Pandemic influenza: origin and impact Susan M. Kellie, MD, MPH Associate Professor of Medicine Division 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 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:

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 Mortality In US Populations Affected (A/H1N1) 675,000Infants, elderly and yr-olds (A/H2N2) 70,000Infants, elderly (A/H3N2) 36,000Infants, elderly

Pandemic influenza: a prolonged disaster : 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--20 th 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 US Hospitalizations: 314, ,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

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 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 –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 –H3N2 appeared in 1968 and replaced H2N2 –Causes pandemics Influenza Antigenic Changes

Modeling the Impact at UNM Admits 1,320 Deaths 259

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:

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