Transcript 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 101F); 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