Pandemic influenza: origin and impact

Susan M. Kellie, MD, MPHAssociate Professor of MedicineDivision of Infectious Diseases

UNMSOM

How are avian, pandemic, and seasonal flu different?

• Avian influenza is caused by avian influenza viruses, which occur naturally among birds

• Pandemic influenza is flu that causes a global outbreak, or pandemic, of illness that spreads easily from person to person. This results from emergence of a completely new strain of influenza. Currently there is no pandemic influenza.

• Seasonal influenza is the epidemic of influenza we experience every year, and results from minor mutations in the influenza virus.

Avian Influenza Poultry Outbreaks, Eurasia/Africa 2003-6• Historically unprecedented scale of outbreak

in poultry due to H5N1 with human disease at over 218 cases to date

• Deaths in other species: ferrets, felids, domestic cats

• >124 human deaths (Vietnam, Thailand, Cambodia, Indonesia, Turkey) – No sustained person-to-person transmission

identified

The threat of avian influenza

• A panzootic of avian influenza strain H5N1 continues to spread in the Eastern Hemisphere.

• This strain could adapt to be easily transmitted between humans, causing a human pandemic– Fufills ¾ criteria for serious pandemic: virus can infect

people, population is immunologically naïve, virus is highly lethal

– Lacks capability for efficient person-to-person transmission

– Could acquire this through mutation (as occurred in 1918) or reassortment (as in 1957 and 1968)

– John Bartlett. Planning for avian influenza. Ann Intern Med 2006; 145:141-144

Pandemic influenza: key facts • Pandemic influenza is rare but recurrent event• Another pandemic may be imminent• All countries will be affected• Widespread illness will occur• Medical supplies will be inadequate• Large numbers of deaths will occur• Economic and social disruption will be great• Every country (and every locality) must be

prepared

Pandemic stages per WHO

• Phase 0-interpandemic phase• Phase 1: novel influenza virus is causing

outbreaks in at least one country, high morbidity and mortality observed

• Phase 2: outbreaks and epidemics with global spread

• Phase 3: end of first pandemic wave• Phase 4: possible second wave• Phase 5: pandemic ends, high immunity

Interpandemic period• Phase 1-no new virus subtypes in humans• Phase 2-as above, but a circulating animal influenza virus

subtype poses a substantial risk

• PREPARATIONS START HERE

• Pandemic alert

• Phase 3-human infections with new subtype but no or very limited human-to-human spread

• Phase 4-small clusters, highly localized

• Phase 5-larger clusters suggesting better adaptation to humans

• Phase 6-PANDEMIC: increased and sustained transmission in larger population

Impact of pandemic influenza

• Disease burden of seasonal influenza

• Estimations of mortality in past pandemics

• Changes in the healthcare environment and society which could modulate the impact of pandemic influenza

• Modelling the impact at UNM

• Limitations of conventional response measures

Seasonal influenza

• 10-20% of population infected per year• Annual deaths: 36,000*• Hospitalizations: >200,000** Average annual estimates during the 1990’s

• #1 cause of vaccine-preventable deaths in US• Disease features:

– Fever, chills, body aches, sore throat, cough, runny nose, headache

– Complications: pneumonia, exacerbation of underlying conditions, death

– Significant work and school absenteeism– Influenza vaccine is the only commonly used medical

intervention which is cost-saving

Impact of Past Influenza Pandemics/Antigenic Shifts

Pandemic, or Antigenic Shift

Excess MortalityIn US

Populations Affected

1918-19(A/H1N1)

675,000 Infants, elderly and 20-40 yr-olds

1957-58(A/H2N2)

70,000 Infants, elderly

1968-69(A/H3N2)

36,000 Infants, elderly

Pandemic influenza: a prolonged disaster

• 1918-19: three waves 4 months apart– Estimated 50 million deaths worldwide

• 1957: second wave began 3 months after peak of the first wave

• 1968: second wave began 12 months after peak of the first wave

Infectious Disease Mortality, United States--20th Century

Armstrong, et al. JAMA 1999;281:61-66.

Next pandemic: estimates of impact

Attack rate ranging from 15% to 35%:

30% attack rate would cause 90 million cases in US

Typical mortality ~0.1%

• US Deaths: 89,000 - 207,000• US Hospitalizations:• 314,000 - 733,000• Current mortality rate for avian influenza is 20-

fold-higher than that for the influenza of 1918 (1-2%)

Key differences in the healthcare environment since 1967

• Increased age of population in developed countries

• More immunocompromised patients• More patients maintained with advanced

interventions: dialysis, chemotx, home TPN

• Fewer hospital beds, shorter lengths of stay

• Healthcare worker shortages

Numbers of persons by age category in New Mexico: US Census 1990 and 2000

0

50000

100000

150000

200000

250000

300000

350000

age <1 age 1-4 age 5-14 age 15-24 age 25-34 age 35-44 age 45-54 age 55-64 age 65-74 age 75-84 age 85+

Num

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of p

erso

ns

1990

2000

Co-pathogens with potential to worsen impact of pandemic influenza• HIV: Influenza is more severe in HIV-infected

persons and runs a more prolonged course with greater likelihood of hypoxia, also with prolonged shedding of virus

• Community-acquired methicillin-resistant S. aureus (colonizing 0.35% of US population outside of institutions and military as of 2002)– Implicated in multiple cases of necrotizing pneumonia

following influenza– Implicated in 10-15% of pediatric flu deaths in 2003

Societal changes with the potential to facilitate pandemic spread

Longterm Care Facilities• 2.4 million US residents live in LTCFs• In New Mexico: • Nursing facilities-82 facilities-6k residents• Facilities for Developmentally Disabled• Assisted living/residential care-171 facilities ranging from 2-200

residents– Data from New Mexico Healthcare Association

Congregate living/day care settings• Residential substance abuse rehab• Prisons and jails• Group youth homes and detention centers• Senior centers, adult day care• Child day care• Retirement complexes and assisted living

Effects on operations of civil society

• Work absenteeism • Business closure• Failure of delivery of essential commodities

internationally and within US• School closures• Closure of congregate living facilities• Failure of utilities through lack of maintenance

and repair• Absenteeism in public safety-police, fire, etc

Pandemic influenza and globalization

• Interruption of trade and transport, closure of borders

• Political destabilization in already unstable areas

• “Zero-inventory” business management makes developed world even more vulnerable

• Nine countries with 12% of the world’s population, have vaccine production capability

Limitations of classic infectious disease interventions

• Unknown effectiveness of current antivirals in prophylaxis and therapy– Limited drug production capacity

• Vaccine production and administration– A novel formulation requiring two doses is likely to be

needed

• Ineffectiveness of quarantine and isolation as practiced for other outbreaks– “Social distancing” is recommended

Structure of hemagglutinin (H) and neuraminidase (N) periodically change:

• Drift: Minor change, same subtype– In 1997, A/Wuhan/359/95 (H3N2) virus was dominant– A/Sydney/5/97 (H3N2) appeared in late 1997 and became the dominant virus

in 1998– Causes re-emergence of new strain of influenza able to infect 10-20% of

population each year

• Shift: Major change, new subtype– H1N1 appeared in 1918– H2N2 circulated in 1957-67– H3N2 appeared in 1968 and replaced H2N2– Causes pandemics

Influenza Antigenic Changes

Structure of hemagglutinin (H) and neuraminidase (N) periodically change:

• Drift: Minor change, same subtype– In 1997, A/Wuhan/359/95 (H3N2) virus was dominant– A/Sydney/5/97 (H3N2) appeared in late 1997 and became the dominant virus

in 1998– Causes re-emergence of new strain of influenza able to infect 10-20% of

population each year

• Shift: Major change, new subtype– H1N1 appeared in 1918– H2N2 circulated in 1957-67– H3N2 appeared in 1968 and replaced H2N2– Causes pandemics

Influenza Antigenic Changes

Modeling the Impact at UNM

Admits1,320

Deaths259

Response

• Basic respiratory hygiene and droplet precaution measures

• “None of my classmates died and very few became ill. Perhaps the masks, gowns and handwashing did more to protect us than we had a right to expect. Certainly, with death all around us, we had every encouragement to be as careful as we could, but we were so busy and so tired that we forgot about precautions, and patient after patient coughed into our faces as we tended to their needs.”– Starr. Influenza in 1918: recollections of the epidemic in

Philadelphia. Ann Intern Med 2006: 145:138-40.

Response• Build capacity for yearly influenza vaccine manufacture and administration*

• Place pandemic influenza response in the context of disaster planning for a prolonged worldwide disaster with limited responders

• Educate communities and individuals

• Establish two-way communication with community physicians through local public health task forces*

• Plan for care in alternate settings, licensing of volunteers, clear and fair infection control measures*

• Grassroots community preparedness and building of social cohesion through existing institutions: schools, religious and civic orgs, etc

• Prepare for aftermath and recovery– *Position Paper. American College of Physicians. The Health Care Response to

Pandemic Influenza