2AgendaEverything you wanted to know about pandemic influenza but couldn’t find anyone to askWhat you can do to prepare your familyWhat you can do to prepare your schoolWhat you can do to prepare your students & their families
3Everything you wanted to know. . . DefinitionsExamine reasons pandemics occurLook at the progress of Avian H5N1 InfluenzaDiscuss why we are concernedReview current prevention effortsConsider the state of the science
5Epidemiology of Avian flu in humans Avian (Bird) Flu is a disease of birdsAll Avian Flu viruses are endemic in waterfowl & do not harm themWild birds mix with domestic chickens in back yard farmsDomestic chicken flocks mix in live poultry marketsPeople mix with sick or dead chickensPeople catch Avian Flu
6Seasonal vs Pandemic Flu AnnuallyKnown virusVaccine available (usually)High mortality young & old esp. w/ health problemsPandemicIrregular intervalsNovel virusNo or mismatched vaccineHigh mortality in year olds; mortality in young similar to seasonal flu
7Pandemics of the 20th Century YearNameStrainDeaths1918SpanishH1N1>50 million(US 675,000)1957AsianH2N21 – 2 million1968Hong KongH3N2700,000
9Composition of Seasonal Vaccines 2004 – 2005A / New Caledonia / 99 / H1N1A / Fugian / 02 / H3N22005 – 2006A / California / 03 / H3N22006 – 2007 (recommended)A / Wisconsin / 05 / H3N2Looking at the A viruses what observations can you make?The H&Ns are the same as for the Spanish Flu and the Hong Kong flu but they have different names.The H3N2s have different names each year.
10Pandemics of the 20th Century YearNameStrainDeaths1918SpanishH1N1>50 million(US 675,000)1957AsianH2N21 – 2 million1968Hong KongH3N2700,000Going back – these are the same strains that cause pandemics in the past. What happened?
11Antigenic change Antigenic ‘drift’ occurs in HA and NA Associated with seasonal epidemicsContinual development of new strains secondary to genetic mutationsAntigenic ‘shift’ occurs in HA and NAAssociated with pandemicsAppearance of novel influenza A viruses bearing new HA or both HA & NAHere is an analogy. Dogs come in various broad classes (Saint Bernards, Collies, Dachshunds, etc.) that are very different from each other. They are all dogs, but they don’t look much alike. These are the H1, H2, etc. and N1, N2, etc. classes of glycoproteins. Within each breed there are also smaller variations: some variation in size, hair color, pattern, etc. These are the strains of virus within each H–N subtype combination. If the only dog you know is a black Saint Bernard with a rough coat you may be a bit confused when confronted with a red Saint Bernard with a smooth coat, and if you encounter a chihuahua you may not even recognize the animal before you is a dog. Similarly your immune system may be slow and ineffective in recognizing different strains of the same viral subtype and not even ‘see’ a different subtype at all. Our immune systems have no experience with the H5 subtype of influenza A virus, which is one of the main reasons public health officials are so concerned: one of our main defense systems, the immune system, may be ineffective until it learns to recognize this subtype, and the learning only takes place after infection. In the case of previous infections with the same subtype, even if the strain is different, there may some recognition and the response, while delayed, may still have some effectiveness. But with the H5 subtype, the virus will reproduce unhindered for much longer and your immune system may not have enough time to make antibodies at all.
12Mechanisms of Antigenic Shift Reassortment in humansDirect InfectionNon-humanvirusHumanvirusSince the H5N1 and the 1918 H1N1 (found last year) investigations we have learned that a reassortment event that could create a pandemic strain could directly occur in humans potentially increasing the likelihood of a pandemic. Recent research on the 1918 Spanish Flu virus seems to have done this.Indirect InfectionReassortedvirus
18Countries with H5N1 Influenza in animals & humans Countries with H5N1 influenza in humans5118111052122003200420052006Through June 15, 2006
19Bird and Human Cases H5N1June 13, 2006Bird CasesHuman Cases
20Risk factors:Handling sick or dead birdsExposure to feces of sick or dead birdsInhaling dust contaminated with fecesRisk locations areas of overlapOpen backyard chicken flocks Green East Atlantic flyway overlapping in Canada w/ Atlantic American &Open air bird markets Mississippi AmericanDead birds in the wild Blue East Asian overlapping with the Pacific Americas & Mississippi AmericasPrevention is the keyIncreased surveillance in wild birds – migratory overlapThis will provide early warning for usBans on imported birds – England’s case was an imported parrotIndoor facilities for chicken productionExcellent surveillance and control in chicken production facilitiesVaccination – French and Dutch have program approved to vaccinate free-range chickens and backyard chickens and for producers in 3 areas deemed high risk
21The H5N1 Flu Threat to Humans A new virus to which humans have no immunity - YesThe virus causes significant human illness or death - YesThe virus spreads easily from person-to-person – NOThe Avian Flu (H5N1) virus has 2 out of 3 of these today…
22Why the Concern with H5N1?1918 (H1N1) flu and H5N1 avian flu are the only “kissing cousins” among the 169 known avian flu viruses.
231918 Influenza Pandemic20-40 million persons died worldwide, possibly moreDeath rate 25 times higher than previous epidemics,000 deaths in the U.S.: Ten times as many Americans died of flu than died in WW IThe epidemic preferentially affected and killed younger, healthy personsThe epidemic was so severe that the average life span in the U.S. was depressed by 10 years
24MOST FATAL EVENT IN THE LAST 300 YRS U.S. LIFE EXPECTANCY AT BIRTH
251918 H5N1 Incident rate (0-75)1555Young through middle age are most likely to become infected; elderly less likely.Remember the to 55 year olds
26Case fatality rate comparison (0-75) U-shaped is seasonal flu case fatality rateW is pandemic; pattern is being seen with H5N1Middle age has healthiest immune system. Over reacts to the highly virulent virus, Over reaction called cytokine storm. People die of Adult Respiratory Distress Syndrome. This was also seen with SARS.1555
28Cytokine StormHas been suggested as an explanation for the devastating nature of the 1918 fluIs an over reactive immune response that causes multiple organ system failureEvidence indicates H5N1 deaths are caused by thisChemokines and cytokines are the "messengers of the immune system" and are critical in coordinating and regulating the immune response. Altering this balance is likely to lead to an uncontrolled inflammatory response in the lung and probably explains, at least in part, the severe lung inflammation associated with avian flu virus H5N1.One of the many possible effects of cytokines is to summon other immune cells to the site of microbial attack and to activate those cells so that they, too, elaborate cytokines which in turn summon still more cells. This is a positive feedback loop and is ordinarily damped down by other cytokines signalling still other cells to elaborate still more cytokines that put the brakes on the process. Ordinarily this works well. But most regulatory mechanisms can get out of kilter and this can happen in a variety of different ways.The cytokines do not turn off, immune cells become overstimulated and run amok.Occurs in people with excellent immune systems.
2950% of workforce over 1 year Worst Case ScenarioPatientSevere (1918-like)NationalTexasNumber sick150M11.5MOutpatient75M (50%)5.75MHospitalized16.5M (11%)1,265,000ICU Care2.5M (15%)199,750Ventilator1.25M (50%)94,780Death3.225M (2.15%)247,250Absenteeism50% of workforce over 1 year
33Society during a pandemic Healthcare systemWorkSchoolTravelSuppliesServicesWorst case scenario – anarchy. We are expecting less.HCDSOverwhelmed. Enough beds for 15% of those who become illSick needing professional care in alternate buildingsNo elective surgeriesFlu clinics in tents to limit exposure in hospitalsWorkBusiness contingency planning – ID critical tasks, cross train, telecommutingSchools close because staff and kids ill before health offiicial closes themParents stay home not only because they are sick, but kids at home, and possibly need to care for sick family memberSupplies and servicesFood in short supply as staff in stores, distributors, manufactures illCritical services – limited; garbage pick-up rare, power outages, critical system maintenance issuesBanks may be closed.Limited law enforcement
34Prevention & Containment – Nonpharmaceutical Public Health population focused measuresPersonal protective measuresBusiness contingency planningCare of sick at homeIn actuality this is probably all we’ll really have during the first wave.
36Potential Community Measures to Decrease Transmission Travel advisories/limit travel to affected areasScreening travelers from affected areas*Limit large public gatherings; close schoolsEncourage telecommutingLimit availability of public transportationHand hygiene, respiratory hygiene/cough etiquetteQuarantine of exposed persons*Education to allow early identification and isolation of cases** Note: Some measures may be most useful early in outbreak and with strains that are not efficiently transmitted
37Evidence for use of masks Limited evidence available on benefits of masks in preventing healthcare or community influenza transmissionUse prudent at least in healthcare settingsSARS studies have shown clear benefit mask use in healthcare settingShort incubation periodDifficult to trace source of outbreak since cases usually occur during community outbreaksUnknown if type of mask may make a difference (N-95 versus surgical, etc.)Did not appear to be helpful in , but quality of masks and adherence to use questionable
38Influenza Antiviral Drug Questions How much supply will there be?Will feds or state have control over distribution decisions?How should it be used?Who should get it?How can it be delivered?Where does the $$ come from?Antivirals are marginally useful even if available:For treatment – must be started w/I 48 hour of beginning of symptomsWill then reduce length of illness by a few days and possibly reduce chances of secondary infectionsFor prophylaxis after exposure – must be able to know when you have been exposed. Difficult since a person is contageous 1=2 days before symptoms.Tamiflu and Relenza can only be used post exposure not long termOne strain is showing some resistance to antivirals all ready
3912/07?? 50 million coursesTexas: M people. The federal goal is to have enough stockpiled to treat 25% of the population and have 4 post-exposure prophy courses for critical service providers.SNS share of 50 M courses = 3.3 M courses which are totally paid for by the feds.TX option on 31M federal contract 75/25 split = 2.3M courses = $32.5MTotal of 5.6M courses leaves us 150,000 short of treatment for 25% of the population – none for prophylaxis of health care personnel or critical service providers even though CDC calls for 4 post-exposure courses This works assuming: you know when you are exposed and it happens only 4 times during a pandemic that lasts 1 year with 3 waves totaling 180 days.To prophylax the 4 suggested times would require purchase on state contract price of $40 = $47M for a grand total of ~80MWe need to let CDC know by 7/1/06 how much of our allotment we want to reserve for purchaseIssues: Do we want to purchase; where will the $$ come from; priorities (science and ethics)Just this month CDC announced AVs in their control will be used for illness only.We are seeking clarification for the state option purchaseWhere do the dollars come from? General revenue after legislative budged approval.
40Influenza Antiviral Drug Questions How much supply will there be?Will feds or state have control over distribution decisions?Where do the $$ come from?How should it be used?Who should get it?How can it be delivered?Next 4 are intertwinedExpert panel 5/18 – scientists, flu experts, ethicists, lawyers, faith community, consumer advocates – 3 separate groups hand divided to be balanced representation – similar conclusions: highest priorities should be:outbreak control for early containment which is a treatment/prophy mix, andcritical service providers. If we have no health care providers, no police or fire protection, and utilities or no foodSick patients should be treated by the usual private sector routine; public sector should be concerned about outbreak control, prophy for target groups, and tx for safety net populationsShould we buy it and how much? Depends on the second and third bullets
41Influenza Vaccine Questions When will it be available?How much will there be?How effective will it be?Who will own it?How should it be delivered?Who should get it?Who will pay for it?What about vaccine – that’s a better alternativeWhen will it be available and how effective will it be we’ll discuss in a minuteWho will own it? While it is in short supply my guess is the feds and/or states. I don’t beiieve it will be in the private sector until there is plenty.Who will pay for it? So far the public has through taxes. Once doses are available I suspect it will be government owned. Whether or not you will be charged, I have not heard anything. When it is plentiful, it will revert to private sector control as seasonal vaccine is today.How should it be delivered ties in with who should get it. CDC has a recommended priority list that states will consider and may possibly alter to reflect needs.If a pandemic occurs before vaccine is available and while the vaccine is in short supply, it will be given to priority groups in settings easily accessible, e.g hospitals for staff with direct patient contact; fire stations for EMS, etc.When we’re ready for the general public, we will potentially do mass clinics. Unlike antivirals which are all ready circulating in the private domain, vaccines won't be.
42Current method 1950’s technology Depends on eggs and chicks Shortages often due to problems hereRequires 4-6 months for vaccine production*One current vaccine in trials now uses traditional technology.At a minimum and that’s beginning production after ~2 months to prepare the virus – total 6-8 months to begin production. It will take longer to produce enough to reach risk groups.
44New method Cell cultures Less room More dependable Requires 4-6 weeks for vaccine productionCell culture – a new way to grow the old method.No eggs and sacrificing embryosReduces time for start of production from 6-8 mos to 4-6 weeksVical also uses cell culture technologyHowever, cell culture technology is complex and potentially longer than egg-based 6-8 mos.DNADNA technique breaks down the virus allowing scientists to pick and choose components to be used as antigens whereas traditional methods use the whole virus either live engineered to be less virulent or severe or an inactivated virus. The antigens the human immune system responds to are the surface antigens – the H and N – that mutate almost annually. DNA technology allows for introduction of specific components, in this case the M2 protein which is internal and which rarely mutates.Vical, a pharmaceutical research lab in San Diego received 2.6M from the government on 6/6/06 to assist in completing its animal trials soon and begin phase 1 human trials of its DNA vaccinein collaboration with Sts Judes Hosp. Is testing a DNA vaccine based on both the HA and NA surface proteins which mutate easily & M2 protein and another internal protein which are “conserved” proteins that do not mutate significantly over time.What does this mean? That an H5N1 vaccine made from the strain currently transmissible from birds to humans using the NA & M2 proteins would be effective against H5N1 that mutates to be easily transmissible between humans.What else? It means that a super vaccine could be produced to provide long acting immunity to all current human strains. Animal studies show some unintended cross protection to seasonal strains even with this H5N1 strain only.Bacterial fermentationDNA of interest is inserted into E.coli bacteria. Bacteria are allowed to grow and replicate in a fermentation vat. As the bacteria replicate, the DNA is copied. The genes of interest are removed and combined with an agent that increases the ability of the vaccine to elicit an immune response.Extremely easyProduce large quantities quickly = estimated significantly less than the 6 months targeted and in sufficient quantity for the population in short order.The exciting thing is that this will be moving to clinical trials shortly
45Vaccine ConsumptionI’ve identified mismatch of produced vaccine with circulating virus as the first issue and time for production as the second.The third is that 70% of vaccine production in Europe; 90% of use in US.Some experts predict that the only vaccine that will be available to a region during a pandemic is what is produced in that region.During a pandemic when travel is restricted and countries are panicking, what are the chances that those who produce will get vaccine to those who purchase?The federal government has been pumping $$$ into the effort – I mentioned Sanofi pasteur in Pennsylvania just opening – we built the plant with tax $$.May 2006 – over $!B in a new emergency funding was divided between 5 vaccine companies to build, do research in vaccine methods, and produce vaccine in the US>Source: WHO Global Influenza Program
46Vaccine Production Capacity Green in the US is a new Sanofi Pasteur plant in Pennsylvania that opened last year.The administration aiming to have 600 million flu vaccine doses available within six months of a pandemic, two for every American. To meet this target, the US Health and Human Services Department (HHS) is looking to diversify the production of influenza vaccines by using cell-based vaccine manufacturing, and also to have more of such manufacturing take place in American territory. Toward this end, last week, the govmt funded 6 companies to open production facilities in he US.
47Texas Plan Challenges In Health Systems Response Assuring essential workers are prophylaxed and/or vaccinatedSurge CapacityEmergency Systems for Advance Registration of Volunteer Health Professionals Program (ESAR-VHP)Availability of PPEDisaster Mental HealthDead bodiesESSENTIAL WORKERSIn a coordinated manner (many independent entities- example major metro areas developing their own plans independentlyESAR-VHPRedundancy is not helpful here – e.g., nurses on multiple volunteer lists such and American Red Cross, TX Ready Nurse, etc.Personal Protective EquipmentCostDisaster Mental HealthFundingAvailable staff (surge capacity)SURGE CAPACITY# hospital beds vs # staffed bedsHealth care worker availability
48Texas Plan Challenges In Communication Risk CommunicationPre-event message preparation for the publicEducating decision makersCommunication technologyInteroperabilityRISK COMMUNICATIONWhat messages are developed at the federal – state – local levels and attempting to eliminate mixed messagesHow to start preparing the public without eliciting panic and fearConsider what you might do to educate through the PTA or take-home messages for the kids.Your school nurse should be a resource for you.PRE-EVENT MESSAGE PREPProviding shelf-kits with messages prepared in advance costs $Communication technologyKeeping up with new technology and staff trainingRedundant systemsInteroperabilitySystems interacting with systems w/o special effort on the part of the consumerMixing softwareEducating decision makersIf you have identified any issues relating to PI and school which need school board or legislative approval, get it taken care of early.
49How can you prepare? Visit the DSHS website at: www.dshs/state/tx/us Follow the Pandemic Influenza link to the state’s plan.Appendix F “Personal Protective Strategies
50How can you prepare? Get seasonal flu vaccine Stay informed Stockpile supplies, food, & some $$Talk to MD and RPh about extra routine medsDon’t forget petsHave a family planKnow your business’ continuity plan
51Websites http://www.pandemicflu.gov http://www.cidrap.umn.edu/cidrap/ Center for Infectious Disease Research and Policy, (Univ. of Minnesotta)Avian Flu and Pandemic Flu
53Considerations in School Planning ▶THE ROLES OF SCHOOLS IN THE COMMUNITY ▶ COMMUNICATING/COORDINATING WITH PUBLIC HEALTH/GOVERNMENT OFFICIALS ▶ UPDATING SCHOOL CRISIS PLANS ▶ LEARNING ABOUT PREVENTING INFECTIONS ▶ EDUCATING PARENTS, KIDS, STAFF ▶ INFORMING/COUNTERING DISINFORMATION ▶ MAINTAINING THE LEARNING ENVIRONMENT
54Local Planning Is Critical Planning must be broad/interactive/cross-cutting/coordinated: city government, civil agencies health departments, community centers, medical providers, businesses, schools, private/voluntary/faith based organizations
56Federal and State Resources Focus on Local Planning
57Mitigation and Prevention Activities ►Liaison with state/local health officials ►Clear Roles/responsibilities of staff ►Roles of school nurses ►Assign key roles ►Review health needs of students ►Improve health activities
58Pandemic Preparedness ►Update crisis plans ►Educate staff, students & parents ►Account for Procedures►Delegate CrisisCommunication/Authority
59Local School Considerations ►Maintain operations & the learning environment ►Triage/isolate students and staff ►Use good health practices: handwashing, disinfect, etc. ►Address misinformation ►Plan for school closure ►Disseminate community information► Utilize schools as clinics, hospitals, morgues, vaccination sites or vaccine storage sites
60School Houses were turned into temporary hospitals during the 1918 Influenza Pandemic
61Pandemic Recovery Period ► Allocate time for recovery ► Involve kids & parents ► Counsel ► Debrief ► Plan anniversaries ► Facility remediation