Pg. 80AVIAN BIRD FLU-DISCUSSIONWHAT IS A VIRUS?1.) It is considered simply as genetic material in a

protective shell.2.) This genetic material may be RNA or DNA depending

on the kind of virus A) RNA (ribonucleic acid)can’t locate and fix mutations

a) single strand b) has a hydroxyl group which makes RNAmore susceptible to hydrolysis=unstable

B) DNA (deoxyribonucleic acid)locates and fixes mutationsa) double strandb) no hydroxyl group (has hydrogen)less susceptible to hydrolysis=stable

3.) The protective coating is called a capsid

Pg. 80AVIAN BIRD FLU-DISCUSSIONWHAT IS A VIRUS?4.) Some viruses have an additional outer protective layer

called an envelope. This may be made of sugars, lipids (fats), or proteins. These materials are acquired from the host cell where the virus

was made. THEIF!!!!

5.) The surface of the virus is covered withreceptor-binding proteins.

Pg. 80-81HOW DO VIRUSES REPRODUCE animation1.) All viruses reproduce by taking over the reproductive

mechanism of the host cell.

2.) Receptor-binding proteins (RPB {hemmagglutinin}) areattached to the capsid or envelope.

3.) RPB stick out of the virion and hook up to specificreceptors on the host cell.

4.) Only certain RPBs can bind with certain host cellreceptors.

5.) The host cell “believes” that the virion is something itneeds or “wants”.

Pg. 80-81HOW DO VIRUSES REPRODUCE animation6.) The virus “tricks” the host cell and it is then

internalized/injects material.

7.) After internalization the virus sheds its capsid and/or envelope.

8.) The virus then takes over the host cells reproduction

mechanism.

9.) The virus (parasite) then builds up large amounts of

“offspring” which are released into various systems of the body.

10.) These offspring repeat the process with other host cells.

Pg. 81A LITTLE MORE DETAIL ON VIRUS REPRODUCTIONLET’S START TO CONSIDER THE H5N1

1.) On the outside of a virion there are a number of“nails” or “spikes” sticking out.

2.) About 80% of these is the viral protein hemagglutinina.) This is the same protein that helps red blood

cells stick together.b.) hemagglutinin is the receptor-binding protein.c.) This is what “sticks” to the host cell.d.) And helps the virus get into the host cell.

Pg. 81A LITTLE MORE DETAIL ON VIRUS REPRODUCTIONLET’S START TO CONSIDER THE H5N13.) The other 20% is a viral protein called neuraminidase.

a.) this protein destroys a molecule in the host cell

called neuraminic acid. b.) It is thought (possibly) that this protein

mayhelp the virus enter the host cell.

c.) It does help the “offspring” virus (virions) to

get out of the host cell.

ADD 4.) What does the H and N mean in H5N1?a.)H5 stands for the fifth of several

known types of the protein hemagglutinin.

b.) N1 stands for the first of several known types of the protein neuraminidase

Pg. 81-82HOW DOES OUR BODY FIGHT VIRUSES

1.) The virus produces an antigen (a specific viral protein).

2.) Your body’s immune system recognizes these antigensas a threat.

3.) They produce an antibody that specifically goes afterand attaches to the antigen.

4.) The antigen and antibody fit together like a lockand key. This coupling renders the antigenineffective stopping further attacking of hostcells and virion production. The antibody focuses on“docking” on the hemaglutinin sites.

Pg. 81-82HOW DOES OUR BODY FIGHT VIRUSES

5.) Now that your body has antibodies for that antigen

you will not ever get that same strain of flu. BUT……

6.) You are still susceptible to other strains because they result in different antigens for which you have no

antibodies. Yet.

Pg. 82WHERE DO THESE NEW STRAINS COME FROM?There are two basic methods for the development of

new flu virus strains.1.) Antigenic DRIFT

a.) This is basically molecular evolution.b.) Genetic material (DNA and RNA) have small

mutations or errors. RNA tends to have moreerrors or mistakes.

c.) This means that RNA viruses evolve faster thanDNA viruses AND human DNA.

d.) If these changes are beneficial to the survival ofthe virus the virus will persist and may laterchange into another strain.

Pg. 821.) Antigenic DRIFT continued

e.) The antigen for this new strain is of a different shape and does not “fit” the antibodies from the old strain. You can now get sick from it.

f.) This mode of change is responsible for many local and regional outbreaks of influenza B.

g.) Problem? There is no antiviral medication for these new strains until they happen

WHERE DO THESE NEW STRAINS COME FROM?There are two basic methods for the development of

new flu virus strains.

Pg. 82-832.) Antigenic SHIFT

a.) This is the one we are most worried about.b.) Happens because of gene sharing that

occurs in influenza A types not B and C. c.) Occurs when two type A influenza strains

infect a host cell simultaneously.d.) The offspring virions can then have

genetic material from BOTH parent viruses.

Pg. 82-832.) Antigenic SHIFT

e.) For example: 1.) H3N5 and H2N4 infect a host cell.2.) You may get H3N5 and H2N4 offspring,

but also…3.) because of recombining you may get H3N4

and/or H2N54.) This occurs very rapidly.

HOW CHANGE ANTIBODY ANTIGEN RELATIONSHIP?

Pg. 82-832.) Antigenic SHIFT

f.) So even though the bird flu cannot go from person toperson easily (yet) the idea is that with eachinfection (and antigenic SHIFT) there is a greaterrisk of the recombination occurring that would allowit to be transmitted person to person very easily.

g.) The problem is that there is no medication until ithappens. Talk about NOT being proactive. You can’t.

Pg. 84 PANDEMIC vs. SEASONAL OUTBREAKS(EPIDEMICS)

PANDEMIC: pandemic outbreaks are caused by threepossible conditions:1.) new subtypes2.) subtypes that have never circulated among

people3.) subtypes that have not circulated among

people for a long time.***Usually spread to numerous continents.

SEASONAL OUTBREAKS: Seasonal outbreaks are causedby subtypes of influenza viruses that alreadycirculate among people

Pg.87CONSIDER PAST PANDEMICSDuring the 20th century, the emergence of several new

influenza A virus subtypes caused three pandemics,

all of which spread around the worldwithin a year of being detected.

Pg.871.) 1918-19, "Spanish flu," [A (H1N1)]

a.) caused the highest number of known influenza

deaths. b.) More than 500,000 people died in the

United Statesc.) up to 50 million people may have died

worldwide. d.) Many people died within the first few days

after infection, and others died of secondary

complications. **e.) Nearly half of those who died were

young,healthy adults.

Pg. 872.) 1957-58, "Asian flu," [A (H2N2)].

a.) caused about 70,000 deaths in the United States.

b.) First identified in China in late February 1957, the Asian flu spread to the United States by June 1957.

3.) 1968-69, " Hong Kong flu," [A (H3N2)].a.) caused about 34,000 deaths in the United

States

b.) This virus was first detected in Hong Kong in early 1968 and spread to the United States later that year.

Pg. 87****Both the 1957-58 and 1968-69 pandemics were caused by viruses containing a combination of genes from a human influenza virus and an avian influenza virus. Remember Antigenic SHIFT????

The 1918-19 pandemic virus appears to have an avian origin. Possibly from Antigenic DRIFT????

Pg. 88STAGES OF A PANDEMIC

INTERPANDEMIC PERIODPhase 1 : No new influenza virus subtypes have been

detected in humans. May be present in animals.

Phase 2 : No new influenza virus subtypes have beendetected in humans. However, there is a circulatingsubtype that poses a substantial risk of humandisease.

Pg. 8PANDEMIC ALERT PERIOD

Phase 3 : Human infection(s) with a new subtype, but no human-to-human spread, or at most rare instances

of spread to a close contact.

Phase 4 : Small cluster(s) with limited human-to-human transmission but spread is highly localized, suggesting that the virus is not well adapted to humans.

Phase 5 : Larger cluster(s) but human-to-human spread still localized, suggesting that the virus is becoming increasingly better adapted to humans but may not yet be fully transmissible (substantial pandemic risk).

Pg. 88PANDEMIC PERIOD

Phase 6 : Pandemic: increased and sustained transmission in general population.

Pg. 89PANDEMIC PREDICTIONS1.) Many scientists believe it is only a matter of time

until the next influenza pandemic occurs. 2.) The severity of the next pandemic cannot be exactly

predicted, but…

a.) modeling studies suggest that the impact of apandemic on the United States could besubstantial.

Pg. 89PANDEMIC PREDICTIONS (continued)

b.) without any control measures (vaccination or drugs),

it has been estimated that in the United States a “medium–level” pandemic could cause….

1.) 89,000 to 207,000 deaths.2.) 314,000 and 734,000 hospitalizations.3.) 18 to 42 million outpatient visits.4.) and another 20 to 47 million people being

sick. 5.) Between 15% and 35% of the U.S.

population could be affected by an influenza pandemic.

6.) The economic impact could range between $71.3 and $166.5 BILLION.

Pg. 90HOW IS A PANDEMIC DIFFERENT FROM OTHERNATURAL DISASTERSINFLUENZA PANDEMICS ARE DIFFERENT from many of

the natural disaster threats for which public healthand health-care systems are currently planning:

1.) A pandemic will last much longer than most publichealth emergenciesa.) May include “waves” of influenza activity

separated by months (occurred with other 20th century pandemics).b.) In the past a second wave of influenza

activity occurred 3 to 12 months afterthe first wave.

Pg. 90HOW IS A PANDEMIC DIFFERENT FROM OTHERNATURAL DISASTERS (continued)

2.) The numbers of health-care workers and first

responders available to work can be expected to be reduced more profoundly than other natural disasters.

a.) They will be at high risk of illness through exposure in the community and in health-care settings.

b.) Some may have to miss work to care for ill family members.

3.) Resources in many locations could be limited, depending on the severity and spread of an influenza pandemic. Socioeconomic class issues?

Pg. 91WHY SO MUCH CONCERN ABOUT H5N1?1.) H5N1 mutates rapidly

2.) Has a documented propensity to acquire genesfrom viruses infecting other animal species.Hence, the bird flu affects us.

3.) Its ability to cause severe disease in humans hasnow been documented on two occasions.

4.) Laboratory studies have demonstrated that isolatesfrom this virus have a high pathogenicity(nastiness)with potential to cause severe disease in humans.

5.) Birds that survive infection excrete virus for at least10 days, orally and in feces. Facilitates furtherspread. Transmission.

Pg. 94-95INTERNATIONAL EFFORTSWorld Health Oraganization (WHO)ANTIVIRAL DRUGS: their role during a pandemic1.) Following a donation by industry, BIG ASSUMPTION

WHO will have a dedicated stockpile of antiviraldrugs (oseltamivir), sufficient for 3 milliontreatment courses, by early 2006.

2.) These drugs are strictly reserved for use in the firstareas affected by an emerging pandemic virus.

3.) Mathematic modeling suggest these drugs could beused in a prophylactic way in the early onset ofpandemic outbreak.

Pg. 94-95INTERNATIONAL EFFORTSWorld Health Oraganization (WHO)

4.) This would allow for two things:a.) reduce risk of mutation because number of

transmissions is decreased.b.) gain time to augment vaccine supplies

(development and delivery)

5.) The drugs will be stored centrally; WHO hasconsiderable experience in the rapid dispatch

ofmedical supplies during emergencies.

Pg. 94-95INTERNATIONAL EFFORTSWorld Health Oraganization (WHO)

6.) This strategy has never been tested. AND it depends on several assumptions…

a.) The behavior of the pandemic virus in the early

stages, which cannot be fully known.b.) Excellent surveillance to detect clusters of

cases closely related in time and space.This needs to improve.

c.) Excellent logistic capacity in initially affected

areas. This needs to improve.

Pg. 94-95INTERNATIONAL EFFORTSWorld Health Oraganization (WHO)

7.) Countries must decide who will get the drug.Who do you think?

8.) Mass deployment not advisable as it may contribute

to resistance. We can’t anyways.

9.) At present manufacturing capacity, which has

recently quadrupled, it will take a decade to

produce enough oseltamivir to treat 20% of the

world’s population.

Pg. 95-96NON-PHARMACEUTICAL INTERVENTIONS(reducing transmission and spread)

FACT: at the start of a pandemic the world will haveinadequate supplies of antiviral drugs.

1.) The effectiveness of several measures will depend

on the characteristics of the pandemic virus(attack rate, virulence, principal age groupsaffected, modes of spread within and betweencountries), and these cannot be known in advance.

2.) Evaluation of these measures has been based on limitedexperience/data during past pandemics and on what isknown about the behavior of normal influenza viruses.

Pg. 95-96NON-PHARMACEUTICAL INTERVENTIONS(reducing transmission and spread)

3.) After a pandemic is declared, WHO will monitor its

evolution in real time. Problems ????

4.) Recommendations about the most effective measures

will therefore become more precise as theepidemiological potential of the virus

unfolds. Forall these reasons, the recommendations

below should be taken as general guidance, and not as formal WHO advice.

Recommended measures are specific to the phase of alert in the WHO six-phase scale. BUT WILL CHANGE “ON THE FLY”

SO WHERE ARE WE AT???

CURRENT DISTRIBUTION OF AVIAN FLU CASES

CONFIRMED CASES RECORDED BY WORLD HEALTH ORGANIZATION (WHO)

WHAT DO YOU THINK? DEFEND YOUR POSITION.AGREEDISAGREESTRONGLY DISAGREESTRONGLY AGREE

There is great cause for concern that world populationswill be heavily impacted by an H5N1 pandemic

QUIZ

1.) What best describes how WHO and other agencies willhave to deal with developing problems regardinga pandemic?

a)Figure it out ahead of time using modelsb) Have it figured prior to outbreak using info. from past

pandemicsc) Have no clued) Deal with new problems “on the fly”

QUIZ

2.) Regarding adequate drug supplies what best describesthe BIG ASSUMPTION?

a)Industry will donate adequate drug suppliesb) People will respond poorly to drugsc) Drugs may cause allergic reactionsd) Drug supplies will be insufficient

3.) What is the main concern with mass deployment ofdrugs and the reason drugs will be used in areas ofinitial outbreak??

a)People will react poorly to drugsb) Drug supplies will be insufficientc) May cause resistance in influenza virusd) Difficulty in distribution

QUIZ

4.) What is true concerning current drug production?a)There are adequate drug suppliesb) At current capacity it will take about a year to supply

world populationc) At current capacity it will take about a year to supply

20% of world populationd) At current capacity it will take about a decade to

supply 20% of world population

QUIZ

5.) Why do RNA virions mutate faster than DNA virions?a)RNA produces less mistakesb) RNA produces more mistakesc) There are more RNA virionsd) There are less DNA virions

6.) What best describes antigenic shift?a)The mixing of the genetic material from two

virions-fast mutationb) The slow mutation of genetic material within a

single virionc) The fast mutation of genetic material within a

single viriond) The mixing of the genetic material from two

virions- slow mutation

QUIZ

7.) Why are we most concerned about the H5N1 strain?a) Mutates slowly b) Acquires genes from viruses only in humansc) Surviving birds can excrete virus for 10 daysd) We think it will hit isolated populations hard

8.) What is different about pandemics compared to othernatural disasters?

a)May last longer, come and go in wavesb) Will hit isolated populations hardc) Will have large effects for short period of timed) Mitigation is a more straight forward

QUIZ9.) What phase are we in currently for the H5N1 strain?a) Phase 1b) Phase 2c) Phase 3d) Phase 4e) Phase 5

10.) What best describes the current situation with H5N1?a) Human infection(s) with a new subtype, but no

human-to-human spread, or at most rare instances

of spread to a close contact

b) Larger cluster(s) but human-to-human spread still localized, suggesting that the virus is becoming increasingly better adapted to humans but may not yet be fully transmissible (substantial pandemic risk).

c) increased and sustained transmission in general population.

d) No new influenza virus subtypes have been detected in humans. However, there is a circulating subtype that poses a substantial risk of human disease.

QUIZ11.) What are the little spikes on a virion that allow it to

hook up to receptors on the host cell?a)Hemaglutininb) Neuraminidasec) Capsidd) Envelope

QUIZ12.) On the figure below what does A, B, C, D represent?

Consider this a model for H5N1.

antibody

A

B

C

virionD