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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 – – – – – – – 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 • • • • • • • • Fever Cough Sore throat Malaise Headache Chills Myalgias Arthralgias • Vomiting and diarrhea common with H1N1 – (unusual for seasonal influenza) • Lab Findings: – – – – Increase AST/ALT Anemia Leukopenia or leukocytosis Thrombocytopenia or thrombocytosis – Elevated bilirubin – Severe illness: elevation in CK and LDH H5N1 clinical characteristics in outbreaks • • • • 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 – – – – – 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 – – – – 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: • • • • 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: – – – – 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: – – – – – – 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