns regarding autism and vaccines?

- The idea that autism is increasing and seems to be diagnosed around the same time kids are getting their vaccine; assumed link

What is meant by "flu season"?

- The period where there is a high positive percentage of respiratory tests when looking for influenza - >10% positive consistently over a period of weeks indicates the start - October (earliest) to May (latest). January is usually the peak.

Why can it be difficult to identify rare risks from vaccines ahead of release to the public?

- The risks can be so rare that even the large studies miss it and they are unable to identify the problem - This is helped through constant tracking after release

Why are influenza A viruses prone to reassortment?

- There are multiple hosts, which can lead to there being mixing within the vessel (usually pigs) that causes shift - Reassortment: two or more influenza viruses infect the same cell, cause a mutant combination that can infect humans, and humans have no immunity because of the genetic diversity

Explain the controversy surrounding the H5N1 dual purpose research. DO you think the research should have been published?

- Two labs, two papers, looking at what makes H5N1 transmissible through ferret models - Moratorium placed on all research - Arguments against publication: bioterrorism potential, accident release - Arguments for publication: potential for vaccine, can have better understanding of transmission, protection if there is an outbreak, techniques weren't new

How is Whooping cough prevented?

- Vaccination - DTaP and Tdap - Difference is dosage - Recommend DTaP first then Tdap for boosters

When are the viruses to be included in the flu vaccine for the upcoming season decided upon? What are the decisions based upon?

- WHO recommendations are made in February; need to make months in advance in order to have vaccine for everyone - They used the strains previously prevalent in order to make the vaccine

Be able to outline the case against Dr. Bruce Ivins.

- Worked at USAMRIID for 27 years as a senior microbiologist - Expert on anthrax; vaccine development - Worked in lab alone, access to ames strand, access to spore preps - Vaccine program was about to be shut down after 20 years - Language and codes similar to ones he had access to - Drove long distances to mail letters - Obsessed with KKG, mailbox that was used to mail letters was near a KKG chapter in Princeton - Threw away code book - Tried to blame others - Decontaminated lab without proper procedure - Only found anthrax in his lab in USAMRIID

How has Variola major been used negatively in the past?

British gave clothing and blankets to Native Americans that were used by those infected with smallpox

Describe the three types of disease caused by infection with Bacillus anthracis.

Cutaneous - Enters through skin - Small sore like blister or laceration, then necrosis because of potent toxins - 1% fatality, 20% without treatment Gastrointestinal - Comes from consuming spores - Usually undercooked meat from infected animal - 25-75% morality Inhalation - When it gets into the lungs - Cold or flu-like symptoms to severe pneumonia, shortness of breath, coughing - Without treatment, 80% mortality

What are the three stages of symptoms associated with Whooping cough?

Stage 1: Catarrhal Stage - 1 to 2 weeks - Highly contagious - Symptoms: runny nose, low-grade fever, occasional cough Stage 2: Paroxysmal Stage - 1-6 weeks; may extend to 10 - Symptoms: fits of numerous, rapid coughs followed by "whoop" sound; vomiting and exhaustion after coughing fits (paroxysms) Stage 3: Convalescent Stage - 2-3 weeks - Susceptible to other respiratory infections

Why is measles increased in the United States and in other countries?

Vaccine hesitancy, lower vaccination rates