What's the Big Deal about Influenza? 
Brenda Naizby and Patricia Many 
Epidemiologists
New York State Department of Health 


Really Short Answer

. Kills +/- 36,000 annually across age groups

. May lead to significant health complications

. Increases hospitalizations 

. Expensive:
.. fiscally
.. socially 

. Viral mutations can result in pandemics 


Learning Objectives

. The participant will be able to discuss and describe:

. Basics of Viral Structure and Function

. Epidemiology and Clinical Presentations of Influenza

. Elements of Influenza Prevention, Control and Intervention

. Influenza Surveillance Activities

. Basics of pandemic influenza


'Flu Facts 


(Cartoon)


What is Influenza?

. Influenza aka "the 'flu" is a contagious respiratory illness caused by the influenza virus.  Infections with influenza viruses cause illnesses ranging from mild to severe and life-threatening.

. An Ancient Foe
.. Origin of the name Influenza 15th century Italy
.. Epidemics attributed to "influence of the stars"

. Cross Species Infectivity


Influenza Virus Types 

. 3 types of influenza - A, B, C

. Influenza A and B viruses responsible for annual epidemics

. Influenza C produces mild disease and has not been associated with widespread outbreaks 


Influenza Type C viruses

. Rarely reported as a cause of human illness

. Most cases probably sub clinical

. Not associated with epidemic disease


Influenza viruses

. Characterized by ability to change continually and occassionally drastically

. Antigenic drift
.. Influenza A and B viruses 

. Antigenic shift 
.. Influenza A viruses only 


Influenza Type A 

. Characterized by moderate to severe illness

. Affects all age groups. 

. Widely distributed in nature

. Infect a wide variety of animal species 
.. { humans, pigs, birds, seals, whales }

. Undergo antigenic shift and drift 

. Main cause of death among the hugh risk during epidemics


Structure of the Influenza A Virus

. (Graphic)


Role of the Spikes 

. 2 types of Spikes 

. #1 contains the enzyme hemagglutinin {H}

. #2 contains the enzyme neuraminidase {N}

. Both enzymes are antigens* 

* antigen = chemical substance that stimulates a response by the immune system 


Influenza Antigens

. Hemagglutinin {H} spike
.. Has role in virus attachment to the host cell membrane
.. 3 types have established lineage in humans
... H1
... H2
... H3

. Neuraminidase {N} spike
.. Has role in virus penetration into cells
.. Two types have established lineage in humans
... N1 
... N2

. H1N1, H1N2, H3N2 most common viruses 


Antigenic Shift

. Replacement of HA or HA + NA (i.e. new subtype)
.. Reassortment
.. Adaptation of virus from non-human host

. Sporadic event

. Can result in pandemic


Antigenic Drift

. Gradual, continual process

. Result of an accumulation of point mutations in the HA and NA genes during viral replication

. AlloWs for repeated infections over a lifetime and recurrent epidemics 

. Vaccine updated twice yearly


Influenza Type B Viruses 

. Generally milder disease than type A 

. No subtypes

. Primarily affects children; infects humans almost exclusively 

. More stable than "A" with less antigenic drift with consequent immunologic stability


Influenva: Nomenclature

. Virus Type
.. Geographic origin
.. Strain number
.. Year of isolation
.. Virus Subtype

. Influenza A: HA and NA surface antigen types also contribute to the classification of the strain.

. A/Sydney/5/97(H3N2) = influenza A strain + Sydney (virus was isolated) + strain number 5 + 1997 (year) + Hemagglutinin type 3 + Neuraminidase type 2 surface antigens.

. B/Beijing/184/93 = influenza B strain + Beijing (virus was isolated) + strain number 184 + 1993 (year)

. In animal strains, the original host is also included in the classification
.. A/Duck/Ukraine/1/63/(H4N8)


Definitions

. Seasonal flu is a contagious respiratory illness caused by influenza viruses 

. Pandemic flu is flu that causes a global outbreak, or pandemic, of serious illness that spreads easily from person to person. Currently there is no pandemic flu.

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


Seasonal Influenza

. Acute, febrile respiratory illness affecting nose, throat, bronchial tubes and lungs; symptoms appear rapidly

. Epidemics caused by influenza viruses A and B (Type C uncommon in people; no epidemics)

. Occurs worldwide, causing considerable morbidity and mortality each year

. Systemic Symptoms
.. Lasts 2-3 rarely > 5 days 
.. Recovery usually rapid; some experience lingering depression and asthenia for several weeks
.. Palliative treatment includes aspirin* or acetaminophen
* Aspirin should NEVER be used for infants, children or teens.  Reye Syndrome concerns.

. Highly Infectious


Influenza Epidemiology 

. Occurrence: worldwide

. Reservoir: influenza types B and C, humans only known reservoir; influenza A, humans and animals.

. Chronic Carrier state: NO

. Temporal Pattern: year round in tropical areas. Peaks from December-March in temperate climates.

. Incubation: 1-4 days; average of 2 days

. Communicability (Infectious Period)
.. Adults can shed virus 1 day before to 5 days after onset s/s
.. Children can shed > 10 days
.. Young children may shed virus for < 6 days
.. Severely immunocompromised can shed virus for weeks/months
.. Viral shedding occurs in respiratory secretions


"Droplet" Transmission

. Flu virus is present
.. In large droplets expelled when you cough or sneeze, which fall quickly to the ground or onto surfaces.
.. On the hand of ill people. 

. Transmission occurs:
.. Usually from direct hand-to-hand or hand-to-surface contact.
.. Flu virus on the hands is easily transferred to the eyes, nose and mouth Where flu virus can enter the body and cause infection.
.. Less frequently by direct inhalation of flu virus in the air.

. Implication: hand washing is as important as respiratory precautions.


What is "Droplet Transmission"? 

. Droplets from a cough or sneeze of an infected person are propelled (generally up to 3 feet) through the air! Droplet Precautions include:
.. placing patient in a private room or cohort, when not possible maximize distance between patients.
.. wearing a mask when working within 3 feet of patient
.. limiting patient transport and use a mask for patient if movement is unavoidable


Influenza: A Viral Pirate

. the virus particle lands on the cell surface 

. genetic information -> cell -> cell nucleus

. viral genes -> new viral components -> new virus particles

. budding -> to infect other cells


Seasonal Influenza Symptoms 

. Classic Influenza
.. abrupt onset of fever, sore throat, myalgia and non-productive cough
.. fever usually 101-102F, often with prostration
.. myalgias usually affect back muscles
.. patients can often recollect exact hour of onset; may say "feels like a truck hit me"


Influenza Love Poem 

I shall seek you and find you...
I shall take you to bed and control you...
I will make you ache, shake and sweat and groan...
I will make you beg for mercy...
I will exhaust you to the point that you will be relieved when I leave you...
and you will be weak for days.
All my love,
The flu


Answer Summary
 
. Check out Epidemiology and Prevention of Vaccine Preventable Disease, aka "The Pink Book" at cdc.gov

. Influenza causes +/- 36,000 excess deaths per year

. >90% of deaths in people >/= to 65 years of age

. Highest rate of complications in seniors and young children age 0-4 years

. Average of > 200,000 influenza related excess hospitalizations annually; 57% among people < age 65

. Nursing home attack rates may = 60% with fatality rates as high as 30%

. H3N2 years see even higher rates of hospitalizations**

. Estimated cost of a severe epidemic = $12 billion

. Influenza complications include:
.. Pneumonia {secondary bacterial and also primary influenza viral}
.. Reye Syndrome
.. Myocarditis
.. worsening of chronic bronchitis and other chronic pulmonary symptoms


Influenza: Treatment, Prevention and Control 

. Antiviral Therapy 

. vaccination

. Infection Control 

. Diagnostic Testing 

. Surveillance


Antivirals 

. Treatment
.. can decrease duration of illness (by 1-3 days) and severity of uncomplicated seasonal influenza
.. Treatment should be initiated within 48 hours of symptom onset

. Prophylaxis (protection) to prevent illness in:
.. Persons at high-risk for complications
.. To control outbreaks in nursing homes and other institutions

. Drug resistant viruses can emerge
.. Some strains of flu no longer respond to the most common antivirals
.. "Newest generation" of antivirals (Tamiflu, Relenza) remain in limited supply

. Not a substitute for vaccination


Vaccination 

(Cartoon)


World Health Organization Meeting

. Vaccine strains chosen 9-10 months prior to influenza season, based on WHO lab data

. In young adults, vaccine 70-90% effective. In elderly and immunocompromised, vaccine less effective in preventing influenza infection but very effective in reducing ilness severity, complications (70%) and death (85%)

. Antigenic variation:
.. Influenza viruses are able to change their antigenicity and thereby evade their host's immune mechanisms.
.. Antibodies which have formed in people who have previously suffered from influenza may not, therefore, provide effective protection against a subsequent infection with a new strain.
.. This is why major epidemics of influenza occur repeatedly and why new vaccines have to be devised and produced very frequently if they are to provide effective protection.


'Flu Vaccine is Effective 

. Actual efficacy depends on degree of similarity between viruses in vaccine and viruses in circulation currently.

. Vaccine strains chosen 9-10 months prior to influenza season, based on WHO lab data.

. Vaccine efficacy may be reduced because of changes in circulating strains.

. Individuals >/= 65 years of age who received influenza vaccine have reduced risk of hospitalization for:
.. Heart disease (reduction of 19%)
.. Stroke (reduction of 16%-23%)
.. Pneumonia or influenza (reduction of 29% to 32%)
.. Risk of death from all causes (reduction of 48-50%)


Influenza Vaccines

. Most efficient method to control influenza

. Must be administered annually

. 2 vaccines available 
.. Trivalent inactivated vaccine
... Injection
.. Live attenuated vaccine
... Nasal spray


When to Get Vaccinated 

. October and November are best times. 

. As 'flu has historically peaked between late December-early March, vaccination efforts should continue through December and beyond. 

. It takes about 2 weeks to become immune post vaccination

. Unsure about getting vaccinated this year??
.. H3N2 virus has been most common in past few decades 
... {Letters "H" and "N" refer to molecules on the surface of the virus}
.. H3 years tend to be more severe and Southern Hemisphere is reporting H3 this season! 


Infection Control Measures 

. respiratory hygiene/cough etiquette 

. hand hygiene

. environmental cleaning 

. social distancing 


What is Respiratory Hygiene/Cough Etiquette?

. Cover mouth/nose when sneezing or coughing
.. If no tissue, use elbow instead of hands 

. Use tissues and dispose of appropriately 

. Perform hand hygiene after contact with respiratory secretions 

. Distance yourself from others (more than 3 feet)


Influenza: Prevention 

. Cover your nose and mouth 
.. Cover your mouth and nose with a tissue when coughing or sneezing


Individual Infection Control Strategies

. Respiratory hygiene/cough etiquette and hand hygiene are effective strategies to stop the spread of germs. 

. We should make good hygiene a habit now. 


Influenza: Prevention 

. HANDWASHING! 
. HANDWASHING! 
. HANDWASHING! 


What is Hand Hygiene?
 
. Traditional hand washing 
.. Soap and warm water 
.. Minimum of 20 seconds (the time it takes to sing "Happy Birthday" twice) 

. Alcohol based hand rubs 
.. Acceptable means to disinfect/sanitize EXCEPT when hands are visibly soiled 


Policy and Personal Decision 

. Avoid close contact
.. Avoid close contact with people who are sick
.. When you are sick, keep your distance from others to protect them from getting sick too
.. If possible, stay home from work, school, and errands when you are sick. You will help prevent others from catching your illness.


Influenza: Prevention and Control in Healthcare Facilities 

. Droplet/Contact Precautions
.. Use of gloves, gowns, masks
.. Infectious within 3 feet of patient
.. Contaminated surfaces

. Respiratory hygiene/cough etiquette
.. Incorporate into infection control practices

. Discourage visitors with respiratory symptoms

. Restrict ill healthcare workers

. Vaccination of residents and healthcare workers

. Identify outbreaks
.. Report to regional epidemiologist
.. Report to your local Department of Health


Institutional Outbreak Control

. Outbreak Control
.. Prior planning key to minimizing impact
... maximize resident and staff vaccination
... educate staff impact, signs, symptoms, diagnosis influenza
... establish surveillance early detection
.. Prompt diagnosis and institution of control measures

. Control Measures
.. Cohort influenza and ILI cases
... droplet precautions
... consider antiviral tratment
.. Limit group activities and staff floating
.. Restrict ill staff and visitors
.. Re-offer vaccine to staff and residents
.. Antiviral prophylaxis - all residents and unvaccinated staff
.. Continue to monitor for new cases and assess control measures


Environmental Disinfection

. Disinfectants that are currently in use should be sufficient to kill the flu virus

. Influenza viruses typically can live on inanimate objects for several hours 

. Increased environmental cleaning during any cold/flu season should be a part of an infection control program 


Influenza: Diagnosis

. Viral culture* 
.. only culture isolates can provide specific information regarding circulating influenza subtypes and strains

. Rapid antigen testing* 
.. 30 minutes 
.. Differentiate between A & B 
.. Back-up negatives with culture?? 

* nasopharyngeal specimens are typically more effective than throat swab specimens


Influenza Surveillance Objectives

. Determine: 
.. which viruses are circulating; where and when they are circulating
.. intensity and impact of influenza activity strains and detect new strains

. Detect unusual events
.. Infection by unusual viruses
.. Unusual syndromes caused by influenza viruses 
.. Unusually large/severe outbreaks of influenza

. Rapid outbreak detection

. Assist disease control through rapid preventative action

. Estimate influenza-related morbidity, mortality and economic loss


Global Surveillance

. World Health Organization Initiative

. Emerging Infections 

. Enhanced Communications

. U.S. Influenza Surveillance System Components
.. Virologic surveillance
.. Morbidity surveillance
.. State influenza activity level assessment
.. Mortality surveillance

. Practical Uses of Influenza Surveillance Data
.. Vaccine strain selection
.. Treatment decisions
.. Public health resource allocation
.. Influenza prevention and control policy
.. Pandemic planning
.. General Information: public and media


Influenza: Surveillance Systems 

. Sentinel Family Physician Network 

. Nosocomial Reporting

. Local Health Departments

. Pneumonia and Influenza Mortality Process 

. Laboratory Surveillance
.. WHO/NREVSS virology labs
.. 13 in NYS participate 

. HERDS

. Pediatric Death Reporting 


Sentinel Physician Influenza Surveillance Program

. Voluntary participation

. Weekly reporting to CDC throughout influenza season (Oct-May)

. Reporting on total number of patients seen and number of those with influenza like illness (ILI) in 4 broad age groups
.. ILI - Temperature >= 100 degrees and cough or sore throat

. Submission of up to 6 patient specimens to Wadsworth Laboratory for rapid testing, culture, and sub-typing 

. Compensation
.. Subscriptions to MMWR and Emerging Infectious Diseases Journal
.. Certificate from CDC


Internet sites for influenza surveillance 

. NYSDOH: www.health.state.ny.us/nysdoh/flu/index.htm

. CDC: www.cdc.gov/flu/weekly/fluactivity.htm


Internet sites for avian influenza surveillance 

. CDC: http://www.cdc.gov/flu/avian

. WHO: http://www.who.int/csr/disease/avian_influenza/en/

. NYDOH:
.. HAN Advisory dated February 17, 2004: "Respiratory Illness Surveillance for Influenza A(H5N1) and SARS", https://commerce.health.state.ny.us/hpn/hanweb/btpostings/doc040218_0.pdf


"The pandemic clock is ticking, we just don't know what time it is" 
- E. Marcuse


Seasonal vs.Pandemic Flu

. A pandemic is a world-wide epidemic.

. Pandemics result from the emergence of a new virus to which the overall population has no immunity. 

. Unlike seasonal flu, which typically affects the elderly, frail, sick and young, pandemic flu could present as much risk to the young and healthy. 

. Could begin at any time of year. 

. Asia is the source of many outbreaks 
.. ex: current Avian Influenza Outbreak 


What is an influenza pandemic?

. Worldwide outbreak of a novel influenza virus

. Occur infrequently and at irregular intervals

. Potential for substantial impact
.. Morbidity and mortality
... 18-42 million outpatient care
... 314,000-734,000 hospitalized
... 89,000-207,000 deaths
.. Social disruption
.. Economic costs


The Great Influenza Pandemic 1918-1919 

. "For a period of approximately eighteen months influenza ravaged the world claiming three time the number of lives lost in World War One."
. "It was the worst plague in recorded history, killing more people in a shorter time than even the Black Death of the fourteenth century."

. References: Beveridge, W., Influenza: The Last Great Plague (1977); Crosby, Alfred, Epidemic and Peace, 1918 (1976)


How does this happen?

. 4 key factors must be present
.. Novel virus 
... Reassortment of animal and human viruses
... Direct transmission of animal virus to humans
... Adaptation of non-human virus in intermediate host prior to transmission to humans
.. Susceptible population
.. Virus capable of causing disease in humans
.. Virus that is transmissible from person-to-person

Bird Flu - What's the Big Deal? 

. Avian strains can infect humans 

. Re-assortment of avian and human strains to create novel strain (antigenic shift)

. Efficient person-to-person transmission 

. Little/low immunity/protection to new virus 

. Probable higher morbidity/mortality

. Pandemic influenza 


Pandemic Strain Emergence: Reassortment of Influenza A Viruses 

(Graphic - flu transfers from bird into other mammals, reassorts, enters humans)


Pandemic Strain Emergence: Direct Infection 

(Graphic - flu transfers directly from bird into humans)


H5N1 Transmission to Humans 

. People who have gotten sick from bird flu had close contact with sick birds and touched them with their bare hands

. Infected birds shed their virus in their saliva, nasal secretions, and feces

. Fecal - oral transmission

. Virus from bird droppings can remain in the environment for several weeks


Will Avian Flu Cause the Next Pandemic?

. No one knows!

. The H5N1 virus could change to spread more easily among humans - but it might not

. It could "swap genes" with another animal virus, or with a human flu virus

. Death rate may or may not be lower than with current human H5N1 cases
.. Evidence to date finds very few "sub-clinical" cases


If a Pandemic happens, what to expect... 

. At the peak of a moderately severe pandemic influenza outbreak (i.e. 35% attack rate, 6 week duration), New York State (excluding New York City) can expect: 
.. 14,916 influenza-related hospital admissions per week
.. 3,728 influenza-related deaths per week
... 2,609 deaths in the hospital

. Influenza patients will most likely utilize:
.. 63% of hospital bad capacity
.. 125% of intensive care capacity
.. 65% of hospital ventilator capacity
.. resource allocation ethical issues


What can we do?

. Strengthen global virologic surveillance for earlier detection of novel virus
.. Increases chance to take actions to stop development of novel virus outbreak to pandemic
.. Gives more lead time to respond

. Develop plans/make preparations NOW to reduce health, social, and economic impact
.. Planning the response
.. Maintaining and strengthening key capacities and infrastructure


General Pandemic Planning Concepts

. Goals
.. Limit total burden of disease (morbidity & mortality)
.. Decrease social disruption
.. Decrease economic loss

. Engage all levels of health care system, public health, and emergency response

. Include public and private sectors

. Key similarities (& differences) between pandemic response and other health emergencies
.. Planning, resources, and implementation


Influenza Resources 

. WWW.cdc.gov - U.S. public health guidlines

. www.pandemicflu.gov - U.S. pandemic plan

. www.who.int - Global updates and official case reports 

. www.nyhealth.gov - New York State surveillance summaries 


One day on the road in the English countryside a clergyman happened to meet the plague.  "Where are you bound?" asked the clergyman. "To London," responded Plague, "to kill a 1000." They chatted a few moments longer, then parted.

Some months later they chanced to meet again, and the clergyman inquired, "As I recall, you were going to kill a 1000. How is it that 2000 died?" "Ah, yes," replied Plague. "I killed but a thousand. Fear killed the rest."


The End and a bit of History 

. 1918 Influenza Practices
.. Personal:
... Wearing camphor balls or garlic bulbs
... Consuming hot peppers or bootleg whiskey
... Sleeping with a deer by the bed!!!
.. Public Health:
... Fumigated street cars and trains with phenol on a daily basis
... Prohibited standing on a public conveyance
... Law enforcement arrested people for not wearing masks and spitting in the streets
... Schools closed
.... Homework published in paper
.... Students mailed in assignments