Download INFLUENZA

PMDA 2006
Alex T. Makris, MD, CMD
INFLUENZA
New Issues and New
Challenges
Clinically Relevant Influenza
Viruses
Type A
Potentially severe illness
Epidemics and pandemics
Rapidly changing
Type B
Usually less severe illness
Epidemics
Genetically more stable
Centers for Disease Control and Prevention. Influenza Prevention and Control. Influenza.
Available at: http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm.
Confirmed Influenza Isolates –
Type A vs Type B (1992-1999)
0.1%
0.3%
Percentage of Type A
and B Isolates
100
8%
86%
22%
19%
21%
80
Type B
Type A
60
99.9%
78%
92%
81%
99.7%
79%
3,963
3,423
4,132
6,344
11,439
6,529
40
20
14%
0
Total = 2,087
1992-93
93-94
94-95
95-96
96-97
97-98
98-99
CDC MMWR Weekly. Update: Influenza activity (1992-94 to 1998-99 seasons).
Available at: http://www.cdc.gov/epo/mmwr/preview/mmwrhtml.htm.
Influenza Pandemics in the 20th
Century
Years
Flu
1918-19
“Spanish”
1957-58
“Asian”
Virus
Mortality
Type A (H1N1) 20 million worldwide
550,000 US
Type A (H2N2)
70,000 US
1968-69 “Hong Kong” Type A (H3N2)
34,000 US
Glezen WP. Epidemiol Rev. 1996;18:65.
Centers for Disease Control and Prevention. Influenza Prevention and Control. Influenza. Available at:
http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm.
Pneumonia and Influenza
Mortality
Rates by Age
Per 10,000
120
100
80
60
40
20
0
<5
5-9 10-14 15-19 20-24 25-34 35-44 45-54 55-64 ≥65
Age (yr)
Glezen WP. Epidemiol Rev. 1996;18:73, with permission.
Influenza Surface Proteins
Neuraminidase
Hemagglutinin
RNA
M2 protein
(only on type A)
INFLUENZA
Transmission
Pathophysiology
Clinical Manifestations
Influenza
Transmission
Aerosolized droplet spread
Incubation period 18 - 72 hours
Attack rate 10% - 50%
Outbreaks generally begin in confined
locations
After initial cases, numbers usually peak
over 2-3 weeks
Usually occurs Dec - April
Laver, WG, et. al. Scientific American: Disarming Flu Viruses: January 1999 Illustration: Bryan Christie
Flu vs. Cold Symptoms
Signs & Symptoms
Onset
Fever
Cough
Headache
Myalgia (aches and pains)
Fatigue; weakness
Extreme exhaustion
Chest discomfort
moderate
Stuffy nose
Sneezing
Sore throat
Flu
Sudden
Characteristic, high (over
101F); lasting 3 to 4 days
Nonproductive; can
become severe
Prominent
Usual; often severe
Can last up to 2 to 3 weeks
Early and prominent
Common
Cold
Gradual
Rare
Sometimes
Sometimes
Sometimes
Common
Usual
Common
Adapted from the National Institute of Allergy and Infectious Diseases.
Hacking
Rare
Slight
Very mild
Never
Mild to
Diagnostic Tools
Weekly CDC activity reports
Clinical suspicion
Viral isolation
Serology
PCR
Immunofluorescence assays
Rapid diagnostic tests
MANAGEMENT OPTIONS
Early vaccination
Infection Control Measures
Anti-influenzal agents
Prophylaxis with anti-influenzal
agents
Influenza &
Pneumococcal
Immunizations
Guidance Training
CFR 483.25(n) F334
Effective October 1, 2006
CMS
Determination of Compliance
Synopsis of Regulation
The influenza & pneumococcal vaccination
requirement has five aspects:
1. The resident is provided education regarding
the benefits & potential side effects of the
vaccinations;
2. The facility must determine if a resident is
eligibility to receive the vaccinations.
3. The resident, or the resident’s legal
representative, has the right to refuse the
vaccinations.
CMS
Determination of Compliance
Criteria for Compliance
4. Each eligible resident is administered the
influenza & pneumococcal vaccine (unless
refused or contraindicated or the resident
has already been immunized); and
5. The facility must document that education
was provided and that the resident either
received the vaccine(s) or, if not received,
that the vaccine(s) was (were) refused or
medically contraindicated or the resident
had already been immunized.
CMS
Vaccination Program
Generally, vaccinate in late September,
October
Vaccinate through March
– New admissions should be offered vaccine
– Generally takes ~ 2 weeks for protection
– If vaccination occurs during high activity levels
may need to provide chemoprophylaxis during
the 2 weeks after vaccination
Efficacy of the Influenza
Vaccine
Most effective (70%-90%) in preventing
illness in persons aged <65 yrs
30%-70% in preventing P/I hospitalization in
elderly not in chronic care facility
30%-40% in preventing illness in frail elderly
50%-60% in preventing P/I hospitalization in
nursing home elderly
80% in preventing death in nursing home
elderly
MMWR. 1999;48:4.
Naming Influenza Viruses
A (H1N1)/Sydney/5/93
Strain
Type Hemagglutinin Neuraminidase OriginSequence
No.
B/Beijing/18
4/93
Yr
2006 – 2007 Vaccine Composition
A/New Caledonia/20/1999 (H1N1)-like
A/Wisconsin/67/2005 (H3N2)-like
B/Malaysia/2506/2004-like antigens
Inactivated vaccine
Live, Attenuated Influenza Vaccine (LAIV)
Characteristics of Influenza
Vaccines
Characteristic
Inactivated
LAIV (FluMist™)
Route of
administration
Intramuscularly annually
Intranasally - annually
Composition
Killed virus:
Same antigenic
makeup
Live, attenuated
Same antigenic
makeup
Indication
≥ 6 months
5 – 49 years
Clinical Illness
Mild, local
Mild signs/symptoms
of influenza
MMWR July 28, 2006/55(RR10); 1-42 Prevention and Control of Influenza
Avian Influenza
H5N1 epizootic
Human infections from direct contact with
infected poultry/wild birds
Person → person transmission
– Rare, Limited, Unsustained
If sustained transmission, pandemic may
result
Little pre-existing immunity
CDC August 9, 2006 Avian Influenza: Current Situation
Avian Influenza
No available vaccine
Sx & Sx similar to circulating strains
Cases/deaths 2003 through August 2006
– 241/141
Cases/deaths 2006
– 96/64
Oseltamivir and Zanamivir are currently
effective for treatment and
chemoprophylaxis
www.who.int/csr/disease/avianinfluenza/en
Infection Control
And
Outbreak Management
Outbreak Control
Recognize when a potential outbreak
exists
– Any activity above the usual for the Facility
Manage the active residents
Prevent transmission to other residents
and staff
– Infection Control Measures
– Treatment of active residents
– Chemoprophylaxis of uninfected residents
Mode of Transmission
Droplets
– Person → person
– Generated via cough, sneezing ( 3 feet)
Mucosal surfaces
Inanimate surfaces laden with virus
– Transmission from 24 hours prior and 5 days
after onset
CDC December 23, 2005. Infection Control Measures for Preventing and Controlling Influenza
Transmission in Long-Term Care Facilities
General Infection Control Measures
Annual influenza vaccination
Standard and Droplet Precautions
Private room if possible
Cohort when possible
Active surveillance
Testing for new cases
Limit visitation
Limit communal activities
Limit admissions
Prophylactic antivirals
CDC December 23, 2005. Infection Control Measures for Preventing and Controlling Influenza
Transmission in Long-Term Care Facilities
Infection Control Measures
Staff Management
Reinforce hand washing importance
Provide alcohol based hand gels
Do not allow ill employees to work
If outbreak confined to one unit; limit staff
cross over to other units
If possible, assign care givers to only ill or
well residents
If not, care for well residents first, then ill
residents
Influenza Treatment
Antiviral Agents for Influenza
Amantadine, Rimantadine
– Only active against influenza A
– Significant CNS adverse effects
– Rapid, high levels of resistance
192/209 (92%) influenza A, 26 States
– No longer recommended for treatment or
chemoprophylaxis of influenza
MMWR July 28, 2006/55(RR10); 1-42 Prevention and Control of Influenza
Antiviral Agents for Influenza
Zanamivir, Oseltamivir phosphate
–
–
–
–
–
Neuraminidase inhibitors
Treatment initiated within 48 hours of onset
Active against A, B
Approved for treatment of acute illness
Approved for prophylaxis
Oseltamivir ≥ 1yr
Zanamivir ≥ 5 yrs
– Zanamivir – inhalation
– Oseltamivir – oral
Neuraminidase Inhibition
Influenza Treatment
Zanamivir (Relenza)
– Delivery via inhalation
Diskhaler device
10 mg BID X 5 days
Begin within 48 hours of onset
Oseltamivir phosphate (Tamiflu)
– Delivery via oral route (suspension available)
75mg BID X 5days
Begin within 48 hours of onset
Influenza Prophylaxis
CDC encourages the use of oseltamivir for
chemoprophylaxis
– 75 mg daily
Vaccinated elderly in aggregate living
settings may develop influenza or be
susceptible to influenza
www. cdc.gov/flu/professionals/treatment/0506antiviralguide.htm. CDC Influenza Antiviral
Medications: 2005-06 Interim Chemoprophylaxis and Treatment Guidelines.
Chemoprophylaxis Management
If confined to one unit
– Implement infection control measures
– Provide chemoprophylaxis to unvaccinated
staff and uninfected, unvaccinated residents
on the unit
– If vaccinated residents have Sx & Sx provide
chemoprophylaxis
– Continue prophylaxis for at least two weeks
and for as long as one week after the last
resident case occurred
CDC December 23, 2005. Infection Control Measures for Preventing and Controlling Influenza
Transmission in Long-Term Care Facilities
Chemoprophylaxis Management
If active cases occur on several units
– Implement infection control measures
– Provide chemoprophylaxis to all unvaccinated
staff and uninfected, unvaccinated residents
– If vaccinated residents have Sx & Sx provide
chemoprophylaxis
– Continue prophylaxis for at least two weeks
and for as long as one week after the last
resident case occurred
CDC December 23, 2005. Infection Control Measures for Preventing and
Controlling Influenza Transmission in Long-Term Care Facilities
Clostridium difficile Infection
New Strain
New Challenges
Clostridium difficile
Prevalence
4% - 20% - LTCF without outbreak¹
10% - 20% may acquire during their stay²
Rate of acquisition – 1 yr. follow up
0.52/1,000 rcds³
Incidence - AAD
– 1,600 per 1,000 resident years¹
¹Gerding DN, et al. Infect Control Hosp Epidemiol 1995;16:459. ²Monsieur I, et al. Arch Gerontol
Geriatr 1991;13:255. ³Simor AE, et al. Clin Infect Dis 1993;17:672
Clostridium difficile
Principles of Treatment - CDAD
Discontinue antimicrobial therapy if
possible
Fluids and electrolytes
Avoid anti – peristaltic agents
Avoid opiates
Mild cases
– 15% - 20% will resolve with above measures¹
¹Olson MM et al. Infect Control Hosp Epidemiol 1994;15:371
Clostridium difficile
Principles of Treatment - CDAD
Specific therapy should be given orally
when possible
Specific therapy should be continued for
10 days
Test of Cure cultures or toxin assays
should not be done in asymptomatic
patients¹
– Does not predict clinical relapse
¹Fiengold SM Academic Press 1988:341
Clostridium difficile
Treatment Options - CDAD
Metronidazole
Vancomycin
Vancomycin + Rifampin
Probiotics
– Lactobacillus
– Saccharomyces boulardii
Ion-exchange resins - colestipol
Clostridium difficile Current
Guidelines for
Treatment - CDAD
Initial therapy
– Metronidazole PO – 10 days
1.0 – 1.5 gm/day for 10 days¹
– Vancomycin PO – 10 days
500 – 1,000 mg/day for 10 days²
Relapse
– Retreat with initial agent³
Cures 90% of recurrences
¹Peterson LR et al. Verlog 1990:115 ²Gerding DN Infect Control Hosp Epidemiol 1995;15:8:459
3Simor
et al Infect Control Hosp Epidemiol 2002;23:696
Clostridium difficile
Treatment Outcomes - CDAD
Clinical improvement 2 – 4 days
Symptoms remit 7 – 10 days
Relapse rates 10% - 20%¹‫׳‬²‫׳‬³
– Metronidazole – 7%²,16%³
– Vancomycin – 10%², 16%³
¹Teasley DG et al. Lancet 1983;5: 1043 ²Olson MM et al. Infect Control Hosp Epidemiol 1994;15:371 ³Wenisch C et al.
Clin Infect Dis 1996;22:813
Clostridium difficile
Asymptomatic Carriers
No increased risk of CDAD in
asymptomatic carriers vs. non colonized
patients¹
Treatment of colonization does not reduce
risk of CDAD²
Metronidazole ineffective in eliminating the
carrier state³
Vancomycin may prolong carrier state
¹Johnson S et al. Lancet 1990;336:97 ²Bender BS et al. Lancet 1986;ii:11 ³Johnson S et al. Ann Int
Med 1992;117:297
Epidemic Strain
New strain
– Appears to produce greater quantities of
toxins A and B1,2
– Is more resistant to fluoroquinolones3,4
– Has a tcdC gene deletion2
– Binary toxin genes are present
1.
2.
3.
4.
CDC Fact Sheet, July 2005.
Warny M, et al. Lancet. 2005;366:1079-1084.
McDonald LC, et al. 42nd Annual Meeting of the Infectious Diseases Society
of America (IDSA); 2004. Abstract LB-2.
McDonald LC, et al. N Engl J Med. 2005;353:2433-2441.
Markers of Severe Disease
Decreased mental status
Severe abdominal distension, pain
Marked increase in white blood cell count
Hemodynamic instability
Clostridium difficile
Treatment Outcomes - CDAD
Jacques Pepin et al. Clin Inf Dis 2005;40:1591
– Retrospective review 1991-2004
Clinical diagnosis + toxin assay
Metronidazole therapy
– 250 mg QID – 500 mg TID
Relapse rates
Metronidazole → Vancomycin
– Clinical failure
Clostridium difficile
Treatment Outcomes - CDAD
1991-2002
– Treatment failure with Metronidazole
9.6% (66/688)
– Recurrence rate < 60 days
15.2%
2003-2004
– Treatment failure with Metronidazole
25.7% (112/435)
– Recurrence rate < 60 days
47.2%
Clostridium difficile
Treatment Outcomes - CDAD
Daniel M Musher et al. Clin Infect Dis
2005;40:1586
– 207 patients treated with Metronidazole
Clinical cure - 50% (103/207)
Persistent symptoms – 22% (46/207)
Recurrence – 28% (58/207)
Clostridium difficile
Treatment Outcomes - CDAD
Jacques Pepin et al. Clin Inf Dis
2005;41:1254
– 1/1/03 – 6/30/04
– All hospital admissions
– Clinical CDAD
Clostridium difficile
Treatment Outcomes - CDAD
293 incident cases CDAD
– 50.5% (148/293) in patients > 80 y.o.
– 63.5% (186/293) received Fluoroquinolones
– 21.8% (64/293) mortality < 30 d of diagnosis
Summary
Expanding spectrum of disease
Epidemic strain has been identified
Await updated guidelines (Spring 2007)
Role of vancomycin may be re-defined
Prevention is key!
– Infection control measures
– Judicious use of antibiotics
Treatment – Complicated
Infections
Vancomycin +
– Saccharomyces boulardii¹
– Rifampin²
– Lactobacillis³
– Colestipol¹
¹Feckety R Am J Gastroenterol 1997;92:739 ²Buggy BE J Clin Gastroenterol 1987;9:155 Gorbach SL Lancet
1987;ii:1519
Infection Control
Clostridium difficile
Mode of Transmission
Direct Contact
– Hand carriage - HCW¹‫׳‬²
Most likely plays major role
– Environmental surfaces
Spores – weeks or months
Commodes, rectal thermometers
¹McFarland LV et al. N Engl J Med 1989;320:204 ²Fekety R et al. Am J Med1981;70:906
Clostridium difficile
Infection Control
Two major potential reservoirs
– Infected humans
Symptomatic
Colonized
– Inanimate objects
Nosocomial acquisition – 20%¹
– Most asymptomatic
¹McFarland LV et al. N Engl J Med 1989;320:204
Clostridium difficile
Infection Control
Patients with CDAD and incontinence
should be in private rooms
Contact isolation
– Barriers with direct contact
– Barriers when contact with environment
Dedicated equipment when possible
Simor AE et al. SHEA Position Paper. Clostridium difficile in Long-Term Care Facilities for the Elderly
2002;23:696
Clostridium difficile
Infection Control
Meticulous hand hygiene
– Alcohol based hand gels are not sporocidal
Environmental cleaning with sporocidal
agents
Discontinuation of isolation when diarrhea
subsides
Do not treat asymptomatic carriers
Simor AE et al. SHEA Position Paper. Clostridium difficile in Long-Term Care Facilities for the Elderly
2002;23:696