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
• gt 60 Yamagata
• gt 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
UNMs 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 gt 65 yo
• Flublok
• Egg free, grown in cell culture
• Early vaccination of inpatients

13
Influenza Vaccination by Group at UNMH, Influenza
Season 2013-2014
  Compliant Total Number of Employees
UNMH 99.4 6,099
UNM Residents 65.6 633
CRTC 76.8 323
UNM MG 58.4 351
UNMH Cred Providers 100.0 245
UNM Cred Providers 74.4 1,102
Date of Report 1.10.14
Courtesy Dr. Meghan Brett
14
Influenza Vaccination Rates by Dept,
1.10.2014Courtesy Dr. Meghan Brett
Department Percent Compliant
Radiology 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
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 pulm dz
• cant be used in mechanical ventilation
• Clinical trials for optimal dosing for IV form,
  compassionate use.
• RX10 mg inhaled twice daily for 5 days (approved
  for gt 7 yr old)
• Prophylaxis is given once daily for 10 days (up
  to28 days) agegt 5
• Higher activity for influenza B H1N1 strains
  than oseltamivir, less activity against H3N2
• Doesnt 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
References
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 200948 1003-1032 H1N1 hitting
young and middle-aged adults ACP Hospitalist
Weekly, Jan 8 2014 Kamali A, Holodniy M,
Infection and drug Resistance Nov18 20136
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 9/20/201362 No7
Nature Reviews Drug Discovery 6, 967-974
(December 2007) Useful web sites http//www.cdc.g
ov/flu/ http//google.org/flutrends www.tricore.or
g