Influenza

1. Influenza Peggy Beeley, MD Best Practice 1/15/14

2. Outline • Current Outbreak • Brief review of Influenza structure & subtypes • Transmission and Prevention • Available Testing • Treatment • Prophylaxis

3. Signs & Symptoms Complications • Fever • Cough • Sore throat • Coryza or nasal congesting • Headache • Myalgias and fatigue • Nausea and vomiting may occur • Illness occurs during influenza season • Abrupt onset • Primary viral pneumonia • Secondary Bacterial Pneumonia • Croup • Exacerbation of Chronic Pulm Dz • Otitis Media • Sinusitis • Myositis • Cardiac Complications • Toxic Shock Syndrome • Reyes Syndrome

4. Most Recent Surveillance from CDC

5. UNMH Admissions for 2013-2014 Influenza Season Courtesy Dr. Meghan Brett

6. Characteristics of Admitted Patients with Influenza Average age: 36.7 years Range: 0 – 64 years Sex: 53% Female 47% Males Admitted from: 71% from ED 29% from Clinics All positive for Influenza A Courtesy Dr. Meghan Brett

7. Influenza • RNA viruses Orthomyxoviradae • Influenza A • Most morbidity & mortality • Pandemic • Influenza B • > 60% Yamagata • > 30% Victoria • Influenza C

8. Structure of Virus • Glycoprotein's. • Hemagglutinin(HA) • attaches to sialic acid residues on host cells • Neuraminidase (NA) • glycoproteins attach to host cells and releases viral progeny • Once infected, direct necrotic effects on human cells as virus begins to use host cell machinery for replication Mandell, 2010

9. National Data for Influenza 2013-2014

10. Tricore Report Respiratory Virus Detection by • DFA, RESPAN and the FLURSV Assay Methods • 889 requests with 418 positive(s) • Influenza A H1 (2009) 109 • Influenza A H3 1 • Influenza A 108 • Influenza B 1

11. Transmission & Prevention: • Transmission • Person to Person: Large particle respiratory droplet (cough or sneeze) within 6 ft or less • Indirect contact via hand transfer of virus-contaminated surfaces or objects to mucosal surfaces of the face • All respiratory secretions, bodily fluids, including diarrheal stools are potentially infectious • Airborne transmission via small particle aerosols may occur • Procedures • Prevention • Vaccinations • Good hand hygiene • Cough etiquette • Wear mask if sick and on clinical service • Wear mask if unable to get vaccinated

12. UNM’s Vaccine • Efficacy for Influ A 70-90% • Fluzone • Split-virus vaccine • Contains H3N2, H1N1, B • Trivalent vs. Quadravalent • Standard dosing vs High dose for Patients > 65 yo • Flublok • Egg free, grown in cell culture • Early vaccination of inpatients

13. Influenza Vaccination by Group at UNMH, Influenza Season 2013-2014 Date of Report: 1.10.14 Courtesy Dr. Meghan Brett

14. Influenza Vaccination Rates by Dept, 1.10.2014Courtesy Dr. Meghan Brett

15. Laboratory Testing • Tricore runs all tests • No clinic Ag testing • 3 types of tests available • DFA • RESPAN • FLURSV • Coinfections: ~10% • Usually rhinovirus and flu or RSV • 1 Influenza A & B

16. Anti-flu therapy and prophylaxis • Neuraminidase Inhibitors: • oseltamivir (Tamiflu) • zanamivir (Relenza) • Japan has two others • laninamivir • peramivir, IV form • Adamantanes: • Amantadine • Rimantadine • Ribavirin

17. Targets of Antivirals Itzstein, M :Nature Review of Drug discovery, vol 6 2007

18. Zanamivir • Trade name: Relenza • Higher affinity to the NA binding site than does native sialic acid. • Poorly absorbed in GI tract and thus delivered as an inhaled agent • Only 15% of drug deposits within lower respiratory tract • Can precipitate bronchospasm • in pts with pulmdz • cant be used in mechanical ventilation • Clinical trials for optimal dosing for IV form, compassionate use. • RX:10 mg inhaled twice daily for 5 days (approved for > 7 yr old) • Prophylaxis is given once daily for 10 days (up to28 days) age> 5 • Higher activity for influenza B & H1N1 strains than oseltamivir, less activity against H3N2 • Doesn’t have the H275Y neuraminidase mutation • N294S (N295S) neuraminidase mutation seen in immunocompromised causes decreased sensitivity to zanamivir

19. Oseltamivir • Trade name: Tamiflu • Prodrug converted in liver to active form • Dosing based on weight and renal function • Most common side effect is GI upset, improved with food • Neurologic side effects reported in children mostly in Japan • No IV admin • Resistance can occur

20. CDC

21. Combination Therapy • zanamivir and oseltamivir has been studied but showed no benefit and greater viral loads (competition for site) • Triple combination of oseltamivir, amantadine and ribavirin are being studied • In vitro study (Hoopes, et al) looked promising • Nguyen et al: looked at TCAD in murine model • 90% survival with TCAD vs 20% with single agent oseltamivir • Korean study (Kim et al) • showed 24 pts, at 14 days 17% mortality for TCAD compared with 35% oseltamivir alone • low powered, no difference in 90 d mortality

22. Moscona A. N Engl J Med 2009; 360 (10): 953-6

23. Who Gets Treated • Antiviral treatment is recommended as early as possible for any patient with confirmed or suspected influenza who • is hospitalized; • has severe, complicated, or progressive illness; or • is at higher risk for influenza complications. This list includes: • children aged younger than 2 years; • adults aged 65 years and older; • persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), metabolic disorders (including diabetes mellitus), or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability [mental retardation], moderate to severe developmental delay, muscular dystrophy, or spinal cord injury); • persons with immunosuppression, including that caused by medications or by HIV infection; • women who are pregnant or postpartum (within 2 weeks after delivery); • persons aged younger than 19 years who are receiving long-term aspirin therapy; • American Indians/Alaska Natives; • persons who are morbidly obese (i.e., body-mass index is equal to or greater than 40); and • residents of nursing homes and other chronic-care facilities. • Consider in healthy individuals based on severity at presentation and how soon they present.

24. Prophylaxis • Neuraminidase Inhibitors • Close household contacts of persons with influenza who have not received the vaccine and who have comorbidities that could lead to complications • HCW who had not practiced proper precautions • Person living in NH or LT care facilities • Adamantanes class (amantidine and rimantidine) are rarely used due to resistance

25. Summary Points • Vaccinating health care workers is vital • Vaccinate patients on admission when possible • FLURSV has quickest turn around time, may be preferred • If influenza is suspected, start oseltamivir or zanamivir (if available) before test results are available. • Avoid Adamantanes as all circulating flu is resistant this year

26. Boltz A, Drugs 2010; 70 (11): 1349-1362 CDC Health Alert Network, December 24, 2013 CDC Web site Ginsberg J et al, Detecting Influenza epidemics using search engine query data Nature 2009; 457 Groom A, Pandemic Influenza Preparedness and Vulnerable Populations in Tribal Communities American Journal of Public Health 2009; 99, No S2 271-277 Harper S, et al IDSA Clinic Practice Guidelines: Seasonal Influenza in Adults and Children CID 2009;48 1003-1032 H1N1 hitting young and middle-aged adults ACP Hospitalist Weekly, Jan 8 2014 Kamali A, Holodniy M, Infection and drug Resistance Nov18 2013:6 187-198 Polgreen P, et al Using Internet Searches for Influenza Surveillance, CID 2008; 47 Prevention and control of Seasonal Influenza with Vaccines, ACIP, MMWR 9/20/2013;62 No7 Nature Reviews Drug Discovery 6, 967-974 (December 2007) Useful web sites http://www.cdc.gov/flu/ http://google.org/flutrends www.tricore.org References: