Prevention of Influenza in Prevention of Influenza in Nursing Home Residents: Nursing Home Residents:

An UpdateAn UpdateSuzanne F. Bradley, M.D.Suzanne F. Bradley, M.D.

GRECC - VAAAHSGRECC - VAAAHSDecember 2, 2010December 2, 2010

Influenza in LTCFInfluenza in LTCFObjectivesObjectives

• Significance of influenza/winter viruses

• Update on measures to reduce transmission– infection control measures

– vaccination

• Antiviral treatment and prophylaxis

Neuraminidase (N1,N2)

Hemagglutinin (H1-H3)

RNA

M2 protein(only on type A)

Influenza AInfluenza AViral StructureViral Structure

RNA transcriptases polymerasestructural proteins

Common Human A VirusesH1N1,H3N2, H1N2

Trifonov V et al. N Engl J Med 2009;10.1056/NEJMp0904572

2009 Influenza A (H1N1) Virus - Evolution2009 Influenza A (H1N1) Virus - Evolution

Seasonal Influenza Seasonal Influenza Mortality and HospitalizationMortality and Hospitalization

Thompson WW, et al. J Infect Dis. 2006;194:(suppl 2):S92-S97.

0.3 0.3 0.3 6.3 18.5 3365.3

129.1

357.9

050

100150200250300350400

Deaths per 100,000 population

Age group, years

10821

84190

321431

686

1195

0200400600

800100012001400

Hospitalization per 100,000 population

Age group, years

<1 1-4

5-49

50-6

4

65-6

9

70-7

4

75-7

9

80-8

4≥8

5 <55-

49

50-6

4

65-5

9

70-7

4

75-7

9

80-8

4≥8

5

2009 H1N12009 H1N1 Neutralizing AntibodiesNeutralizing Antibodies

• Born 1915 or earlier (n=32)

• Range 91-101 yrs old

– 2-12 yrs in 1918

• 1918 strain Ab (100%)

• Mean titer 1:562 (> 1:40)

• B cells isolated - functional Ab

Yu et al. Nature 2008;455:532

Hancock K NEJM 10.1056/NEJMoa0906453

It is Good to be Old!!!It is Good to be Old!!!

Year

Age

1918 1957 1968 1977

91 52 41 32

H1N1 sw

H2N2

H3N2

H1N1

2001 2009

H1N1 sw

Immunity

With thanks to Ann Falsey

Nasopharynx

Trachea

(ciliated respiratory epithelium)

Influenza InfectionInfluenza InfectionPathophysiologyPathophysiology

Lungs (rare)

Release/cell killedEnter the cell Rapid replicationBind to respiratory cell

Pathology of Influenza InfectionPathology of Influenza Infection

short incubation period (24-48 hours) /highly contagious

SymptomsAsymptomatic

CoughCoughEtiquetteEtiquette

EducationEducation

InfluenzaInfluenzaDetectionDetection

AntiviralsAntivirals

HandHandHygieneHygiene

VaccinationVaccination

IsolationIsolationDisinfectionDisinfection

InfluenzaInfluenzaPreventionPrevention

Influenza in LTCF Influenza in LTCF DetectionDetection

• Clinical suspicion/flu season• Serology (2 wks)• Surveillance cultures (3-7 days)• Rapid Tests (hours)

– EIA, immunofluorescence, PCR– nasopharyngeal secretions

Confirmed InfluenzaConfirmed InfluenzaPredictive SymptomsPredictive Symptoms

Symptom (%) OR (95% CI) P value*T >100F 3.26 (3.87-2.75) <.001Cough 2.85 (3.68-2.21) <.001Congestion 1.98 (2.54-1.54) <.001Weakness 1.54 (2.22-1.07) .008Anorexia 1.43 (1.86-1.10) .008* especially if symptoms severeFever+cough PPV 79% NPV 49% <.001< 48 hrs Sensitivity 63% Specificity 67%

Monto et al. Arch Intern Med 2000;160:3243

Older Hospitalized PtsOlder Hospitalized PtsInfluenza DiagnosisInfluenza Diagnosis

• Epidemic influenza documented• Lab confirmed cases• Symptom triad

– T > 38C, cough, illness < 7 days

• Flu (58%) vs Non-Flu (18%)– RR 2.99 (95% CI 1.9-4.8)– sensitivity 78%, specificity 73%– PPV 47%, NPV 91%

Walsh et al. JAGS 2002;50:1498.

Influenza in LTCFInfluenza in LTCFRapid Diagnostics-CalgaryRapid Diagnostics-Calgary

• Controlled study use vs non-use• Test all suspected flu cases• Similar influenza attack rates• Outcomes testing vs non-testing

– Reduction outbreak 9 vs 16 days, p=.03– No difference use:

amantadine, ATB, labs, isolation, hospitalizations

Church et al. CID 2002;34:790.

Influenza in Long-Term CareInfluenza in Long-Term CareInterventionsInterventions

• Isolation/Social Distancingsymptomatic patients, staff, visitorscough etiquettebarrier precautions/PPE

• Disinfectionfomites, environment,hand hygiene

• Antiviral agentstreat cases prophylaxis exposed

• Vaccination - patients, staff

2009 H1N1 Influenza2009 H1N1 InfluenzaHierarchy for Controls In Healthcare FacilitiesHierarchy for Controls In Healthcare Facilities

1. Elimination potential exposures - pt admissions - elective procedures - non-essential or ill visitors - send ill HCW home

2. Engineering controls - triage areas/public areas

physical barriers (partitions), limit entryseparate ill from well, protect pts & HCW

- closed suctioning systems - hands-free dispensers, receptacles

www.cdc.gov/h1n1 (10/14/09)

2009 H1N1 Influenza2009 H1N1 InfluenzaHierarchy for Controls In Healthcare FacilitiesHierarchy for Controls In Healthcare Facilities

3. Administrative controls/polices- work place practices and polices- policies - vaccination, sick leave for HCW- policies - cough etiquette, hand hygiene, isolation- triage stations to detect the sick- dedicated/essential staff for possible/confirmed flu

4. Personal protective equipment- lowest priority, last line of defense- not effective if exposures not recognized- adherence incomplete- equipment not used or maintained properly

Influenza IsolationInfluenza IsolationDroplet Precautions Returns!Droplet Precautions Returns!

• Standard precautions plus• Large droplets travel ~ 3 ft• Surgical mask within 3 ft pt with RTI sx**• Single room or cohort• Bed placement > 3 ft/curtains• Masks for symptomatic pts outside of the room• Duration isolation 7 days after onset or 24 hrs after fever/sx

resolved which ever is longer** except immunocompromised, ** unless aerosols occur

Siegel JD et al. APIC 2007;35:S65-164Bradley SF. Infect Control Hosp Epidemiol 1999;20:629,www.cdc.gov/flu/professionals/infectioncontrol

Respiratory ProtectionRespiratory ProtectionN95 vs Surgical MasksN95 vs Surgical Masks

• Small particles ? role in transmission—Ferret/guinea pig models, human outbreaks

• Filtration capacity—Surgical masks 4-90%—N95 respirators 95-99%—N95 vs mask efficacy 75% (study retracted)

• Limitations—N95s short supply—compliance 30%—N95 no better than masks during H1N1 outbreak/studies

• Prioritize use where aerosols likely (bronch, intubation)• Use in addition other preventative measures• CDC issues interim guidance for surgical mask useShine KI et al. N Engl J Med 10.1056/NEJM p0908437; MacIntyre CRQ et al. ICAAC Abstract K-1918b, 2009; Loeb M et al. JAMA. 2009;302(17):(doi:10.1001/jama.2009.1466)

Seasonal InfluenzaSeasonal InfluenzaVaccine 2010-2011Vaccine 2010-2011

• Killed and Live virus vaccines

A/California/7/2009 (H1N1)-likeA/Perth/16/2009 (H3N2)-like

B/Brisbane/60/2008=like

CDC. MMWR 2010;1-61

Influenza in LTCFInfluenza in LTCFVaccination 2010-2011Vaccination 2010-2011

• All persons > 6 months annually• High risk persons should still be targeted• If vaccine in short supply:

– Ages 6 mo-4 yrs, > age 50 yrs– Chronic diseases - pulmonary, renal, hepatic,

neurologic, hematologic, metabolic (DM)– Immunosuppressed– Pregnancy during influenza season– BMI > 40– Native AmericansMMWR 2010;59:1-62.

Influenza in LTCFInfluenza in LTCFVaccination 2010-2011 (Cont)Vaccination 2010-2011 (Cont)

• Residents chronic care facilities

• HCW

• Caregivers at risk populations

Influenza in the ElderlyInfluenza in the ElderlyNational Health Objective-2010National Health Objective-2010

• > 90% vaccination high risk pt• Vaccination rates > age 65 (%)

1973-1985 22-331993* 522006-08 662009 69

• NH pts vaccinated1997 64-82% 1998 83%

* Medicare benefit initiated

Inactivated VaccinesInactivated VaccinesInfluenza 2010-11Influenza 2010-11

Approved

• Afluria > 6 mo

• Fluarix > 3 yrs

• Agriflu > 18 yrs

• Fluzone High Dose > 65 yrs

Influenza in LTCFInfluenza in LTCFFluzone High DoseFluzone High Dose

• High-dose Inactivated Vaccine– Trivalent injectable– FDA approved > 65 yrs– 60 g vs 15 g HA per strain– Higher

• antibody titers• local injection reactions 36% vs 24%• fever 1.1% vs 0.3%

– ? protective flu or pneumonia not known– no recommendation re useFalsey AR et al. J Infect Dis 2009;2009;200:172; MMWR 59:485, 2010.

Influenza Vaccination in LTCFInfluenza Vaccination in LTCFRole of HCW InterventionsRole of HCW Interventions

Cluster RCT - 40 Parisian LTCF (3483 pts)Post interview vaccination yes vs nopt vaccinated 84.3% vs 82.5%HCW vaccinated 69.9% vs 31.8%

OR CI (95%) p valuept mortality all cause 0.80 (0.66-0.96) .02pt ILI 0.69 (0.52-0.91) .007HCW sick leave 0.58 (0.36-0.96) .03

Lemaitre M, et al. JAGS 2009;57:1580; Thomas RE et al. Lancet ID 2006;6:273.Potter J et al. J Infect Dis 1997;175:1; Carman WF et al. Lancet 2000;355:93;

Influenza VaccineInfluenza VaccineImproving ComplianceImproving Compliance

• Physician recommendation• Patient reminders• Pre-printed physician orders• Blanket orders• Nurse-initiated • Active declination• National societies endorse mandatory HCW vaccination

CDC Influenza Surveillance Report September 26, 2009CDC guidance 11/24/2010

Antiviral ResistanceAntiviral ResistanceInfluenza 2009Influenza 2009

Seasonal Influenza Seasonal Influenza Rx Hospitalized Patients - MortalityRx Hospitalized Patients - Mortality

OR P value• Oseltamivir 0.21 .02

– > 65 yrs 0.24• ICU 10.5 <.001• Charleson score 1.3 .03• Days ill PTA 0.51 .03

Rx Started6% - 24 hours29% - 48 hours51% - 72 hours72% - 96 hoursMcGeer A et al. Clin Infect Dis 2007 45:1568

Seasonal Influenza in LTCFSeasonal Influenza in LTCFEfficacy ProphylaxisEfficacy Prophylaxis

0

20

40

60

80

100

Perc

ent E

ffic

acy

Rimantadine Oseltamivir Zanamivir

ILIConfirmed Flu

Risebrough et al. JAGS 2005;53:444.Hirji et al. ICHE 2002;23:604.

Zanamivir (Relenza)Zanamivir (Relenza)Proper Use (10/9/09)Proper Use (10/9/09)

• Diskhaler use only

• Do not reconstitute in any liquid

• Do not nebulize– efficacy, safety, stability not established

• Lactose carrier - malfunction ventilatorwww.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlerts

InfluenzaInfluenzaProphylaxisProphylaxis

•High risk patients– context of an outbreak– vaccine contraindicated– vaccinated late (Rx 2 wks)– ILI in vaccinated group– poor antibody response– caretakers

InfluenzaInfluenzaProphylaxisProphylaxis

• Rx daily for:– duration outbreak ~ 14 days– one week after last case– peak season– unvaccinated– outbreak vaccinated pop.

• Rx daily for 2 wks– post-vaccinationBradley SF et al. Infect Control Hosp Epidemiol 1999;20:629

Influenza in LTCFInfluenza in LTCFOutbreak - Clinical DefinitionOutbreak - Clinical Definition

• Significance of documented flu in the facility?– attack rates 35-40%– case-fatality rates ~ 55%– rapid initiation prophylaxis for the affected ward or entire facility

• Normal respiratory infection background rate– 1 case every 7 days per 40-resident ward

• Likelihood cases unrelated within 72 hrs– 2 cases ~ 7%– 3 cases ~ 2%

• If 2-3 cases in 48-72 hrs?– initiation of isolation procedures– confirmatory rapid testing if feasible in 3-4 pts– assumes sensitivity test ~ 70% – if a single pt + declare an outbreakHota S et al. Clin Infect Dis 2007;45:1362.www.cdc.com/flu/professionals/infectioncontrol/longtermcare.htmwww.health.gov.on.ca/english/providers/pub/pubhealth/ltc_respoutbreak.html

Outbreaks in LTCFOutbreaks in LTCFWhat if ILI Continues?What if ILI Continues?

Virus Season Incubationdays

Transmission

Influenza winter 1-2 sm particleaerosols

RSV fall-spring 2-8 lg dropletsfomites

hMPV late winter 5-6 lg dropletformites

PIV fall-spring 2-8 lg dropletformites

Coronaviruses winter 1-3 lg dropletformites

Rhinovirus all year 0.3-2 fomites

Falsey AR et al. CID 2006;42:518.

Outbreaks in LTCFOutbreaks in LTCFNon-Influenzal IllnessNon-Influenzal Illness

Virus Attack

Rate %

LRTI%

Transfer %

Death

Rate %

Culture

(+)

RT-PCR

(+)

RSV 42 - 0.1 14.3 2/22 7/22

hMPV 22-72

18

21-50

31

-

5

16.1

-

2/13

0/20

6/13

5/14Rhinovirus 24

62

100

33

52

27

38

16

1.8

5

6

21

-

-

7/13

4/10

6/19

7/13

Caram LB et al., JAGS 2009;57:482.; Boivin G et al. CID 2007;44:1152.;

Louie JK et al. CID 2007;196:705.; Hicks LA et al., JAGS 2006;54:284.

Outbreaks in LTCFOutbreaks in LTCFCo-Circulating Viral InfectionsCo-Circulating Viral Infections

0

50

100

150

200

250

No.

Ser

olog

ic C

onve

rsio

ns

1998 1999 2000 All

Years

PIV-2PIV-3229EOC43hMPVFlu BFlu ARSV

Falsey AR et al. J Am Geriatr Soc 2008;56:1281.Drinka PJ et al. J Am Geriatr Soc 1999;1087.

617 residents/13 NH followed 52 wkspaired sera/clinical assessments

2009 H1N1 Influenza2009 H1N1 InfluenzaBacterial Co-InfectionsBacterial Co-Infections

• Confirmed H1N1 influenza infection

• PCR on 77 pt specimens who died—S. aureus, S. pyogenes, S.

pneumoniae, H. flu—22/77 (29%) evidence

bacteria infection—16/21( eligible for 23 valent

vaccine

• Pneumococcal vaccine!

34%

20%23%

7%3%

13%

S. pneumoniae (10) S. pyogenes (6)S. aureus (7) S. mitis (2)H. influenzae (1) Multiple (4)MMWR 2009;58:1071

Influenza in LTCFInfluenza in LTCFPriorities in 2010Priorities in 2010

• HCW vaccination– a patient safety issue– to keep HCW/families healthy & working

• Patient vaccination– still a priority– role of high HA vaccine?

• Antiviral susceptibility remains an issue– still relying on NA inhibitors– what strain is circulating can’t be known quickly– zanamavir administration an issue

Influenza in LTCFInfluenza in LTCFPriorities in 2010Priorities in 2010

• Isolation continues to be a challenge– clarification droplet precautions/surgical masks– lack of private rooms/baths– cohorting, other strategies may be necessary– emergence of resistance in pts on antivirals?

• Diagnostic testing - what role?– rapid accurate PCR tests now available– improve influenza detection?– reduce unnecessary antiviral use?– cost effective?– how often to screen?

Contact Information

• For questions about this audio conference please contact Dr. Suzanne Bradley at sbradley@umich.edu

• For any questions about the monthly GRECC Audio Conference Series please contact Tim Foley at tim.foley@va.gov or call (734) 222-4328

• To evaluate this conference for CE credit please obtain a “Satellite Registration” form and a “Faculty Evaluation” form from the Satellite Coordinator at you facility. The forms must be mailed to EES within 2 weeks of the broadcast