- •Global Impact
- •Epidemics and Pandemics
- •Current Situation
- •Individual Impact
- •The Virus
- •Requirements for Success
- •Virology
- •Natural Reservoir + Survival
- •Transmission
- •H5N1: Making Progress
- •Individual Management
- •Epidemic Prophylaxis
- •Exposure Prophylaxis
- •Vaccination
- •Antiviral Drugs
- •Epidemic Treatment
- •Pandemic Prophylaxis
- •Pandemic Treatment
- •Global Management
- •Epidemic Management
- •Pandemic Management
- •Containment
- •Drugs
- •Vaccines
- •Distribution
- •Conclusion
- •Golden Links
- •Interviews
- •References
- •Avian Influenza
- •The Viruses
- •Natural hosts
- •Clinical Presentation
- •Pathology
- •LPAI
- •HPAI
- •Differential Diagnosis
- •Laboratory Diagnosis
- •Collection of Specimens
- •Transport of Specimens
- •Diagnostic Cascades
- •Direct Detection of AIV Infections
- •Indirect Detection of AIV Infections
- •Transmission
- •Transmission between Birds
- •Poultry
- •Humans
- •Economic Consequences
- •Control Measures against HPAI
- •Vaccination
- •Pandemic Risk
- •Conclusion
- •References
- •Structure
- •Haemagglutinin
- •Neuraminidase
- •M2 protein
- •Possible function of NS1
- •Possible function of NS2
- •Replication cycle
- •Adsorption of the virus
- •Entry of the virus
- •Uncoating of the virus
- •Synthesis of viral RNA and viral proteins
- •Shedding of the virus and infectivity
- •References
- •Pathogenesis and Immunology
- •Introduction
- •Pathogenesis
- •Viral entry: How does the virion enter the host?
- •Binding to the host cells
- •Where does the primary replication occur?
- •How does the infection spread in the host?
- •What is the initial host response?
- •Cytokines and fever
- •Respiratory symptoms
- •Cytopathic effects
- •Symptoms of H5N1 infections
- •How is influenza transmitted to others?
- •Immunology
- •The humoral immune response
- •The cellular immune response
- •Conclusion
- •References
- •Pandemic Preparedness
- •Introduction
- •Previous Influenza Pandemics
- •H5N1 Pandemic Threat
- •Influenza Pandemic Preparedness
- •Pandemic Phases
- •Inter-Pandemic Period and Pandemic Alert Period
- •Surveillance
- •Implementation of Laboratory Diagnostic Services
- •Vaccines
- •Antiviral Drugs
- •Drug Stockpiling
- •General Measures
- •Seasonal Influenza Vaccination
- •Political Commitment
- •Legal and Ethical Issues
- •Funding
- •Global Strategy for the Progressive Control of Highly Pathogenic Avian Influenza
- •Pandemic Period
- •Surveillance
- •Treatment and Hospitalisation
- •Human Resources: Healthcare Personnel
- •Geographically Targeted Prophylaxis and Social Distancing Measures
- •Tracing of Symptomatic Cases
- •Border Control
- •Hygiene and Disinfection
- •Risk Communication
- •Conclusions
- •References
- •Introduction
- •Vaccine Development
- •History
- •Yearly Vaccine Production
- •Selection of the yearly vaccine strain
- •Processes involved in vaccine manufacture
- •Production capacity
- •Types of Influenza Vaccine
- •Killed vaccines
- •Live vaccines
- •Vaccines and technology in development
- •Efficacy and Effectiveness
- •Side Effects
- •Recommendation for Use
- •Indications
- •Groups to target
- •Guidelines
- •Contraindications
- •Dosage / use
- •Inactivated vaccine
- •Live attenuated vaccine
- •Companies and Products
- •Strategies for Use of a Limited Influenza Vaccine Supply
- •Antigen sparing methods
- •Rationing methods and controversies
- •Pandemic Vaccine
- •Development
- •Mock vaccines
- •Production capacity
- •Transition
- •Solutions
- •Strategies for expediting the development of a pandemic vaccine
- •Enhance vaccine efficacy
- •Controversies
- •Organising
- •The Ideal World – 2025
- •References
- •Useful reading and listening material
- •Audio
- •Online reading sources
- •Sources
- •Laboratory Findings
- •Introduction
- •Laboratory Diagnosis of Human Influenza
- •Appropriate specimen collection
- •Respiratory specimens
- •Blood specimens
- •Clinical role and value of laboratory diagnosis
- •Patient management
- •Surveillance
- •Laboratory Tests
- •Direct methods
- •Immunofluorescence
- •Enzyme immuno assays or Immunochromatography assays
- •Reverse transcription polymerase chain reaction (RT-PCR)
- •Isolation methods
- •Embryonated egg culture
- •Cell culture
- •Laboratory animals
- •Serology
- •Haemagglutination inhibition (HI)
- •Complement fixation (CF)
- •Ezyme immuno assays (EIA)
- •Indirect immunofluorescence
- •Rapid tests
- •Differential diagnosis of flu-like illness
- •Diagnosis of suspected human infection with an avian influenza virus
- •Introduction
- •Specimen collection
- •Virological diagnostic modalities
- •Other laboratory findings
- •New developments and the future of influenza diagnostics
- •Conclusion
- •Useful Internet sources relating to Influenza Diagnosis
- •References
- •Clinical Presentation
- •Uncomplicated Human Influenza
- •Complications of Human Influenza
- •Secondary Bacterial Pneumonia
- •Primary Viral Pneumonia
- •Mixed Viral and Bacterial Pneumonia
- •Exacerbation of Chronic Pulmonary Disease
- •Croup
- •Failure of Recovery
- •Myositis
- •Cardiac Complications
- •Toxic Shock Syndrome
- •Reye’s Syndrome
- •Complications in HIV-infected patients
- •Avian Influenza Virus Infections in Humans
- •Presentation
- •Clinical Course
- •References
- •Treatment and Prophylaxis
- •Introduction
- •Antiviral Drugs
- •Neuraminidase Inhibitors
- •Indications for the Use of Neuraminidase Inhibitors
- •M2 Ion Channel Inhibitors
- •Indications for the Use of M2 Inhibitors
- •Treatment of “Classic” Human Influenza
- •Antiviral Treatment
- •Antiviral Prophylaxis
- •Special Situations
- •Children
- •Impaired Renal Function
- •Impaired Liver Function
- •Seizure Disorders
- •Pregnancy
- •Treatment of Human H5N1 Influenza
- •Transmission Prophylaxis
- •General Infection Control Measures
- •Special Infection Control Measures
- •Contact Tracing
- •Discharge policy
- •Global Pandemic Prophylaxis
- •Conclusion
- •References
- •Drug Profiles
- •Amantadine
- •Pharmacokinetics
- •Toxicity
- •Efficacy
- •Resistance
- •Drug Interactions
- •Recommendations for Use
- •Warnings
- •Summary
- •References
- •Oseltamivir
- •Introduction
- •Structure
- •Pharmacokinetics
- •Toxicity
- •Efficacy
- •Treatment
- •Prophylaxis
- •Selected Patient Populations
- •Efficacy against Avian Influenza H5N1
- •Efficacy against the 1918 Influenza Strain
- •Resistance
- •Drug Interactions
- •Recommendations for Use
- •Summary
- •References
- •Rimantadine
- •Introduction
- •Structure
- •Pharmacokinetics
- •Toxicity
- •Efficacy
- •Treatment
- •Prophylaxis
- •Resistance
- •Drug Interactions
- •Recommendations for Use
- •Adults
- •Children
- •Warnings
- •Summary
- •References
- •Zanamivir
- •Introduction
- •Structure
- •Pharmacokinetics
- •Toxicity
- •Efficacy
- •Treatment
- •Prophylaxis
- •Children
- •Special Situations
- •Avian Influenza Strains
- •Resistance
- •Drug Interactions
- •Recommendations for Use
- •Dosage
- •Summary
- •References
Rimantadine 211
Patients with any degree of renal insufficiency should be closely monitored, with dosage adjustments being made as necessary.
For treatment, rimantadine should be initiated within 48 hours after the onset of signs and symptoms of influenza A infection. Therapy should be continued for approximately seven days from the initial onset of symptoms.
Children
In the US, rimantadine is licensed for prophylactic use only. Children less than 10 years of age should receive 5 mg/kg but not exceeding 150 mg. Children 10 years of age or older receive the adult dose.
Warnings
Rimantadine should be used with caution in patients with epilepsy.
Summary
Trade name: Flumadine®
Drug class: M2 inhibitor
Indications: prophylaxis (adults and children) and treatment (adults only) of influenza A infection. Treatment must be initiated within 48 hours after the onset of symptoms.
Standard Dosage for Treatment: 100 mg bid.
A dose reduction to 100 mg daily is recommended in patients with severe hepatic dysfunction, renal failure (CrCl ≤ 10 ml/min) and in elderly nursing home patients.
Standard Dosage for Prophylaxis: 100 mg bid.
A dose reduction to 100 mg daily is recommended in patients with severe hepatic dysfunction, renal failure (CrCl ≤ 10 ml/min) and in elderly nursing home patients. Children less than 10 years of age should receive 5 mg/kg but not exceeding 150 mg. Children 10 years of age or older receive the adult dose.
Pharmacokinetics: peak plasma concentration is reached 6 hours after oral administration. The elimination half-life is 30 hours. Prolonged elimination in elderly people. Extensive metabolisation in the liver – less than 25 % is excreted unchanged in the urine. Increased plasma concentration in patients with severe hepatic and renal insufficiency.
Interactions: no significant interactions. Side effects: gastrointestinal symptoms.
References
1.Anderson EL, Van Voris LP, Bartram J, Hoffman HE, Belshe RB. Pharmacokinetics of a single dose of rimantadine in young adults and children. Antimicrob Agents Chemother 1987; 31: 1140-2. Abstract: http://amedeo.com/lit.php?id=3662473 – Full text at http://www.pubmedcentral.gov/articlerender.fcgi?pubmedid=3662473
2.Belshe RB, Smith MH, Hall CB, Betts R, Hay AJ. Genetic basis of resistance to rimantadine emerging during treatment of influenza virus infection. J Virol 1988; 62: 1508-12. Abstract: http://amedeo.com/lit.php?id=3282079
212 Drug Profiles
3.Belshe RB, Burk B, Newman F, Cerruti RL, Sim IS. Resistance of influenza A virus to amantadine and rimantadine: results of one decade of surveillance. J Infect Dis 1989;
159:430-5. Abstract: http://amedeo.com/lit.php?id=2915166
4.Brady MT, Sears SD, Pacini DL, et al. Safety and prophylactic efficacy of low-dose rimantadine in adults during an influenza A epidemic. Antimicrob Agents Chemother 1990;
34:1633-6. Abstract: http://amedeo.com/lit.php?id=2285274
5.Bright RA, Medina MJ, Xu X, et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005; 366: 1175-81. Epub 2005 Sep 22. Abstract: http://amedeo.com/lit.php?id=16198766
6.Bui M, Whittaker G, Helenius A. Effect of M1 protein and low pH on nuclear transport of influenza virus ribonucleoproteins. J Virol 1996; 70: 8391-401. Abstract: http://amedeo.com/lit.php?id=8970960 – Full text at http://jvi.asm.org/cgi/reprint/70/12/8391?pmid=8970960
7.Capparelli EV, Stevens RC, Chow MS, Izard M, Wills RJ. Rimantadine pharmacokinetics in healthy subjects and patients with end-stage renal failure. Clin Pharmacol Ther 1988;
43:536-41. Abstract: http://amedeo.com/lit.php?id=3365917
8.CDC 2006. CDC Recommends against the Use of Amantadine and Rimantadine for the Treatment or Prophylaxis of Influenza in the United States during the 2005–06 Influenza Season. Available from http://www.cdc.gov/flu/han011406.htm – Accessed 13 February 2006.
9.Clover RD, Crawford SA, Abell TD, Ramsey CN Jr, Glezen WP, Couch RB. Effectiveness of rimantadine prophylaxis of children within families. Am J Dis Child 1986; 140: 706-9. Abstract: http://amedeo.com/lit.php?id=3521258
10.Clover RD, Waner JL, Becker L, Davis A. Effect of rimantadine on the immune response to influenza A infections. J Med Virol 1991; 34: 68-73. Abstract: http://amedeo.com/lit.php?id=1885945
11.Crawford SA, Clover RD, Abell TD, Ramsey CN Jr, Glezen P, Couch RB. Rimantadine prophylaxis in children: a follow-up study. Pediatr Infect Dis J 1988; 7: 379-83. Abstract: http://amedeo.com/lit.php?id=3292997
12.Demicheli V, Jefferson T, Rivetti D, Deeks J. Prevention and early treatment of influenza in healthy adults. Vaccine 2000; 18: 957-1030. Abstract: http://amedeo.com/lit.php?id=10590322
13.Dolin R, Reichman RC, Madore HP, Maynard R, Linton PN, Webber-Jones J. A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. N Engl J Med 1982; 307: 580-4. Abstract: http://amedeo.com/lit.php?id=7050702
14.Doyle WJ, Skoner DP, Alper CM, et al. Effect of rimantadine treatment on clinical manifestations and otologic complications in adults experimentally infected with influenza A (H1N1) virus. J Infect Dis 1998; 177: 1260-5. Abstract: http://amedeo.com/lit.php?id=9593010 – Full text at http://www.journals.uchicago.edu/cgi-bin/resolve?JIDv177p1260PDF
15.Englund JA, Champlin RE, Wyde PR, et al. Common emergence of amantadineand rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Clin Infect Dis 1998; 26: 1418-24. Abstract: http://amedeo.com/lit.php?id=9636873 – Full text at http://www.journals.uchicago.edu/cgi-bin/resolve?CIDv26p1418PDF
16.Hall CB, Dolin R, Gala CL, et al. Children with influenza A infection: treatment with rimantadine. Pediatrics 1987; 80: 275-82. Abstract: http://amedeo.com/lit.php?id=3302925
17.Hayden FG, Minocha A, Spyker DA, Hoffman HE. Comparative single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride in young and elderly adults. Antimicrob Agents Chemother 1985; 28: 216-21. Abstract: http://amedeo.com/lit.php?id=3834831 – Fulltext at http://www.pubmedcentral.gov/articlerender.fcgi?pubmedid=3834831
18.Hayden FG, Monto AS. Oral rimantadine hydrochloride therapy of influenza A virus H3N2 subtype infection in adults. Antimicrob Agents Chemother 1986; 29: 339-41. Abstract: http://amedeo.com/lit.php?id=3521480