Influenza: Preparing to Prevent a Pandemic Disaster: Influenza: Preparing to Prevent a Pandemic Disaster Alan M. Ducatman, MD, MSc
Professor and Chair, Department of Community Medicine
West Virginia University School of Medicine
Annual Toll of Influenza: Annual Toll of Influenza Pandemic Influenza: Pandemic Influenza The Three Types of Influenza: The Three Types of Influenza Shifting Nature of Influenza: Shifting Nature of Influenza Antigenic drift – small, ceaseless changes in the genetic structure. New strains continually replace old strains.
Antigenic shift – major change, usually occurs when species hosting virus trade viral genes. Novel strain appears without natural immunity in host population. Pandemic Threshold: Pandemic Threshold Source: Centers for Disease Control, http://www.cdc.gov/flu/weekly/fluactivity.htm Recent Virus Hitchhikers (Zoonoses): Recent Virus Hitchhikers (Zoonoses) HIV
Several viral hemorrhagic fevers
Variant CJD (“mad cow”) Environmental Health and Infectious Disease: Environmental Health and Infectious Disease The toll can be substantial.
HIV is estimated to have caused 20 million deaths, so far.
There is very little international investment in wild (or even domestic) animal pathogen surveillance.
H5N1 Timeline: H5N1 Timeline From WHO website http://www.who.int/csr/disease/avian_influenza/Timeline_28_10a.pdf
Avian Influenza in Asia(22 August, 2005): Avian Influenza in Asia (22 August, 2005) Why H5N1?: Why H5N1? It is endemic, now found in domestic fowl, pigs, and even tigers. There is no way to eradicate it.
Porcine hosts can replicate both avian and human influenza viruses. It is inevitable that recombination will occur, and human-human transmission capability may increase.
World poultry population has grown tenfold since the last (1968) pandemic (750,000 deaths), from 1.3 billion birds to 13 billion birds. Reengineered Virulence: 1918 vs. Modern (Texas) Strains: Reengineered Virulence: 1918 vs. Modern (Texas) Strains Viral particle release in human lung cell culture: 50 times
Viral particle replication in mouse lung tissue at 4 days: 39,000
Mortality in mice: all vs. none 1918 Hemagglutinin Causes Severe Lung Damage: 1918 Hemagglutinin Causes Severe Lung Damage M88 M88/Hsp Kobasa et al. Nature 2004;431:703 H5N1 Toll: H5N1 Toll Fall 2005: > 100 reported infections, > 60 deaths, millions of birds culled. Vietnam has culled millions of chickens, accounting for 0.5% of its GNP.
In addition, the virus is gaining the ability to infect its natural host, waterfowl. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) since 26 December 2003 to 10 October 2005: Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) since 26 December 2003 to 10 October 2005 Species Surveillance: Species Surveillance In the US, poultry surveillance is in place (“required” reporting by farmers).
In addition, ornithologists, veterinarians, park rangers, and amateur bird watchers have been recruited to trap sentinel bird species, test, and release, or else test hunted game birds.
Estimated investment: $10 million/yr. Overcoming Barriers: Surveillance for Avian Influenza (H5N1): Overcoming Barriers: Surveillance for Avian Influenza (H5N1) Countries affected may be reluctant to share specimens. This limits ability to track mutations.
The PCR tests may be out of date, providing false negative results.
The ability to find the virus and track genetic changes is essential to vaccine preparation. Barriers to Surveillance: Barriers to Surveillance Inadequate human surveillance
Grossly inadequate domestic and wild animal surveillance
Political barriers to cooperation
Lack of reimbursement for economic losses Barriers to Surveillance: Barriers to Surveillance Overcoming anarchy in animal and human surveillance
Distribution and cost of validated diagnostic tests Human View of Path of Spread: Human View of Path of Spread Wild Fowl Domestic Birds Domestic Livestock Humans Mode of Spread: Mode of Spread Birds shed virus for about 10 days.
Initial transmission mode is bird feces, feathers, tissue, or saliva to humans (oral).
Virus is hardy in cool weather, so surface contact may intervene.
The fear is direct human-to-human droplet transmission. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) since 26 December 2003 to 10 October 2005: Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) since 26 December 2003 to 10 October 2005 Transmission: Transmission Intensified surveillance in Vietnam by reverse transcriptase polymerase chain reaction testing of patient contacts suggests the evidence of mild cases and clusters. The concern is that the Vietnamese H5N1 is adapting to residence in human hosts. Incubation Period: Incubation Period Probably 2 to 5 days, possibly as long as 8 days
Reports of 17 days suggest intermediate hosts Most Common Symptoms and Findings in H5N1 Patients: Most Common Symptoms and Findings in H5N1 Patients Fever > 38° C
Pulmonary infiltrates (can progress to ARDS)
Detection: Detection Diagnostic yields of different approaches to detection are problematic.
Viral RNA can be detected in throat swabs; sensitivity and specificity are both lower than desired. Household Contact Treatment: Household Contact Treatment Frequent handwashing
N95 masks/eye protection (feasible?)
Monitor temperature twice daily for 7 days
Public health concept of “ring treatment”
Quarantine: Quarantine In the US, community-level quarantine experience essentially ended in . . . . 1954. Quarantine Compliance Issues: Quarantine Compliance Issues Contact tracing is not a HIPAA problem.
Enforcement measures are unprecedented in US living memory; education is essential to public and professional enforcement.
Those ordered into quarantine will have concerns about vacation, sick leave, and wages (as will employers). No funds or laws address this issue for nonmilitary personnel.
Differential health services and policies may have border effects (traffic flow, preferential seeking of or fleeing from services). Quarantine Needs: Quarantine Needs Public health access to airline and other passenger lists
Support for contact tracing
Speedy appeals process
Legal authority to immunize or treat prophylactically Health Care Facility Precautions: Health Care Facility Precautions Patient precautions: standard, contact, droplet, airborne
Protective equipment: N95 mask, cuffed gowns, face shields or goggles, gloves
Room: negative pressure.
Alternative 1: Isolation with door closed
Alternative 2: Multibed wards one meter apart with physical barriers.
attending personnel Local Resources and Public Health: Local Resources and Public Health Reality Check: most Vietnamese hospitals do not have designated isolation wards. Health Care Worker Surveillance: Health Care Worker Surveillance Record temperature twice daily Prophylaxis Normal Abnormal Symptoms Remove from workplace Evaluate for influenza Treatment More Reality: Surge Capacity in a Just-in-Time Economy: More Reality: Surge Capacity in a Just-in-Time Economy Source: Osterholm MT. Preparing for the next epidemic. N Engl J Med 2005; 352: 1839-42. Travelers’ Precautions: Travelers’ Precautions Immunization > 2 weeks before travel
Avoid chickens, ducks, geese, wild birds, open markets, fecally contaminated surfaces
Wash hands frequently
Consult health care provider for fever or symptoms
Avoid raw eggs, mayonnaise, hollandaise sauce, and ice cream in endemic areas Influenza: An International Problem: Influenza: An International Problem Up to 20% of the world’s population may become ill.
Our point of reference for pandemic flu may be something that comes from elsewhere and affects us.
For Asian nations such as China, pandemic flu is a threat to civil order as well as health. Vaccination capability is much lower in the countries likely to be most affected. What Predicts Community Cohesiveness vs. Divisiveness?: What Predicts Community Cohesiveness vs. Divisiveness? Infrastructure in place
Communications without politics
Policy makers accustomed to public health input Influenza: The International Response: Influenza: The International Response There are important differences in national capabilities to prevent, detect, and respond to an influenza pandemic.
Geographic differences in production of host species, including
mixing domestic and wild species
proximity to populations
measures to protect workers
Virologic, serologic, clinical, and public health capabilities vary greatly. Influenza and the Global Economy: Influenza and the Global Economy An influenza pandemic will cause national leaders to suppress foreign travel and trade. Vastly disruptive, this action is unlikely to achieve the goal.
Domestic economic investment in many nations will be directed toward surge capacity and possibly national defense against civil unrest.
Unequal distribution of inadequate health care resources, including immunizations, will create tensions within and across borders.
What about state lines? Threats to Health: Threats to Health Consequences of infection
Uncoordinated efforts of individuals to avoid infection
Local Economies and Public Health: Local Economies and Public Health In Vietnam, large commercial poultry farms cull infected birds successfully. But local households with small flocks have no resources and only negative incentives for participating.
Poultry vaccination may address the problem, but it is so far mandated only for flocks of > 200 birds.
A number of European countries have banned the outdoor penning of poultry. Antiviral Treatment: Antiviral Treatment Chinese farmers have been using Amantadine (the least expensive antiviral agent) to treat chicken flocks and prevent the spread of H9 viruses. H5N1 strain of avian influenza has been resistant to Amantadine since 2003.
More expensive antivirals such as Oseltamivir (Tamiflu) and Zanamivir (Relenza) may still work. Tamiflu: Tamiflu Tamiflu is an neuraminidase inhibitor that can be taken as a pill or dissolved powder. The inhibitor diminishes release of virus from infected cells if taken within 48 hours of infection.
Cost per treatment: $10 (less for stockpile)
Availability % population: Britain, 25%; Canada, 5%; US, 1%
As with immunization, health care workers will be treated first. Can Statins and Pneumovac Fill the Tamiflu Shortage Gap?: Can Statins and Pneumovac Fill the Tamiflu Shortage Gap? In previous influenza epidemics from 1996-2003, statin users experienced 26% less incidence of pneumonia.
Pneumovac (pneumococcal pneumonia vaccine) may also help.
Cabbage and untested hypotheses.
Long-Term Planning: Long-Term Planning NIH is developing three attenuated vaccines for each of the known avian flu subtypes. In theory, this will allow speedy scale-up of vaccine production in the event of a pandemic. In addition, NIH researchers are looking for antigens that are conserved across several strains. Vaccine Development: Vaccine Development The US president has made vaccine industry development and liability protection a cornerstone of his $1.7 billion program to safeguard America against pandemic influenza.
Media accounts suggest cell-based vaccines will cut production time.
They are more likely to increase production quality (surge capacity).
Scrambling for An Egg Alternative: Scrambling for An Egg Alternative Source: Centers for Disease Control, http://www3.niaid.nih.gov/news/focuson/flu/research/prevention/hillegas_egg.htm General Conditions for Vaccine Success: General Conditions for Vaccine Success Immunogenic (achieved!)
Effective against rapidly mutating pandemic strain
Produced in sufficient quantities
Administered at sufficient dose
Administered in time to achieve protection in population at risk Immunization Quantities: Immunization Quantities In a typical year, hundreds of millions of flu vaccine doses are available. In an epidemic, billions of doses are needed.
Bridging this gap requires planning and investment. Immunization and Adjuvant: Immunization and Adjuvant Immunizations work better (and require much less material) if “boosted” with adjuvant, a chemical additive that stimulates the immune system.
This is hopeful news, but it requires more complex clinical trials which include adjuvant. Bird Immunization: Bird Immunization US Leadership in a Pandemic: US Leadership in a Pandemic In an influenza pandemic, leadership would be split between the Department of Homeland Security and DHHS. Immediate declarations:
preparedness plan implementation
travel and trade
internal migrations (much worse in other countries)
multiple moves Pandemics and US Public Health Ethics: Pandemics and US Public Health Ethics The realization of autonomy is a strong health trend, nurtured even during the AIDS epidemic.
The role of informed consent is central to autonomy.
The absence of a public health view that accounts for rapidly spreading infection has been noted by international observers. Clinician’s Uneasy Role in Public Health Emergencies: Clinician’s Uneasy Role in Public Health Emergencies Normal Conditions:
The clinician is accustomed to acting as a patient advocate, for reasonable, requested interventions.
The clinician must refuse “reasonable but not recommended” requests for scarce resources.
The clinician may report families or populations for quarantine, and patients may object to intrusions initiated by their doctors. Can a Pandemic Be Contained?: Can a Pandemic Be Contained? Will it occur this year, or in 5 years?
The “basic reproductive number” (Ro) is crucial. If Ro is < 2, public health models (isolation, immunization, and early antibiotics) have more chance to minimize spread.
Tamiflu resistance (already found in a Vietnamese patient) would further compromise ability to contain spread. Is Pandemic Flu “Containable”?: Is Pandemic Flu “Containable”? In a preimmunized population, rapid recognition, followed by isolation, combined with “social distance” strategies (reducing places for masses of people to meet), and augmented by wide-scale antiviral treatment and prophylaxis (i.e., treat the 20,000 people nearest the outbreak), can be modeled to contain a local outbreak. Education: Thai Children at Risk for H5N1 Infection: Education: Thai Children at Risk for H5N1 Infection * Before and after a public education campaign
Olsen et al. EID 2005;11: Police Powers in Epidemics and Emergencies: Police Powers in Epidemics and Emergencies Who can quarantine or isolate? (Laws usually say “quarantine.”)
State health officer
County board of health, usually acting through health officer
Any detention is “least restrictive means necessary” Police Powers in Epidemics and Emergencies: Police Powers in Epidemics and Emergencies
Who can declare a public health emergency?
(Federal authorities can preempt) Legal Control of Zoonoses: Legal Control of Zoonoses Authority is shared through a welter of regulations by:
CDC: public health, inspection, detention
Customs/Border: inspection, seizure, destruction
Plant protection: formerly part of USDA
DOT: approval to transport
Fish and Wildlife: reporting, licensing, destruction
FDA: similar to CDC
USDA: farm issues Legal Control of Zoonoses: Legal Control of Zoonoses WV specifically regulates rabies
Very little clarity about exotics Good News . . . And Bad: Good News . . . And Bad For avian flu, its inability to make much headway in the human population (so far) may mean that it cannot do so.
If not, some pandemic is still predictable.
Average time between 20th-century pandemics: 30 years.
Last pandemic: 1968. Rank Order of Treatment Priorities in a Shortage: Rank Order of Treatment Priorities in a Shortage Treat patients hospitalized with flu
Treat health care (direct patient contact) and EMS
Treat pandemic health, public safety, “key” government
Treat other high-risk patients
Nontreatment group: Post-exposure prophylaxis
Pandemic Priority Groups for Vaccination and Antivirals:: Pandemic Priority Groups for Vaccination and Antivirals: Priority Group 1 – Critical Response and Most Vulnerable Source: National Vaccine Advisory Committee, July 19, 2005 Pandemic Priority Groups for Vaccination and Antivirals:: Pandemic Priority Groups for Vaccination and Antivirals: Other Priority Groups: 2-4 Source: National Vaccine Advisory Committee, July 19, 2005 Reasons for Optimism: Reasons for Optimism No H5 subtype has ever caused a pandemic (the 1918 avian source was an H1N1 virus)
The current H5N1 virus has been circulating for 8 years, without reassorting for efficient human-human transmission. Slide71: Munch’s “Self-Portrait after the Spanish Influenza” Please copy this url into a web browser to complete the survey and fill out a form for your continuing education credit.http://tinyurl.com/827qa thanks: Please copy this url into a web browser to complete the survey and fill out a form for your continuing education credit. http://tinyurl.com/827qa thanks