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Influenza Lecture
Lauri Washburn, PA-C
Infectious Disease Consultants
2011
Influenza
• Seasonal: Influenza A; Influenza B
• Pandemic influenza A : 2009 H1N1 (“swine
flu”)
• H5N1 (“avian flu”)
Biology of Influenza
• Influenza A
– Subtypes based on 2 surface Ag:
• Hemagglutinin (H)
• Neuraminidase (N)
– Antigenic drift
• Result from point mutations and recombination events that
occur during viral replication
– Antigenic shift
• New subtype of influenza A virus appears – results in
emergence of novel influenza
• Potential to cause a pandemic
The eight segments shown within each
virus code for the following proteins of
the influenza A virus (top to bottom):
polymerase PB2, polymerase PB1,
polymerase PA, hemagglutinin, nuclear
protein, neuraminidase, matrix proteins,
and nonstructural proteins. The
segments of the human 2009 influenza
A (H1N1) virus have coexisted in swine
influenza A virus strains for more than
10 years. The ancestors of
neuraminidase have not been observed
for almost 20 years. The mixing vessel
for the current reassortment is likely to
be a swine host but remains unknown.
Reproduced with permission from:
Trifonov, V, Khiabanian, H, Rabadan, R.
Geographic Dependence, Surveillance,
and Origins of the 2009 Influenza A
(H1N1) Virus. N Engl J Med 2009;
360(28). Copyright ©2009
Massachusetts Medical Society. All
rights reserved.
Biology of Influenza
• Influenza B
– 2 lineages
• Yamagata
• Victoria
– Not categorized into subtypes
– Antigenic drift less rapidly than Influenza A
Epidemiology
• Seasonality
– Almost exclusively during winter months in
northern and southern hemispheres
• Typically peak over 2-3 week period and
lasts for 2-3 months
• Influenza B viruses are generally less
extensive and less severe than influenza A
Transmission: Human to Human
• Respiratory secretions of infected person
– Sneezing, coughing, talking
– Contaminated surfaces
• Viral shedding begins day before illness
can last 5-7+ days
• Incubation period
– 1-4 days = average of 2 days
Transmission: Animal to Human
• Role of pigs
– Receptors for both avian and human influenza
strains
• Infected poultry – Avian influenza
– Incubation period 7 days or less from time of
exposure
Transmission: Environment to Human
• Fomite objects
• Ingested contaminated water
– Avian influenza
Signs and Symptoms
• Abrupt onset of constitutional and respiratory
signs and symptoms
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Fever – up to 102-103; chills
Myalgia
Headache
Malaise
Non-productive cough
Sore throat
Rhinitis
• Self-limited in general population
2009 H1N1 Signs and Symptoms
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Fever
Cough
Sore throat
Malaise
Headache
Chills
Myalgias
Arthralgias
• Vomiting and diarrhea
common with H1N1
– (unusual for seasonal
influenza)
• Lab Findings:
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Increase AST/ALT
Anemia
Leukopenia or leukocytosis
Thrombocytopenia or
thrombocytosis
– Elevated bilirubin
– Severe illness: elevation in
CK and LDH
H5N1 clinical characteristics in
outbreaks
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Fever
Pneumonia
Diarrhea
Encephalopathy
Lab: leukopenia, lymphopenia,
thrombocytopenia, elevated
aminotransferases
May be mildly symptomatic
to life-threatening disease
• Exposure to ill or dead
poultry
• Recent travel history
– Preceding 10 days
• Striking feature:
– Children and young adults
Risk Factors
• Children younger than 2 years old
• Adults 65 years of age or older
– Except for 2009 H1N1
• Pregnant women and women up to 2 weeks postpartum
• Medical conditions:
– Asthma; Chronic lung disease; Heart disease; Weakened
immune system; Kidney,Liver disorders; Metabolic disorders;
Endocrine disorders; Neurological/neuro-developmental
conditions; Long-term aspirin therapy under age 19
• Residents of nursing homes or chronic care facilities
Complications of Influenza
• Pneumonia
– “Primary” viral
• Suspect when sx increase rather than resolve
– Secondary bacterial
• S. pneumoniae; H. influenza; S. aureus
– Exacerbation of fever and resp sx after initial
improvement after acute influenza
– Mixture of both
• Features of both viral and bacterial pneumonia
Complications of Influenza
• Otits Media – children; sinusitis
• Myositis and rhabdomyolysis
– Children
• Extreme tenderness of affected ms. (legs)
– Can see swelling and bogginess of muscles
• Elevated CK; myoglobinuria with renal failure
• CNS involvement
– Encephalitis; transverse myelitis; asceptic meninigitis;
Guillain-Barre syndrome
• Myocarditis and pericarditis – infrequent
• Toxic shock syndrome
– S. aureus infection and acute influenza
Diagnosis of Influenza
• May be made clinically
– During outbreaks
• Fever, cough within 48 hours; malaise or chills
– Vs.: rhinoviruses or coronaviruses
• Sneezing- NOT likely influenza
• Laboratory testing
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Rapid Ag tests
Immunofluorescence
Polymerase chain reaction (PCR)
Viral culture
Serologic testing
Whom to test
• High risk immunocompetent outpatients
• Immunocompromised outpatients with acute febrile respiratory
illness
– Regardless of time since illness onset
• Inpatients with acute febrile respiratory illness
– Including those with dx CAP
– Regardless of time since illness onset
• If results helpful for providing local surveillance date, then
individuals with acute febrile respiratory illness who are not at high
risk complications may be tested
• Health care workers, residents or visitors in institution experiencing
influenza outbreak who present with acute febrile respiratory illness
with 5 days illness onset
• Individuals epidemiologically linked to influenza outbreak
– Travelers from endemic area; cruise ship passengers; household and
close contacts of individuals with suspected influenza
Whom to test
• Most patients with an uncomplicated
influenza-like illness who reside in areas
where influenza viruses are known to be
circulating do not need to be tested for
influenza infections
Treatment
• Early tx with antivirals may reduce duration and
severity of illness
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Decreased hospitalizations
Decreased complications
Decreased use of antibiotics
Decreased viral shedding
• Most effective when administered within 48
hours onset of sx
– Reduced mortality and duration of hospitalization in
persons symptomatic >48 hours
• Also in those with complicated illness that requires
hospitalization
Neuraminidase Inhibitors
• Zanamivir – oral inhalation administration
– Beware in persons with asthma or other chronic
respiratory disorders
• Oseltamivir –orally administered
– High rates of resistance emerging in seasonal H1N1
virus isolates to oseltamivir
– Pandemic H1N1 found to be sensitive to oseltamivir
and zanamivir
– Thought to be effective against avian flu
• Adverse effects: Zanamivir – bronchospasm;
Oseltamivir – N/V
Adamantanes
• Amantadine
• Rimantadine
• Effective only against influenza A viruses
– Substantial rates of resistance
• 2008 Advisory Committee on Immunization Practices
recommend that adamantanes NOT be used for tx of
influenza in the Unitied States
– Exception: contraindication to zanamivir but require tx during
outbreak of oseltamivir-resistant influenza
• Use combination amantadine 100mg BID or rimantadine 100mg BID
WITH oseltamivir 75 mg BID
• Adverse Effects: Amantadine – CNS toxicity;
Rimantadine less CNS side effects
Adjunctive treatment
• General symptomatic management
– Acetaminophen or NSAIDS
• Tx: fever, HA and myalgias associated with influenza
– AVOID use of salicylates – especially in children
below 18 years of age
• Antibiotics – only for use of bacterial
complications of acute influenza such as
bacterial pneumonia, otitis media, or sinusitis
– Based on gram stain/culture results
• Common pathogens: S. pneumo, S. aureus, H. influenza
• Empiric tx examples: 3rd gen cephalosporin; extended
spectrum quinolone with nafcillin or oxacillin or vancomycin
Prevention
• Vaccination!
– Seasonal flu: yearly
– H1N1 swine flu: became available in October 2009
• Antiviral drugs - chemoprophylaxis
– NOT to be substitute for vaccination
– Choice of drug depends on circulating strain
– Duration depends upon how exposure occurred
• Infection control: healthcare and community
– Frequent hand washing
– Limit face to face contact –stay home from work
– Cover mouth; dispose of tissues immediately
• Cough into sleeve of clothing rather than hands
All children aged 6 months--18 years should be vaccinated annually.
Children and adolescents at higher risk for influenza complications should
continue to be a focus of vaccination efforts as providers and programs
transition to routinely vaccinating all children and adolescents, including
those who:
• are aged 6 months--4 years (59 months);
• have chronic pulmonary (including asthma), cardiovascular (except
hypertension), renal, hepatic, cognitive, neurologic/neuromuscular,
hematological or metabolic disorders (including diabetes mellitus);
• are immunosuppressed (including immunosuppression caused by
medications or by human immunodeficiency virus);
• are receiving long-term aspirin therapy and therefore might be at risk for
experiencing Reye syndrome after influenza virus infection;
• are residents of long-term care facilities; and
• will be pregnant during the influenza season.
Note: Children aged < 6 months cannot receive influenza vaccination.
Household and other close contacts (e.g., daycare providers) of children
aged < 6 months, including older children and adolescents, should be
vaccinated.
Annual vaccination against influenza is recommended for any adult who wants
to reduce the risk of becoming ill with influenza or of transmitting it to others.
Vaccination is recommended for all adults without contraindications in the
following groups, because these persons either are at higher risk for
influenza complications, or are close contacts of persons at higher risk:
• persons aged 50 years and older;
• women who will be pregnant during the influenza season;
• persons who have chronic pulmonary (including asthma), cardiovascular
(except hypertension), renal, hepatic, cognitive, neurologic/neuromuscular,
hematological or metabolic disorders (including diabetes mellitus);
• persons who have immunosuppression (including immunosuppression
caused by medications or by human immunodeficiency virus;
• residents of nursing homes and other long-term care facilities;
• health-care personnel;
• household contacts and caregivers of children aged <5 years and adults
aged 50 years and older, with particular emphasis on vaccinating contacts
of children aged <6 months; and
• household contacts and caregivers of persons with medical conditions that
put them at higher risk for severe complications from influenza.
Vaccination: Seasonal influenza
• Trivalent Inactivated Vaccine
– Intramuscular
– Recommended for persons 6 months of age and
older: healthy and high risk
Preferred method of immunization when live with
immunosuppressed person
• Side Effects: soreness, redness or swelling at
injection site, low grade fever, body aches –
usually last 1-2 days
– Inactivated virus – will not cause influenza
Vaccine: Seasonal influenza
• Live Attenuated Influenza Vaccine
– Intranasal administration – made from weakened virus
– Indicated for healthy persons aged 2-49 years
– Not to be used in those with:
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Immunosuppression
Underlying condition of asthma
Age 2-4 with wheezing episodes in past year
Close contact with immunosuppressed persons
• Side Effects: mild upper respiratory symptoms may
include runny nose, HA, sore throat, vomiting, muscle
aches, or fever
• Transmission of vaccine viruses to close contacts has
occurred only rarely
Vaccine: Seasonal influenza
• Children under 8 yrs not previously vaccinated
or received only single dose in previous season
should be given 2 doses of either TIV or LAIV
separated by 4 weeks
• Contradictions to influenza vaccination:
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Hypersensitivity to eggs
Hx of GBS following previous dose
Not approved for children under 6 months old
Wait until current febrile illness symptoms have
subsided
Vaccine: Pandemic H1N1
• Became available in October 2009
• Since no vaccine is 100 percent effective,
individuals who have been vaccinated against
pandemic H1N1 influenza A who have signs
and/or symptoms of influenza infection and have
indications for treatment should be treated
• Is now a part of the seasonal influenza vaccine
Vaccine: H5N1 (avian)
• Approved by the FDA in April 2007
• Intended for use in adults from 18 to 65
years of age and is given as two doses
one month apart
• Vaccine will not be sold commercially;
instead it will be purchased by the US
government for inclusion in the National
Stockpile for distribution by public health
officials, as needed
Concomitant vaccinations
• Pneumococcal vaccine
• If antiviral therapy given within 48 hours
before or up to two weeks after influenza
vaccination, the vaccine dose should be
repeated
Prevention in Healthcare Settings:
For Healthcare Personnel
Vaccination – up to date of all personnel
Do not report to work if have fever and respiratory
symptoms until 24 hours after no longer have fever
(without aide of antipyretics)
Adherence to respiratory hygiene and cough etiquette:
wear facemask during patient-care activities if cough or
sneezing persist
Hand washing – before and after patient-care activities
Reassignment out of environment where care for patients
severely immunocompromised: for 7 days from
symptom onset or resolution of symptoms (whichever
longer)
Adhere to Standard Precautions
• Hand hygiene
– When visibly soiled hands – use soap and water
rather than alcohol based rub
• Gloves
– Do not wash gloves and reuse
• Gowns
– Use with ANY potential infectious body fluid exposure
– including respiratory
– Do not wear same gown for care of more than one
patient
Adhere to Droplet Precautions
• should be implemented for patients with
confirmed or suspected influenza for 7
days after illness onset or until 24 hours
after resolution of fever (whichever longer)
while patient in healthcare facility – longer
for immunocompromised patients
• Place patients in private room or area
• Wear facemask – entering room, dispose
when leaving room: wash hands
Use Caution when involved with
Aerosol-generating Procedures
• Planned settings:
– Bronchoscopy, sputum induction, elective intubation and extubation,
autopsies
• Emergent settings:
– CPR, emergent intubation, open suctioning of airways
• In confirmed or suspected influenza patients:
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only perform if medically necessary and cannot postpone
Limit personnel present
Ideally perform in isolation room when feasible
Use STANDARD precautions: gloves, gowns, face shield
Respiratory protection equivalent fitted N9 filter facepiece
Await sufficient time for infectious particle clearance before NONprotected personnel enter room where procedure performed
– Environmental surface cleaning following procedures
Influenza: Role of RT
Be aware of signs and symptoms
Educate your patients – particularly chronically ill,
high risk patients: need for vaccination; proper
respiratory hygiene and cough etiquette
Vaccination: patient and yourself
Practice infection control measures
know who you are treating and what you are
treating; be aware of your surroundings
Adhere to standard and droplet precautions
Stay home from work when you are acutely ill