1. Rouhani Teching Hospital Treatment and Prophylaxis of Influenza Mehran shokri specialist of infectious disease

2. Prophylaxis and Treatment
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
Efficacy (vs placebo or no drug)
Strategy
AM/RM
ZNV
OSEL
Seasonal
Non-immunized adults
85%-91%
84%1
84%
Immunized NH elderly
58%-75% ?
92%
Post-contact/Post-exposure
Households
3%-100%
82%3
67%-89%2
Nursing homes
Variable
61%4
Yes5
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 ;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
Amantadine*
Rimantadine*
Zanamivir
Oseltamivir
Protein target M2 NA
Activity
A only
A and B
Therapy
Adults and children of 1 year
Adults only
Adults and
children of 5 years
Adults and children of 1 year
Prophylaxis
Yes
children of 7 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 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.

6. Recommended Daily Dosage Treatment and Prophylaxis of Influenza A and B
Antiviral Agent
Age Groups (years)
1-5
>5
Oseltamivir
Treatment
By weight
75 mg BID
Prophylaxis
75 mg QD
Zanamivir
Treatment*
10 mg (2 inhalations) QD
Prophylaxis*
*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 season (CDC. MMWR Dispatch. January 17, 2006).

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

8. Oseltamivir Treatment Combined RCT Database, Confirmed Influenza
Placebo
Oseltamivir
% Reduction
Hospitalizations
Healthy adults
5/662 (0.8%)
3/982 (0.3%)
High-risk + elderly
13/401 (3.2%)
6/368 (1.6%)
Total
18/1063 (1.7%)
9/1350 (0.7%)
59%*
Lower Respiratory Tract Complications Leading to Antibiotic Use
35/662 (5.3%)
17/982 (1.7%)
78/401 (18.5%)
45/368 (12.2%)
109/1063 (10.3%)
62/1350 (4.6%)
55%†
*P = .02; †P < .001
Kaiser L et al. Arch Intern Med. 2003;163:1667.

9. Oseltamivir Resistance Emergence During Treatment
Setting
Resistance Reported/
Number Patients
Rate of Emergence
Adult trials
1/350
<<1%
US pediatric trial
5/147 4%
Japanese children
7/43
16%
9/50
18%
Kaiser L et al. Arch Intern Med. 2003;163:
Whitley R et al. Pediatr Infect Dis J. 2001;20:
Kiso M et al. Lancet. 2004;364:

10. Oseltamivir: Time to Return to Normal Important Quality of Life Assessments
Health Status
Activity Level 12
Difference = 1.9 days*
Difference = 2.8 days† 10 8
Days 6 4 2
Placebo (n = 129)
Oseltamivir 75 mg BID (n = 124)
Placebo (n = 129)
Oseltamivir 75 mg BID (n = 124)
*P < .001
†P = .02
Treanor J et al. JAMA. 2000;283:

11. Zanamivir Resistance
Resistance not recorded in results from clinical trials1, 2, 3
zanamivir-resistant mutant identified was in a virus from 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:
2. Ambrozaitis A et al. J Am Med Dir Assoc. 2005;6:
3. Herlocher M et al. J Infect Dis. 2003;188:
4. Gubareva L et al. J Infect Dis. 1998;178:
5. Moscona A. N Engl J Med. 2005;353:
6. Gupta R and Nguyen-Van-Tam J. N Engl J Med. 2006;354:
7. Yen H et al. Antimicrob Agents Chemother. 2005;49:
8. Mishin V et al. Antimicrob Agents Chemother. 2005;49:

12. New Drug
Peramivir 2OO mg Amp IV Approved formula
NAI Drug

13. Influenza in Children Overview
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

14. 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

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

16. 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 duration and 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

17. 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
Corticosteroids have been used frequently in treating patients with influenza A (H5N1), with uncertain effects.

18. QUESTIONS ?

19. 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?

20. 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.

21. 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

22. 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.

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

24. 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).

25. 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.

26. 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).

27. Pandemic Influenza Prophylaxis and Treatment Summary
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

28. Seasonal Influenza Preparedness
Pandemic Influenza Preparedness