Influenza

Peggy Beeley, MDBest Practice 1/15/14

Outline

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

Signs & Symptoms

• 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

Complications

Most Recent Surveillance from CDC

UNMH Admissions for 2013-2014 Influenza Season

Courtesy Dr. Meghan Brett

Characteristics of Admitted Patients with Influenza

Average age: 36.7 yearsRange: 0 – 64 yearsSex: 53% Female

47% MalesAdmitted from:

71% from ED29% from Clinics

All positive for Influenza A Courtesy Dr. Meghan Brett

Influenza

• RNA viruses Orthomyxoviradae• Influenza A

– Most morbidity & mortality– Pandemic

• Influenza B– > 60% Yamagata– > 30% Victoria

• Influenza C

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

National Data for Influenza 2013-2014

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

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

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

Influenza Vaccination by Group at UNMH, Influenza Season 2013-2014

% CompliantTotal Number of

EmployeesUNMH 99.4% 6,099UNM Residents 65.6% 633CRTC 76.8% 323UNM MG 58.4% 351UNMH Cred Providers 100.0% 245UNM Cred Providers 74.4% 1,102

Date of Report: 1.10.14 Courtesy Dr. Meghan Brett

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

Department Percent CompliantRadiology 97.4%Emergency Medicine 95.2%Anesthesiology & Critical Care Medicine 88.9%Family & Community Medicine 87.7%Internal Medicine 74.8%Obstetrics & Gynecology 73.7%Pediatrics 72.1%Psychiatry 66.7%Orthopedics & Rehabilitation 64.9%Neurology 64.3%Dental Medicine 62.5%Surgery 52.6%Pathology 50.9%Dermatology 50.0%Neurosurgery 47.4%

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

Anti-flu therapy and prophylaxis

• Neuraminidase Inhibitors: – oseltamivir (Tamiflu)– zanamivir (Relenza)

• Japan has two others– laninamivir – peramivir, IV form

• Adamantanes:– Amantadine– Rimantadine

• Ribavirin

Targets of Antivirals

Itzstein, M :Nature Review of Drug discovery, vol 6 2007

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 pulm dz – 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

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

CDC

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

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

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.

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

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

References:Boltz A, Drugs 2010; 70 (11): 1349-1362CDC Health Alert Network, December 24, 2013CDC Web siteGinsberg J et al, Detecting Influenza epidemics using search engine query data

Nature 2009; 457Groom A, Pandemic Influenza Preparedness and Vulnerable Populations in Tribal Communities

American Journal of Public Health 2009; 99, No S2 271-277Harper S, et al IDSA Clinic Practice Guidelines: Seasonal Influenza in Adults and Children

CID 2009;48 1003-1032H1N1 hitting young and middle-aged adults ACP Hospitalist Weekly, Jan 8 2014Kamali A, Holodniy M, Infection and drug Resistance Nov18 2013:6 187-198Polgreen P, et al Using Internet Searches for Influenza Surveillance, CID 2008; 47Prevention 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 siteshttp://www.cdc.gov/flu/http://google.org/flutrendswww.tricore.org