1 / 38

Treatment and Prophylaxis of Influenza Masoud Mardani M.D. Professor of Infectious Diseases

Treatment and Prophylaxis of Influenza Masoud Mardani M.D. Professor of Infectious Diseases. Seasonasl Influenza. Prophylaxis and Treatment. Antiviral Therapies for Influenza. Neuraminidase (NA). NA Inhibitors Oseltamivir Zanamivir. Matrix protein (M2 ). M2 Inhibitors Amantadine

coral
Download Presentation

Treatment and Prophylaxis of Influenza Masoud Mardani M.D. Professor of Infectious Diseases

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Treatment and Prophylaxis of InfluenzaMasoud Mardani M.D.Professor of Infectious Diseases

  2. Seasonasl Influenza • Prophylaxis and Treatment

  3. Antiviral Therapies for Influenza Neuraminidase (NA) • NA Inhibitors • Oseltamivir • Zanamivir Matrix protein (M2 ) • M2 Inhibitors • Amantadine • Rimantadine

  4. Antiviral Chemoprophylaxis of Influenza 1. Monto A et al. JAMA. 1999;282:31. 2. Hayden F et al. N Engl J Med. 1999; 341:1336. 3. Hayden F et al. N Engl J Med. 2000;343:12882. 4. Gravenstein S et al. J Am Med Dir Assoc. 2005;6:359. 5. Peters P et al. J Am Gerontol Soc. 2001;404:1025.

  5. Approved Antiviral Agents for Influenza Treatment and Prophylaxis *CDC recommends that the previously approved M2 inhibitors amantadine (Symmetrel) and rimantadine (Flumadine) not be used for the treatment or chemoprophylaxis of influenza A infections in the United States for the remainder of the 2005-2006 season (CDC. MMWR Dispatch. January 17, 2006). Treanor J. Influenza Virus. In Mandell, Douglas, and Bennett's Principles and Practice of Infectious diseases. 6th ed. New York: Elsevier/Churchill Livingstone; 2005:2072. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01341.html.

  6. Recommended Daily DosageTreatment and Prophylaxis of Influenza A and B *Zanamivir approved for treatment in children >7 years, for prophylaxis in children >5 years CDC recommends that the previously approved M2 inhibitors amantadine (Symmetrel) and rimantadine (Flumadine) not be used for the treatment or chemoprophylaxis of influenza A infections in the United States for the remainder of the 2005-2006 season (CDC. MMWR Dispatch. January 17, 2006). http://www.cdc.gov/flu/professionals/antiviralback.htm#table1

  7. Oseltamivir: Resolution of All Flu SymptomsIntent to Treat and Laboratory Documented Influenza Groups Difference = 32 hours* Difference = 21 hours† *P < .001 †P = .004 Treanor J et al. JAMA. 2000;283:1016-1024.

  8. Oseltamivir TreatmentCombined RCT Database, Confirmed Influenza *P = .02; †P < .001 Kaiser L et al. Arch Intern Med. 2003;163:1667.

  9. Oseltamivir ResistanceEmergence During Treatment Kaiser L et al. Arch Intern Med. 2003;163:1667-1672. Whitley R et al. Pediatr Infect Dis J. 2001;20:127-133. Kiso M et al. Lancet. 2004;364:759-765.

  10. Oseltamivir: Time to Return to NormalImportant Quality of Life Assessments Health Status Activity Level 12 Difference = 1.9 days* Difference = 2.8 days† 10 8 Days 6 4 2 0 Placebo(n = 129) Oseltamivir75 mg BID(n = 124) Placebo(n = 129) Oseltamivir75 mg BID(n = 124) *P < .001 †P = .02 Treanor J et al. JAMA. 2000;283:1016-1024.

  11. Zanamivir Resistance • Resistance not recorded in results from clinical trials1, 2, 3 • The only zanamivir-resistant mutant identified was in a virus from an immunocompromised child4 • Particular binding mechanisms may account for low levels of resistance to zanamivir5, 6 • Particular mutants are resistant to zanamivir in vitro7, 8 1. Monto A et al. Antimicrob Agents Chemother. 2006;50:2395-2402. 2. Ambrozaitis A et al. J Am Med Dir Assoc. 2005;6:367-374. 3. Herlocher M et al. J Infect Dis. 2003;188:1355-1361. 4. Gubareva L et al. J Infect Dis. 1998;178:1257-1262. 5. Moscona A. N Engl J Med. 2005;353:2633-2636. 6. Gupta R and Nguyen-Van-Tam J. N Engl J Med. 2006;354:1423-1424. 7. Yen H et al. Antimicrob Agents Chemother. 2005;49:4075-4084. 8. Mishin V et al. Antimicrob Agents Chemother. 2005;49:4515-4520.

  12. Influenza in ChildrenOverview • Flu symptoms in school-age children and adolescents are similar to those in adults • Temperature of 101°F or above, cough, muscle ache, headache, sore throat, chills, fatigue, general malaise • Public advised to contact physician for these symptoms • Children tend to have higher temperatures than adults, ranging from 103°F to 105°F • Flu in preschool children and infants is hard to pinpoint, since its symptoms are so similar to infections caused by other viruses

  13. Influenza in Immunocompromised Patients • Immunocompromised patients suffer more complications and have higher morbidity and mortality from influenza infection • High rate of hospitalization and ICU admissions • Higher rate of pulmonary complications • 50% of BMT and 13% renal transplant patients had lower respiratory tract infections • 50% of BMT and 7% of renal transplant patients with influenza complicated by pneumonia • 63% progressed to pneumonia • 43% mortality http://www.shea-online.org/Assets/files/W_-_Seasonal_and_Pandemic_Influenza_-_Children__Immunocompromised_Hosts__Pregnant_Women__and_Nursing_Home_Residents.ppt.

  14. Adjusted Incidence Rates of Acute CardiopulmonaryEvents per 10,000 Women-Months for High Risk Women Influenza In Pregnant Women * Events per 10,000women-months Pregnancy Status (Weeks) *November 1-April 30 period with no influenza activity Neuzil K et al. Am J Epidemiol. 1998;148:1094-1102.

  15. Seasonal Influenza Prophylaxis and Treatment: Summary • Efficacious and well-tolerated medications are available for prophylaxis and treatment of seasonal influenza • Neuraminidase inhibitors are useful to limit durationand severity of influenza if taken early • Use of M2 inhibitors is limited by widespread resistance • Influenza prevention and treatment remain challenging in special populations such as children, pregnant women, and immunocompromised individuals like transplant recipients

  16. Pandemic Influenza Avian Influenza in Humans

  17. Avian H5N1 Swelling of the head and face in an affected bird http://www.aphis.usda.gov/vs/birdbiosecurity/photos.html

  18. Avian H5N1Purple discoloration of the comb in the affected bird http://www.aphis.usda.gov/vs/birdbiosecurity/photos.html

  19. Nations with Confirmed Cases H5N1 Avian Influenza (May 19, 2006) http://pandemicflu.gov/

  20. H5N1 Antiviral Treatment • Most H5N1 viruses sensitive to oseltamivir and zanamivir: 3 H5N1 virus isolates reported resistant to oseltamivir • Most clade 1 H5N1 viruses resistant to amantadine and rimantadine (most clade 2 viruses sensitive to amantadine and rimantadine) • Neuraminidase inhibitor treatment recommended (oseltamivir) http://www.who.int/csr/disease/avian_influenza/guidelines/protocolfinal30_05_06a.pdf. http://www.who.int/csr/disease/avian_influenza/guidelines/pharmamanagement/en/index.html.

  21. Pandemic InfluenzaPotential Antiviral Agents *Investigational in US CDC recommends that the previously approved M2 inhibitors amantadine and rimantadine not be used for the treatment or chemoprophylaxis of influenza A infections in the United States for the remainder of the 2005-2006 season (CDC. MMWR Dispatch. January 17, 2006).

  22. Oseltamivir Therapy in H5N1 Thailand and Vietnam, 2004-2005 Writing Committee. N Engl J Med. 2005;353:1374-1385.

  23. Oseltamivir ResistanceN1 Neuraminidase • Frequency of drug therapy in humans • H1N1: children 16% (7/43), adults 4% (2/50) • H5N1: 2/8 (25%) • Single nucleotide substitution (His274Tyr), leads to • ↓ oseltamivir susceptibility (400–fold) • Reduced replication in cell culture (>2.0 log10), leads to • ↓ infectivity in mouse (1000-fold) and ferret (>10-fold) • Variable ↓ pathogenicity in ferret • Transmissible in ferret model Ives J et al. Antiviral Res. 2002;55:307-317. Herlocher M et al. J Infect Dis. 2004;190:1627-1630.

  24. Management • Most hospitalized patients withavianinfluenzaA (H5N1) haverequired ventilatory support within 48 hours after admission, • Empirical treatment with broad-spectrumantibiotics, antiviral agents, alone or with corticosteroids, have been used in most patients • Cultivable virus generally disappearswithin two or three days after the initiation of oseltamiviramong survivors.

  25. Influenza A (H5N1) Pneumonia

  26. Case Detection and Management • Hospitalization: in isolation whenever possible • Antiviral Agents • These viruses are susceptible in vitro to oseltamivir. • Early treatment will provide the greatest clinical benefit. • oseltamivir • 75 mg twice daily for five days in adults weight-adjusted twice-daily doses for five days in children older than one year of age — twice-daily doses of 30 mg for those weighing 15 kg or less, 45 mg for those weighing more than 15 to 23 kg, 60 mg for those weighing more than 23 to 40 kg, and 75 mg for those weighing more than 40 kg) are reasonable for treating early, mild cases of influenza A (H5N1)

  27. Higher doses (150 mg twice daily in adults) and treatment for 7 to 10 days are considerations in treating severe infections, but prospective studies are needed. • long-acting topical neuraminidase inhibitors, ribavirin and possibly, interferon alfa. • Immunomodulators • Corticosteroidshave been used frequently in treating patientswithinfluenzaA (H5N1), with uncertain effects.

  28. QUESTIONS ?

  29. Should oseltamivir, zanamivir, amantadine, and/or rimantadine be used for treatment or prophylaxis? • Should ribavirin, corticosteroids, immunoglobulin, and/or interferon be used for treatment? • Should broad-spectrum antibiotics be used for the prevention of secondary pneumonia?

  30. To answer these questions, the guidelines include a table with the recommended dose and duration of treatment and chemoprophylaxis for management of human infection with avian influenza A (H5N1) virus in different age groups. • Recommended agents include oseltamivir, zanamivir, amantadine, and rimantadine for treatment and prophylaxis.

  31. Groups at moderate-risk exposure are defined as those with unprotected and very close direct exposure to sick or dead H5N1 infected animals or to poultry implicated directly in human cases, • Those involved in handling sick animals or decontaminating known infected animals or environments without proper use of personal protective equipment, • and healthcare personnel in close contact with strongly suspected or confirmed H5N1 patients or virus-containing samples

  32. To determine who should receive chemoprophylaxis: • We defined high-risk exposure groups as household or close family contacts of a strongly suspected or confirmed H5N1 patient • Because of potential exposure to a common environmental or poultry source as well as exposure to the index case.

  33. In a nonpandemic situation, recommendations for treatment of patients with confirmed or strongly suspected infection with avian influenza A (H5N1) • are as follows:

  34. Patients should receive oseltamivir treatment as soon as possible (strong recommendation). • Clinicians might administer zanamivir (weak recommendation). • If neuraminidase inhibitors are available, clinicians should not administer amantadine alone as a first-line treatment (strong recommendation). • If neuraminidase inhibitors are not available and especially if the virus is known or likely to be susceptible, clinicians might administer amantadine as a first-line treatment (weak recommendation).

  35. If neuraminidase inhibitors are available, clinicians should not administer rimantadine alone as a first-line treatment (strong recommendation). • If neuraminidase inhibitors are not available and especially if the virus is known or likely to be susceptible, clinicians might administer rimantadine as a first-line treatment (weak recommendation). • If neuraminidase inhibitors are available and especially if the virus is known or likely to be susceptible, clinicians might administer a combination of neuraminidase inhibitor and M2 inhibitor (weak recommendation). This should only be done in the context of prospective data collection.

  36. High-risk exposure groups should receive oseltamivir as chemoprophylaxis continuing for 7 to 10 days after the last known exposure (strong recommendation). • In moderate-risk exposure groups, oseltamivir may be administered as chemoprophylaxis, continuing for 7 to 10 days after the last known exposure (weak recommendation). • Low-risk exposure groups should probably not receive oseltamivir for chemoprophylaxis (weak recommendation).

  37. Pandemic InfluenzaProphylaxis and TreatmentSummary • Combating an influenza pandemic includes seasonal influenza vaccination, social distancing techniques, possible ring chemoprophylaxis • Current antiviral possibilities for both prophylaxis and treatment include NA inhibitors and M2 inhibitors • NA inhibitors in limited supply and must be administered within 48 hours from symptom onset • M2 inhibitors could be useful against pandemic influenza, but resistance to M2 inhibitors may develop rapidly • Combinations of antivirals and of antivirals plus host immune response modifiers warrant study

  38. SeasonalInfluenzaPreparedness PandemicInfluenzaPreparedness

More Related